Impact of neoadjuvant pembrolizumab adherence on pathologic complete response in triple-negative breast cancer: a real-world analysis.

BACKGROUND: The addition of pembrolizumab (pembro) to neoadjuvant chemotherapy (NAC) is standard of care for the treatment of early triple-negative breast cancer (TNBC) after KEYNOTE-522 trial demonstrated improved pathologic complete response (pCR) rates with the combination. However, the optimal treatment strategy for TNBC remains uncertain as questions persist about which patients benefit from pembro and the best treatment schedule and regimen. We identified real-world clinical characteristics and treatment variables associated with response to NAC plus pembro. METHODS: Patients with early TNBC treated with NAC plus pembro between February 2020 and September 2023 were identified. Univariate and multivariate analysis was performed using logistic regression to identify factors associated with pCR. Cox proportional hazard prediction models were used to identify predictors of invasive disease-free survival and overall survival in this cohort. RESULTS: A pCR was achieved in 75 (63.6%) of 118 patients. Age at diagnosis (P = .04), Ki-67 (P = .004), duration from start of pembro to surgery (P = .006) and NAC to surgery (P = .01), number of cycles of pembro (P = .04) and NAC (P = .02), and completion of at least 8 cycles of pembro (P = .015) and NAC (P = .015) were each significantly associated with pCR in univariate analysis. In multivariate analysis, patients younger than 55 years at time of diagnosis (vs age > 55 years) and those completing at least 8 cycles of pembro remained predictive of pCR (OR's 2.50, 2.49, P = .035 and .037, respectively). CONCLUSIONS: In this real-world analysis of patients with TNBC treated with NAC plus pembro, younger age and the completion of at least 8 cycles of pembrolizumab were associated with pCR.

Embryonal sarcoma of the liver in pediatric and young adult patients: A report from Children's Oncology Group study ARST0332.

BACKGROUND: Embryonal sarcoma of the liver (ESL) is a rare mesenchymal tumor most common in childhood; the optimal treatment approach is uncertain. The clinical features and outcomes of patients with ESL enrolled in a Children's Oncology Group (COG) clinical trial that evaluated a risk-based strategy for treating soft tissue sarcomas in patients aged <30 years were evaluated. METHODS: This subset analysis included patients with ESL enrolled in COG study ARST0332. Central review of records, pathology, and imaging confirmed the diagnosis, presenting features, and surgery extent and complications. All patients received dose-intensive ifosfamide/doxorubicin chemotherapy, with cycle timing dependent on surgery and radiotherapy. Tumor resection occurred before study entry or after four cycles of chemotherapy; radiotherapy for residual tumor was optional. RESULTS: Thirty-nine eligible/evaluable patients with ESL were analyzed. All tumors were >10 cm in diameter; four were metastatic. Tumor resection was performed upfront in 23 and delayed in 16. Positive surgical margins (n = 6) and intraoperative tumor rupture (n = 6) occurred only in upfront resections. Eight patients received radiotherapy. Estimated 5-year event-free and overall survival were 79% (95% confidence interval [CI], 65%-93%) and 95% (95% CI, 87%-100%), respectively. Positive margins increased the local recurrence risk. One of 13 patients with documented hemorrhagic ascites and/or tumor rupture developed extrahepatic intra-abdominal tumor recurrence. CONCLUSIONS: The treatment strategy used in ARST0332 achieved favorable outcomes for patients with ESL despite a substantial proportion having high-risk disease features. Deferring tumor resection until after neoadjuvant chemotherapy may decrease the risk of intraoperative tumor rupture and improve the likelihood of adequate surgical margins.

Utility of Initial Tumor Reduction as a Prognostic Factor in Esophageal Squamous Cell Cancer Patients Undergoing Neoadjuvant Chemotherapy Followed by Surgery : A Retrospective Cohort Study.

