The relationship of C-Reactive Protein to Albumin Ratio and interval debulking surgery outcome after neoadjuvant chemotherapy in ovarian cancer patients.

OBJECTIVE: To investigate the relationship between the changes of C-reactive protein to Albumin Ratio (CAR) levels and Interval Debulking Surgery (IDS) outcome after Neoadjuvant Chemotherapy (NAC) in ovarian cancer patients. METHODS: A nested case-control study for 209 patients with ovarian cancer who received NAC-IDS therapy from the First Affiliated Hospital of Bengbu Medical College between 2015‒2021 was conducted. Demographic data, laboratory indicators, and imaging examinations were collected. The outcome was regarded as optimal IDS in this study. Univariate and multivariate logistic regression analyses were performed to assess the relationship of CAR before NAC, CAR after NAC and ∆CAR with optimal IDS. The authors also performed the subgroup analysis based on menopausal state. RESULTS: The end time of follow-up was January 24, 2022. A total of 156 patients had been treated with optimal IDS, and 53 with suboptimal IDS. After adjusting age, body mass index, menopausal state, NAC drug, peritoneal perfusion and CAR before NAC, the result showed that CAR after NAC (Odds Ratio [OR = 3.48], 95% Confidence Interval [95% CI 1.28‒9.48], p = 0.015) and ∆CAR (OR = 0.29, 95% CI 0.11‒0.78, p = 0.015) were associated with optimal IDS, respectively. Additionally, the authors found a significant correlation between CAR after NAC and optimal IDS (OR = 3.16, 95% CI 1.07‒9.35, p = 0.038), and ∆CAR and optimal IDS (OR = 0.32, 95% CI 0.11‒0.94, p = 0.038) among ovarian cancer patients with menopause. CONCLUSION: CAR after NAC and ∆CAR were independent prognostic markers of optimal interval debulking surgery for ovarian cancer patients.

Prognostic factors for local recurrence in patients with rectal cancer submitted to neoadjuvant chemoradiotherapy and total mesorectal excision.

Prognostic factors for local recurrence in patients with rectal cancer submitted to neoadjuvant chemoradiotherapy and total mesorectal excision. BACKGROUND: The standard curative treatment for locally advanced rectal cancer of the middle and lower thirds is long-course chemoradiotherapy followed by total mesorectal excision. PURPOSE: To evaluate the prognostic factors associated with local recurrence in patients with rectal cancer submitted to neoadjuvant chemoradiotherapy and total mesorectal excision. METHODS: Retrospective study including patients with rectal cancer T3-4N0M0 or T (any)N + M0 located within 10 cm from the anal border, or patients with T2N0M0 located within 5 cm, treated by long course chemoradiotherapy followed by total mesorectal excision with curative intent. Clinical, demographic, radiologic, surgical, and anatomopathological data were collected. Local recurrence was estimated using the Kaplan-Meier function, and risk was estimated according to each characteristic using univariate and multivariate analyses. RESULTS: 270 patients were included, 57.8% male and mean age 61.7 (30‒88) years. At initial staging, 6.7% of patients were stage I, 21.5% stage II, and 71.8% stage III. Open surgery was performed in 65.2%, with sphincter preservation in 78.1%. Mortality within 30 postoperative days was 0.7%. After 49.4 (0.5‒86.1) months of median follow-up, overall and local recurrences were 26.3% and 5.9%. On multivariate analyses, local recurrence was associated with involvement of the mesorectal fascia on restaging MRI (HR = 9.11, p = 0.001) and with pathologic involvement of radial surgical margin (HR = 8.19, p < 0.001). CONCLUSION: Local recurrence of rectal cancer treated with long-course chemoradiation and total mesorectal excision is low and is associated with pathologic involvement of the radial surgical margin and can be predicted on restaging MRI.

Association of tumor-infiltrating lymphocytes with clinical outcomes in patients with triple-negative breast cancer receiving neoadjuvant chemotherapy: a systematic review and meta-analysis.

