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Early-onset pancreatic cancer: Defining contemporary presentation, treatment, and outcomes in the under 50 age group using real-world data.

533 Background: The incidence of pancreatic cancer is increasing in younger patients (pts). Early onset pancreatic cancer (EOPC) is reportedly diagnosed at a later stage, potentially compromising outcomes compared to later onset pts (LOPC). With recent gains in staging and neo/adjuvant regimens, we sought to elaborate on the characteristics of EOPC and LOPC in a contemporary real-world cohort. Methods: The PURPLE registry, a prospectively collected multi-site data set on consecutive pancreatic cancer pts was interrogated. Patient, tumor, treatment and outcome data were extracted for EOPC vs LOPC. EOPC were those diagnosed prior to age 50 and LOPC after age 50. Resectability status was per MDT consensus. Results: Of 1534 pts, 93 (6%) were EOPC (51% male) and 1442 (94%) LOPC (51% male). EOPC had better ECOG performance status (0-1: 95% vs 81%, Relative Risk [RR] 1.2, p < 0.001) and Charlson Comorbidity Index Score (0-2: 98% vs 28%, RR 3.5, p < 0.001). Primary tumor site (head/body/tail: 66%/11%/20% for EOPC and 68%/17%/14% for LOPC), and staging (resectable/borderline resectable/locally advanced/metastatic: 29%/16%/14%/41% for EOPC vs 28%/9%/21%/41% for LOPC) did not differ. 25 (93%) of EOPC and 320 (79%) LOPC resectable pts underwent resection (p = 0.13). 12 (80%) EOPC and 36 (26%) LOPC borderline resectable pts underwent resection (RR 3.0, p < 0.001). Resection margin status (R0 vs R1 vs R2) did not differ. Resected EOPC more frequently received neoadjuvant therapy (30% vs 9%, RR 3.2, p = 0.001). EOPC were more likely to receive palliative chemotherapy in the advanced/metastatic setting (77% vs 49%, RR 1.6, p < 0.001), and were more likely to receive first line (1L) FOLFIRINOX than gemcitabine-nab-paclitaxel (36% vs 18%, RR 2, p = 0.019). Median overall survival (OS) was superior for EOPC (24 vs 12 months, Hazard Ratio [HR] 0.55, p < 0.001). For resectable pts, relapse free survival (RFS) did not differ but OS was superior for EOPC (undefined vs 27.7 months, HR 0.26, p = 0.004). In borderline resectable pts, RFS was similar and OS only numerically superior for EOPC (31.2 vs 17.7 months, p = 0.20). For locally advanced disease, 1L progression free survival (PFS1) was similar and OS was superior for EOPC (27.8 vs 11 months, HR 0.40, p = 0.008). There was no difference in PFS1/OS for metastatic pts. Conclusions: EOPC are fitter, with similar stage at diagnosis as LOPC. EOPC are more likely to receive neoadjuvant chemotherapy and undergo resection when presenting with borderline resectable disease. EOPC receive more treatment and have superior OS, with RFS/PFS1 not statistically different to LOPC.

Use of Fluoro-[18F]-Deoxy-2-D-Glucose Positron Emission Tomography/Computed Tomography to Predict Immunotherapy Treatment Response in Patients With Squamous Cell Oral Cavity Cancers

Neoadjuvant immunotherapy is a novel approach with the potential to improve outcomes for patients with oral cavity squamous cell cancer (OCSCC). Adverse events of varying severity are reported with immunotherapy, and a biomarker to predict response would be clinically useful to avoid toxic effects in those unlikely to benefit. To correlate changes on fluoro-[18F]-deoxy-2-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) scans with primary tumor pathologic response and immunologic biomarkers in patients with OCSCC receiving neoadjuvant immunotherapy. This was a retrospective analysis of serial FDG-PET/CT scans obtained prospectively as part of a phase 2 open-label randomized clinical trial investigating neoadjuvant immunotherapy in patients with untreated OCSCC between 2016 and 2019. Included were a total of 29 patients from a single academic medical center with untreated OCSCC (≥T2, or clinically node positive) randomized 1:1 to receive neoadjuvant therapy with single agent nivolumab or combination nivolumab and ipilimumab followed by surgery and standard of care adjuvant therapy. The interventions in this study were FDG-PET/CT scans before (T0) and after (T1) preoperative immunotherapy. Data collected from FDG-PET/CT scans included maximum standardized uptake value (SUVmax) of primary OCSCC and cervical lymph nodes (LNs) at T0 and T1 and new LN uptake and uptake consistent with radiologic immune-related adverse events (irAEs) at T1. Primary OCSCC pathologic response reported as percentages of viable vs nonviable tumor. The number of CD8+ cells/mm2 was determined in the primary tumor biopsy specimen and at surgery. There was no correlation between pathologic response and change in SUVmax in the primary OCSCC between T0 and T1. Out of 27 total participants, 13 had newly FDG-avid ipsilateral LNs at T1, most negative on pathology. A total of 9 had radiologic irAEs, most commonly sarcoid-like LN (7 of 27). No correlations were found between primary OCSCC SUVmax at T0 and CD8+ T-cell number in the primary tumor biopsy, and no correlations were found between primary OCSCC SUVmax at T1 and CD8+ T-cell number in the primary tumor at surgery. There were no correlations between changes in FDG uptake after neoadjuvant immunotherapy and pathologic primary tumor response. Importantly, newly FDG-avid ipsilateral LNs following neoadjuvant immunotherapy were commonly observed but did not represent progressive disease or indicate pathologically disease positive nodes in most cases. These findings argue against altering surgical plans in this setting and suggest that the role of FDG-PET/CT may be limited as an early imaging biomarker for predicting pathologic response to preoperative immunotherapy for OCSCC. ClinicalTrials.gov Identifier: NCT02919683.