BACKGROUND: While a neoadjuvant chemotherapy regimen using docetaxel, cisplatin, and 5-fluorouracil (NAC-DCF) is considered the standard treatment for locally advanced esophageal cancer (EC) in Japan, a reliable marker for early prediction of treatment efficacy remains unclear. We investigated the utility of the tumor response after a first course of NAC-DCF as a post-surgery survival predictor in patients with EC. METHODS: We enrolled 150 consecutive patients who underwent NAC-DCF followed by surgery for EC between September 2009 and January 2019. The initial tumor reduction (ITR), defined as the percentage decrease in the shorter diameter of the tumor after the first course of NAC-DCF, was evaluated using computed tomography. We analyzed the relationship between ITR, clinicopathological parameters, and survival. RESULTS: The median ITR was 21.07% (range -11.45 to 50.13%). The optimal cut-off value for ITR for predicting prognosis was 10% (hazard ratio [HR] 3.30, 95% confidence interval [CI] 1.98-5.51), based on univariate logistic regression analyses for recurrence-free survival (RFS). Compared with patients with ITR <10%, patients with ITR ≥10% showed a significantly higher proportion of ypM0 (80.0% vs. 92.5%) and responders in terms of overall clinical response (50.0% vs. 80.8%). Multivariate analysis for RFS revealed that ypN2-3 (HR 2.78, 95% CI 1.67-4.62), non-response in terms of overall clinical response (HR 1.87, 95% CI 1.10-3.18), and ITR <10% (HR 2.48, 95% CI 1.42-4.32) were independent prognostic factors. CONCLUSIONS: Tumor response after the first course of NAC-DCF may be a good predictor of survival in patients with EC who underwent NAC-DCF plus surgery.

Survival outcomes in HER2-low versus HER2-zero breast cancer after neoadjuvant chemotherapy: a meta-analysis.

BACKGROUND: The survival outcomes in HER2-low versus HER2-zero breast cancer (BC) after neoadjuvant chemotherapy (NACT) remain unclear. The meta-analysis was conducted to summarize current evidence about the survival outcomes in HER2-low versus HER2-zero BC. METHODS: We conducted a systematic search in PubMed and EMBASE databases to identify relevant studies. RESULTS: A total of 14 studies with 53,714 patients were included. Overall, 34,037 patients (63.37%) were HER2-low, and 19,677 patients (36.63%) were HER2-zero. Patients with HER2-low tumors had a significantly lower pathological complete response (pCR) rate than patients with HER2-zero tumors, regardless of the hormone receptor status. Compared with HER2-zero breast cancer, the overall survival (OS) and disease-free survival (DFS) of HER2-low BC were longer in the overall cohort (HR = 0.72; 95% CI = 0.61-0.85; P < 0.0001; HR = 0.83; 95% CI = 0.75-0.92; P = 0.0002); however, no differences were observed in terms of OS and DFS between HER2-low and HER2-zero BC in the HR-negative group. In the HR-positive group, HER2-low status had no significant impact on OS, while significantly associated with increased DFS (HR = 0.85; 95% CI = 0.76-0.96; P = 0.007). CONCLUSION: These results suggest that although HER2-low BC has a poor response to NACT, it is correlated with favorable OS and DFS after NACT in the overall cohort as well as longer DFS in the HR-positive group.

Comparing fluorodeoxyglucose positron emission tomography with computed tomography in staging for nodal and distant metastasis in urothelial/bladder cancer.

Objectives: We aim to assess the clinical value of 18F-fluorodeoxyglucose positron (18F-FDG-PET) scan in detecting nodal and distant metastasis compared with computed tomography (CT) scan in patients with urothelial carcinoma or bladder cancer, aiming to improve staging accuracy and thereby better prognosticate and determine therapy. Methods: A retrospective review of 75 patients with invasive bladder cancer (≥T1) who were staged with both CT and 18F-FDG-PET within an 8-week interval was performed for the period between 2015 and 2020. Seventy-two per cent (54/75) had formal pelvic lymph node (LN) dissection or biopsy of lesions suspicious for metastases. FDG-PET definitions for positive sites were assessed depending on SUV Max (nodes with SUVmax >4 at any size, SUV > 2 for lymph nodes >8 mm, or any SUV if the lymph node was >10 mm on axial images). For CT scanning, enlarged LN by RECIST 1.1 criteria (>10 mm) as well as qualitative findings suggesting metastasis were considered positive. The analysis was based on the comparison of CT and 18F-FDG-PET findings to histopathology results from LN dissection or biopsies. Results: Sensitivity, specificity, positive predictive values (PPV) and negative predictive value (NPV) of CT versus FDG-PET for detecting metastasis, in patients who underwent pelvic LN dissection or biopsy of lesions suspicious of metastases, were 46.6% (95% CI: 21%-70%) versus 60% (95% CI: 32%-84%), 100% (95% CI: 91%-100%) versus 83.78% (95% CI: 69%-94%), 100% (95% CI: 63%-100%) versus 60% (95% CI: 32%-84%), and 82.2% (95% CI: 68%-92%) versus 83.78% (95% CI: 69%-94%), respectively. 7/75 (9.3%) patients avoided cystectomy due to 18F-FDG-PET features of metastases that were not detected by CT. Conclusion: FDG-PET may be more sensitive than CT for metastases in the staging of bladder cancer, which resulted in significant avoidance of aggressive local management in cases with occult metastasis.