OBJECTIVE: Triple-negative breast cancer (TNBC) presents a clinical challenge as an aggressive tumor, correlated with unfavorable prognosis. Tumor-infiltrating lymphocytes (TILs) have garnered interest as a potential prognostic biomarker. However, the disparity in outcomes between varying TILs rates remains inadequately explored. METHODS: PubMed, Scopus, Web of Science, and Cochrane databases were searched for studies about the prognostic value of TILs in patients with TNBC receiving neoadjuvant chemotherapy. The hazard ratios (HRs) or odds ratios (ORs) were computed for binary endpoints, with 95% confidence intervals (CIs). RESULTS: Twenty-nine studies were included, involving a population of six thousand one hundred sixty-one (80.41%) with TNBC. The cut-off TILs value ranged from 10 to 60%, with 50% being the most related value. Compared with the low-TIL expression group, the disease-free survival (DFS) (HR 0.71; 95% CI 0.61-0.82; p < 0.00001) and overall survival (OS) (HR 0.76; 95% CI 0.63-0.90; p = 0.002) rates showed significant improvement with higher TIL infiltrations. In the subgroup analyses of the lymphocyte subtypes CD4 + and CD8 + , there was statistical significance favoring higher TILs rates in both subtypes, each associated with improved DFS (HR 0.48; 95% CI 0.33-0.71; p = 0.0002) and OS (HR 0.53; 95% CI 0.36-0.78; p = 0.001), regardless of which cell subtype was predominantly infiltrated. The complete pathological response analysis showed better rates for the higher TIL group than the control for both the TIL (OR 1.29; 95% CI 1.13-1.48; p = 0.0003) and Ki-67 (OR 2.74; 95% CI 2.01-3.73; p < 0.00001) analyses. CONCLUSION: Higher expressions of TILs in patients with TNBC were associated with improved significantly DFS, OS, and pCR outcomes.

The Expression Profiles of lncRNAs Are Associated with Neoadjuvant Chemotherapy Resistance in Locally Advanced, Luminal B-Type Breast Cancer.

lncRNAs are noncoding transcripts with tissue and cancer specificity. Particularly, in breast cancer, lncRNAs exhibit subtype-specific expression; they are particularly upregulated in luminal tumors. However, no gene signature-based laboratory tests have been developed for luminal breast cancer identification or the differential diagnosis of luminal tumors, since no luminal A- or B-specific genes have been identified. Particularly, luminal B patients are of clinical interest, since they have the most variable response to neoadjuvant treatment; thus, it is necessary to develop diagnostic and predictive biomarkers for these patients to optimize treatment decision-making and improve treatment quality. In this study, we analyzed the lncRNA expression profiles of breast cancer cell lines and patient tumor samples from RNA-Seq data to identify an lncRNA signature specific for luminal phenotypes. We identified an lncRNA signature consisting of LINC01016, GATA3-AS1, MAPT-IT1, and DSCAM-AS1 that exhibits luminal subtype-specific expression; among these lncRNAs, GATA3-AS1 is associated with the presence of residual disease (Wilcoxon test, p < 0.05), which is related to neoadjuvant chemotherapy resistance in luminal B breast cancer patients. Furthermore, analysis of GATA3-AS1 expression using RNA in situ hybridization (RNA ISH) demonstrated that this lncRNA is detectable in histological slides. Similar to estrogen receptors and Ki67, both commonly detected biomarkers, GATA3-AS1 proves to be a suitable predictive biomarker for clinical application in breast cancer laboratory tests.

A Research Protocol for a Phase II Single-Arm Clinical Trial Assessing the Feasibility and Efficacy of Neoadjuvant Anastrozole in Patients With Luminal Breast Cancer and Low Proliferative Index: The ANNE Trial.

INTRODUCTION: Neoadjuvant endocrine therapy (NET) is recommended for the treatment of invasive breast cancer (BC), particularly luminal subtypes, in locally advanced stages. Previous randomized studies have demonstrated the benefits of aromatase inhibitors in this context. However, NET is typically reserved for elderly or frail patients who may not tolerate neoadjuvant chemotherapy. Identifying non-responsive patients early and extending treatment for responsive ones would be ideal, yet optimal strategies are awaited. AIMS: This non-randomized phase 2 clinical trial aims to assess NET feasibility and efficacy in postmenopausal stage II and III luminal BC patients, identifying predictive therapeutic response biomarkers. Efficacy will be gauged by patients with Ki67 ≤ 10% after 4 weeks and Preoperative Endocrine Prognostic Index (PEPI) scores 0 post-surgery. Study feasibility will be determined by participation acceptance rate (recruitment rate ≥50%) and inclusion rate (>2 patients/month). METHODS: Postmenopausal women with luminal, HER2-tumors in stages II and III undergo neoadjuvant anastrozole treatment, evaluating continuing NET or receiving chemotherapy through early Ki67 analysis after 2 to 4 weeks. The study assesses NET extension for up to 10 months, using serial follow-ups with standardized breast ultrasound and clinical criteria-based NET suspension. Clinical and pathological responses will be measured overall and in the luminal tumor A subgroup. Toxicity, health-related quality of life, and circulating biomarkers predicting early NET response will also be evaluated.

