Background: Inflammatory blood biomarkers (IBMs), including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), lymphocyte-to-monocyte ratio (LMR), systemic inflammation response index (SIRI), pan-immune-inflammation value (PIV), and systemic inflammation index (SII), have been proposed as prognostic and predictive markers in cancer. This study evaluated their predictive value for pathological complete response (pCR), disease-free survival (DFS), overall survival (OS), and neoadjuvant chemotherapy (NACT)-related toxicities in early and locally advanced breast cancer (BC). Methods: A retrospective analysis was conducted on 284 BC patients receiving NACT. Associations between IBMs, treatment response, survival outcomes, and chemotherapy-related toxicities were analyzed. Results: -IBMs were significantly associated with chemotherapy-related toxicities. Neutrophils, lymphocytes, monocytes, NLR, SII, SIRI, and PIV (all p < 0.001) strongly predicted febrile neutropenia, along with doublet anti-HER2 therapy (p = 0.032). Predictors of neutropenia included neutrophil, monocyte, NLR, MLR, LMR, SII, SIRI, PIV (p < 0.05), HER2-positive status, and doublet anti-HER2 therapy. -Subgroup analyses showed IBM predictive performance varied by subtype. NLR predicted DFS in HER2+ patients (AUC = 0.839, p = 0.010); neutrophil count was linked to peripheral neuropathy in HR+/HER2− patients (p = 0.042). PLR and LMR showed excellent discrimination for febrile neutropenia in TNBC (AUCs > 0.92). In TNBC, MLR, SIRI, and PIV showed moderate-to-high discrimination for OS (AUCs 0.71–0.74). Neutrophil (p = 0.0058) and lymphocyte (p = 0.0248) levels were associated with pCR in HER2+ patients. HR+ subtypes showed limited IBM predictive value. Conclusion: IBMs demonstrated strong predictive value for chemotherapy-related toxicities and showed subtype-specific relevance for survival and treatment response. These findings support the integration of molecular stratification to enhance the predictive utility of IBMs in breast cancer, highlighting their clinical potential in anticipating and managing treatment-related adverse events and guiding personalized supportive care strategies.

Tertiary lymphoid structures (TLSs) in rectal cancer (RC) are closely associated with immunotherapy response and patient prognosis, yet their assessment currently relies on invasive biopsy. This study aimed to investigate whether TLSs can be accurately and noninvasively predicted using multi-dimensional magnetic resonance imaging (MRI) features and to evaluate the model's utility in predicting immunotherapy response and prognosis. A total of 606 RC patients from four cohorts were included. A development cohort was used for model construction, while both a validation cohort and a prospective cohort were used to assess its generalizability. An additional immunotherapy cohort was utilized to evaluate the model's ability in predicting immune responses. The proposed multi-dimensional features comprised: (1) radiomic features extracted from region of interest; (2) dimensionality-reduced features derived using principal component analysis and singular value decomposition; and (3) tumor heterogeneity features extracted via habitat analysis. XGBoost was employed to construct the TLSs classification model (positive vs. negative). Shapley Additive exPlanations analysis was used to interpret the contributions to model decisions, and the model's performance was further tested in predicting immunotherapy response and survival outcomes. The TLSs model demonstrated strong discriminatory performance, with area under the receiver operating characteristic curve (AUROC) of 0.88 in the internal validation set, 0.81 in external test set 1, and 0.84 in external test set 2. Features such as "subregion3_firstorder_MeanAbsoluteDeviation" had the greatest impact on model decisions. Furthermore, the TLSs score derived from the model showed promising predictive value for pathological complete response to immunotherapy, with an AUROC of 0.74. Kaplan-Meier analysis revealed that the high TLSs score group had significantly better disease-free survival compared to the low-score group. The multi-dimensional MRI-based TLSs model shows robust performance in predicting TLSs status, immunotherapy response and prognosis in RC, providing a novel tool for guiding personalized immunotherapy and prognostic assessment.

The association between pathological complete response and prognosis of gastric or adenocarcinoma of esophagogastric junction cancer following neoadjuvant chemotherapy: A meta-analysis.