Lymph Nodes With Germinal Centers Are Not Associated With Tumor Response After Neoadjuvant Treatment in Locally Advanced Rectal Cancer.

In patients with locally advanced rectal cancer, neoadjuvant radiotherapy or chemoradiotherapy followed by total mesorectal excision as a standard of care. We aimed to explore the number, size, germinal centers, extracapsular invasion of lymph nodes (LN), and their impact on overall survival and disease free survival. Furthermore we also investigated the characteristics of lymph nodes in patients who received neoadjuvant therapy and those who underwent surgery between 2011 and 2018. The count and measurement of lymph nodes was assessed by careful visual inspection and manual palpation. The predictive cut-off value of the lymph node ratio (LNR) was determined based on the receiver operating characteristic (ROC), method and the survival outcomes based on Kaplan-Meier curves. We found that the size and the number of lymph nodes decreased significantly after neoadjuvant treatment. The mean LN for patients who received neoadjuvant therapy was 12.68 ± 6.69 and for patients who did not receive neoadjuvant therapy was 16.29 ± 5.61 (P = .012). The average size for patients who received neoadjuvant therapy followed by surgery was 3.30 ± 1.10 versus 4.22 ± 1.18 mm for control group (surgery only) (P < .001), an LNR of 0.13 (sensitivity: 86%, specificity: 47%, AUC: 60%, 95% CI, 0.41%-0.76%) predicted recurrence and metastasis. Presence of lymph nodes with germinal centers was significantly associated with absence of vascular invasion, nodal tumor deposits, distant metastasis, and lower age group (<50 years). However there was no association seen between overall survival and relapse free, total number of lymph nodes enlarged and extracapsular invasion in positive nodes. Finally there is no association between lymph nodes with germinal centers and tumor response after neoadjuvant treatment in locally advanced rectal cancer.

Video-assisted thoracoscopic lobectomy and bilobectomy versus open thoracotomy for non-small cell lung cancer: Mortality and survival

Background In this study, we aimed to evaluate patients who had non-small cell lung cancer and underwent resection, to investigate our tendency to prefer video-assisted thoracic surgery or open thoracotomy, and to compare 30- and 90-day mortalities and survival rates. Methods Between January 2013 and January 2019, a total of 706 patients (577 males, 129 females; mean age: 61.9±8.6 years; range, 17 to 84 years) who underwent lobectomy or bilobectomy due to primary non-small cell lung cancer were retrospectively analyzed. The patients were divided into two groups as operated on through video-assisted thoracic surgery and through open thoracotomy. The 30- and 90-day mortality rates and survival rates were compared. Results Of the patients, 202 (28.6%) underwent video-assisted thoracic surgery and 504 (71.4%) underwent open thoracotomy. Lobectomy was performed in 632 patients (89.5%) and bilobectomy was performed in 74 patients (10.5%). Patients who were chosen for video-assisted thoracic surgery were statistically significantly older, did not require any procedure other than lobectomy, did not receive neoadjuvant therapy, had a small tumor, and did not have lymph node metastases. The 30- and 90-day mortality rates in the video-assisted thoracic surgery and open thoracotomy groups were 1.8% vs. 2% and 2.6% vs. 2.5%, respectively. The five-year survival rates of video-assisted thoracic surgery and open thoracotomy groups were 74.1% and 65.2%, respectively (p>0.05). The 30- and 90-day mortality and five-year survival rates were 2.1%, 2.6%, and 73.5% in the video-assisted thoracic surgery group and 2.1%, 2.1%, and 68.5% in the open thoracotomy group, respectively, indicating no statistically significant difference between the two groups. Conclusion Throughout the study period, video-assisted thoracic surgery was more preferred in patients with advanced age, in those who had a small tumor, who did not receive neoadjuvant therapy, did not have lymph node metastasis, and did not require any procedure other than lobectomy. In the video-assisted thoracic surgery and open thoracotomy groups, 30- and 90-day mortality and five-year survival rates were similar. Based on these findings, both procedures seem to be acceptable in this patient population.

Lymph node ratio-based the ypTNrM staging system for gastric cancer after neoadjuvant therapy: a large population-based study.

The lymph node ratio (LNR) has been considered a better prognostic factor than traditional N staging in patients with gastric cancer (GC), but its accuracy is unclear for those who receive neoadjuvant therapy (NAT). We aimed to compare the node ratio (Nr) staging with the ypN staging and to thereby develop a modified staging system incorporating Nr staging. A total of 1791 patients who underwent gastrectomy after NAT in the Surveillance, Epidemiology, and End Results database were retrospectively analyzed. ypTNrM staging was established based on the overall survival (OS). The Nr staging was generated using 0.2 and 0.5 as the cutoff values of LNR and represented patients with more homogeneous OS compared with ypN staging. The 5-year OS rates for ypTNrM stages IA, IB, II, IIIA, and IIIB were 70.2%, 54.2%, 36.0%, 21.2%, and 6.6%, respectively, compared with 58.8%, 39.1%, and 21.6% for ypTNM stages I, II, and III, respectively. Compared with the ypTNM staging system, the ypTNrM staging system had a lower misclassification rate (3.0% vs. 50.9%) and better prognostic predictive power (C-index: 0.645 vs. 0.589, P < 0.001). The ypTNrM staging system incorporating Nr staging may provide a more accurate assessment in the clinical decision-making process for GC after NAT.

