Neoadjuvant Research Articles

Drug prioritization identifies panobinostat as a tailored treatment element for patients with metastatic hepatoblastoma.

Patients with metastatic hepatoblastoma are treated with severely toxic first-line chemotherapies in combination with surgery. Yet, inadequate response of lung metastases to neo-adjuvant chemotherapy still compromises patient outcomes making new treatment strategies, tailored to more efficient lung clearance, mandatory. We harnessed a comprehensive patient-derived xenograft platform and a variety of in vitro and in vivo assays to establish the preclinical and biological rationale for a new drug for patients with metastatic hepatoblastoma. The testing of a library of established drugs on patient-derived xenografts identified histone deacetylase inhibitors, most notably panobinostat, to be highly efficacious on hepatoblastoma cells, as compared to non-cancerous cells. Molecularly, the anti-tumor effect of panobinostat is mediated by posttranslational obstruction of the MYC oncoprotein as a result of dual specificity phosphatase 1 upregulation, thereby leading to growth inhibition and programmed cell death. Of clinical importance, upregulation of the MYC target gene nucleophosmin 1 is indicative of response to panobinostat and associated with metastatic disease in patients with hepatoblastoma. The combination of panobinostat with the current SIOPEL 4 induction protocol, consisting of cisplatin and doxorubicin, revealed high synergies already at low nanomolar levels. The simulation of a clinical trial, with this combination therapy, in patient-derived xenograft models, and ultimately heterotypic lung metastasis mimics clearly underscored the potency of this approach. Integrated studies define MYC inhibition by panobinostat as a novel treatment element to be introduced into the therapeutic strategy for patients with metastatic hepatoblastoma.

The Advancement Stage of Gastric Cancer and the Levels of CEA and Ca19-9 in Serum and Peritoneal Lavage

Background: This study aimed to analyze the relationship between the levels of tumor markers—specifically, carcinoembryonic antigen (CEA) and Ca19-9 antigen—determined in both serum (sCEA and sCa19-9) and intraoperative peritoneal washings (pCEA and pCa19-9) and the advanced stage of gastric cancer (including the occurrence of cancer cells in cytology from abdominal fluid). Methods: This study included 47 patients with histopathologically confirmed gastric cancer or gastroesophageal junction cancer who underwent surgical treatment. The material for the cytological examination and assessment of CEA and Ca19-9 concentrations in peritoneal fluid was collected intraoperatively. Later, blood was drawn to assess the CEA and Ca19-9 concentrations in blood serum. Results: There was a statistical correlation between a positive cytology result or the presence of peritoneal carcinomatosis and a positive result for the tumor markers obtained from abdominal washings. This correlation was not observed with marker levels obtained from blood serum. The pCEA marker was highly sensitive (93.3%) and specific (93.8%) for detecting cancer cells. The pCa19-9 marker was less effective in detecting cancer but matched pCEA in identifying the absence of cancer. No differences were observed in sCEA and sCA19-9 levels between patients who underwent neoadjuvant chemotherapy and those who did not receive this treatment. However, statistical analysis showed that this relationship did not apply to pCEA and pCa19-9 levels. Conclusions: Intraoperative determinations of tumor marker levels in peritoneal washings may be a predictive factor for a poor prognosis in patients with gastric cancer.

Prediction of tumor response to neoadjuvant chemotherapy in high-grade osteosarcoma using clustering-based analysis of magnetic resonance imaging: an exploratory study.

To evaluate the ability of magnetic resonance imaging (MRI)-based clustering analysis to predict the pathological response to neoadjuvant chemotherapy (NACT) in patients with primary high-grade osteosarcoma. Twenty-two patients were included in this retrospective study. All patients underwent MRIs before and after NACT. The entire tumor volume was manually delineated on post-contrast T1-weighted images and subsegmented into three clusters using the K-means algorithm. Histogram-based parameters were calculated for each lesion. The response to NACT was obtained from the histopathological assessment of the tumor necrosis rate following resection. The Mann-Whitney test was used to compare poor and fair-to-good responders. The receiver operating characteristic curve was used to evaluate the diagnostic performance of the optimal parameters. At baseline, poor responders showed a significantly larger volume of cluster1 (Vol1) than fair-to-good responders (p = 0.038). After NACT, they exhibited a lower 10th percentile (P10) and kurtosis (p = 0.038 and 0.002, respectively). Vol1 at baseline and P10 after NACT had an AUC of 77% (95% CI 56-98%). The kurtosis after NACT had the best discriminative power, with an AUC of 89.7% (95% CI 75-100%). The MRI-based histogram and clustering analysis provided a good ability to differentiate between poor and fair-to-good responders before and after NACT. Further investigations using larger datasets are required to corroborate our findings.