4027 Background: Studies have shown overall survival improvements with nCRT + surgery vs surgery alone in locally advanced ESCC. However, preoperative CRT may have additional safety concerns, leading to some patients (pts) receiving nCT rather than nCRT. PET-computed tomography maximum standardized uptake value (SUV max ) change after induction CT (IC) has been shown to have reliable predictive value of pathological complete response (pCR) for R-ESCC in pts with nCRT and may optimize neoadjuvant tx selection. TIS (anti-PD-1) has improved survival in pts with ESCC. We report the final analysis of RATIONALE-213, a phase 2, open-label, multicenter study in China evaluating PET-guided nTIS + CT/CRT in R-ESCC (NCT04974047). Methods: Eligible adult pts had histologically confirmed R-ESCC (cT1-2N + M0 or cT3N any M0), ECOG performance status 0/1, adequate organ function, no fistula risk, and had received no prior tx. Pts had a baseline (BL) PET scan, 1 cycle of IC (cisplatin-paclitaxel [Cis-Pac]), and a PET scan 15-21 days later. Pts were grouped into 2 cohorts by response to IC based on the percentage decrease in 2nd PET SUV max in the primary tumor: responders (R, ≥35%) or nonresponders (NR, < 35%). Both cohorts received 3 cycles of TIS 200 mg IV Q3W, the first 2 with CT (2 cycles Cis-Pac) for R, or with CRT (2 cycles investigator [Inv]-chosen CT [Cis-Pac, or 5-FU + Cis] + RT [40 Gy/20 fractions]) for NR, then surgery. Primary endpoint was pCR per local pathologist. Secondary endpoints were 1-year disease-free survival (DFS), 1-year event-free survival (EFS), objective response rate (ORR) before surgery, R0 resection rate by Inv, and safety. Results: Of 70 pts enrolled, 15 (21.4%), 48 (68.6%), and 7 (10.0%) had stage II, III, and IVA disease at BL, respectively. As of 25 Oct 2024 (median follow-up 25.5 mo), 30 pts were R and 40 NR. Of R, 20 (66.7%) had surgery. Of NR, 32 (80.0%) had surgery. Efficacy endpoints are shown in the table. Median DFS and EFS were not reached for R and NR. Grade ≥3 treatment-related adverse events (TRAEs) in R (15 [50.0%]) and NR (33 [82.5%]) were consistent with known CT or CRT toxicity; serious TRAEs occurred in 5 R (16.7%) and 7 NR (17.5%). No TRAEs led to surgery cancellation or death. Conclusions: APET-guided approach may help optimize neoadjuvant tx of R-ESCC. nTIS + CT/CRT showed promising efficacy and a tolerable safety profile in both responders and nonresponders. Clinical trial information: NCT04974047 . R NR pCR, a n (%)(95% CI) 6 (30.0) (11.9, 54.3) 11 (34.4)(18.6, 53.2) 1-year DFS, b %(95% CI) 79.0 (47.9, 92.7) 74.2(53.3, 86.8) 1-year EFS, c %(95% CI) 87.1 (64.3, 95.8) 67.8 (48.3, 81.2) R0 resection, a n (%) 19 (95.0) 29 (90.6) ORR, d n (%) 15 (71.4) 14 (42.4) a Efficacy analysis set (EAS) R=20; NR=32. b EAS with R0 resection R=19; NR=29. c Safety analysis set (SAS) R=30; NR=40. d SAS with measurable disease at BL R=21; NR=33.

Neoadjuvant immune checkpoint inhibitors (ICIs) have emerged as a promising treatment strategy for resectable non-small cell lung cancer (NSCLC). However, optimal combination strategies, treatment cycles, and predictive indicators for long-term outcomes remain unclear. This study aimed to evaluate the efficacy of various neoadjuvant ICI-based therapies in resectable NSCLC, identify the optimal treatment cycles for neoadjuvant immunochemotherapy, and assess the prognostic value of pathological complete response (pCR) and major pathological response (MPR) for event-free survival (EFS). A systematic literature search was conducted in PubMed, EMBASE, Cochrane CENTRAL, and Web of Science, including studies published up to October 2024. Bayesian models were used to analyze the efficacy of different ICI-based treatment combinations, assess the impact of immunochemotherapy cycles on MPR and pCR, and examine the predictive value of MPR and pCR for EFS. Data from 34 studies were included, consisting of 32 single-arm studies (reported in 26 papers) and 8 RCTs, involving 4,593 patients. Immunochemotherapy combined with anti-angiogenesis agents was the most effective treatment strategy, significantly improving both MPR and pCR. No significant improvement in efficacy was observed when the number of neoadjuvant immunochemotherapy cycles exceeded 3 cycles. Both MPR and pCR were strong predictors of EFS. MPR showed a stronger negative correlation with event risk compared to pCR, with a log (HR) of -2.110 (95% CI: -4.150, -0.071) for MPR, and a log (HR) of -1.665 (95% CI: -2.419, -0.992) for pCR. Neoadjuvant immunochemotherapy combined with anti-angiogenesis agents appears to be a highly effective strategy for resectable NSCLC. Three cycles of neoadjuvant immunochemotherapy demonstrated optimal efficacy in this study. Both MPR and pCR are valuable prognostic indicators for EFS, with MPR showing a stronger predictive value. These findings offer important insights for optimizing treatment strategies and informing clinical decision-making in resectable NSCLC. PROSPERO, identifier CRD42024592346.