Drug Repositioning Based on the Reversal of Gene Expression Signatures Identifies TOP2A as a Therapeutic Target for Rectal Cancer.

Simple SummaryRectal cancer is the 8th most common cancer globally. Most patients with locally advanced rectal cancer receive neoadjuvant therapy based on 5-fluorouracil and radiotherapy showing variable responses. About 70–90% of patients present partial response, while 20% show treatment resistance. Repositioning drugs approved by regulatory agencies or drugs currently in clinical trials is a strategy to accelerate the development of drug-based cancer therapies. We compared rectal cancer gene expression signatures with reverse drug-induced gene-expression profiles of cancer cell lines to identify potential drugs for repositioning. Our analyses revealed that approved topoisomerase II inhibitors are candidate drugs for rectal cancer treatment. We also verified TOP2A copy number gains and increased expression in rectal tumors. These TOP2A alterations were independent predictive markers of topoisomerase inhibitor efficacy in colorectal cancer cells that closely represent rectal cancer signatures. Topoisomerase inhibitors are potentially helpful to treat rectal cancer patients with TOP2A imbalances.Rectal cancer is a common disease with high mortality rates and limited therapeutic options. Here we combined the gene expression signatures of rectal cancer patients with the reverse drug-induced gene-expression profiles to identify drug repositioning candidates for cancer therapy. Among the predicted repurposable drugs, topoisomerase II inhibitors (doxorubicin, teniposide, idarubicin, mitoxantrone, and epirubicin) presented a high potential to reverse rectal cancer gene expression signatures. We showed that these drugs effectively reduced the growth of colorectal cancer cell lines closely representing rectal cancer signatures. We also found a clear correlation between topoisomerase 2A (TOP2A) gene copy number or expression levels with the sensitivity to topoisomerase II inhibitors. Furthermore, CRISPR-Cas9 and shRNA screenings confirmed that loss-of-function of the TOP2A has the highest efficacy in reducing cellular proliferation. Finally, we observed significant TOP2A copy number gains and increased expression in independent cohorts of rectal cancer patients. These findings can be translated into clinical practice to evaluate TOP2A status for targeted and personalized therapies based on topoisomerase II inhibitors in rectal cancer patients.

Clinical Predictors of Locally Advanced Pathology in Esophageal Adenocarcinoma.

BackgroundIn patients with resectable esophageal adenocarcinoma (EAC), the decision for neoadjuvant treatment depends on clinical staging with endoscopic ultrasound (EUS) and positron-emission tomography (PET) scan. Patients with locally advanced EAC pathology misclassified as early EAC by clinical staging are missing the opportunity to receive neoadjuvant therapy. We aim to identify predictors of locally advanced pathology in EAC to determine more accurately those who benefit from neoadjuvant therapy. MethodsRetrospective study of patients who underwent upfront endoscopic or surgical resection for EAC without neoadjuvant therapy from January 2011 to December 2017 was performed. Clinical characteristics, EUS, PET scan and histologic findings were analyzed. Multivariable analysis of predictors of locally advanced stage was performed and a risk prediction score was developed.ResultsA total of 97 patients were included; 68 patients were staged as early EAC (pT1 or pT2 and pN0) and 29 patients were staged as locally advanced EAC (pT1 or pT2 with pN1 and pT3 or pT4 irrespective of N status). In a predictive model of EAC, patients presenting with dysphagia, tumor size >2 cm, exophytic mass appearance on endoscopy and absence of hiatal hernia were more likely to be have locally advanced pathology with a probability of 70% (C-statistic 0.766).ConclusionsA risk prediction model based on the presence of dysphagia, tumor size >2 cm, exophytic mass appearance and absence of hiatal hernia can be used to identify locally advanced pathology in EAC patients.

Oncoplastic Breast Surgery: Is it reliable in the treatment of multifocal breast cancer? A preliminary report of a prospective randomized controlled trial

Background/Aim: Multifocal breast cancers (MFBCs) still have undiscoverable clinical significance. Being the standard surgical management for early breast cancer, implementation of breast-conservation therapy (BCT) as a surgical procedure for multifocal breast cancers is still questionable and needs a solid basis of clinical evidence via prospective randomized control trials. Methods: A prospective study was conducted on female patients with operable multifocal breast cancer excluding those diagnosed with inflammatory breast cancer and those to receive neoadjuvant therapy. Surgical management was selected randomly and comprised either modified radical mastectomy (MRM) or different techniques of oncoplastic breast surgery (OPS) with a sealed envelope system based on clinical evaluation and recent guidelines for management at the Surgical Oncology Unit, Alexandria University from May 2017-May 2018. The patients were followed up until February 2021 with a median follow-up of 39 months postoperatively to assess recurrence. Analysis of different clinicopathological factors was performed to evaluate the reliability of OPS in the surgical management of MFBCs. Results: A total of 132 patients were initially assessed for the eligibility criteria. Finally, 58 patients in the OPS group and 56 patients in the MRM group were followed up until the end of the study period. After a median follow-up of 39 months post-operatively for both groups, three patients belonging to the oncoplastic group suffered from local recurrence (5.2%). Two patients who had MRM had distant recurrence (3.6%). Although recurrence behavior was different between both groups, this was not statistically significant. Conclusion: OPS is an oncologically safe surgical option for selected cases of multifocal breast cancer.

