Liver-first approach to the treatment of patients with synchronous colorectal liver metastases: a systematic review and meta-analysis.

OBJECTIVE: The optimal approach to the treatment of colorectal carcinoma and synchronous liver metastases remains controversial. The objective of this review was to analyze the outcomes of adopting the liver-first approach for the treatment of patients with colorectal cancer with synchronous hepatic metastases who initially underwent systemic chemotherapy and/or resection of the metastatic lesions and primary colorectal carcinoma. METHODS: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The MEDLINE, EMBASE, LILACS, and Cochrane Central Register of Controlled Trials databases were searched for the identification and retrieval of eligible studies. Studies that included details of using the liver-first approach for the treatment of synchronous liver metastases of colorectal cancer and its outcomes, including the patients' survival data, were included. Proportional meta-analysis was performed using the random-effects restricted maximum likelihood method to summarize the three- and five-year overall survival and recurrence rates of the patients. RESULTS: Eight hundred and fifty-five articles describing the results of studies on the liver-first approach were identified. Three independent reviewers screened the titles and abstracts of the articles and excluded 750 articles. Thereafter, 29 retrospective and comparative studies that met the inclusion criteria were included. No randomized controlled trials were identified in the database search. CONCLUSION: Neoadjuvant treatment with systemic chemotherapy for hepatic metastasis can prepare a patient for resection of liver metastases, offering the opportunity for potentially curative treatment of synchronous hepatic metastases initially considered unresectable. The decision regarding the resection of primary colorectal carcinoma and liver metastases should be based on individualized patient response. Prospero database registration ID: CRD42022337047 (www.crd.york.ac.uk/prospero).

Tumor regression after neoadjuvant hormonal therapy in high risk prostate cancer: pathological outcomes from a randomized phase II trial.

PURPOSE: High-risk localized prostate cancer (HRLPC) commonly progresses to metastatic disease after local treatment. Neoadjuvant androgen deprivation therapy (nADT) before radical prostatectomy (RP) has recently been suggested to improve early oncological outcomes in HRLPC. We aimed to perform an exploratory analysis of the pathological outcomes from a prospective trial testing nADT before RP. METHODS: Prospective, single-centered, phase II, randomized trial performed between October 2018 and July 2021. Random assignment (1:1) for nADT modalities: goserelin (10.8 mg) plus abiraterone acetate (1000 mg/d) plus prednisone (5 mg/d), with or without apalutamide (240 mg/d) for 12 weeks, followed by RP (within 30 days) and extended lymph node dissection. Baseline clinical and pathological variables were assessed in needle biopsies before nADT. Tumor regression was histologically evaluated in surgical specimens using the residual cancer burden index (RCB). RESULTS: Sixty-two patients reached the surgical phase. Good response (RCB ≤ 0.25 cm³) was achieved in 14 patients (22.5%). Overall stage migration rate between baseline status (MRI before nADT) and final status (after surgery) was 27.4%. Late stage detection (high tumor burden, perineural invasion) and altered PTEN/ERG immunostatus showed significant association with poor response in univariate analysis. Higher baseline tumor burden was the only independent factor related to poor response in multivariate analysis. CONCLUSIONS: There are subgroups of patients, such as those with low baseline cancer burden and PTEN/ERG wild-type status, more likely to achieve good response with nADT. In the case of long term oncological benefit to be proven, nADT might be an additional therapeutic resource for these patients.