Advances in neoadjuvant therapy for resectable intrahepatic cholangiocarcinoma: An invited commentary

Abstract Intrahepatic cholangiocarcinoma (ICC) poses a significant threat to human health owing to its high malignancy rate and poor prognosis. Surgery is the most effective treatment option for ICC. However, the prognosis remains unfavorable even after surgical resection. Therefore, neoadjuvant therapy has emerged as a potential treatment option for patients with ICC. Neoadjuvant therapy can improve patient prognosis by reducing the tumor size and eliminating tiny lesions that are not visible to the naked eye. Nevertheless, specific treatment options for neoadjuvant therapy are unavailable. This review summarizes the studies on neoadjuvant therapy for ICC in the last decade, including chemotherapy, radiotherapy, interventional therapy, targeted therapy, and immunotherapy, with the aim of providing suggestions for the selection of clinical treatment options for patients with ICC. Current reports suggest that chemotherapy is the most effective neoadjuvant treatment option. However, radiotherapy and interventional therapies require further investigation to obtain conclusive recommendations. Although targeted therapies and immunotherapies have been studied less extensively, several ongoing clinical trials are investigating these promising approaches.

Neoadjuvant chemotherapy with FLOT scheme in surgical treatment of gastric cancer: short- and long-term outcomes. A retrospective cohort study

Aim. To compare the results of surgical treatment of patients with gastric adenocarcinoma and esophagogastric junction cancer (EGJC) who received neoadjuvant chemotherapy (NCT) FLOT with primary operated patients. Materials and methods. A retrospective cohort study included 177 patients who underwent radical surgical treatment at the Burdenko Faculty Surgery Clinic of Sechenov University for gastric cancer (GC) and/or EGJC Sievert Type II–III in the period from January 2018 to December 2022. The main group consisted of patients (n=28) who received NCT FLOT. Patients in both groups did not statistically significantly differ in average age (p=0.110), ASA status (p=0.541), ECOG status 0–3 (p=0.12), localization (p=0.063), depth of invasion (p=0.099) and histological structure of the tumor (p=0.787). In the main group, more patients with lesion of the regional lymph nodes were expected (p0.001). According to the most significant indicators [postoperative complications, the presence of a "positive" edge of resection (R1), recurrence and/or progression of GC], we performed a quasi-randomization by the matching procedure, taking into account the selection of the nearest neighbors. Results. In 92.9% of patients in the main group and in 94.9% of the control group, R0 resection (p=0.750) was achieved. The number of removed lymph nodes was statistically significantly higher in the main group (average 26 vs 21; p=0.010). There was no difference in intraoperative blood loss (p=0.294) and hospital stay (p=0.992). The average duration of surgery in the main group was 319 minutes, compared to 250 minutes in the control group (p0.001). In the early postoperative period, the total number of complications (CD I–IV) was higher in the main group (p=0.031), however, there was no difference in the number of small (CD I–II; p=0.094) and significant (CD III–V; p=0.142) complications. Postoperative mortality in the first 30 days after surgical treatment was 3.6 and 2.5% in the main and control groups, respectively (p=0.764). The overall 6-month survival rate in the control group was 95.9% vs 90.9% in the main group, and the 12-month survival rate was 88.8% vs 75.7%, respectively. The reccurence-free 6-month survival rate in the control group was 96%, in the main group – 100%; the reccurence-free 12-month survival rate in the control group was 92.1%, in the NCT group – 93.3%. Conclusion. NCT FLOT in the treatment of GC and EGJC Sievert Type II–III does not increase the level of intraoperative blood loss, the number of postoperative complications and the duration of hospitalization. The 6-month and one-year survival rates did not differ in the two groups. Considering that the majority of patients in the NCT group belonged to the cN+ category, with an initially less favorable treatment prognosis, it can be assumed that comparable survival results were achieved thanks to NCT.