Clinicopathological Features of Stage I-III Colorectal Cancer Recurrence Over 5 Years After Radical Surgery Without Receiving Neoadjuvant Therapy: Evidence From a Large Sample Study.

Late recurrence (5 or more years) after radical resection of colorectal cancer (CRC) is rare. This study aims to investigate the features of late recurrence in stage I–III CRC. A total of 9,754 stage I–III patients with CRC who underwent radical surgery without receiving neoadjuvant therapy, at the Fudan University Shanghai Cancer Center (FUSCC), were enrolled in this study. These patients were divided into three groups: early recurrence (3 months−2 years), intermediate recurrence (2–5 years), and late recurrence (over 5 years). The median duration of follow-up was 53.5 ± 30.1 months. A total of 2,341 (24.0%) patients developed recurrence. The late recurrence rate was 11.7%. Patients with a higher risk of late recurrence were more likely to be older, to be at the T4 stage, to have a higher degree of colon cancer, to have a lower frequency of signet ring cell carcinoma, to have fewer poorly differentiated tumors, to be at the early stage of CRC, along with less perineural and vascular invasions. Multivariate logistic regression analysis identified age, differentiation, T stage, N stage, perineural, and vascular invasions as independent factors for late recurrence. Late recurrent CRC has some distinctive characteristics. Although recurrence over 5 years after surgery is infrequent, an enhanced follow-up is still needed for the selected patients after 5 years.

Preoperative biliary drainage for pancreatic cancer.

Pancreatic adenocarcinoma is currently one of the leading causes of cancer-related morbidity and mortality with dismal long term survival after diagnosis. Nearly 85% of pancreatic cancer patients present with advanced disease precluding curative surgical resection. In those who are candidates for surgery, preoperative biliary drainage (PBD) has been developed since the 1960s in order to improve surgical outcomes. While obstructive jaundice in resectable pancreatic cancer has been traditionally treated before surgical resection in all patients, data over the past decade demonstrated increased perioperative complications and morbidity with systematic PBD compared to direct surgery. With new evidence of potential adverse events, the role of routine PBD is being reassessed. Current indications for PBD include cholangitis, delayed surgery, and relief of jaundice in patients planned to receive neoadjuvant therapy (NAT). NAT is being increasingly utilized in borderline resectable as well as resectable pancreatic cancer and a higher proportion of patients with likely require PBD in the future. The evidence for endoscopic retrograde cholangiopancreatography as first line for PBD is robust with supporting data from endoscopic ultrasound assisted biliary drainage. Self-expanding metal stent was shown to be cost-effective in recent studies without increase in morbidity compared to plastic stents in this setting. In this review, we will summarize the current evidence for PBD in patients with pancreatic cancer.

Adult Soft Tissue Sarcoma: A Prospective Observational Real-World Data

Abstract Introduction There is a lacuna of prospective studies on soft tissue sarcoma (STS) from the Indian subcontinent in published literature. Objectives We conducted this study to describe the clinical profile and outcomes of STS in North India. Materials and Methods This is a single-center, prospective, observational study conducted from October 2017 to September 2019. All consecutive patients aged ≥18 years with histopathological diagnosis of STS were enrolled. The study end points included overall response rate, progression-free survival (PFS), and overall survival (OS). Results A total of 140 patients were included with a median duration of follow-up of 14 months (range: 1–25 months). The median age of patients was 45 years. The median duration of symptoms before diagnosis was 5 months (range: 1–18 months). The most common histopathologic subtype was undifferentiated pleomorphic STS (22%). Of 105 localized patients, 21 received neoadjuvant therapy with external beam radiotherapy and/or doxorubicin-based chemotherapy and reported partial response in 38% (8/21) of the patients; the remaining 62% (13/21) of the patients had stable disease. Neoadjuvant therapy resulted in nonsignificantly higher complete resection rates with relative risk of 2.37 (p = 0.19). Of the remaining 35 metastatic STS patients, 31 received chemotherapy and reported partial response in 39.1% (n = 9/23), stable disease in 30.4% (n = 7/23), and disease progression in 30.4% (n = 7/23) of the patients. For localized STS patients, 1-year disease-free survival (DFS) and OS rates were 87.6 ±3.5 and 95.3 ± 2.3%, respectively. The median OS for metastatic STS patients was 23.90 months (95% confidence interval [CI]: 7.43–40.36). Among metastatic STS, median OS was not reached for those who underwent curative resection versus 12.66 months (95% CI: 9.28–16.04) for those who received systemic therapy alone. Conclusion Median age of 45 years is a decade earlier than seen in the Western population. Neoadjuvant therapy improved complete resection rates, though it was statistically nonsignificant. Curative resection among metastatic STS patients improves survival.

The effect of neoadjuvant imatinib therapy on outcome and survival in rectal gastrointestinal stromal tumors: A multiinstitutional study.