Pertuzumab en combinación con trastuzumab, docetaxel y carboplatino para mujeres adultas con cáncer de mama en estadio cT1-T4, ≥cN0, M0 (bien sea mayor de 2cm de diámetro o nódulo positivo), HER2+, ECOG 0-2, como tratamiento neoadyuvante / Pertuzumab in combination with trastuzumab, docetaxel and carboplatin for adult women with stage cT1-T4 breast cancer, ≥cN0, M0 (either greater than 2 cm in diameter or node positive), HER2+, ECOG 0-2, as neoadjuvant treatment

INTRODUCCIÓN: Cuadro clínico: Cuadro clínico En el 2022, se reportaron 2 296 840 casos nuevos y 666 103 muertes por cáncer de mama a nivel mundial. Considerando estas cifras, el cáncer de mama ocupa el segundo lugar entre los cánceres más frecuentes y el cuarto lugar entre las causas de muerte por cáncer más frecuentes a nivel mundial. En el Perú, para el 2022, se estimaron unos 7 797 casos nuevos y 1951 muertes por cáncer de mama, con una tasa de incidencia estandarizada por edad de 39.3 casos 100 000 personas y tasa de mortalidad estandarizada por edad de 9.4 muertes 100 000 personas. En base a ello, ocupa el segundo lugar entre los cánceres más frecuentes y el séptimo lugar entre las causas de muerte por cáncer más frecuentes en el Perú. Esta neoplasia puede ser clasificada según la positividad de para la expresión del receptor 2 del factor de crecimiento epidérmico humano (HER2). La supervivencia global a los 5 años en los pacientes con cáncer de mama HER2 positivo (HER2+) es aproximadamente 77%. Además, la estimación de los años de vida saludables perdidos (AVISA) para pacientes con cáncer de mama fue de 67 060.98 (por 1000 habitantes), en el Perú, en el 2021. La elección del tratamiento para los pacientes con cáncer de mama invasivo se basa en el estado de los receptores hormonales, el estado del receptor HER2, el estadio clínico de la paciente y si la paciente cumple los criterios para recibir terapia sistémica preoperatoria. A nivel internacional, las guías de práctica clínica recomiendan el uso de regímenes terapéuticos como opcione

Real-world evidence of survival outcomes in breast cancer subtypes after neoadjuvant chemotherapy in a Brazilian reference center.

BACKGROUND: Neoadjuvant chemotherapy (NAC), traditionally used for locally advanced disease, is now applied for operable disease, particularly to treat aggressive breast cancer (BC). This study aimed to characterize the pathological complete response (pCR) and its relationship with overall survival (OS) and disease-free survival (DFS) among BC patients receiving NAC in a Brazilian public reference center, as well as the association between pCR and BC subtypes. METHODS: A retrospective cohort study used a comprehensive BC database from a Brazilian women's health reference center, including patients diagnosed between 2011 and 2020 who underwent NAC. We collected demographic, cancer-specific, and treatment-related data, analyzing OS and DFS based on pCR status using the semiparametric Kaplan-Meier method, with the date of BC diagnosis as the starting point. RESULTS: The study included 1,601 patients, with an average age of 49 years and a majority presenting stage IIIa disease (35%). Most had invasive nonspecial type (NST) BC (94%), and a significant portion (86.7%) exhibited a Ki-67 index <14. The overall pCR rate was 22.7%, with higher frequencies observed in the triple negative and luminal B subtypes. Patients who achieved pCR had significantly higher survival rates (89% alive vs. 61%, P<0.001) and better DFS (90% vs. 66%, P<0.001), except in the luminal A subtype, where pCR did not correlate with improved OS or DFS. CONCLUSIONS: These updated real-world data (RWD) from BC patients who underwent NAC in Brazil revealed a pCR rate of 22.7% in all cancer subtypes and stages. pCR was not associated with better outcomes in patients with luminal A, contrasting with other subtypes.

NEOADJUVANT TREATMENT OF LIVER METASTASES OF COLORECTAL CANCER: PREDICTIVE FACTORS OF PATHOLOGICAL RESPONSE.