Identification of radiologic and clinicopathologic variables associated with tumor regression pattern and distribution of cancer cells after short-course radiotherapy and consolidation chemotherapy in patients with rectal cancer.

Background: Knowledge of the pattern of regression and distribution of residual tumor cells may assist in the selection of candidates for rectum-sparing strategies. Objective: To investigate and identify factors associated with tumor regression pattern and distribution of residual tumor cells. Methods: We conducted a prospective study of patients with T3/T4 N0/N+ adenocarcinoma of the middle and lower third of the rectum (≤10 cm) treated with radiotherapy (5×5 Gy) followed by 6 cycles of CAPOX chemotherapy. The pattern of tumor regression was classified as fragmented or solid. Microscopic intramural spread was measured. We used a model of distribution of residual tumor cells not yet applied to rectal cancer, defined as follows: type I (luminal), type II (invasive front), type III (concentric), and type IV (random). Results: Forty patients were included with a median age of 66 years; 23 (57.5%) were men. A fragmented pattern was identified in 18 patients (45.0%), and a solid pattern in 22 (55.0%). Microscopic intramural spread was identified in 25 patients (62.5%), extending from 1 to 18 mm (median, 4 mm). There were 14 cases (35.0%) of microscopic intramural spread ≥10 mm. All cases of fragmented regression pattern, except one, showed microscopic intramural spread. Within the fragmented pattern, microscopic intramural spread was 4-8 mm in 4 cases and ≥10 mm in the remaining cases. All cases of microscopic intramural spread ≥ 10 mm were within the fragmented pattern. Regarding the distribution pattern of residual tumor cells, 11 cases (31.5%) were classified as type I, 14 (40.0%) as type II, 10 (28.5%) as type III, and none as type IV. Carcinoembryonic antigen levels >5 ng/mL, downsizing <50%, residual mucosal abnormality >20 mm, and anatomopathologic lymph node involvement were significantly associated with the occurrence of fragmentation (P<0.05). Having received all 6 cycles of CAPOX chemotherapy and absence of microscopic intramural spread were significantly associated with the type I distribution pattern (P<0.05). Conclusion: The occurrence of a fragmented regression pattern is common, as is the presence of microscopic intramural spread. We could identify radiologic and clinicopathologic factors associated with the pattern of tumor regression and a type I distribution pattern.

Plasma Metabolome Signatures to Predict Responsiveness to Neoadjuvant Chemotherapy in Breast Cancer.

BACKGROUND: Neoadjuvant chemotherapy (NACT) has arisen as a treatment option for breast cancer (BC). However, the response to NACT is still unpredictable and dependent on cancer subtype. Metabolomics is a tool for predicting biomarkers and chemotherapy response. We used plasma to verify metabolomic alterations in BC before NACT, relating to clinical data. METHODS: Liquid chromatography coupled to mass spectrometry (LC-MS) was performed on pre-NACT plasma from patients with BC (n = 75). After data filtering, an SVM model for classification was built and validated with 75%/25% of the data, respectively. RESULTS: The model composed of 19 identified metabolites effectively predicted NACT response for training/validation sets with high sensitivity (95.4%/93.3%), specificity (91.6%/100.0%), and accuracy (94.6%/94.7%). In both sets, the panel correctly classified 95% of resistant and 94% of sensitive females. Most compounds identified by the model were lipids and amino acids and revealed pathway alterations related to chemoresistance. CONCLUSION: We developed a model for predicting patient response to NACT. These metabolite panels allow clinical gain by building precision medicine strategies based on tumor stratification.

Restaging magnetic resonance imaging of the rectum after neoadjuvant therapy: a practical guide.

Colorectal cancer is the third most common cancer and the second leading cause of cancer-related death. Rectal cancer accounts for approximately one-third of new colorectal cancer cases, with adenocarcinoma as the predominant subtype. Despite an overall decline in colorectal cancer incidence and mortality, due to advancements in screening, early diagnosis, and treatment options, there is a concerning increase in incidence rates among young patients. Recent significant advances in managing locally advanced rectal cancer, such as the establishment of different surgical approaches, neoadjuvant treatment using different protocols for high-risk cases, and the adoption of organ-preservation strategies, have increased the importance of the role played by radiologists in locoregional assessment on magnetic resonance imaging at baseline, at restaging, and during active surveillance of patients with rectal cancer. In this article, we review the role of restaging rectal magnetic resonance imaging after neoadjuvant therapy, providing radiologists with a practical, step-by-step guide for assessing treatment response.