This study aimed to characterize the efficacy of neoadjuvant imatinib in rectal gastrointestinal stromal tumors (GISTs) and the prognostic characteristics of patients after surgery. Patients with rectal GISTs who received neoadjuvant imatinib between 2000 and 2019 were selected from 11 large-scale tertiary hospitals in China. The best response to neoadjuvant imatinib was assessed. Propensity score matching (PSM) was conducted to reduce confounders. Recurrence free survival (RFS) and overall survival (OS) were estimated using Kaplan-Meier method. Of the 100 patients, 75, 18, and 7 had a partial response (PR), stable disease (SD), and progressive disease (PD), respectively. The median tumor size decreased from 5 cm before treatment to 4 cm after treatment (p < 0.001). A total of 31 patients underwent genetic testing after surgery; 23 of patients with exon 11 mutation had PR and 2 had SD. One of the patients with exon 9 mutation had PR, 2 had SD, and 1 had PD. Two patients with the wild type GIST had PD. A total of 86 patients underwent surgery of which 85 underwent complete resection; 72 underwent anal preservation and 40 underwent local excision (LE). After PSM, patients who received neoadjuvant therapy had higher rates of LE (p = 0.001) and anal preservation (p = 0.033) than those of patients without neoadjuvant therapy. The median follow-up time was 37 months. Nine patients experienced recurrence and one patient died. The 3-year RFS and OS rates were 95.0% and 100%, respectively. After PSM, we found that there was no significant difference in RFS between patients who received or did not receive neoadjuvant therapy (p = 0.623). Univariate analysis showed postneoadjuvant tumor size (p = 0.469) and mitotic count (p = 0.294) were not associated with the RFS in patients who received neoadjuvant imatinib. Neoadjuvant imatinib can shrink rectal GIST size, increasing the possibility of complete resection and anal preservation. Further studies are warranted to understand the long-term outcomes of rectal GISTs in patients receiving neoadjuvant imatinib.

Laparoscopic Partial Gastrectomy for Large Gastric GISTs.

Gastrointestinal stromal tumors (GISTs) are considered the most common mesenchymal tumors in the gastrointestinal tract and the stomach is the most frequently site affected (50-60%). The safety and feasibility of laparoscopic surgery for gastric GISTs of sizes larger than 5cm remains unclear. It depends on the surgical skills, tumor location, and the learning curve of the surgeons. Between December 2013 and January 2021, 30 patients diagnosed with gastric GISTs underwent laparoscopic partial gastrectomy. This is a retrospective study done in Surgical Oncology unit, Oncology Center, Mansoura University, Egypt. The most common tumor location was in the greater curvature in (46.7%). The mean tumor size was 9.5cm (range 5-17cm). All of the patients underwent laparoscopic partial gastrectomy. Associatedsplenectomy was done for onlyone patient. The mean operative time was 152.67min and the estimated blood loss (EBL) was 139.33ml. The mean hospital stay was 3.53days. The mean follow-up period was 32.4months. Laparoscopic resection for gastric GISTs has become a feasible method. Patients with large tumors have the same favorable outcomes as small tumors. Large-sized GISTs may receive neoadjuvant therapy to downstage the disease and make it amenable for laparoscopic resection.

Associations between preexisting nociplastic pain and early discontinuation of aromatase inhibitor therapy in breast cancer.

12068 Background: Aromatase inhibitors (AI) are recommended for at least five years to reduce risk of breast cancer recurrence in postmenopausal women with hormone receptor-positive disease. Despite the potential benefit, up to 50% of patients discontinue AI early, primarily because of musculoskeletal side effects. Some patients, including those with fibromyalgia and other chronic pain conditions, have preexisting pain that arises from altered nociception without clear evidence of tissue or peripheral nerve damage, called nociplastic or centralized pain. We hypothesized that preexisting nociplastic pain is associated with early discontinuation of AI therapy due to toxicity. Methods: Patients diagnosed with breast cancer between 2012-19 and who enrolled in the Michigan Genomics Initiative (MGI) were identified. Patients who were female, had hormone receptor-positive breast cancer, had not received neoadjuvant therapy, and who initiated adjuvant AI therapy were included in the analysis. Prior to breast cancer surgery patients completed surveys about pain in the affected breast and overall worst pain (Brief Pain Inventory [BPI]), nociplastic pain (2011 Fibromyalgia Survey [FS], which assesses widespread pain plus somatic symptom severity), and anxiety (PROMIS Anxiety 4a v.1). Demographics, cancer characteristics, and treatment history, including date and reason for discontinuation of AI therapy, were abstracted from the medical record. Patients were censored at date of last oncology follow-up. Univariate and multivariable analyses were conducted to assess relationship between age, BMI, surgical site pain, overall worst pain, FS score, anxiety, and time to discontinuation of initial AI medication. Results: Of 207 analyzed patients, the average age was 61 years, average BMI was 30.3 kg/m2, 181 (87%) were postmenopausal at the time of breast cancer diagnosis, and 31% received chemotherapy. The majority were prescribed anastrozole (n=196); 6 took letrozole and 5 took exemestane. Average scores prior to surgery were 1.5/10 for worst pain, 0.2/10 for surgical site pain, 4.2/31 for FS score, and 54.1/100 for anxiety. On univariate analysis, only use of exemestane (HR 5.55, p&lt;.001) and use of letrozole (HR 3.11, p&lt;.001) were associated with shorter time to ET discontinuation; age, BMI, surgical site pain, worst pain, FS score, and anxiety were not statistically significantly associated with time to AI discontinuation. On multivariable analysis, only higher FS score was statistically significantly associated with time to AI discontinuation (HR 1.11, p=.021). Conclusions: Greater pre-existing nociplastic pain was associated with early discontinuation of AI therapy. For these patients, early interventions that target centralized pain, or treatment with tamoxifen instead of AI therapy, may be appropriate in order to reduce risk of nonpersistence with AI therapy.