BACKGROUND: Surgery after neoadjuvant chemotherapy (CT) improves the prognosis of colorectal liver metastases (CRLM). AIMS: The aim of this study was to evaluate the predictive factors of the histological response of CRLM after neoadjuvant treatment. METHODS: A retrospective monocentric study including patients with CRLM operated after neoadjuvant treatment. Assessment of histological response was based on the Rubbia-Brandt tumor regression grading score. The scores were grouped into two types of response: Response Group (R) and No Response Group (NR). RESULTS: The study included 77 patients (mean age=56 years, sex ratio=1.57). Node metastases were noticed in 62% of cases. Synchronous liver metastasis was present in 42 cases (55%) and metachronous liver metastasis in 45%. Neoadjuvant treatment consisted of CT only in 52 patients (68%) and CT with targeted therapy in 25 patients (32%). Chemo-induced lesions were present in 44 patients (57%). Histological response was presented (Group R) in 36 cases (47%) and absent (Group NR) in 41 cases (53%). The overall survival of our patients was 32 months. For Group R, survival was significantly greater (p=0.001). The predictive factors of histological response identified were delay in the onset of liver metastasis greater than 14 months (p=0.027) and neoadjuvant treatment combining CT and targeted therapy (p=0.031). In multivariate analysis, the type of neoadjuvant treatment (p=0.035) was an independent predictive factor of histological response. CONCLUSIONS: Predictive factors of histological response would allow us to identify patients who would benefit most from neoadjuvant treatment. These patients with CRLM onset of more than 14 months and treated with CT combined with targeted therapy would be the best candidates for a neoadjuvant CT strategy followed by surgical resection.

Impact of Minimally Invasive Surgery on Early and Late Outcomes of Patients With Gastric Cancer Treated Using Neoadjuvant Chemotherapy.

BACKGROUND: Gastric cancer is the fifth most common neoplasm and the third leading cause of cancer-related death worldwide. Neoadjuvant chemotherapy is recommended for Stages II-III resectable tumors, but the comparative effectiveness of minimally invasive surgery (MIS) versus open gastrectomy (OG) post-neoadjuvant therapy has not been adequately investigated. METHODS: A retrospective cohort analysis was performed on patients with clinical Stage II and III gastric adenocarcinoma who underwent neoadjuvant chemotherapy followed by either MIS or OG between 2007 and 2020. Propensity score matching was utilized to compare the clinical and surgical outcomes, morbidity, and mortality, and the influence of MIS on 3-year survival rates was evaluated. RESULTS: After matching, no statistical differences in clinical aspects were noted between the two groups. MIS was associated with increased D2 lymphadenectomy, curative intent, and complete neoadjuvant therapy. Furthermore, this therapeutic approach resulted in reduced transfusion rates and shorter hospital stays. Nonetheless, no significant differences were observed in global, clinical, or surgical complications or mortality between the two groups. Weight loss emerged as a significant risk factor for complications, but MIS did not independently affect survival rates. Extended resection and higher American Society of Anesthesiology scores were independent predictors of reduced survival. CONCLUSION: MIS after neoadjuvant chemotherapy for gastric cancer appears to be a viable option, with oncological outcomes comparable to those of OG, less blood loss, and shorter hospital stays. Although MIS did not independently affect long-term survival, it offered potential benefits in terms of postoperative recovery and morbidity. Further studies are needed to validate these findings, especially across diverse populations.

In-Depth Analysis of the Peripheral Immune Profile of HER2+ Breast Cancer Patients on Neoadjuvant Treatment with Chemotherapy Plus Trastuzumab Plus Pertuzumab.

Currently, therapy for early-stage human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) is based on the combination of trastuzumab and pertuzumab plus chemotherapy in a neoadjuvant regimen. The INMUNOHER study aimed to detect immunological markers in peripheral blood and their association with treatment response. Sixty-two HER2+ BC patients were recruited. Pre-treatment samples were obtained before the start of treatment, while post-treatment samples were obtained after completing therapy and before surgery and were analyzed by flow cytometry. The pathologic complete response (pCR) rate achieved was 82.3%. The expression of the NKp30, PD-1, and TIM-3 receptors was reduced in the Natural Killer (NK)-CD56dim subset of patients who did not achieve pCR. Following therapy, many changes were found in leukocytes, including alterations in T cell lymphocyte proportions. Also, the percentage of NK cells decreased, and several phenotypic changes were observed in this population. After treatment, IFN-γ production by NK cells against HER2+-cells with or without trastuzumab was significantly reduced. HER2-targeted therapy plus chemotherapy demonstrated high efficacy in most patients, reducing the statistical power for finding immunological markers. However, NK subset phenotypes correlated better with response groups, and numerous changes in the percentage of leukocytes and T and NK cells, as well as changes in the functionality of NK cells, were observed in most patients after treatment, encouraging further research into these immune populations.