Neoadjuvant chemotherapy does not improve survival for patients with high volume colorectal peritoneal metastases undergoing cytoreductive surgery.

BACKGROUND: Colorectal peritoneal metastases (CRPM) affects 15% of patients at initial colorectal cancer diagnosis. Neoadjuvant chemotherapy (NAC) prior to cytoreductive surgery (CRS) has been demonstrated to be a safe and feasible option, however there is limited data describing its efficacy in advanced peritoneal disease. This study evaluated the effect of NAC on survival in patients with high volume CRPM undergoing CRS with or without HIPEC. METHODS: A retrospective review of all patients who underwent CRS with or without HIPEC for CRPM from 2004 to 2019 at our institution was performed. The cohort was divided based on peritoneal carcinomatosis index (PCI) at surgery: Low Volume (PCI ≤ 16) and High Volume (PCI > 16). RESULTS: A total of 326 patients underwent CRS with HIPEC for CRPM. There were 39 patients (12%) with High Volume disease, and 15 of these (38%) received NAC. Patients with High Volume disease had significantly longer operating time, lower likelihood of complete macroscopic cytoreduction (CC-0 score), longer intensive care unit length of stay and longer hospital stay compared to Low Volume disease. In High Volume disease, the NAC group had a significantly shorter median survival of 14.4 months compared to 23.8 months in the non-NAC group (p = 0.046). CONCLUSION: Patients with High Volume CRPM achieved good median survival following CRS with HIPEC, which challenges the current PCI threshold for offering CRS. The use of NAC in this cohort did not increase perioperative morbidity but was associated with significantly shorter median survival compared to upfront surgery.

Effect of tumor-infiltrating immune cells (mast cells, neutrophils and lymphocytes) on neoadjuvant chemotherapy response in breast carcinomas.

INTRODUCTION: Despite screening, the incidence of breast cancer is increasing worldwide. Neoadjuvant chemotherapy (NAC) response is one of the most important parameters taken into consideration in surgery, optimal adjuvant chemotherapy planning and prognosis prediction. Research on predictive markers for the response to NAC is still ongoing. In our study, we investigated the relationship between tumor-infiltrating neutrophils/mast cells/lymphocytes and NAC response in breast carcinomas. MATERIAL AND METHOD: Study included 117 patients who were diagnosed with invasive breast carcinoma using core needle biopsy. In these biopsies tumor-infiltrating neutrophils/mast cells/lymphocytes were evaluated and Miller Payne Score was used for NAC response. RESULT: 53 patients exhibited high TILs, 36 had high TINs, and 46 showed high TIMs. While pathological complete response was 27 % in all patients, it was 38 % in high TINs patients, 35 % in high TILs patients, and 28 % in high TIMs patients. High TIMs were observed to be statistically associated with survival. TILs, TINs, nuclear grade, ER, PR and HER2 expression, Ki-67 proliferation index were found to be associated with the Miller - Payne score. In multivariate analysis, TINs, nuclear grade, pathological stage, and molecular subtype were found to be independent risk factors for treatment response. CONCLUSION: TINs have better prognostic value to predict neoadjuvant treatment than TILs. High TIMs are associated with increased overall survival. The inclusion of TINs in NAC response and TIMs in overall survival in pathology reports and treatment planning is promising in breast carcinomas as they are simple to use and reproducible markers.

Impact of pCR after neoadjuvant chemotherapy and radical D2 dissection in locally advanced gastric cancers: Analysis of 1001 cases.

BACKGROUND: Advances in perioperative chemotherapy have improved outcomes in patients with gastric cancers (GC). This strategy leads to tumour downstaging and may result in a pathologic complete response (pCR). The study aimed to evaluate the predictors of pCR and determine the impact of pCR on long-term survival. METHODS: At the Department of Gastrointestinal and HPB Oncology at the Tata Memorial Centre, Mumbai, 1001 consecutive patients with locally advanced GCs undergoing radical resection following neoadjuvant chemotherapy from January 2005 to June 2022 were included. RESULTS: At a median follow-up of 61 months, the median OS was 53 months with a 5-year OS of 46.8 %. Ninety-five patients (9.49 %) realized pCR. Non-signet and well-differentiated histology were associated with pCR. pCR was significantly associated with improved OS, 5-year OS 79.2 % vs 43.2 % (HR 0.30, p < 0.001). On multivariable analysis, the realization of pCR and completion of adjuvant chemotherapy had superior OS. Whereas, signet-ring histology, linitis-like tumours, and high lymph node ratio had adverse outcomes. CONCLUSION: Tumour grade and signet-ring histology predict achievement of pCR in locally advanced GCs after neoadjuvant chemotherapy. Patients with pCR have significantly improved survival. Future neoadjuvant strategies should focus on enhancing pCR rates to improve overall outcomes.