BackgroundThe prognostic value of pathological complete response (pCR) in HR+/HER2− breast cancer patients following neoadjuvant chemotherapy (NAC) is limited, as many of these patients achieve long-term survival regardless of pCR status. The effectiveness of current tools—residual cancer burden (RCB), the Miller-Payne (MP) score, CPS-EG score and the immunohistochemical 4 (IHC4)—in this subgroup remains uncertain. In this study, we validated the prognostic role of these approaches and developed a COMBINED score capable of more accurately stratifying patients into distinct risk groups, effectively identifying low-risk patients with favorable outcomes who may be suitable for treatment de-escalation.MethodsThis study retrospectively analyzed 601 HR+/HER2− breast cancer patients at Sun Yat-sen Memorial Hospital who did not achieve pCR following NAC. Patients were stratified using the IHC4, RCB, MP, CPS-EG, and a novel COMBINE score (integrating CPS-EG and IHC4). Survival outcomes, including disease-free survival (DFS) and overall survival (OS), were evaluated using Kaplan–Meier analysis and Cox regression, with time-dependent ROC and concordance index (C-index) calculations to assess prognostic performance.ResultsThe IHC4 and CPS-EG scores outperformed the RCB and MP scores in predicting DFS and OS for non-pCR HR+/HER2− patients. The COMBINE score further enhanced prognostic accuracy, stratifying patients into four risk groups with significant differences in 5-year DFS (96.5% for low-risk vs. 55.1% for high-risk) and OS (100% for low-risk vs. 63.4% for high-risk). The COMBINE score consistently demonstrated superior AUC and C-index values compared to the CPS-EG and IHC4 scores individually at all time points (all p-values < 0.05).ConclusionThe IHC4 score adds prognostic value beyond the CPS-EG score in HR+/HER2− breast cancer patients post-NAC. The COMBINE score, integrating both systems, offers superior prognostic stratification, highlighting the importance of combining clinical staging with tumor biology. Future studies with independent datasets are needed to validate these findings. This study provides valuable insights for optimizing treatment decisions in HR+/HER2− breast cancer.

Breast cancer ranks as one of the most prevalent malignant tumors among women, significantly endangering their health and lives. While radical surgery has been a pivotal method for halting disease progression, it alone is insufficient for enhancing the quality of life for patients. To investigate the correlation between ultrasound characteristic parameters of breast cancer lesions and clinical efficacy in patients undergoing neoadjuvant chemotherapy (NAC). Employing a case-control study design, this research involved 178 breast cancer patients treated with NAC at our hospital from July 2019 to June 2022. According to the Miller-Payne grading system, the pathological response, i.e. efficacy, of the NAC in the initial breast lesion after NAC was evaluated. Of these, 59 patients achieved a pathological complete response (PCR), while 119 did not (non-PCR group). Ultrasound characteristics prior to NAC were compared between these groups, and the association of various factors with NAC efficacy was analyzed using univariate and multivariate approaches. In the PCR group, the incidence of posterior echo attenuation, lesion diameter ≥ 2.0 cm, and Alder blood flow grade ≥ II were significantly lower compared to the non-PCR group (P < 0.05). The area under the curve values for predicting NAC efficacy using posterior echo attenuation, lesion diameter, and Alder grade were 0.604, 0.603, and 0.583, respectively. Also, rates of pathological stage II, lymph node metastasis, vascular invasion, and positive Ki-67 expression were significantly lower in the PCR group (P < 0.05). Logistic regression analysis identified posterior echo attenuation, lesion diameter ≥ 2.0 cm, Alder blood flow grade ≥ II, pathological stage III, vascular invasion, and positive Ki-67 expression as independent predictors of poor response to NAC in breast cancer patients (P < 0.05). While ultrasound characteristics such as posterior echo attenuation, lesion diameter ≥ 2.0 cm, and Alder blood flow grade ≥ II exhibit limited predictive value for NAC efficacy, they are significantly associated with poor response to NAC in breast cancer patients.