Experts' Cognition-Driven Ensemble Deep Learning for External Validation of Predicting Pathological Complete Response to Neoadjuvant Chemotherapy from Histological Images in Breast Cancer

In breast cancer, neoadjuvant chemotherapy (NAC) provides a standard treatment option for patients who have locally advanced cancer and some large operable tumors. A patient will have better prognosis when he has achieved a pathological complete response (pCR) with the treatment of NAC. There has been a trend to directly predict pCR to NAC from histological images based on deep learning (DL). However, the DL-based predictive models numerically have better performances in internal validation than in external validation. In this paper, we aim to alleviate this situation with an intrinsic approach. We propose an experts’ cognition-driven ensemble deep learning (ECDEDL) approach. Taking the cognition of both pathology and artificial intelligence experts into consideration to improve the generalization of the predictive model to the external validation, ECDEDL can intrinsically approximate the working paradigm of a human being which will refer to his various working experiences to make decisions. ECDEDL was validated with 695 WSIs collected from the same center as the primary dataset to develop the predictive model and perform the internal validation, and was also validated with 340 WSIs collected from other three centers as the external dataset to perform the external validation. In external validation, ECDEDL improves the AUCs of pCR prediction from 61.52(59.80-63.26) to 67.75(66.74-68.80) and the Accuracies of pCR prediction from 56.09(49.39-62.79) to 71.01(69.44-72.58). ECDEDL was quite effective for external validation of predicting pCR to NAC from histological images in breast cancer, numerically approximating the internal validation.

Ki-67 With MRI in Predicting the Complete Pathological Response Post-neoadjuvant Chemotherapy.

Neoadjuvant chemotherapy (NAC) is increasingly used for high-risk breast cancer to achieve pathologic complete response (pCR), an indicator of event-free survival and favorable survival outcomes. Integrating MRI and Ki-67 biomarker analysis into predictive models offers a promising approach to optimize NAC response assessment and guide personalized treatment strategies. This study evaluates the validity of combined MRI and Ki-67 metrics for predicting pCR. We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, including studies on NAC-treated breast cancer patients assessed by MRI and Ki-67. The predictive models were evaluated based on key parameters, including MRI-based tumor size reduction and Ki-67 levels, with outcomes measured by area under the receiver operating characteristic curve (AUC) and calibration metrics. Findings across ten studies consistently show that high Ki-67 levels and significant tumor size reduction on MRI are predictive of pCR, achieving AUCs near 0.90. The analysis highlighted that models integrating MRI with Ki-67 metrics outperformed single-modality approaches, showing enhanced predictive accuracy and calibration. However, high heterogeneity (I² = 77%) was noted, suggesting variability in imaging and Ki-67 assessment protocols across studies. Thisstudy underscores the combined utility of MRI and Ki-67 for the non-invasive prediction of pCR, offering both structural and biological insights into tumor responsiveness. The results align with prior research, affirming the role of Radiomic-clinicopathological models in providing a more comprehensive assessment compared to individual markers. Further refinement of imaging and biomarker protocols could improve model reproducibility and applicability. Our findings highlight the robust predictive accuracy of MRI-Ki-67 integrated models for assessing pCR, marking a significant step toward personalized cancer care. Future studies should focus on refining these models with additional biomarkers and standardized protocols, facilitating their integration into routine clinical oncology to enhance treatment decision-making and patient outcomes.

QLTI-20. BRIDGING THE GAP: UNDERSTANDING THE CURRENT TREATMENT RESPONSES TO ENHANCE THE STANDARD OF CARE AND OUTCOMES FOR MALIGNANT PERIPHERAL NERVE SHEATH TUMORS

Abstract Malignant peripheral nerve sheath tumor (MPNST) are a rare and aggressive cancer that make up 5-10% of all sarcomas. There is currently no effective targeted therapy to treat MPNST and surgical resection remains the mainstay of treatment, though often not feasible due to location, size of the tumor, or presence of metastases. Evaluation of MPNST treatment response to palliative chemotherapy regimens could serve as a reference point for target response rates in clinical trials going forward. We performed a retrospective electronic health record analysis of patients with biopsy-proven diagnoses of MPNST at Washington University and Johns Hopkins University. We evaluated tumor characteristics along with treatment response, overall survival (OS), and progression free survival (PFS) rates for different chemotherapeutic regimens. The cohort comprises 140 patients, with ages at diagnosis ranging from 21 to 40 years. Most patients had tumors located in the extremities, with sizes ranging from 5-10 cm at the time of diagnosis. We identified 66 patients who received adjuvant chemotherapy, 44 received neoadjuvant chemotherapy and 28 did not receive any chemotherapy. We will present objective response rate (ORR) and clinical benefit rate (CBR) for neoadjuvant chemotherapy. Among patients with metastatic disease (n=53), 12 chemotherapy regimens were assessed. All regimens other than gemcitabine-docetaxel chemotherapy regimen performed better than the median PFS of 1.77 months which has been observed in clinical trials of targeted agents to date with the most compelling response to vincristine-irinotecan-temozolomide regimen. Despite advancements in our understanding of MPNST pathogenesis, these tumors carry a poor prognosis. Our study has identified several systemic therapies which should be further evaluated prospectively to improve treatment options and outcomes for patients with this aggressive sarcoma. These results can serve as a benchmark for future clinical trials.