O câncer colorretal é o terceiro câncer mais comum e a segunda principal causa de morte relacionada ao câncer. O câncer retal representa aproximadamente um terço dos novos casos de câncer colorretal, sendo o adenocarcinoma o subtipo predominante. Apesar de uma diminuição geral na incidência e mortalidade, impulsionada por avanços na prevenção do câncer, diagnóstico precoce e opções de tratamento aprimoradas, há uma preocupante elevação nas taxas entre os pacientes jovens. Avanços recentes significativos no manejo do câncer retal localmente avançado, como abordagens cirúrgicas, o uso de diferentes protocolos de tratamento neoadjuvante para casos de alto risco e a adoção de estratégias de preservação de órgãos, aumentaram o papel dos radiologistas na avaliação locorregional por meio da ressonância magnética na avaliação inicial, reestadiamento e vigilância ativa de pacientes com câncer retal. Este manuscrito tem como objetivo revisar o papel da ressonância magnética retal no reestadiamento após terapia neoadjuvante, fornecendo aos radiologistas um guia prático para revisar exames nesse contexto.

Immune mechanisms and predictive biomarkers related to neoadjuvant immunotherapy response in stage III melanoma.

The treatment for stage III melanoma has advanced significantly, nevertheless, a substantial proportion of patients experience relapse. Neoadjuvant immune checkpoint blockade has emerged as a promising approach, allowing early micrometastatic disease treatment, reduction of tumor burden before surgery, and enhanced tumor-specific T-cell responses. However, not all patients respond to treatment, highlighting the need for understanding immune mechanisms behind failure and identification of predictive markers. Here we performed a robust evaluation of systemic and tumoral immune profiles in a well-defined cohort of advanced melanoma patients treated with immune checkpoint inhibitors. Elevated CTACK and CXCL9 chemokines pre-treatment suggested their potential as predictive tools for treatment response. Furthermore, CD95 expression in CD8+ T lymphocytes surfaced as a favorable prognostic indicator, while PD-1, CD161, and PD-L2 exhibited correlations with worst outcomes. These findings shed light on the intricate interplay between immune markers and melanoma response to neoadjuvant immune checkpoint therapy, offering insights into personalized treatment strategies.

Survival outcomes of Zo-NAnTAx: a five-year analysis of zoledronic acid added to a neoadjuvant regimen for HER2-positive breast cancer.

Background: Zoledronic acid (ZA) improved outcomes in breast cancer. In pre-clinical studies, ZA increased tumour regression in combination chemotherapy and anti-human epidermal growth factor receptor 2 (HER2) target therapy. The Zo-NAnTax study, a clinical trial combining ZA with neoadjuvant therapy for HER2-positive tumours met the primary endpoint, showing a higher pathological complete response (pCR) rate than predicted in patients receiving surgery. Here, we report the exploratory relapse-free survival (RFS) and overall survival (OS) analysis after five years of follow-up. Methods: Adult women with HER2-positive breast cancer amendable to curative surgery who consented to the study received four cycles of ZA at 4 mg + doxorubicin 60 mg/m2 + cyclophosphamide 600 mg/m2 followed by four cycles of ZA at 4 mg + docetaxel 100 mg/m2 + trastuzumab 6 mg/kg (8 mg/kg as a loading dose), all in a 21 days-cycle, totalizing 8 cycles before surgery. To achieve the primary endpoint of pCR rate between 22% and 35%, 56 patients were needed. The secondary endpoints included safety, gene expression according to treatment response, prediction of pCR rate by an interim breast magnetic resonance imaging (bMRI). Results: Beyond the overall pCR rate of 42%, alongside a good safety profile, we showed similar pCR rates in both hormonal receptor (HR) positive (40%) and HR-negative (44%). RFS and OS at five years were evaluated in 58 subjects, and the overall rate was 79.3% and 86.2%, respectively. Numerically higher values of both RFS and OS were observed in patients achieving pCR vs. non-achieving, respectively 83.3% vs. non-pCR 76.5% (P=0.57) and 95.8% vs. non-pCR 79.4% (P=0.08). Although not statistically significant, OS was numerically equivalent according to HR status, respectively 85.7% vs. 87.5% for HR-positive and HR-negative (P=0.91), which contrasted with RFS, HR-positive 81% vs. HR-negative 75% (P=0.58). None of the assessed clinicopathological biomarkers significantly correlated with survival. Conclusions: ZA plus neoadjuvant therapy in HER2-positive breast cancer shows provoking survival outcomes. Clinical and pre-clinical investigation with dual anti-HER2 blockage is warranted.