Abstract Purpose: Low molecular weight isoforms of cyclin E (LMW-E) have been implicated in various human cancers, including triple negative breast cancer (TNBC), and are associated with a poor prognosis. However, targeted therapies for TNBC based on biomarkers are currently lacking. This study aims to investigate LMW-E as a potential therapeutic target in TNBC and evaluate the efficacy of RP-6306, a selective inhibitor of the Protein Kinase, Membrane Associated Tyrosine/Threonine 1 (PKMYT1), in LMW-E-positive breast tumors. Experimental Design: Immunohistochemical (IHC) analysis was performed on pre-treatment tumor specimens from TNBC patients (n=36) to assess the correlation between LMW-E expression, CDK1 phosphorylation at Threonine 14 (pT14), and pathologic complete response to neoadjuvant chemotherapy. LMW-E inducible human mammary epithelial cells (hMEC) and breast cancer cell lines were used to investigate the regulatory effect of LMW-E on PKMYT1, the kinase responsible for CDK1 phosphorylation at T14, and the response to RP-6306, a first in-class and selective inhibitor of PKMYT1. Patient-derived xenograft (PDX) models and transgenic mouse mammary tumor virus (MMTV) models of TNBC expressing human LMW-E (hLMW-E) were also utilized to assess LMW-E as a biomarker for predicting response to RP-6306. Results. Analysis of TNBC tumor biopsies revealed a significant positive correlation between LMW-E expression and CDK1 pT14, and both biomarkers were associated with a lack of pathological complete response to neoadjuvant chemotherapy. In vitro results using LMW-E inducible hMECs and breast cancer cell lines demonstrated that LMW-E up-regulates PKMYT1 and CDK1 pT14, acting as a PKMYT1 binding protein and enhancing PKMYT1 protein stability. High LMW-E protein levels predicted a favorable response to RP-6306, resulting in the accumulation of sub-G1 and polyploid cells, decreased tolerance to replication stress, increased DNA damage, chromosomal breakage, and apoptosis. In vivo treatment of TNBC PDX models and hLMW-E transgenic tumors with RP-6306 resulted in a significant reduction in tumor volume only in mice harboring high LMW-E tumors, while low cyclin E models showed no response. Immunohistochemical analysis confirmed increased γ-H2AX and decreased CDK1-pT14 and Ki67 levels, indicating the efficacy of RP-6306 in both PDX and transgenic models. Conclusion: This study highlights the regulatory axis from LMW-E to PKMYT1 and its predictive value for pathological complete response in TNBC patients receiving neoadjuvant chemotherapy. The selective PKMYT1 kinase inhibitor RP-6306 consistently induced DNA damage and inhibited tumor growth in in vitro and in vivo pre-clinical breast tumor models. Co-expression of LMW-E and CDK1-pT14 in TNBC can be used to stratify patients whose tumors are likely to respond to RP-6306, emphasizing its therapeutic significance. Citation Format: Mi Li, Amriti Lulla, Cansu Karakas, Spiridon Tsavaschidis, Yan Wang, Tuyen Nguyun, Tuyen Bui, Gary Marshall, Kelly Hunt, Khandan Keyomarsi. Targeting PKMYT1 Kinase as a Therapeutic Strategy for Treatment of Triple Negative Breast Cancer with Low Molecular Weight Cyclin E (LMW-E) Expression [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-16-04.