Predicting ipsilateral supraclavicular lymph node pathological complete response: nomogram based on the inflammatory markers

BackgroundThe prediction of ISLN pCR after neoadjuvant chemotherapy (NAC) based on inflammatory markers and its prognostic value have rarely been investigated.MethodsPatients diagnosed with ISLN-involved breast cancer who received NAC in West China Hospital between September 2009 and December 2020 were enrolled in the derivation cohort for model construction and survival analysis, and patients with the same criteria between January 2021 and July 2024 were involved in validation cohort for external validation. After randomly dividing patients into training and testing groups at 7:3 ratio, a nomogram predicting ISLN pCR was constructed based on logistic regression in training group. Internal validation was performed in the testing group and external validation was performed in the independent validation cohort. The ROC curves were applied to validate the accuracy of the model. Survival analysis was performed using Kaplan−Meier plots.ResultsA total of 120 eligible patients were involved in the derivation cohort to establish the nomogram (84 patients in training group and 36 patients in testing group), and 45 patients were involved in the independent validation cohort for external validation of the nomogram. Pretreatment NLR and hormone receptor (HR) status, as well as preoperative SII, CEA, CA15-3 and anti-HER2 therapy were included in the nomogram predicting ISLN pCR. The AUC were 0.906 (95% CI 0.837-0.975, P<0.001), 0.888 (95% CI 0.751-1.000, P<0.001) and 0.828 (95% CI 0.703-0.953, P< 0.001) in training, testing groups and the validation cohort respectively. ISLN pCR was significantly associated with better prognosis (all P<0.05).ConclusionInflammatory factors combined with tumor makers, hormone receptor status and anti-HER2 therapy could predict ISLN pCR effectively, which was significantly associated with improved survival outcomes.

Neuroendocrine differentiation and serotonin expression in oesophageal adenocarcinomas after neoadjuvant therapy: correlation with clinicopathological features and outcome.

Oesophageal adenocarcinoma (EAC) is a glandular or mucinous epithelial malignancy that can show immunohistochemical evidence of neuroendocrine differentiation (NED) and express the hormone serotonin. The objective of this study was to correlate the presence of NED and serotonin with clinicopathological characteristics and patient outcome after neoadjuvant chemoradiation. A retrospective cohort of patients treated between 2002 and 2021 was established and included 218 oesophagectomy specimens with residual tumour. Representative full-face sections of tumour were stained for synaptophysin, chromogranin-A and serotonin by immunohistochemistry, and staining results were correlated with disease-free survival (DFS) and overall survival (OS). In total, 129 (59%) tumours showed evidence of NED, defined as immunohistochemical expression of synaptophysin or chromogranin-A, while 40 (18%) showed evidence of NED and expressed serotonin. Patients with neuroendocrine-positive tumours had significantly shorter median OS compared to those with neuroendocrine-negative tumours (22.5 versus 48.8 months, P = 0.006), but similar median DFS (13.3 versus 17.8 months, P = 0.34). Using Cox regression, the association between NED and OS was significant in univariate [hazard ratio (HR) = 1.68, 95% confidence interval (CI) = 1.16-2.45] and multivariate (HR = 1.65, 95% CI = 1.08-2.52) analysis. Patients with serotonin-expressing tumours had similar median OS (21.7 versus 25.9 months, P = 0.24) and DFS (7.3 versus 15.6 months, P = 0.12) compared to those with NED but lacking serotonin. Using Cox regression, serotonin expression was associated with reduced OS in univariate (HR = 1.62, 95% CI = 1.06-2.47) but not multivariate (HR = 1.03, 95% CI = 0.64-1.65) analysis. Our findings support NED as independent predictor of OS in EAC after neoadjuvant chemoradiation. While a subset of tumours with NED expressed serotonin, this did not provide additional prognostic information.