Brazil-TNT: A Randomized Phase 2 Trial of Neoadjuvant Chemoradiation Followed by FOLFIRINOX Versus Chemoradiation for Stage II/III Rectal Cancer.

BACKGROUND: Neoadjuvant radiation and oxaliplatin-based systemic therapy (total neoadjuvant therapy-TNT) have been shown to increase response and organ-preservation rates in localized rectal cancer. However, trials have been heterogeneous regarding treatment protocols and few have used a watch-and-wait (WW) approach for complete responders. This trial evaluates if conventional long-term chemoradiation followed by consolidation of FOLFIRINOX increases complete response rates and the number of patients managed by WW. METHODS: This was a pragmatic randomized phase II trial conducted in 2 Cancer Centers in Brazil that included patients with T3+ or N+ rectal adenocarcinoma. After completing a long-course 54 Gy chemoradiation with capecitabine patients were randomized 1:1 to 4 cycles of mFOLFIRINOX (Oxaliplatin 85, irinotecan 150, 5-FU 2400)-TNT-arm-or to the control arm, that did not include further neoadjuvant treatment. All patients were re-staged with dedicated pelvic magnetic resonance imaging and sigmoidoscopy 12 weeks after the end of radiation. Patients with a clinical complete response were followed using a WW protocol. The primary endpoint was complete response: clinical complete response (cCR) or pathological response (pCR). RESULTS: Between April 2021 and June 2023, 55 patients were randomized to TNT and 53 to the control arm. Tumors were 74% stage 3, median distance from the anal verge was 6 cm, 63% had an at-risk circumferential margin, and 33% an involved sphincter. The rates of cCR + pCR were (31%) for TNT versus (17%) for controls (odds ratio 2.19, CI 95% 0.8-6.22 P = .091) and rates of WW were 16% and 9% (P = ns). Median follow-up was 8.1 months and recurrence rates were 16% versus 21% for TNT and controls (P = ns). CONCLUSIONS: TNT with consolidation FOLFIRINOX is feasible and has high response rates, consistent with the current literature for TNT. This trial was supported by a grant from the Brazilian Government (PROADI-SUS - NUP 25000.164382/2020-81).

Expression of CD28, FAS, PD1, and CTLA4 molecules in the blood of women with triple-negative breast cancer.

BACKGROUND: Locally advanced triple-negative breast cancer (TNBC) represents a public health problem in Brazil. Its standard treatment consists of neoadjuvant chemotherapy (NAC). METHODS: This was a longitudinal study with follow-up performed between the years 2015 and 2017. Thirty women with locally advanced TNBC submitted to NAC, and 30 healthy were included. Peripheral blood samples were collected before NAC (Pre-NAC) and after NAC (Post-NAC). RESULTS: Patients with TNBC had elevated levels of CD28+ T, FAS+ T, CTLA4+ T, PD1+ T, CD28+CD4+ T, PD1+CD4+ T and CD8+ T and PD1+ CD8+ T cells compared to controls (p < 0.05). Patients with pathological complete response (pCR) had low FAS+ T cells, FAS+CD4+ T cells, and PD1+CD8+ T cells compared to the non-pCR (p < 0.05). Significant differences were observed in the levels of CD28+ T cells, FAS+ T and PD1+ T, CD4+ T, CD28+CD4+ T, FAS+CD4+ T, PD1+CD4+ T, CD8+ T, and PD1+CD8+ T cells between Pre-NAC and Post-NAC groups (p < 0.05). CONCLUSION: Alterations in the circulating FAS+CD4+ T and PD1+CD8+ T cell levels Pre-NAC are associated with pCR, suggesting potential predictive biomarkers of NAC response in TNBC. The largest changes in the cellular immune response profile Post-NAC showed that chemotherapy treatment can modulate the immune response and that it is associated with prognosis in TNBC.

LC-MS metabolomics analysis of serum metabolites during neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