Camrelizumab combined with paclitaxel and nedaplatin as neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (ESPRIT): A phase Ⅱ, single-arm, exploratory research.

e16033 Background: Camrelizumab has been approved as a standard therapy in the second-line treatment of esophageal squamous cell carcinoma (ESCC). This study aimed to explore the efficacy and safety of camrelizumab combined with commonly used neoadjuvant chemotherapy (paclitaxel and platinum) in neoadjuvant treatment of ESCC. Methods: In this single-arm, phase Ⅱ study, patients with advanced ESCC who were expected to receive neoadjuvant therapy followed by radical surgery were recruited. The patients received 2-4 cycles of camrelizumab (200mg, iv, q3w) in combination with paclitaxel (155mg/m2, iv, q3w) and nedaplatin (80mg/m2, iv, q3w) as neoadjuvant therapy, and the therapeutic effects were determined every 2 cycles. The radical surgery was performed on patients whose tumors were evaluated as resectable. The primary endpoint was pCR, and the secondary endpoints were objective response rate (ORR) and disease control rate (DCR). Results: From May 2020 to January 2021, 24 patients with a median age of 60.5 years (50-73) were enrolled. Among them, 21 patients were available for efficacy analysis, of which 1 achieved complete response (CR), 7 achieved partial response (PR), and 13 had stable disease (SD). The ORR was 38.1% and DCR was 100%. The tumor in 10 patients shrank significantly after neoadjuvant therapy and these patients preferred radiotherapy instead of surgery as the radical therapeutic method. 2 patients abandoned surgery because of personal reasons. 2 patients were in the process of neoadjuvant therapy and had not undergone surgery yet. The remaining 7 patients underwent radical surgery and 4 patients (57.14%) achieved pCR (pT0N0M0). The main treatment-related grade 3/4 adverse event (AE) was neutropenia (1/21). All the AEs were manageable. The average intraoperative blood loss was 221mL and the average hospitalization time after operation was 12.7 days (range 8-19 days). No anastomotic leakage and treatment-related death occurred. Conclusions: Camrelizumab in combination with paclitaxel and platinum as a neoadjuvant therapy was well tolerated. The pCR rate of 57.14% was higher than the expected 40%. This encouraging result promoted us to continue this phase Ⅱ study. Clinical trial information: ChiCTR2000033761.

Abstract PD4-05: Axillary recurrence is a rare event in node-positive patients. treated with sentinel node biopsy alone after neoadjuvant chemotherapy: Results of a prospective study

Abstract Background: Four prospective multi-institutional trials have demonstrated that clinically node-positive patients (cN1) who receive neoadjuvant therapy (NAC) and convert to cN0 can be reliably staged with sentinel lymph node biopsy (SLNB) with false-negative rates (FNRs) of &amp;lt; 10%, when ≥ 3 SLNs are retrieved. Since study patients all had axillary lymph node dissection (ALND), the rate of axillary recurrence after SLNB alone is unknown. Of concern is the possibility that residual chemotherapy-resistant axillary disease could lead to higher recurrence rates than seen in the primary surgery setting for cN0 patients where SLN FNRs of 5-10% result in axillary recurrence in &amp;lt; 1% of cases. Here we report regional recurrence rates in a prospectively defined cohort of cN1 patients receiving NAC, followed by a negative SLNB using a standardized technique, and no further axillary surgery. Methods: From 06/2014 to 02/2019, patients with cT1-3 biopsy-proven cN1 breast cancer who received NAC and converted to cN0 by physical exam were prospectively managed with SLNB with dual tracer mapping and omission of ALND if ≥ 3 SLNs were pathologically negative. Nodes were not routinely clipped, and retrieval of clipped metastatic nodes was not required. Pathologically negative SLNs were defined as the absence of any metastases including isolated tumor cells. Results: Of 610 cN1 patients treated with NAC, 555 (91%) converted to cN0 and had SLNB; 234 (42%) had ≥ 3 negative SLNs and were treated with SLNB alone. Median patient age was 49 years and median tumor size at presentation was 3 cm; 61% were HER2+ and 18% triple negative. Most (91%) received doxorubicin-based NAC and 88% received adjuvant radiotherapy (RT), with 80% (n = 164) of RT patients receiving nodal RT (Table). At a median follow-up of 35 months, there was only 1 (0.4%) axillary recurrence for the entire cohort, synchronous with a breast recurrence, in a patient who refused RT. Among patients who received RT (n = 205), there were no axillary recurrences. The 4-year rate of distant recurrence for all patients was 6.1% (95% CI, 3.4-10.7%) and 4-year overall survival was 93.9% (95% CI, 87.6-97.1%). Conclusion: In cN1 patients treated with NAC, rates of axillary recurrence in patients with ≥ 3 pathologically negative SLNs treated with SLNB alone were low, without routine nodal clipping. Although further follow-up is needed, multiple studies have shown that nodal recurrence is an early event, particularly in HER2+ and triple negative patients, who comprised the majority of the population. Our findings support omitting ALND in cN1 patients after NAC when the SLNs are negative using an optimal SLNB technique. Table. Patient PopulationOverall cohort (n = 234)Age, years (median, IQR)49 (40, 58)Tumor size at presentation, cm (median, IQR)3.0 (2.2, 5.0)Number SLNs retrieved (median, IQR)4 (3, 5)Palpable nodes at presentation (n, %)179 (76%)HistologyDuctal211 (90%)Lobular and mixed7 (3%)Micropapillary and mixed10 (4%)Other3 (1%)Occult3 (1%)DifferentiationWell1 (0.5%)Moderate36 (15%)Poor196 (84%)Unknown1 (0.5%)Receptor StatusHR+/HER2-47 (20%)HR+/HER2+80 (34%)HR-/HER2+64 (27%)HR-/HER2-43 (18%)Breast SurgeryBCS118 (50%)Mastectomy116 (50%)Breast pCR¥Yes161 (70%)No70 (30%)NAC regimenAC-T197 (84%)AC-T + carbo15 (6.4%)TC8 (3.4%)Other14 (6%)Neoadjuvant anti-HER2 treatmentHP (dual-therapy)144 (100%)Adjuvant RTYes205 (88%)No*29 (12%)¥3 patients had occult primary breast cancer and were not included in breast pCR calculation; *6/29 patients who did not receive RT enrolled in NSABP B-51 Citation Format: Andrea V Barrio, Giacomo Montagna, Anita Mamtani, Varadan Sevilimedu, Hiram S Cody, III, Mahmoud El-Tamer, Mary L Gemignani, Alexandra S Heerdt, Tracy-Ann Moo, Melissa Pilewskie, George Plitas, Lisa Sclafani, Kimberly J Van Zee, Monica Morrow. Axillary recurrence is a rare event in node-positive patients. treated with sentinel node biopsy alone after neoadjuvant chemotherapy: Results of a prospective study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD4-05.