Develop and Validate a Nomogram Combining Contrast-Enhanced Spectral Mammography Deep Learning with Clinical-Pathological Features to Predict Neoadjuvant Chemotherapy Response in Patients with ER-Positive/HER2-Negative Breast Cancer.

RATIONALE AND OBJECTIVES: To develop and validate a nomogram that combines contrast-enhanced spectral mammography (CESM) deep learning with clinical-pathological features to predict neoadjuvant chemotherapy (NAC) response (either low Miller Payne (MP-L) grades 1-2 or high MP (MP-H) grades 3-5) in patients with ER-positive/HER2-negative breast cancer. MATERIALS AND METHODS: In this retrospective study, 265 breast cancer patients were randomly allocated into training and test sets (used for models training and testing, respectively) at a 4:1 ratio. Deep learning models, based on the pre-trained ResNet34 model and initially fine-tuned for identifying breast cancer, were trained using low-energy and subtracted CESM images. The predicted results served as deep learning features for the deep learning-based model. Clinical-pathological features, including age, progesterone receptor (PR) status, estrogen receptor (ER) status, Ki67 expression levels, and neutrophil-to-lymphocyte ratio, were used for the clinical model. All these features contributed to the nomogram. Feature selection was performed through univariate analysis. Logistic regression models were developed and chosen using a stepwise selection method. The deep learning-based and clinical models, along with the nomogram, were evaluated using precision-recall curves, receiver operating characteristic (ROC) curves, specificity, recall, accuracy, negative predictive value, positive predictive value (PPV), balanced accuracy, F1-score, and decision curve analysis (DCA). RESULTS: The nomogram demonstrated considerable predictive ability, with higher area under the ROC curve (0.95, P < 0.05), accuracy (0.94), specificity (0.98), PPV (0.89), and precision (0.89) compared to the deep learning-based and clinical models. In DCA, the nomogram showed substantial clinical value in assisting breast cancer treatment decisions, exhibiting a higher net benefit than the other models. CONCLUSION: The nomogram, integrating CESM deep learning with clinical-pathological features, proved valuable for predicting NAC response in patients with ER-positive/HER2-negative breast cancer. Nomogram outperformed deep learning-based and clinical models.

Impact of neoadjuvant chemotherapy on short-term outcomes after simple and complex minimally invasive minor hepatectomy for colorectal liver metastases: A propensity-score matched and coarsened exact matched study.

BACKGROUND: In the last three decades, minimally invasive liver resection has been replacing conventional open approach in liver surgery. More recently, developments in neoadjuvant chemotherapy have led to increased multidisciplinary management of colorectal liver metastases with both medical and surgical treatment modalities. However, the impact of neoadjuvant chemotherapy on the surgical outcomes of minimally invasive liver resections remains poorly understood. METHODS: A multicenter, international, database of 4998 minimally invasive minor hepatectomy for colorectal liver metastases was used to compare surgical outcomes in patients who received neoadjuvant chemotherapy with surgery alone. To correct for baseline imbalance, propensity score matching, coarsened exact matching and inverse probability treatment weighting were performed. RESULTS: 2546 patients met the inclusion criteria. After propensity score matching there were 759 patients in both groups and 383 patients in both groups after coarsened exact matching. Baseline characteristics were equal after both matching strategies. Neoadjuvant chemotherapy was not associated with statistically significant worse surgical outcomes of minimally invasive minor hepatectomy. CONCLUSION: Neoadjuvant chemotherapy had no statistically significant impact on short-term surgical outcomes after simple and complex minimally invasive minor hepatectomy for colorectal liver metastases.

Development of an Ultrasound-based Nomogram for Predicting Pathologic Complete Response and Axillary Response in Node-Positive Patients with Triple- Negative Breast Cancer.