Abrocitinibe, dupilumabe e upadacitinibe para o tratamento de adolescentes com dermatite atópica moderada a grave e dupilumabe para o tratamento de crianças com dermatite atópica grave / Abrocitinib, dupilumab, and upadacitinib for the treatment of adolescents with moderate to severe atopic dermatitis and dupilumab for the treatment of children with severe atopic dermatitis

INTRODUÇÃO: A dermatite atópica é uma condição crônica e inflamatória da pele. O sintoma mais comum é o prurido associado a lesões eritematosas e escamosas. Estima-se, no Brasil, uma taxa de prevalência de 2.664,44 por 100.000 pessoas. No SUS, o PCDT de dermatite atópica inclui dois tratamentos tópicos (dexametasona e acetato de hidrocortisona) e a ciclosporina oral. Quando um paciente não estiver bem controlado com as terapias tópicas e sistêmica, é indicada a introdução de terapias imunobiológicas e inibidores da Janus-quinase. Esses medicamentos não são disponibilizados, no SUS, para dermatite atópica. PERGUNTAS: Qual é a eficácia, a segurança e a custo-efetividade dos medicamentos abrocitinibe, dupilumabe e upadacitinibe (adolescentes); e dupilumabe (crianças) para o tratamento de pacientes com dermatite atópica moderada a grave com falha, intolerância ou contraindicação à ciclosporina e com indicação à terapia sistêmica? EVIDÊNCIAS CLÍNICAS: foi realizada uma busca sistematizada da literatura no dia 04 de janeiro de 2024. Foram identificadas 24 revisões sistemáticas de estudos clínicos randomizados (ECRs) que atenderam às perguntas de pesquisa. Aquela com a busca mais recente foi selecionada para a descrição detalhada dos resultados. Para adolescentes e crianças, os ensaios clínicos foram descritos de forma individual para cada tecnologia. Entre adolescentes com dermatite moderada a grave, quando comparadas a placebo, todas as tecnologias avaliadas (abrocitini

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.

Deciphering the Dilemma: Choosing the Optimal Total Neoadjuvant Treatment Strategy for Locally Advanced Rectal Cancer.

Rectal cancer management has evolved significantly, particularly with neoadjuvant treatment strategies. This narrative review examines the development and effectiveness of these therapies for locally advanced rectal cancer (LARC), highlighting the historical quest that led to current neoadjuvant alternatives. Initially, trials showed the benefits of adding radiotherapy (RT) and chemotherapy (CT) to surgery, reducing local recurrence (LR). The addition of oxaliplatin to chemoradiotherapy (CRT) further improved outcomes. TNT integrates chemotherapy and radiotherapy preoperatively to enhance adherence, timing, and systemic control. Key trials, including PRODIGE 23, CAO/ARO/AIO 12, OPRA, RAPIDO, and STELLAR, are analyzed to compare short-course and long-course RT with systemic chemotherapy. The heterogeneity and difficulty in comparing TNT trials due to different designs and outcomes are acknowledged, along with their promising long-term results. On the other hand, it briefly discusses the potential for non-operative management (NOM) in select patients, a strategy gaining traction due to favorable outcomes in specific trials. As a conclusion, this review underscores the complexity of rectal cancer treatment, emphasizing individualized approaches considering patient preferences and healthcare resources. It also highlights the importance of interpreting impressive positive or negative results with caution due to the variability in study designs and patient populations.