A case of intraoperative detection of a central venous catheter in azygos vein arch during esophageal cancer surgery.

Central venous catheter (CVC) is often used in the perioperative management of esophageal cancer. The position of the CVC tip has been reported to shift with body positioning and, although infrequent, may traverse into the azygos vein arch. Herein, we describe a case where a migrated CVC tip in the azygous vein arch was identified during esophageal cancer surgery, preventing CVC dissection concurrent with azygous vein arch resection. A 65-year-old man was diagnosed with advanced esophageal cancer and was referred to our department for surgery after undergoing neoadjuvant chemotherapy. He underwent robot-assisted subtotal esophagectomy, followed by gastric conduit reconstruction via the posterior sternal route. Thoracic manipulation was performed with the patient in the prone position. During the surgery, a foreign body was found in the azygos vein arch, indicating that a central venous catheter had inadvertently entered the azygos vein arch. The catheter was retracted by 5cm, and after confirming that no catheter remained in the azygos arch, the azygos vein arch was separated using an autosuture device. Central venous catheter migration can occur in a various vessels. During prone esophageal cancer surgery, elevating the right upper extremity may alter the catheter tip's position from its the preoperative position. CVC amputation should be observed because the azygos vein arch is often amputated to facilitate upper mediastinal dissection during esophageal cancer surgery.

Comparison of the efficacy of neoadjuvant chemotherapy with FLOT regimen and adjuvant chemotherapy with XELOX/FOLFOX regimen in patients with locally advanced gastric cancer: A retrospective study

Background. To date, there is no consensus on the preferred sequence of combined treatment in patients with locally advanced gastric cancer (perioperative chemotherapy – POCT or primary surgical treatment). No direct comparison of these approaches had been conducted before. Aim. To compare, in retrospective analysis, 3-year relapse-free (RFS) and overall survival (OS) in patients receiving POCT FLOT or adjuvant chemotherapy XELOX/FOLFOX for locally advanced gastric cancer. Materials and methods. The assessment included 153 patients who underwent POCT FLOT and 171 patients who underwent surgical treatment at the first stage. When evaluating the initial characteristics, it was shown that patients with ECOG (The Eastern Cooperative Oncology Group) stage 1-2, clinical stage cT4a-b, cN2-3 and Bormann type 4 to were significantly more common in the POCT group. Morphological characteristics: grade, presence of signet cell carcinoma, HER2/neu overexpression, microsatellite instability, sensitivity to immunotherapy (Combined Positive Score) didn't differ. Results. With a median follow-up of 40 months, it was shown that the long-term results assessed in all included patients were better in the group with primary surgical treatment: 3-year RFS was 55 and 40% (risk ratio – RR 1.33, 95% confidence interval – CI 1.08–1.64; р=0.007). 3-year OS was 68 and 56% (RR 1.36, 95% CI 1.02–1.8; р=0.04), respectively. However, when evaluating patients who received surgical treatment in the POCT group (n=121, 79%), the results did not differ: 3-year RFS 55 and 50% (RR 0.9, 95% CI 0.71–1.16; р=0.97), 3-year OS 68 and 63% (RR 1.1, 95% CI 0.84–1.59; р=0.97). Insufficient volume of adjuvant chemotherapy (75% of the dose) significantly worsened long-term results (3-year OS 43 and 71%; p=0.002). Conclusion. The obtained data of a retrospective analysis did not reveal the advantages of any of the approaches provided that the surgical stage was performed in patients receiving POCT. To obtain more objective results, it is necessary to conduct randomized multicenter studies in the high volume centers, providing the necessary sample capacity, quality of diagnosis and treatment. Thus, the design of future studies should be based on the hypothesis of non-inferiority, which inevitably entails a significant increase in the required number of observations to obtain reliable sampling power.

Current technologies of response assessment in rectal cancer after neoadjuvant treatment: A review

Improvement of the multidisciplinary approach to the treatment of rectal cancer over recent years has led to the fact that in specialized high-volume oncology clinics it is possible to achieve a complete pathomorphological response to neoadjuvant therapy in a third of patients. The emergence of new knowledge about the development of tumor complete response and the accumulation of clinical experience opens up possibility for the wider use of an organ-sparing approach. Undoubtedly, making such a critical strategic decision requires reliable and effective tools for complete response predicting. This review is devoted to methods for assessing tumor response in patients diagnosed with rectal cancer. A look at the problem is presented from the perspective of modern methods of medical imaging, molecular and genetic studies, the study of the characteristics of the immune response, and a new look at clinical data. New data can form the basis for new patient selection algorithms for personalized treatment protocols for rectal cancer, thereby improving long-term results and quality of life for patients.