BACKGROUND: The accurate prediction of pathological complete response (pCR) in the breast and axillary lymph nodes (ALN) before neoadjuvant chemotherapy (NAC) is of utmost importance for the development of treatment strategies. We aim to construct a nomogram on ultrasound (US) and clinical-pathologic factors to predict breast and ALN pCR in node-positive triple-negative breast cancers (TNBCs). METHODS: Patients identified with TNBCs from institution 1 (n = 328) were used for training cohort and those from institution 2 (n = 192) were for validation cohort. US was conducted before and after NAC, and characteristics were obtained from medical records. Univariate and multivariate regression analysis were performed to identify US and clinical-pathologic factors associated with breast and ALN pCR in the training cohort. The assessment of predictive performance was conducted using the receiving operating characteristic curve (ROC), discrimination, and calibration. RESULTS: Overall, 34.6% of patients achieved breast pCR and 48.1% of patients achieved ALN pCR. The nomogram 1 used for predicting pCR in the breast (AUC, 0.84; 95% CI: 0.79, 0.88) outperformed the clinical (AUC, 0.73; 95% CI: 0.68, 0.78) and US models (AUC, 0.79; 95% CI: 0.74, 0.83). The nomogram 2 used for predicting pCR in the axllia (AUC, 0.83; 95% CI: 0.78, 0.87) also outperformed the clinical (AUC, 0.64; 95% CI: 0.58, 0.69) and US models (AUC, 0.80; 95% CI: 0.75, 0.84). The calibration curve and discrimination curve indicate that the nomogram has good calibration performance and clinical applicability. CONCLUSION: The nomogram showed promising predictive performance for predicting breast and ALN pCR in patients with TNBCs.

Efficacy of sentinel lymph-node biopsy after neoadjuvant chemotherapy in clinically axilla node-negative patients.

PURPOSE: Breast cancer is the most common cancer in women. Developments in breast cancer treatment have extended the life expectancy of these patients, raising the issue of morbidity of breast cancer surgery, the major cause of which is axillary dissection. The aim of the present study was to establish the safety of sentinel node biopsy (SLNB) in patients with a clinically node-negative axilla after neoadjuvant chemotherapy (NACT). METHODS: We recorded demographic data, as well as the findings of physical examination, imaging, and pathology before and after NACT. SLNB with indocyanine green + isosulfan blue and axillary dissection were performed and the surgical and pathology findings were recorded. RESULTS: A sentinel lymph node was detected in 80 of 90 patients who underwent surgery. When ≥ three sentinel lymph nodes were removed as negative in the patient group with cN0 after treatment, we evaluated the axilla as being negative with an accuracy of 100%. CONCLUSIONS: Axillary lymph-node dissection may not be necessary for patients with cNO confirmed by physical and radiological examination using positron emission tomography (PET) computed tomography (CT), and breast magnetic resonance imaging (MRI) after NACT, if ≥ three negative SLNB are removed. Further studies are needed to confirm our findings.

Ultrasound-based radiomics for early predicting response to neoadjuvant chemotherapy in patients with breast cancer: a systematic review with meta-analysis.

OBJECTIVE: This study aims to evaluate the diagnostic accuracy of ultrasound imaging (US)-based radiomics for the early prediction of response to neoadjuvant chemotherapy (NAC) in breast cancer patients. METHODS: We comprehensively searched PubMed, Cochrane Library, Embase, and Web of Science databases up to 1 January 2023 for eligible studies. We assessed the methodological quality of the enrolled studies with Radiomics Quality Score (RQS) and the Quality Assessment of Diagnostic Accuracy Studies-2 tools. We performed meta-analyses to summarize the diagnostic efficacy of US-based radiomics in response to NAC in breast cancer patients. RESULTS: Eight studies proved eligible. Eligible studies exhibited an average RQS score of 12.88 (35.8% of the total score), with the RQS score ranging from 8 to 19. In the meta-analyses, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.87 (95% CI 0.81-0.92), 0.78 (95% CI 0.72-0.83), 4.02 (95% CI 3.18-5.08), 0.16 (95% CI 0.10-0.25), and 25.17 (95% CI 15.10-41.95), respectively. Results from subgroup analyses indicated that prospective studies apparently exhibited more optimal sensitivity than retrospective studies. Sensitivity analyses exhibited similar results to the primary analyses. CONCLUSION: US-based radiomics may be a potentially crucial adjuvant method for evaluating the response of breast cancer to NAC. Due to limited data available and low quality of eligible studies, more multicenter prospective studies with rigorous methods are required to confirm our findings.

Neoadjuvant Chemotherapy in Locally Advanced Sinonasal Teratocarcinosarcoma a Rare Malignancy: An Audit From an Academic Tertiary Care Centre in India.