BACKGROUND: This study aimed to investigate the serum metabolite profiles during neoadjuvant chemoradiotherapy (NCRT) in locally advanced rectal cancer (LARC) using liquid chromatography-mass spectrometry (LC-MS) metabolomics analysis. METHODS: 60 serum samples were collected from 20 patients with LARC before, during, and after radiotherapy. LC-MS metabolomics analysis was performed to identify the metabolite variations. Functional annotation was applied to discover altered metabolic pathways. The key metabolites were screened and their ability to predict sensitivity to radiotherapy was calculated using random forests and ROC curves. RESULTS: The results showed that NCRT led to significant changes in the serum metabolite profiles. The serum metabolic profiles showed an apparent separation between different time points and different sensitivity groups. Moreover, the functional annotation showed that the differential metabolites were associated with a series of important metabolic pathways. Pre-radiotherapy (3Z,6Z)-3,6-Nonadiena and pro-radiotherapy 1-Hydroxyibuprofen showed good predictive performance in discriminating the sensitive and non-sensitive group to NCRT, with an AUC of 0.812 and 0.75, respectively. Importantly, the combination of different metabolites significantly increased the predictive ability. CONCLUSION: This study demonstrated the potential of LC-MS metabolomics for revealing the serum metabolite profiles during NCRT in LARC. The identified metabolites may serve as potential biomarkers and therapeutic targets for the management of this disease. Furthermore, the understanding of the affected metabolic pathways may help design more personalized therapeutic strategies for LARC patients.

Triple-Negative Breast Cancer Subclassified by Immunohistochemistry: Correlation with Clinical and Pathological Outcomes in Patients Receiving Neoadjuvant Chemotherapy.

The intrinsic subtype of triple-negative breast cancer (TNBC) is based on genomic evaluation. In this study, we report the survival and pathological complete response (pCR) rates of TNBC patients subtyped by IHC and treated with neoadjuvant chemotherapy (NACT). A retrospective cohort of 187 TNBC patients who received NACT between 2008 and 2017 was used, and IHC subtyping was performed on biopsy specimens before chemotherapy. The subtyping revealed predominantly basal-like tumors (IHC-BL, 61%), followed by basal-like immune-suppressed tumors (IHC-BLIS, 31%), mesenchymal tumors (12.5%), luminal androgen receptor tumors (IHC-LAR, 12%), and basal-like immune-activated tumors (IHC-BLIA, 10.9%). The pCR rate varied among subtypes, with IHC-BLIA showing the highest (30.0%) and IHC-LAR showing the lowest (4.5%). IHC-BLIS led in recurrence sites. Overall and disease-free survival analyses did not show significant differences among subtypes, although IHC-BLIA demonstrated a trend toward better survival, and IHC-mesenchymal, worse. Patients who achieved pCR exhibited significantly better disease-free survival and overall survival than non-responders. This study underscores the potential of IHC-based subtyping in TNBC management, highlighting distinct response patterns to neoadjuvant chemotherapy and potential implications for treatment strategies. Further research is warranted to validate these findings and explore tailored therapeutic approaches for specific TNBC subtypes.

TP53 Gene Polymorphism at Codon 72 as a Response Predictor for Neoadjuvant Chemotherapy.

Introduction: Breast cancer is the most prevalent cancer in women worldwide, and neoadjuvant chemotherapy is a favored method for achieving pathologic complete response (pCR). The TP53 gene is involved in inducing the response to chemotherapy drugs. Objectives: The present study sought to correlate polymorphism variants at codon 72 with pCR to neoadjuvant chemotherapy. Casuistry and Methods: The study was conducted in the state of Sergipe, in northeastern Brazil. A total of 206 patients with a histopathological diagnosis of breast cancer who underwent neoadjuvant chemotherapy from 2019 to 2022 were included. DNA samples were collected for the evaluation of TP53 polymorphism at codon 72. A prospective evaluation of the cases was conducted to verify the surgical pathologic response after chemotherapy; the Response Evaluation Criteria in Solid Tumors (RECIST) were used. The study was approved by the University of São Paulo Ethics and Research Committee. Results: Of the 168 patients, 44.6% were Arg72Arg, 17.3% were Pro72Pro, and 38.0% were Arg72Pro; pCR was achieved in 21.4% of the patients; 10.1% had progressive disease, 13.7% had stable disease, and 54.2% had a partial pathologic response. The only predictor of pCR in multivariate regression was immunohistochemistry (p < 0.001). In the multivariate analysis, Arg72Pro and Pro72Pro increased the odds of the patient evolving with stable disease. This study was innovative in demonstrating a predictor of stable disease in response to neoadjuvant chemotherapy. Conclusion: TP53 polymorphism at codon 72 is not a predictor of pCR, but it can be a predictor of stable disease.

Neoadjuvant Treatment of Locally Advanced Thyroid Cancer: A Preliminary Latin American Experience.