MR tomographic evaluation of the effectiveness of neoadjuvant chemotherapy for breast cancer based on pharmacokinetic numerical analysis of tumor uptake of paramagnetic contrast in intravenous contrast enhancement

Background. In clinical practice, MRI pathophysiological and pharmacokinetic models with calculations of contrast transport indicators are unacceptably little used.Aim of the study. To propose a pharmacokinetic technique for the quantitative assessment of primary tumors and metastases, the effectiveness of breast cancer chemotherapy (BC), from dynamic contrast enhancement MRI. Material and methods. 18 patients were included who underwent neoadjuvant chemotherapy (NACHT) in four cycles for breast cancer T1-3N0-1M0, followed by radical surgical removal of the tumor. According to the results of a three — year follow-up, patients with a relapse — free course (n = 11) formed group 1, and seven patients with detected metastatic lesions (3 in the liver, 2 in the lungs, 2 in the brain) — group 2. For the initial 120–180 s of MRI with contrast after the injection of a paramagnetic, the simplification is valid for concentrations in tumor and blood and for tranfer coefficient: d{СОПУХОЛЬ(t)} / dt = ККр-Оп * СКРОВЬ (t) , from which it is obvious: ККр-Оп = (СОПУХОЛЬ(Т)) / (∫CКРОВЬ(t) dt), which was used in all calculations of the contrast transfer constant. Gadobutrol contrast is 0.1M/10 kg of body weight, TR = 5.5–6 ms, TE = 2.5 ms. Results. If, after the first cycle of NACHT, the ККр-Оп of the primary breast cancer is < 0.22 ml/min/g of tissue, the probability of subsequent relapse-free course = 0.78. Similarly, a decrease in the KCr-Op Ккр-Оп of the sentinel lymph node after the first cycle of NAHT < 0.08 ml/min/g of tissue with a probability of 0.75 predicts a relapse-free course. Conclusion. The proposed method for calculating the ККр-Оп transfer coefficient allows obtaining additional diagnostic and prognostic information in patients with local and locally advanced forms of breast cancer.

Predictive and Prognostic Value of Inflammatory and Nutritional Indexes in Patients with Breast Cancer Receiving Neoadjuvant Chemotherapy

Background and Objectives: Neoadjuvant chemotherapy (NAC) improves survival by increasing pathologic complete response (pCR). Blood-based indexes have been studied in breast cancer for predicting pCR and prognosis, but the results are conflicting. We aimed to assess the impact of inflammatory and nutritional indexes on pCR and survival. Materials and Methods: We retrospectively analyzed 304 patients. Pre-NAC laboratory data were used to calculate their neutrophil-to-lymphocyte ratios (NLR), pan-immune inflammation values (PIV), lactate dehydrogenase–albumin ratios (LAR), and prognostic nutritional indexes. The optimal cut-off values were determined through an analysis of the receiver operating characteristic curve. Survival analyses were performed using the Kaplan–Meier method. Multivariate regression analyses were performed to reveal the factors predicting pCR. Univariate and multivariate survival analyses were conducted to identify prognostic factors predicting survival. Results: The median follow-up was 38.5 months. pCR was achieved in 41.4% of the patients. In the univariate analyses, the NLR (p = 0.032) and PIV (p = 0.002) were indexes associated with pCR. In the multivariate analysis, the PIV (p = 0.008) was the only index significantly correlated with pCR. According to the multivariate Cox regression analyses, clinical stage 3 (p = 0.032), a pathologic response other than pCR (p = 0.021), and a high LAR (≥4.72) (p = 0.002) were correlated with increased recurrence risk. The univariate Cox regression analyses revealed that failure to achieve pCR (p = 0.037) and the presence of a high LAR (p = 0.044) were significant predictors of overall survival. However, the multivariate analyses failed to identify any significant predictors of death. Conclusions: We found that the PIV was more effective than the other indexes in predicting pCR. To our knowledge, this study is the first to determine an association between the LAR and disease-free survival in patients with breast cancer receiving NAC. We concluded that a high LAR was a poor prognostic factor, especially in patients without a pCR. Therefore, close postoperative monitoring and the intensification of adjuvant treatment should be considered for these patients. However, further studies are needed to confirm our findings.