Triple negative breast cancer (TNBC) represents an aggressive disease associated with a high risk of recurrence after curative treatment and a poor prognosis in the metastatic setting. Chemotherapy was for years the only treatment available in the early and metastatic setting, due to the lack of actionable targets. Clinical practice has changed following the results obtained with the addition of immunotherapy to standard chemotherapy, the development of novel drugs [i.e. antibody-drug conjugates (ADCs)], and the use of targeted treatments for patients carrying germline pathogenic breast cancer susceptibility genes (BRCA) 1 or BRCA 2 variants. The treatment of early-stage disease has had a shift in clinical practice since July 2021, after the Food and Drug Administration (FDA) approval of pembrolizumab in association with chemotherapy as neoadjuvant treatment for TNBC and as a single agent in the subsequent adjuvant setting. This intensive treatment based on the combination of a poly-chemotherapy and an immune checkpoint inhibitor (ICI) led to the improvement of short- and long-term outcomes, but it has highlighted some new unmet clinical needs in the treatment of early-stage TNBC: the selection of the most effective adjuvant therapy and the integration of pembrolizumab with other therapeutic strategies [capecitabine, poly(ADP-ribose) polymerase (PARP) inhibitors] based on the achievement of pathologic complete response (pCR); the identification of predictive biomarkers to select patients who could most benefit from the addition of ICI, to minimize toxicities and to maximize outcomes; the possibility of de-escalating chemotherapy in favor of immune-combo or novel agents, such as ADCs; the role of immunotherapy in estrogen receptor (ER)-low patients. The advent of immunotherapy not only addresses current challenges in TNBC treatment but also holds the promise of a radical transformation in its therapeutic paradigm, enhancing significantly clinical outcomes and offering new perspectives for patients grappling with this aggressive form of breast cancer.

Studies have shown that 2.2-30% of patients with gastric cancer achieve a pathologic complete after neoadjuvant chemotherapy. 1,2 Pathologic complete response (pCR) status has been used as the primary endpoint for the short-term efficacy in many studies, but whether it is a good indicator for long-term clinical outcome is still unknown. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune severity index (SII), and prognostic nutritional index (PNI) are associated with the prognosis of gastric, lung, and breast cancers. However, the predictive value of pathological complete response (pCR) rates in patients with breast cancer treated with neoadjuvant chemotherapy (NAC) remains unclear. This retrospective study explored the correlation between each index and the efficacy of neoadjuvant chemotherapy in patients with breast cancer and assessed the relationship between changes before and after neoadjuvant chemotherapy. We enrolled 95 patients with locally advanced breast cancer who received neoadjuvant therapy for breast cancer at the Second Affiliated Hospital of Fujian Medical University from April 2020 to April 2022. Based on postoperative pathology, patients were divided into pCR and non-pCR groups. Between-group differences and efficacy prediction ability of NLR, PLR, SII, and PNI were analyzed. Patient characteristics and changes in NLR, PLR, SII, and PNI before and after neoadjuvant chemotherapy (NAC) were compared between groups. Patients were divided into two groups according to the optimal diagnostic thresholds of the SII before treatment. Between-group differences in terms of neoadjuvant therapy efficacy and patient characteristics were evaluated. The pCR exhibited significantly lower ER (χ2 = 10.227, P = 0.001), PR (χ2 = 3.568, P = 0.049), pretreatment NLR (χ2 = 24.930, P < 0.001), pretreatment PLR (χ2 = 22.208, P < 0.001), pretreatment SII (χ2 = 26.329, P < 0.001), and post-treatment PNI (P = 0.032), but higher HER-2 (χ2 = 7.282, P = 0.007) and ΔNLR (P = 0.015) than the non-pCR group. ROC curve analysis revealed that the areas under the curve (AUC) of pretreatment SII, NLR, and PLR for predicting pCR of NAC for breast cancer were 0.827, 0.827, and 0.810, respectively, indicating a higher predictive value for response to NAC in patients with breast cancer. According to the Youden index, the optimal cut-off value of SII pretreatment was 403.20. Significant differences in age (χ2 = 6.539, P = 0.01), ER (χ2 = 4.783, P = 0.029), and HER-2 (χ2 = 4.712, P = 0.030) were observed between high and low-SII groups. In conclusion, pretreatment NLR, PLR, and SII can be used as predictors of pCR in patients with breast cancer receiving neoadjuvant chemotherapy. The predictive value of pretreatment SII is higher, and patients with low SII are more likely to achieve pCR.