Abstract PS1-15: Does breast cancer subtype impact margin status in patients undergoing partial mastectomy?

Abstract BACKGROUND: It is known that breast cancer subtype (e.g., luminal vs. triple negative (TN)) can affect response to systemic therapy and prognosis; however, it is less well-understood whether these subtypes affect margin status and should therefore alter surgical management. METHODS: Data from two randomized trials evaluating cavity shave margins (CSM) on margin status in patients undergoing partial mastectomy (PM) were used for this analysis. The data were restricted to patients who had invasive carcinoma present in the PM specimen, and in whom data for all three receptors (ER, PR and HER-2) were known. Patients were classified as luminal if they were ER and/or PR+, HER-2 enriched if they were ER and PR negative but HER-2 positive, and TN if they were negative for all three receptors. We evaluated the impact of subtype on the margin status at the time the surgeon had completed their standard PM, prior to randomization to CSM vs. no CSM. Non-parametric statistical analyses were performed using SPSS Version 26. RESULTS: 350 patients were included in this cohort for analysis. The median patient age was 64 (range; 32-94 years) and the median invasive tumor size was 1.2 cm (range; 0.6-8.0 cm). 326 (93.1%) were luminal type, 22 (6.3%) were triple negative, and 2 (0.6%) were HER-2 enriched. Subtype was significantly correlated with race (black patients were more likely to have TN disease than white patients, 22.2% vs. 3.8%, p=0.001), palpability (TN tumors were more likely to be palpable than luminal cancers 54.5% vs. 29.8%, p=0.007) and grade (78.9% of TN cancers were high grade vs. 13.5% of luminal cancers p&amp;lt;0.001). Subtype did not correlate with Hispanic ethnicity, node positivity, nor lymphovascular invasion (p&amp;gt;0.05 for all). While patients with TN and HER-2 enriched tumors were more likely to receive neoadjuvant therapy, this did not reach statistical significance (p=0.117). Surgeons were no more likely to take selective margins on the basis of molecular subtype (p=0.413). In this cohort, the overall positive margin rate was 33.7%. This did not vary based on molecular subtype (positive margin rate: 33.7% for patients with luminal tumors vs. 36.4% for those with TN tumors, p=0.425). On multivariate regression controlling for molecular subtype, race, grade and palpability, the only factor which predicted positive margin status was grade (p=0.005), with high grade tumors being significantly more likely to have a positive margin than low grade tumors, independent of other factors (OR=3.503, 95% CI: 1.638-7.494, p=0.001). CONCLUSION: While molecular subtype correlates with race, tumor grade and palpability, it does not predict margin status. Therefore, molecular subtype should not, independent of other factors, influence surgical decision-making. Citation Format: Andrew Fenton, Elisabeth Dupont, Theodore Tsangaris, Carlos Garcia-Cantu, Marissa Howard-McNatt, Akiko Chiba, Adam Berger, Edward Levine, Jennifer Gass, Kristalyn Gallagher, Sharon Lum, Ricardo Martinez, Alliric Willis, Sonali Pandya, Eric Brown, Amanda Mendiola, Mary Murray, Naveenraj Solomon, Maheswari Senthil, David Ollila, David Edmonson, Melissa Lazar, Jukes Namm, Fangyong Li, Meghan Butler, Noreen McGowan, Maria Herrera, Yoana Avitan, Brian Yoder, Laura Walters, Tara McPartland, Victor Haddad, Hongwei Ma, Ming Xie, Anees Chagpar. Does breast cancer subtype impact margin status in patients undergoing partial mastectomy? [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-15.

Sintilimab plus oxaliplatin/capecitabine (CapeOx) as neoadjuvant therapy in patients with locally advanced, resectable gastric (G)/esophagogastric junction (GEJ) adenocarcinoma.