Real-world data on adjuvant capecitabine after standard neoadjuvant chemotherapy for triple negative breast cancer.

Objective: Neoadjuvant chemotherapy (NACT) has become the standard of care for patients with triple-negative breast cancer (TNBC) with tumors > 1 cm or positive axillary nodes. Pathologic complete response (pCR) has been used as an endpoint to select patients for treatment scaling. This study aimed to examine the benefit of adding adjuvant capecitabine for TNBC patients who did not achieve pCR after standard NACT in a real-world scenario. Methods: This retrospective cohort study included all patients with TNBC who underwent NACT between 2010 and 2020. Clinicopathological data were obtained from the patient records. Univariate and multivariate analyses were conducted at the 5 years follow-up period. Results: We included 153 patients, more than half of whom had stage III (58.2%) and high-grade tumors (60.8%). The overall pCR rate was 34.6%, and 41% of the patients with residual disease received adjuvant capecitabine. Disease-specific survival (DSS) among the patients who achieved pCR was significantly higher (p<0.0001). Residual disease after NACT was associated with detrimental effects on DSS. In this cohort, we did not observe any survival benefit of adding adjuvant capecitabine for patients with TNBC subjected to NACT who did not achieve pCR (p=0.52). Conclusion: Our study failed to demonstrate a survival benefit of extended capecitabine therapy in patients with TNBC with residual disease after NACT. More studies are warranted to better understand the indication of systemic treatment escalation in this scenario.

Metabolomic Profiling of Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy for Predicting Disease-Free and Overall Survival.

Breast cancer (BC) remains a significant global health concern, with neoadjuvant chemotherapy (NACT) offering preoperative benefits like tumor downstaging and treatment response assessment. However, identifying factors influencing post-NACT treatment response and survival outcomes is challenging. Metabolomic approaches offer promising insights into understanding these outcomes. This study analyzed the serum of 80 BC patients before and after NACT, followed for up to five years, correlating with disease-free survival (DFS) and overall survival (OS). Using untargeted nuclear magnetic resonance (NMR) spectroscopy and a novel statistical model that avoids collinearity issues, we identified metabolic changes associated with survival outcomes. Four metabolites (histidine, lactate, serine, and taurine) were significantly associated with DFS. We developed a metabolite-related survival score (MRSS) from these metabolites, stratifying patients into low- and high-risk relapse groups, independent of classical prognostic factors. High-risk patients had a hazard ratio (HR) for DFS of 3.42 (95% CI 1.51-7.74; p = 0.003) after adjustment for disease stage and age. A similar trend was observed for OS (HR of 3.34, 95% CI 1.64-6.80; p < 0.001). Multivariate Cox proportional hazards analysis confirmed the independent prognostic value of the MRSS. Our findings suggest the potential of metabolomic data, alongside traditional markers, in guiding personalized treatment decisions and risk stratification in BC patients undergoing NACT. This study provides a methodological framework for leveraging metabolomics in survival analyses.

The Role of CT-guided Core Needle Biopsy in Pancreatic Tumors: An Initial Evaluation in Modern Oncology.

PURPOSE: Neoadjuvant chemotherapy has recently become the standard of care for borderline resectable pancreatic ductal adenocarcinoma (PDAC), and there have even been numerous reports evaluating its potential benefits in resectable PDAC. However, neoadjuvant therapy first requires a histological or cytological diagnosis. This study aimed to analyze the safety and diagnostic yield of CT-guided core needle biopsy (CNB). MATERIAL AND METHODS: A retrospective analysis of patients with pancreatic tumor requiring a CNB during the period 2015 to 2023 were included. Biopsies were performed with an 18-20 G Tru-Core needle using a coaxial system and automatic biopsy gun. Demographics, procedural variables, postoperative outcomes, and histological results were analyzed. RESULTS: A total of 43 pancreatic biopsies were performed in 42 patients. The mean age was 60 years (35 to 81 y), and 24 (56%) were males. Tumors were more frequently localized in the head (42%) and body (42%) of the pancreas. The mean size of the pancreatic lesions was 53.77 mm (17 to 181 mm) and the mean number of samples per biopsy was 4 (1 to 12). Most procedures were performed via direct access (81%). No major complications were observed. Histological diagnosis was obtained in 40 (93%) patients, with a sensitivity of 93%, specificity of 100% and an overall accuracy rate of 93%. The probability of performing a molecular diagnostic test increased with the year of biopsy (OR 3.34, 95% CI 1.33-8.40, P =0.01). CONCLUSIONS: CNB is an efficient and safe method for obtaining high-quality material. This approach could be essential as molecular profiling continues to improve the diagnosis, prognosis, and treatment of PDAC.