Introduction Breast cancer is considered nowadays the most prevalent cancer worldwide. The molecular era has successfully divided breast cancer into subtypes based on the various hormonal receptors. These molecular subtypes play a major role in determining the neoadjuvant chemotherapy to be administered. It was noted that the use of neoadjuvant chemotherapy was associated with higher achievement of pathological complete response. The aim of the study was to determine the predictive role of breast cancer subtypes in the efficacy and prognosis of neoadjuvant chemotherapy regimens. Methods Combining dose dense anthracycline-based, regular dose anthracycline-based, and nonanthracycline-based chemotherapy, we observed data from 87 patients with breast cancer who received surgery after administration of neoadjuvant chemotherapy at our institution between January 2015 and July 2018. The patients were classified into luminal A, luminal B, HER2 overexpression, and triple negative breast cancer as well as low Ki67 (≤14%) and high Ki67 (>14%) expression groups using immunohistochemistry. Pathologic complete response was the only neoadjuvant chemotherapy outcome parameter. To evaluate variables associated with pathologic complete response, we used univariate analyses followed by multivariate logistic regression. Results 87 patients with breast cancer were classified into different subtypes according to the 12th St. Gallen International Breast Cancer Conference. The response rate to neoadjuvant chemotherapy was significantly different (p = 0.046) between the subgroups. There were significant correlations between pathological complete response (pCR) and ER status (p < 0.0001), HER2 (p = 0.013), molecular subtypes (p = 0.018), T stage (p = 0.024), N stage before chemotherapy (p = 0.04), and type of chemotherapy (p = 0.029). Luminal B type patients had the lowest pCR, followed by luminal A type patients. Conclusion Evaluating molecular subtype's significance in breast cancer prognosis warrants additional studies in our region with extensive data about patient-specific neoadjuvant chemotherapy regimens. Our study was able to reproduce results complementary to those present in the literature in other outcomes.

BackgroundFew studies have exclusively investigated the value of pathological complete response (pCR), in esophageal squamous cell carcinoma (ESCC) patients, although it is a clinically significant parameter to evaluate the impact of neoadjuvant chemoradiotherapy (nCRT) on treatment outcome after surgery. The aim of our study was to explore the relationship between pCR after nCRT and survival among patients with local ESCC.MethodsAll patients receiving nCRT followed by surgery in NEOCRTEC5010-trial (NCT01216527) were included. Non-pCR patients were classified into three subgroups: ypTanyN0M0, ypT0NanyM0 and ypTanyNanyM0. The Kaplan-Meier method with log-rank test was employed to evaluate disease-free survival (DFS) and overall survival (OS). Multivariate regression analysis was performed using a Cox proportional hazards model to identify clinicopathological parameters associated with pCR.ResultsAmong the 185 patients included, 80 (43.2%) achieved pCR after nCRT. The mean survival time of the pCR group was significantly longer than that of the non-pCR group (92.6 vs. 69.2 months; HR, 2.70; 95% CI: 1.48–4.92; P=0.001). The 5-year OS and DFS of the pCR group were 79.3% and 77% respectively, compared to 54.8% and 51.2%, respectively, in the non-pCR group. The results showed that the OS and DFS of the ypTanyN0M0 group were better than those of the ypT0NanyM0 group and the ypTanyNanyM0 group. We also found that the number of dissected lymph nodes and pCR were independent risk factors for DFS and OS rates.ConclusionspCR after nCRT is an important prognostic indicator of OS and DFS in patients with ESCC. In addition, lymph-node status could represent an important parameter in the prognostic evaluation of esophageal cancer patients.

BackgroundSuperior sulcus tumors, or Pancoast tumors, are challenging thoracic malignancies to treat due to their anatomical location posing difficult surgical access and potential involvement of adjacent vital structures. The current standard of care is trimodality treatment, which consists of induction chemoradiotherapy followed by radical surgical resection. This study aims to report the clinical outcomes of trimodality approach in British Columbia, Canada.MethodsPatients with Pancoast tumors who underwent trimodality treatment between 2000–2015 were included in this provincial multi-center retrospective study. Patient-, disease-, and treatment-related data were collected, and treatment outcomes were recorded.ResultsWe identified 32 patients who underwent induction chemoradiotherapy and subsequent surgical resection. Mean age was 59 (43–75 years) with median follow-up of 43 months (5–216 months). Complete resection was achieved in 31 patients (97%). Fourteen patients (44%) had pathological complete response after induction chemoradiotherapy. Thirteen (41%) showed minimal microscopic (>90% tumor necrosis) and 5 (16%) macroscopic residual disease (<90% tumor necrosis). Fourteen patients (44%) developed recurrence, which was distant in 9 cases. The 2-, 5-, and 10-year overall survival rates were 67.9%, 50.1%, 31.8% and the 2-, 5-, and 10-year disease-free survival rates were 65.1%, 47.1% and 28.2% respectively. There were no statistically significant differences in overall survival or disease-free survival rates with or without pathological complete response.ConclusionsComplete surgical resection with negative margins can be achieved after induction chemoradiotherapy, and curative-intent trimodality treatment can lead to long-term survival in some patients. This study did not demonstrate any prognostic value of pathological complete response, likely due to small sample size.