Immunohistochemical Status Predicts Pathologic Complete Response to Neoadjuvant Therapy in HER2-Overexpressing Breast Cancers.

Human epidermal growth factor receptor 2 (HER2) overexpression (HER2+) is defined by immunohistochemistry (IHC) and in situ hybridization (ISH) as IHC3+ or IHC2+/ISH+. Response differences to neoadjuvant anti-HER2 therapy (NT) in IHC3+ versus IHC2+/ISH+ breast cancer patients are poorly characterized. We explored whether pathologic complete response (pCR) varies by HER2 IHC status. Patients with stage I-III HER2+ breast cancer undergoing NT and surgery between 2013 and 2020 were identified from the National Cancer Database and stratified by IHC status. Breast and nodal pCR were analyzed. Of 40,711 HER2+ patients, 83% were IHC3+ and 17% were IHC2+/ISH+. IHC3+ patients were more likely to be hormone receptor (HR)-negative (33 vs. 21%), have cT3/4 tumors (24 vs. 21%), and be cN+ (52 vs. 47%; all p < 0.0001). Breast conservation rates were similar (each 43%, p = 0.32), although IHC3+ axillary lymph node dissection rates were lower (41 vs. 45%, p < 0.0001). Among all patients, breast pCR was 49%, while nodal pCR was 64%. Compared with IHC2+/ISH+, IHC3+ had higher unadjusted breast (54 vs. 22%, p < 0.0001) and nodal (69 vs. 37%, p < 0.0001) pCR rates. When stratified by HR status, pCR was lower for HR+ disease but remained higher among IHC3+ patients. Analysis of T1cN0 primaries mirrored these trends. In multivariable analysis, IHC3+ remained an independent predictor of breast (odds ratio [OR] 3.91, confidence interval [CI] 3.65-4.19, p < 0.0001) and nodal (OR 3.40, CI 3.12-3.71, p < 0.0001) pCR. HER2 IHC status predicts pCR and may help select breast cancer patients who derive the greatest benefit from NT. These findings provide further evidence that revision of HER2 classification may improve clinical management.

Ideal outcome post-pancreatoduodenectomy: a comprehensive healthcare system analysis.

Indicators, such as mortality and complications, are commonly used to measure the quality of care. However, a more comprehensive assessment of surgical quality is captured using composite outcome measures such as Textbook Outcome (TO), Optimal Pancreatic Surgery, and a newer 'Ideal Outcome' (IO) measure. We reviewed our institutional experience to assess the impact of demographics, comorbidities, and operative variables on IO after pancreatoduodenectomy (PD). A retrospective study was conducted on PD patients at Northwell Health between 2009 and 2023. IO was determined by the absence of six adverse outcomes, including in-hospital mortality, Clavien-Dindo ≥ III complications, clinically-relevant postoperative pancreatic fistula, reoperation, hospital stay > 75th percentile, and readmission within 30 days. Logistic regression analyzed the effects of various factors on achieving IO. Of the 578 patients who underwent PD, 248 (42.91%) achieved the IO. On multivariable analysis, factors associated with increased odds of achieving IO included neoadjuvant chemotherapy (OR 1.30, 95% CI 1.05-1.62) and the presence of neuroendocrine tumors (OR 3.37, 95% CI 1.35-8.41). Percutaneous transhepatic biliary drainage (PTBD) (OR 0.34, 95% CI 0.14-0.80) and older age (≥ 70 years) (OR 0.48, 95% CI 0.32-0.74) were associated with decreased odds of achieving IO. Patients with IO had significantly improved survival on Kaplan-Meier log-rank test (p = 0.001) as well as adjusted Cox analysis (HR 0.62 95% CI: 0.39-0.97). IO may offer a comprehensive metric for assessing PD outcomes, highlighting the impact of age, chemotherapy, biliary drainage, and tumor types. These findings suggest targeted interventions and quality improvements could enhance PD outcomes by addressing modifiable factors and refining clinical strategies.