AIMS: Sinonasal teratocarcinosarcomas (SNTCS) are rare sinonasal malignancies, the incidence of which is less than 1% of all tumors. There is limited data available on SNTCS's, often as case reports and small case series. The management of SNTCS is complicated because of its location, locally aggressive biology, difficulty in achieving complete resection, and limited data on chemotherapy in these malignancies. This audit was performed to understand the role of neoadjuvant chemotherapy (NACT) in SNTCS's, its ability to downstage the disease, achieve complete resection, and impact on long-term survival outcomes. METHODS: This was a retrospective analysis of a prospectively maintained database approved by the Institutional Ethics Committee (IEC). The baseline characteristics, the extent of tumor, Kadish stage, NACT regimen, and adverse events were extracted from the Electronic Medical Records and the patient's case file. Patients with baseline extensive/inoperable disease were referred for NACT from the multidisciplinary joint clinic followed by response assessment (RECIST v1.1). Patients underwent skull-base surgery if respectable post-completion of NACT, however, if deemed unresectable were treated with non-surgical modalities or palliative therapies. RESULTS: The data of 27 patients were evaluated from the year 2015-2022. The median age was 42 years (IQR:30-56) and 85.2% (n = 23) were males. The ECOG-PS was 0-1 in 88.8% (n = 24) patients. All 27 patients received NACT in view of extensive disease at presentation. 74.1% (n = 20) patients received Cisplatin-Etoposide and 25.9% (n = 7) received other chemotherapy regimens. The median number of chemotherapy cycles was 2(IQR:2-3). 96.3% patients (n = 26) completed the planned NACT cycles. 70.4% (n = 19) patients achieved a partial response in post-NACT imaging. 77.8% (n = 18) underwent surgery, 18.5% (n = 5) received CTRT, and 7.4% (n = 2) received definitive-RT alone. The median PFS and OS of the cohort was 19months (95%CI:12.0-25.6) and 23months (95%CI:5.94-40.06) respectively. CONCLUSION: NACT is safe, feasible, and effective with significant response rates, leading to effective downstaging, resectability and improved survival in patients with locally advanced SNTCS's.

Comparison of neoadjuvant chemotherapy response and prognosis between HR-low/HER2-negative BC and TNBC: an exploratory real-world multicentre cohort study.

Objective: Hormone receptor (HR)-low/HER2-negative breast cancers (BCs) are more likely to be basal-like BCs, with similar molecular features and gene expression profiles to HR-negative (estrogen receptor <1% or negative and progesterone receptor <1% or negative) BCs. Recently, with the clinical application of adjuvant intensive therapy for triple-negative breast cancer (TNBC), the prognosis of TNBC patients without pathological complete response (pCR) has significantly improved. Therefore, it is necessary to reanalyse the prognostic characteristics of clinically high-risk HR-low/HER2-negative BC. Methods: According to the inclusion and exclusion standards, 288 patients with HR-low/HER2-negative BC and TNBC who received NAC and were followed up between 2015 and 2022 at three breast centres in Hunan Province, China, were enrolled. Inverse probability of treatment weighting (IPTW) was utilized to mitigate imbalances in baseline characteristics between the HR-low/HER2-negative BC group and TNBC group regarding event-free survival (EFS) and overall survival (OS). The primary clinical endpoints were pCR and EFS, while the secondary endpoints included OS, objective response rate (ORR), and clinical benefit rate (CBR). Results: The pCR rate (27.1% vs. 28.0%, P = 1.000), ORR rate (76.9% vs. 78.3%, P = 0.827) and CBR rate (89.7% vs. 96.5%, P = 0.113) after NAC were similar between the HR-low/HER2-negative BC and the TNBC group. EFS in patients with non-pCR from the 2 groups was significantly inferior in comparison to patients with pCR (P = 0.001), and the 3-year EFS was 94.74% (95% CI = 85.21% to 100.00%) and 57.39% (95% CI =43.81% to 75.19%) in patients with pCR and non-pCR from the HR-low/HER2-negative BC group, respectively, and 89.70% (95% CI = 82.20% to 97.90%) and 69.73% (95% CI = 62.51% to 77.77%) in the TNBC patients with pCR and non-pCR, respectively. Conclusions: In the real world, the therapeutic effects of NAC for HR-low/HER2-negative BCs and TNBCs were similar. EFS of patients with non-pCR in the HR-low/HER2-negative BC group was inferior to that of the TNBC group with non-pCR, suggesting that it is necessary to explore new adjuvant intensive therapy strategies for these patients.