Because of the strong prognostic value of pathologic complete response (pCR) in early breast cancer (EBC), patients who fail to achieve this outcome have increasingly been eligible to a new treatment modality, namely post-neoadjuvant systemic therapy (PNT). However, adjuvant radiation therapy (RT) retains a crucial role in EBC, and also needs to be timely administered to patients. To address how modern PNT optimally integrates with adjuvant RT is therefore the purpose of this review. How PNT administration optimally integrates with adjuvant RT has varied depending on the type of systemic therapy employed. The introduction of novel "targeted" agents has created new challenges, as for many of them limited information is available on the feasibility of concurrent systemic and RT administration or their optimal sequencing. PNT and RT are both of utmost importance to the management of EBC and need to be timely and safely administered to patients. The optimal strategy to integrate these modalities may vary according to the type of PNT agent and other factors.

Clinical Outcomes of Pancoast Tumors Treated with Trimodality Therapy

This study aims to investigate the factors associated with pathological complete response following neoadjuvant treatment and to examine the prognostic value of pathological complete response in patients with non-small cell lung cancer undergoing surgical resection. Between February 2009 and January 2016, a total of 112 patients (96 males, 16 females; mean age 60±8 years; range, 37 to 85 years) with the diagnosis of non-small cell lung cancer who underwent anatomical pulmonary resection after neoadjuvant treatment were retrospectively analyzed. Demographic, clinical, radiological, and pathological characteristics of the patients were recorded. The patients were classified as pathological complete response and nonpathological complete response according to the presence of tumors in the pathology reports. Predictive factors for pathological complete response and its prognostic significance were analyzed. The mean follow-up was 35±20 (range, 0 to 110) months. Of the patients, 30 (27%) achieved a pathological complete response. Reduction rate in tumor size was significantly higher in the responsive group (32.5±21.6% vs. 19.2±18.8%, respectively) and was a predictor of pathological complete response independent from the T and N factors (p=0.004). Survival of the responsive patients was significantly longer than unresponsive patients (75±9 vs. 30±4 months, respectively; p<0.001). During follow-up, tumor recurrence was seen in 30 patients. Recurrence was observed in only one patient in the responsive group, while 29 patients in the unresponsive group had recurrence or metastasis. Tumor shrinkage rate after neoadjuvant treatment in non-small cell lung cancer is a predictive factor for pathological complete response. Survival of patients with a pathological complete response is also significantly longer than unresponsive patients.

Breast cancer with ipsilateral supraclavicular lymph node metastasis is one of the indicators of poor prognosis. Patients who attain pathologic complete response in breast and axillary sites have improved survival and are highest in aggressive HR-HER2- and HER2-positive tumor subtypes. However, there is no study on the related factors and prognostic value of supraclavicular pathologic complete response in breast cancer after neoadjuvant chemotherapy. The aim of our work was to investigate the factors and prognostic significance of pathologic complete response of ipsilateral supraclavicular lymph node metastasis in breast cancer after neoadjuvant chemotherapy. A total of 214 patients with breast cancer who had primary ISLN metastasis, receiving NAC and subsequent ISLN dissection, were retrospectively and consecutively reviewed. Univariate and multivariate analyses were performed using χ2 test and the logistic regression model, and the prognosis was analyzed by Kaplan-Meier curve. All patients included were women who were 26-74 years old. The rate of supraclavicular pathologic complete response (pCR) was 53.7%. Multivariate analysis showed that the expression of Ki67, breast pCR, and axillary pCR were independent predictors of supraclavicular pCR (P<0.05). After a median follow-up of 16.2 months, the risk of recurrence and metastasis in patients with supraclavicular pCR was half reduced compared to that of the non-pCR group (HR 0.51, 95% CI, 0.32-0.80, P<0.01), mainly manifested in HR-HER2- and HER2-positive disease. The expression level of Ki67, breast pCR, and axillary pCR were independent predictors of supraclavicular pCR. Supraclavicular pCR was an independent predictor of disease-free survival (DFS). Surgical removal of supraclavicular lymph nodes can accurately evaluate the rate of supraclavicular pCR, which is of great significance for patient prognosis.