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.

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.

Emerging Indications for Neoadjuvant Systemic Therapies in Cutaneous Malignancies.

Patients with cutaneous malignancies and locoregional involvement represent a high-risk population for disease recurrence, even if they receive optimal surgery and adjuvant treatment. Here, we discuss how neoadjuvant therapy has the potential to offer significant advantages over adjuvant treatment, further improving outcomes in some patients with skin cancers, including melanoma, Merkel cell carcinoma, and cutaneous squamous-cell carcinoma. Both preclinical studies and in vivo trials have demonstrated that exposure to immunotherapy prior to surgical resection can trigger a broader and more robust immune response, resulting in increased tumor cell antigen presentation and improved targeting by immune cells, potentially resulting in superior outcomes. In addition, neoadjuvant approaches hold the possibility of providing a platform for evaluating pathological responses in the resected lesion, optimizing the prognosis and enabling personalized adaptive management, in addition to expedited drug development. However, more data are still needed to determine the ideal patient selection and the best treatment framework and to identify reliable biomarkers of treatment responses. Although there are ongoing questions regarding neoadjuvant treatment, current data support a paradigm shift toward considering neoadjuvant therapy as the standard approach for selecting patients with high-risk skin tumors.

Pertuzumabe e trastuzumabe em combinação de dose fixa subcutânea no tratamento neoadjuvante de pacientes com câncer de mama HER2-positivo / Pertuzumabe and trastuzumabe in combination of subcutaneous fixed doses in neoadjuvant treatment of patients with HER2-positive breast cancer

INTRODUÇÃO: O câncer de mama (CM) está entre as neoplasias malignas mais frequentes no mundo, sendo a principal causa de óbito por câncer no sexo feminino. Apesar da abrangência crescente do rastreamento para diagnóstico destes tumores, ainda se observa uma incidência de casos iniciais localmente avançados entre 10 e 30% do total de diagnósticos em todo o mundo, podendo chegar a 60-70% em algumas regiões em desenvolvimento ­ incluindo no Brasil. Além disso, cerca de 15 a 20% dos casos de CM apresentam uma mutação genética que leva ao aumento da produção da proteína HER2, acelerando a multiplicação celular e aumentando a agressividade do tumor. Atualmente, o tratamento para CM em estágios iniciais II a III (não metastático) inclui cirurgia e radioterapia, associadas a quimioterapia ou outras terapias medicamentosas pré-cirúrgicas (terapia neoadjuvante) ou pós-cirúrgicas (terapia adjuvante). Uma das alternativas terapêuticas recentes neste cenário é o uso neoadjuvante da formulação de anticorpos monoclonais combinados, como trastuzumabe e pertuzumabe. PERGUNTA: Pertuzumabe e trastuzumabe em combinação de dose fixa subcutânea (associado a quimioterapia) é mais eficaz e seguro no tratamento neoadjuvante de pacientes com CM HER2-positivo inicial não invasivo quando comparado ao uso isolado de trastuzumabe intravenoso (associado a quimioterapia)? EVIDÊNCIAS CLÍNICAS: Foram realizadas buscas de revisões sist

PERIOPERATIVE CHEMOTHERAPY, ADJUVANT CHEMOTHERAPY AND ADJUVANT CHEMORADIOTHERAPY IN THE SURGICAL TREATMENT OF GASTRIC CANCER IN A HOSPITAL OF THE BRAZILIAN UNIFIED HEALTH SYSTEM.