Survival benefits of adjuvant chemotherapy for patients with residual pathologic disease after neoadjuvant chemotherapy and surgery for locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Although preoperative neoadjuvant chemotherapy (NACT) or chemoradiation is the current standard of care for esophageal cancer in China, the impact of subsequent adjuvant therapy on patient prognosis remains unknown. This study aims to analyze the effect of adjuvant chemotherapy (ACT) on the survival rates of patients who have achieved a non-pathological complete response (non-pCR) after NACT and subsequent surgery. METHODS: We reviewed the data of 2193 patients with locally advanced thoracic esophageal squamous cell carcinoma (ESCC) who underwent radical surgery between January 2006 and January 2016. Of these patients, 46 received NACT and ACT, while 109 received NACT only. Propensity score matching was used to compare 86 patients, with 43 patients in the NACT + ACT group and 43 patients in the NACT group. Univariate analysis was performed using the Kaplan-Meier method and log-rank test, while Cox regression analysis was used for multivariate analysis. RESULTS: Multivariate analysis revealed that pathological lymph node status (positive vs negative) (P < .001) and treatment modalities (NACT + ACT vs NACT) (P = .005) were independent prognostic factors. There was a significant difference in long-term survival rates between the NACT + ACT and NACT groups, with 5-year survival rates of 55.8% vs 39.5%, respectively (c2 = 4.270, P = .039). In patients with ypN+ status, the 5-year survival rate was 31.8% for those who received ACT after NACT and surgery, compared to 10.0% for those who did not receive additional ACT (c2 = 6.101, P = .014). The corresponding percentages in patients with ypN- were 81.0% and 65.2%, respectively (c2 = 1.993, P = .158). CONCLUSION: Adjuvant chemotherapy should be recommended for locally advanced ESCC patients with residual cancer after NACT and surgery, especially for patients with nodal metastases after NACT.

Identification of tumour regression in neoadjuvantly treated pancreatic cancer is based on divergent and nonspecific criteria.

AIMS: Following the increased use of neoadjuvant therapy for pancreatic cancer, grading of tumour regression (TR) has become part of routine diagnostics. However, it suffers from marked interobserver variation, which is mainly ascribed to the subjectivity of the defining criteria of the categories in TR grading systems. We hypothesized that a further cause for the interobserver variation is the use of divergent and nonspecific morphological criteria to identify tumour regression. METHODS AND RESULTS: Twenty treatment-naïve pancreatic cancers and 20 pancreatic cancers treated with neoadjuvant chemotherapy were reviewed by three experienced pancreatic pathologists who, blinded for treatment status, categorized each tumour as treatment-naïve or neoadjuvantly treated, and annotated all tissue areas they considered showing tumour regression. Only 50%-65% of the cases were categorized correctly, and the annotated tissue areas were highly discrepant (only 3%-41% overlap). When the prevalence of various morphological features deemed to indicate TR was compared between treatment-naïve and neoadjuvantly treated tumours, only one pattern, characterized by reduced cancer cell density and prominent stroma affecting a large area of the tumour bed, occurred significantly more frequently, but not exclusively, in the neoadjuvantly treated group. Finally, stromal features, both morphological and biological, were investigated as possible markers for tumour regression, but failed to distinguish TR from native tumour stroma. CONCLUSION: There is considerable divergence in opinion between pathologists when it comes to the identification of tumour regression. Reliable identification of TR is only possible if it is extensive, while lesser degrees of treatment effect cannot be recognized with certainty.

Predictors of Unilateral Arm Lymphedema in Non-obese Locoregionally Advanced Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy, Modified Radical Mastectomy, and Postoperative Irradiation.

Objective: The most dreaded long-term complication of axillary lymph node dissection remains upper arm lymphedema. Our study has strategized the three most common identified causes of post treatment arm lymphedema, i.e., obesity, radiation, and neoadjuvant chemotherapy and tried to identify the histopathological and clinical or surgical factors which can predict arm lymphedema. Materials and Methods: This is a prospective observational study was conducted at a tertiary care referral centre in India, with strict inclusion criteria of BMI <30 kg/m2, age <75 years, presence of metastatic axillary node proven by FNAC, received anthracycline based neoadjuvant chemotherapy and postoperative nodal irradiation, and completed 24 months of regular follow-up. Results: Total of 70 patients were included in the study. The mean age of the patients was 50.3 years (±12.9). lymphovascular invasion, total number of lymph nodes removed from level III, total number of days drain was left in situ and maximum drain output were found to be significantly (p<0.05) associated with arm lymphedema. Conclusion: In patients undergoing modified radical mastectomy with level III dissection, and postoperative irradiation, the incidence of unilateral arm lymphedema is significantly influenced by several clinicopathological factors like the total number of lymph nodes removed in level III, higher maximal drain output, prolonged duration of drain placement and the presence of lymphovascular invasion.