Prognostic value of pathologic complete response (pCR) and extent of pathologic response attained with anthracycline-free platinum plus taxane neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) is unknown. We report recurrence-free survival (RFS) and overall survival (OS) according to degree of pathologic response in patients treated with carboplatin plus docetaxel NAC. One-hundred and ninety patients with stage I-III TNBC were treated with neoadjuvant carboplatin (AUC6) plus docetaxel (75 mg/m2) every 21 days × 6 cycles. pCR (no evidence of invasive tumor in breast and axilla) and Residual cancer burden (RCB) were evaluated. Patients were followed for recurrence and survival. Extent of pathologic response was associated with RFS and OS using the Kaplan-Meier method. Median age was 51 years, and 52% were node-positive. pCR and RCB I rates were 55% and 13%, respectively. Five percent of pCR patients, 0% of RCB I patients, and 58% of RCB II/III patients received adjuvant anthracyclines. Three-year RFS and OS were 79% and 87%, respectively. Three-year RFS was 90% in patients with pCR and 66% in those without pCR [HR = 0.30; 95% confidence interval (CI), 0.14-0.62; P = 0.0001]. Three-year OS was 94% in patients with pCR and 79% in those without pCR (HR = 0.25; 95% CI, 0.10-0.63; P = 0.001). Patients with RCB I demonstrated 3-year RFS (93%) and OS (100%) similar to those with pCR. On multivariable analysis, higher tumor stage, node positivity, and RCB II/III were associated with worse RFS. Neoadjuvant carboplatin plus docetaxel yields encouraging efficacy in TNBC. Patients achieving pCR or RCB I with this regimen demonstrate excellent 3-year RFS and OS without adjuvant anthracycline.

e12665 Background: The prognostic value of pathological complete response (pCR) on survival is still debated. Previous studies have revealed that breast cancer intrinsic subtypes show different molecular profiles and several miRNAs have important roles to determine and regulate such subtypes. We investigated the potential role of miRNA signature as predictor of outcome in early breast cancer. Methods: We retrospectively analyzed 12 patients with locally advanced breast cancer who received neoadjuvant chemotherapy (NAD). Purification of miRNA from paraffin-embedded tissue sections was performed by miRNeasy FFPE kit (QIAGEN); miRNA sequencing libraries, prepared with QIAseq miRNA Library Kit (QIAGEN), was sequenced using Illumina NGS system (MiSeq Personal Sequencer). Identification of miRNAs in the samples was performed using software QIAseq miRNA-NGS data analysis. The miRNAs that differed between pre-NAD and post-NAD were taken into consideration. The miRNA targets were predicted by the MiRDB tool (http://www.mirdb.org). Results: Median follow-up was 61 months (range 43 –93 months). We analyze miRNA expression profile in patient who did not obtain pCR but experimented a long term disease free survival. We found that miR-510-3p, a miRNA related to angiogenesis, is down-regulated in post-NAD samples, regardless to breast cancer subtypes. miR-191-5p and miR100-5p, that promote proliferation and migration of cancer cells, are down-regulated in HER2 luminal post-NAD samples. miR196a-5p is down-expressed in triple negative (TN) post-NAD samples and is associated with important signalling pathways in cancer, including breast carcinogenesis, progression and drug resistance. On reverse, we found overexpression of miR-143-3p and miR30a-5p in TN and in HER2 non luminal post-NAD samples: both miRNAs are inversely correlate with invasive capacity. Conclusions: pCR might not be a surrogate prognostic factor of outcome; indeed, modulation of expression of different miRNAs in pre- and post-NAD samples may be better related to breast cancer prognosis in respect of pCR. The profiling of miRNA expression in breast cancer and clarifying molecular mechanisms of breast cancer-specific miRNAs are important future topics for basic and clinical research of breast cancer.