Neoadjuvant immune checkpoint inhibitor reduced recurrence in operable NSCLC patients with pathological complete response: a retrospective analysis

BackgroundThis study aimed to evaluate if neoadjuvant immune checkpoint inhibitor (ICI) plus chemotherapy (CT) reduced tumor recurrence after surgery than neoadjuvant CT alone in non–small cell lung cancer (NSCLC) patients with pathologic complete response (pCR).MethodsFrom January 1st 2019 to April 30th 2022, 16 NSCLC patients with pCR who received both neoadjuvant ICI and CT were designated as ICI/CT group. Another 8 patients, who received neoadjuvant CT alone, were designated as CT group. The tumor recurrence and patients’ survival status were analyzed.ResultsSquamous cell carcinoma was the predominant histology type in both groups. The CT group had higher percentage of patients who received adjuvant CT than the ICI/CT group (100% vs. 75%, p = 0.046). All patients had been followed up for at least 20 months. At 20 months after surgery, the ICI/CT group had a tumor recurrence rate of 6.25%, which was significantly lower than 37.5% recurrence rate of the CT group. One patient of the CT group died of gastrointestinal hemorrhage and severe anemia at 11 months after surgery, and no patient in the ICI/CT group died. During adjuvant therapy, the ICI/CT group had significantly lower risk of anemia (12.5% vs. 50%) than the CT group (p = 0.046).ConclusionThe study found that in NSCLC patients with pCR, neoadjuvant ICI reduced tumor recurrence rate. This indicated that like in advanced stage NSCLC, the ICI might bring similar long-term anti-tumor effect in operable NSCLC patients.

Determining optimal clinical target volume margins based on microscopic extracapsular extension of metastatic nodes in patients with non-small-cell lung cancer after chemotherapy or chemotherapy combined with immunotherapy

BackgroundNo standard has been established for the clinical target volume (CTV) margins of lymph nodes (LNs) in patients with non-small-cell lung cancer (NSCLC) receiving chemotherapy or chemotherapy combined with immunotherapy followed by radiotherapy. This study aimed to discuss the CTV range of NSCLC after chemotherapy or chemotherapy combined with immunotherapy by observing the microscopic extent of tumor spread beyond the LN capsule.MethodsWe retrospectively analyzed the data of 240 patients with stage II and III NSCLC who underwent surgery without neoadjuvant therapy, with neoadjuvant chemotherapy (NAC), or with NAC combined with immunotherapy (NACI). We measured the maximal distance of extracapsular extension (ECE) using a digital microscope, analyzed the correlation between clinicopathological features and ECE distance, and determined the CTV margins of metastatic LN under different treatment methods.ResultsThe ECE distance differed significantly among the three groups (p < 0.001). We determined appropriate margin widths based on a 5% error risk as 3.00, 2.30, and 1.40 mm for direct surgery, NAC, and NACI, respectively. Multivariate analysis revealed that the ECE of metastatic LN correlated with the treatment methods and LN size.ConclusionThe existing CTV delineation standards may increase the radiation toxicity of patients. We believe that different CTV margins should be used for LN in patients with NSCLC receiving different treatments. To ensure 95% coverage of ECE, the gross tumor volume of untreated, chemotherapy-treated, and chemotherapy combined with immunotherapy-treated patients should be expanded by 3.00, 2.30, and 1.40 mm, respectively, to obtain the CTV.

Efficacy of Mammographic Artificial Intelligence-Based Computer-Aided Detection in Predicting Pathologic Complete Response to Neoadjuvant Chemotherapy

This study evaluates the potential of an AI-based computer-aided detection (AI-CAD) system in digital mammography for predicting pathologic complete response (pCR) in breast cancer patients after neoadjuvant chemotherapy (NAC). A retrospective analysis of 132 patients who underwent NAC and surgery between January 2020 and December 2022 was performed. Pre- and post-NAC mammograms were analyzed using conventional CAD and AI-CAD systems, with negative exams defined by the absence of marked abnormalities. Two radiologists reviewed mammography, ultrasound, MRI, and diffusion-weighted imaging (DWI). Concordance rates between CAD and AI-CAD were calculated, and the diagnostic performance, including the area under the receiver operating characteristics curve (AUC), was assessed. The pre-NAC concordance rates were 90.9% for CAD and 97% for AI-CAD, while post-NAC rates were 88.6% for CAD and 89.4% for AI-CAD. The MRI had the highest diagnostic performance for pCR prediction, with AI-CAD performing comparably to other modalities. Univariate analysis identified significant predictors of pCR, including AI-CAD, mammography, ultrasound, MRI, histologic grade, ER, PR, HER2, and Ki-67. In multivariable analysis, negative MRI, histologic grade 3, and HER2 positivity remained significant predictors. In conclusion, this study demonstrates that AI-CAD in digital mammography shows the potential to examine the pCR of breast cancer patients following NAC.