211 Background: The application of anti-programmed death 1 (PD-1) antibodies in neoadjuvant setting has not been well established. This phase 2 study (NCT04065282) was conducted to evaluate the efficacy and safety of sintilimab plus CapeOx as neoadjuvant therapy for resectable G/GEJ adenocarcinoma. Methods: Patients with histologically confirmed resectable G/GEJ adenocarcinoma (stage cT3-4NxM0) were enrolled to receive neoadjuvant therapy with sintilimab (3mg/kg for wt &lt; 60kg, 200mg for wt ≥60kg, Q3W) plus CapeOx (oxaliplatin 130mg/m2 iv D1, capecitabine 1000mg/m2 bid po D1-14, Q3W) for 3 cycles. Gastrectomy was scheduled within 4 weeks after last dose of neoadjuvant treatment. Tumor imaging evaluation was performed at baseline and within 1 week before gastrectomy. The primary endpoint was pathological complete response (pCR) per Becker criteria. Results: As of August 4, 2020, 36 pts were enrolled. Patients who had received gastrectomy after neoadjuvant treatment (n = 26) were included in this analysis. 25 (96.2%) pts completed 3 cycles of neoadjuvant treatment, except one completed 2 cycles due to grade 3 AST increased. All pts received complete resection (R0). 6 (23.1%) pts achieved pCR (TRG1a) and 14 (53.8%) pts achieved major pathologic response (MPR, TRG1a/b). 3 pts had partial response (ORR was 3/5 among pts with target lesions) and no patients progressed per RECIST 1.1 before surgery. Among 18 pts who received PET-CT evaluation per PERCIST, 11 (61.1%) achieved partial metabolic response (PMR). Neoadjuvant treatment-related AEs (neoTRAEs) to any drug were reported in 25 (96.2%) pts. Mostly TRAEs were grade 1-2, and only 6 (23.1%) pts experienced grade 3 TRAEs (Neutropenia in 4 pts, Leukopenia, Thrombocytopenia, AST increased, and GGT increased in 1 pt each). One patient experienced grade 1 hypothyroidism which is considered to be immune-related AE. There is no serious peri-operative complication and mortality. Conclusions: Sintilimab plus oxaliplatin/capecitabine showed promising efficacy with high pCR and MPR rate and well-tolerated safety profile in neoadjuvant settings. This combination regimen might present a new option for patients with locally advanced, resectable G/GEJ adenocarcinoma. Clinical trial information: NCT04065282.

The correlation between tumor size, lymph node status, distant metastases and mortality in rectal cancer patients without neoadjuvant therapy.

Tumor size has an effect on decision making for the treatment rectal cancer. Transanal local excision can be selected to remove rectal cancer with favorable histopathological features. It is generally recognized that the risk of lymph node involvement and distant metastases increases as the tumor enlarges. However, the majority of the studies classified patients into two groups using concrete value as a cutoff point. The coarse classification was not sufficient to reveal a correlation between the tumor size and lymph node status or distant metastases across the full range of sizes examined. Between 1988 and 2015, a total of 77,746 patients were diagnosed with first primary rectal cancer who had not received neoadjuvant therapy. These subjects were identified using the Surveillance, Epidemiology and End Results (SEER) database. The association between tumor size, lymph node status, distant metastases and cancer-specific mortality was investigated. Tumor size was examined as a continuous (1-30 mm) and categorical variable (11 size groups; 10-mm intervals). A non-linear correlation between increasing tumor size and the prevalence of lymph node involvement was observed, while a near-positive correlation between tumor size and distant metastases was presented. In addition, the 5-year and 10-year rates of rectal cancer-specific mortality were increased as the tumor enlarged. For small tumors (under 30 mm), a positive correlation was noted between tumor size and lymph node involvement. The clinical value of the tumor size should be reevaluated by exact classification.

Impact of Obesity on Treatment Approach for Resectable Esophageal Cancer

With the prevalence of obesity and its known association with esophageal cancer, there is increasing need to understand how obesity affects treatment. Using The Society of Thoracic Surgeons General Thoracic Surgery Database, we retrospectively evaluated all patients who underwent esophagectomy with gastric conduit reconstruction between 2012 and 2016. Patients were categorized into five body mass index groups. Associations between body mass index and surgical technique, resection, lymphadenectomy, staging, and neoadjuvant treatment were evaluated using multivariable logistic regression models. In all, 8547 patients were included in the analysis. Obese and morbidly obese patients were more likely to undergo open procedures compared with normal-weight patients (odds ratio [OR] 1.18, P= .016; and OR 1.45, P= .007), with longer operative times. Morbidly obese patients had a higher rate of intraoperative conversion from minimally invasive to open approaches (OR 3.75, P= .001). There were no differences in R0 resection or lymphadenectomy, and staging workup was similar. Obese patients were less likely to receive neoadjuvant therapy (OR 0.75, P= .048), and overweight and obese patients were less likely to receive preoperative radiation (OR 0.75, P= .017; and OR 0.71, P= .010). Analyzing by stage, overweight and obese patients with cT2N0 disease were less likely to receive neoadjuvant treatment (OR 0.54, P= .016; and OR 0.37, P< .001). There were no differences in neoadjuvant therapy for cT3 or node-positive disease. Higher body mass index is associated with increased use of open versus minimally invasive esophagectomy and intraoperative conversion. Whereas staging workup and oncologic outcomes of surgery are similar, overweight and obese patients with cT2N0 disease are less likely to undergo neoadjuvant treatments.