Background: Surgical resection is not always achievable in thyroid cancer patients. Neoadjuvant therapy is rarely used, but recent trends favor multikinase inhibitors or selective tyrosine kinase inhibitors. These aim to reduce tumor volume, enabling previously unfeasible surgeries. Patients and Methods: Consecutive patients with locally advanced malignant thyroid tumors who received systemic therapies with a neoadjuvant intention were included in this retrospective multicenter case series conducted in five Latin American referral centers. Primary outcomes were pre- versus postneoadjuvant response evaluations using the Response Evaluation Criteria in Solid Tumors, feasibility of surgery, and completeness of resection. Secondary outcomes were mortality and status at the last visit. Results: Twenty-seven patients were included in this analysis. Patients with unresectable differentiated thyroid cancer (DTC) or poorly differentiated thyroid cancer (PDTC) received sorafenib (n = 6) or lenvatinib (n = 12), those with medullary thyroid cancer (MTC) were treated with vandetanib (n = 5) or selpercatinib (n = 1), and those with anaplastic thyroid cancer (ATC) harboring a BRAFV600E mutation (n = 3) received dabrafenib and trametinib. The median patient age was 66 years (range 12-82), and 52% of the patients were female. In patients with PTC and PDTC, the median reduction in the diameter of the primary tumor was 25% (range 0-100%) after a median of 6 months of treatment. Surgical intervention was performed in 10 (55%) of the patients. Among these, six patients (60%) achieved R0/R1 resection status. Six patients with MTC had a median reduction in tumor diameter of 24.5% (range 1-49) after a median treatment time of 9.5 months. Only one patient receiving selpercatinib, with a tumoral reduction of 25% could undergo surgery, resulting in an R2 resection due to extensive mediastinal extension. Three patients with ATC showed a median tumor diameter reduction of 42% (range 6.7-50) after a median treatment time of 2 months. Two patients underwent surgical intervention and achieved R1 and R2 resection, respectively. Conclusions: While neoadjuvant therapy achieved tumoral responses, surgical resection was feasible in 55% of DTC, 33% of ATC, and 16% of MTC patients, with R0/R1 resection in 26% of the cohort, underscoring the need for patient selection and further research in this area.

Management of early-stage HER2-positive breast cancer and attitudes towards HER2DX test in Spain: insights from a nationwide survey.

PURPOSE: This study aimed to investigate the current therapeutic management of patients with early-stage HER2-positive (HER2+) breast cancer in Spain, while also exploring the perceptions surrounding HER2DX in terms of its credibility, clinical relevance, and impact on therapeutic decision-making. Understanding these aspects is crucial for optimizing treatment strategies and enhancing patient outcomes in the context of HER2+ breast cancer. METHODS: An online questionnaire was conducted by an independent third-party between April and May 2022 across 70 medical oncologists highly specialized in breast cancer management in Spain. The survey included 37 questions regarding treatment decision making in HER2+ early breast cancer. RESULTS: The management of patients with HER2+ early breast cancer exhibited a high degree of heterogeneity. Among the interviewed oncologists, 53% would recommend upfront surgery for node negative tumors measuring 1 cm or less. Interestingly, 69% and 56% of interviewers were open to deescalate the duration of adjuvant trastuzumab in pT1a and pT1b N0 tumors, respectively. Certain clinicopathological characteristics, such as high grade, high Ki-67, and young age, influenced the decision to prescribe neoadjuvant treatment for patients with clinical stage 1 disease. In cases where neoadjuvant treatment was prescribed for cT1-2 N0 tumors, there was a wide variation in the choice of chemotherapeutic and anti-HER2 regimens. Regarding the use of adjuvant trastuzumab emtansine (T-DM1) in patients with residual disease after neoadjuvant therapy, there was diversity in practice, and a common concern emerged that T-DM1 might be overtreating some patients. HER2DX, as a diagnostic tool, was deemed trustworthy, and the reported scores were considered clinically useful. However, 86% of interviewees believed that a prospective trial was necessary before fully integrating the test into routine clinical practice. CONCLUSION: In the context of early-stage HER2+ breast cancer in Spain, a notable diversity in therapeutic approaches was observed. The majority of interviewed medical oncologists acknowledged HER2DX as a clinically valuable test for specific patients, in line with the 2022 SEOM-GEICAM-SOLTI clinical guidelines for early-stage breast cancer. To facilitate the full integration of HER2DX into clinical guidelines, conducting prospective studies to further validate its efficacy and utility was recommended.

Prognostic model based on B cell marker genes for NSCLC patients under neoadjuvant immunotherapy by integrated analysis of single-cell and bulk RNA-sequencing data.