The Relationship of Pathological Response and Visceral Muscle and Fat Volume in Women With Breast Cancer Who Received Neoadjuvant Chemotherapy.

Objective: Differences in individual muscle/fat volumes may change the effectiveness of chemotherapy. In this study, the relationship between trunkal muscle and fat volume and body mass index (BMI) obtained before receiving neoadjuvant chemotherapy (NCT) in patients with breast cancer and complete pathological response (pCR) was investigated. Materials and Methods: The volumes of psoas, abdominal and paraspinal muscles, and trunkal subcutaneous and visceral fat were calculated using CoreSlicer AI 2.0 opensource program from the F-18 fluorodeoxyglucose positron emission tomography/computed tomography (CT) and CT images before NCT and postoperative pCR rates to NCT were recorded. Muscle/fat volumes and BMI prior to NCT were compared in terms of pathological pCR rates. Patients were followed up regularly for recurrence and survival. Results: Ninety-three patients were included with median (range) values for age, BMI, and body weights of 48 (28-72) years, 27 (16.8-51.6) kg/m2, and 71.94 (43-137) kg, respectively. The median follow-up time was 18.6 (6.7-59.6) months. No significant correlation was found between total muscle or fat volumes of patients with and without pCR. BMI [26.2 (16.8-51.6) kg/m2 vs. 24.6 (20.3-34.3) kg/m2, p = 0.03] and pCR rates in patients with low right-psoas muscle volume [11.74 (7.03-18.51) vs. 10.2 (6.71-13.36), p = 0.025] were significantly greater. A significant relationship was found between right psoas muscle volume and disease-free survival (DFS) (11.74 cm3 (7.03-18.51) vs. 10.2 cm3 (6.71-13.36), p = 0.025). However, no significant relationship was detected between total muscle-fat volume, BMI and overall survival and DFS (p>0.05). Conclusion: This is the first published study investigating the relationship between the pCR ratio and body muscle and fat volume measured by CoreSlicer AI 2.0 in patients with breast cancer who received NCT. No correlation was found between the pCR ratio and total muscle plus fat volume. However, these results need to be validated with larger patient series.

Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in cN0 Breast Cancer: Impact of HER2-Positive Status on Survival.

Objective: High rates of negative sentinel lymph node biopsy (SLNB) in clinically node-negative (cN0) breast cancer (BC) after neoadjuvant chemotherapy (NAC) have been described. These results are associated with triple-negative (TNBC) and human epidermal growth factor receptor 2 (HER2+) subtypes achieving pathologic complete response (pCR). This study evaluates predictive variables and survival in order to assess the possible omission of SLNB after NAC. Materials and Methods: Prospective study of women with cN0 BC treated with NAC and subsequent surgery, between April 2010 and May 2021. SLNB technique included, performing axillary lymphadenectomy in the absence of detection or SLNB-positivity. Multivariable logistic regression was used for analysis of NAC-response and SLNB-results in molecular subtypes: HR-/HER2+, TNBC, HR+/HER2- and HR+/HER2+. Kaplan-Meyer and log-rank were used for survival analysis. Results: A total of 179 patients (50.5±10.1 years) were included. Of these, 39.7% achieved pCR (ypT0/Tis). HR-negative subtypes had higher pCR rates (HR-/HER2+: 59.4%; TNBC: 53.4%), with no cases of SLNB-positive. With residual disease, HR-/HER2+ and TNBC showed low rates of SLNB-positivity (6.7% and 10.3%) versus HR+ (HR+/HER2+: 20%; HR+/HER2-: 44%; p<0.001). Multivariable analysis identified independent predictors of SLNB-negativity (p<0.0001) to be: HR- [odds ratio (OR)=0.15; 95% confidence interval (CI): 0.06-0.37; p = 0.0001], HER2+ (OR=0.34; 95% CI: 0.14-0.81; p = 0.015) and high-grade Nottingham (OR=0.42; 95% CI: 0.18-0.99; p = 0.048). Disease-free survival showed worse outcomes with SLNB-positivity (p<0.0001), HR+/HER2- (p = 0.0277), larger tumor size (p = 0.002) and residual disease after NAC (p<0.0001). Conclusion: Patient selection based on NAC response, molecular subtype, and survival outcomes is a priority for establishing individualized therapeutic strategies after NAC. Molecular subtypes with higher pCR rates and lower rates of SLNB-positivity could benefit from non-invasive strategies that include omission of SLNB.