BACKGROUND: Despite the preference for multimodal treatment for gastric cancer, abandonment of chemotherapy treatment as well as the need for upfront surgery in obstructed patients brings negative impacts on the treatment. The difficulty of accessing treatment in specialized centers in the Brazilian Unified National Health System (SUS) scenario is an aggravating factor. AIMS: To identify advantages, prognostic factors, complications, and neoadjuvant and adjuvant therapies survival in gastric cancer treatment in SUS setting. METHODS: The retrospective study included 81 patients with gastric adenocarcinoma who underwent treatment according to INT0116 trial (adjuvant chemoradiotherapy), CLASSIC trial (adjuvant chemotherapy), FLOT4-AIO trial (perioperative chemotherapy), and surgery with curative intention (R0 resection and D2 lymphadenectomy) in a single cancer center between 2015 and 2020. Individuals with other histological types, gastric stump, esophageal cancer, other treatment protocols, and stage Ia or IV were excluded. RESULTS: Patients were grouped into FLOT4-AIO (26 patients), CLASSIC (25 patients), and INT0116 (30 patients). The average age was 61 years old. More than 60% of patients had pathological stage III. The treatment completion rate was 56%. The pathological complete response rate of the FLOT4-AIO group was 7.7%. Among the prognostic factors that impacted overall survival and disease-free survival were alcoholism, early postoperative complications, and anatomopathological status pN2 and pN3. The 3-year overall survival rate was 64.9%, with the CLASSIC subgroup having the best survival (79.8%). CONCLUSIONS: The treatment strategy for gastric cancer varies according to the need for initial surgery. The CLASSIC subgroup had better overall survival and disease-free survival. The INT0116 regimen also protected against mortality, but not with statistical significance. Although FLOT4-AIO is the preferred treatment, the difficulty in carrying out neoadjuvant treatment in SUS scenario had a negative impact on the results due to the criticality of food intake and worse treatment tolerance.

Significance of Pathologic Response in Patients With Early and Locally Advanced Breast Cancer Treated With Neoadjuvant Chemotherapy in a Middle-Income Country. A Real-World Historical Cohort.

PURPOSE: Breast cancer (BC) is the most frequent neoplasm in women in Colombia and is associated with a higher mortality rate than in other countries and regions. Neoadjuvant chemotherapy (NACT) has become a standard treatment in locally advanced BC and provides an opportunity to improve clinical outcomes in BC. This study aims to describe characteristics, treatment patterns, and outcomes after NACT in a cohort of Colombian patients with BC. METHODS: We performed a retrospective cohort study. We included adult patients with BC treated with NACT. Clinical charts were retrospectively reviewed. Descriptive statistics and time to event for overall survival analyses were performed. Recursive partitioning was performed for survival curves to assess the complex relationship between survival times and other variables. RESULTS: Three hundred and fourteen patients were included for analysis. The pathologic complete response after neoadjuvant chemotherapy (ypCR) rate was 34.4%, with a higher ypCR in triple-negative BC (TNBC; 46.9%) and human epidermal growth factor receptor 2-positive BC (72.7%). Those who did not achieve ypCR had a higher percentage of death and relapse. The median follow-up was 4.9 years, with an 88.2% 5-year overall survival (OS). CONCLUSION: A total of 62.6% of the total patients identified were not treated with NACT, indicating a low utilization. Our global ypCR rate was higher when compared with similar studies in Colombia, likely because of differences in the NACT treatment regimens. ypCR was only associated with OS in the TNBC subgroup, emphasizing the importance of pursuing ypCR in these patients. We consider the use of NACT a valuable opportunity to implement innovative treatment approaches that improve outcomes in Colombian patients with BC.