BACKGROUND: Neoadjuvant immunotherapy has evolved as an effective option to treat non-small cell lung cancer (NSCLC). B cells play essential roles in the immune system as well as cancer progression. However, the repertoire of B cells and its association with clinical outcomes remains unclear in NSCLC patients receiving neoadjuvant immunotherapy. METHODS: Single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing data for LUAD samples were accessed from the TCGA and GEO databases. LUAD-related B cell marker genes were confirmed based on comprehensive analysis of scRNA-seq data. We then constructed the B cell marker gene signature (BCMGS) and validated it. In addition, we evaluated the association of BCGMS with tumor immune microenvironment (TIME) characteristics. Furthermore, we validated the efficacy of BCGMS in a cohort of NSCLC patients receiving neoadjuvant immunotherapy. RESULTS: A BCMGS was constructed based on the TCGA cohort and further validated in three independent GSE cohorts. In addition, the BCMGS was proven to be significantly associated with TIME characteristics. Moreover, a relatively higher risk score indicated poor clinical outcomes and a worse immune response among NSCLC patients receiving neoadjuvant immunotherapy. CONCLUSIONS: We constructed an 18-gene prognostic signature derived from B cell marker genes based on scRNA-seq data, which had the potential to predict the prognosis and immune response of NSCLC patients receiving neoadjuvant immunotherapy.

Can neoadjuvant systemic therapy provide additional benefits for T1 HER2+ breast cancer patients: a subgroup analysis based on different high-risk signatures.

INTRODUCTION: Neoadjuvant systemic therapy (NAST) is vital in the management of HER2-positive (HER2+) breast cancer. Nevertheless, the indications for NAST in tumors <2 cm remain controversial. METHOD: A total of 7961 patients were screened from the Surveillance, Epidemiology, and End Result database. Independent prognostic factors were identified using multivariate Cox analysis. Subgroup analyses and Kaplan-Meier analyses were used to simulate whether NAST would provide a survival benefit with different high-risk characteristics. Nomograms were constructed, and an internal validation cohort was employed. RESULTS: Of the 7961 included patients, 1137 (14.3%) underwent NAST. In the total population, NAST was associated with poorer overall survival (OS) and breast cancer-specific survival (BCSS) (OS: P = 0.00093; BCSS: P  <  0.0001). Multivariate Cox analysis confirmed that NAST markedly affected the prognosis of enrolled patients. Besides, a direct association between T, N, age, subtype, and prognosis was observed. Subgroup analyses yielded in these three subgroups, T1c, hormone receptor-negative, and 61-69 years of age, NAST and AST had comparable OS, while NAST possessed worse BCSS. Notably, even in the N3, we still did not observe any additional benefit of NAST. The calculated C-index of 0.72 and 0.73 confirmed the predictability of the nomograms. The AUCs exhibit consistency in the training and validation cohorts. CONCLUSION: Our findings suggest that NAST does not provide additional benefit to patients with T1 HER2+ breast cancer, even in the presence of lymph node metastasis, T1c, or hormone receptor negativity. This study facilitates the implementation of individualized management strategies.

Determining individual suitability for neoadjuvant systemic therapy in breast cancer patients through deep learning.

BACKGROUND: The survival advantage of neoadjuvant systemic therapy (NST) for breast cancer patients remains controversial, especially when considering the heterogeneous characteristics of individual patients. OBJECTIVE: To discern the variability in responses to breast cancer treatment at the individual level and propose personalized treatment recommendations utilizing deep learning (DL). METHODS: Six models were developed to offer individualized treatment suggestions. Outcomes for patients whose actual treatments aligned with model recommendations were compared to those whose did not. The influence of certain baseline features of patients on NST selection was visualized and quantified by multivariate logistic regression and Poisson regression analyses. RESULTS: Our study included 94,487 female breast cancer patients. The Balanced Individual Treatment Effect for Survival data (BITES) model outperformed other models in performance, showing a statistically significant protective effect with inverse probability treatment weighting (IPTW)-adjusted baseline features [IPTW-adjusted hazard ratio: 0.51, 95% confidence interval (CI), 0.41-0.64; IPTW-adjusted risk difference: 21.46, 95% CI 18.90-24.01; IPTW-adjusted difference in restricted mean survival time: 21.51, 95% CI 19.37-23.80]. Adherence to BITES recommendations is associated with reduced breast cancer mortality and fewer adverse effects. BITES suggests that patients with TNM stage IIB, IIIB, triple-negative subtype, a higher number of positive axillary lymph nodes, and larger tumors are most likely to benefit from NST. CONCLUSIONS: Our results demonstrated the potential of BITES to aid in clinical treatment decisions and offer quantitative treatment insights. In our further research, these models should be validated in clinical settings and additional patient features as well as outcome measures should be studied in depth.