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10 pages, 494 KB  
Article
BRCA1 and 2 Mutations and Efficacy of Pembrolizumab-Based Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer: A Real-World Multicenter Analysis
by Palma Fedele, Alessandro Rizzo, Matteo Landriscina, Stefania Luigia Stucci, Maria Morritti, Francesco Giuliani, Lucia Moraca, Giuseppe Cairo, Raffaele Ardito, Marianna Giampaglia, Domenico Bilancia, Assunta Melaccio, Antonella Terenzio, Antonio Gnoni, Antonella Licchetta, Federica Fumai, Laura Lanotte and Gennaro Gadaleta-Caldarola
J. Clin. Med. 2025, 14(24), 8854; https://doi.org/10.3390/jcm14248854 - 14 Dec 2025
Viewed by 714
Abstract
Background: Pembrolizumab has reshaped the neoadjuvant treatment landscape for triple-negative breast cancer (TNBC). However, the influence of BRCA1/2 mutational status on the efficacy of chemo-immunotherapy remains unclear, particularly in real-world settings. Since BRCA-mutated tumors exhibit homologous recombination deficiency (HRD) and high genomic instability, [...] Read more.
Background: Pembrolizumab has reshaped the neoadjuvant treatment landscape for triple-negative breast cancer (TNBC). However, the influence of BRCA1/2 mutational status on the efficacy of chemo-immunotherapy remains unclear, particularly in real-world settings. Since BRCA-mutated tumors exhibit homologous recombination deficiency (HRD) and high genomic instability, they may be more immunogenic and responsive to immune checkpoint inhibitors. This multicenter study investigated the association between BRCA1/2 mutations and pathologic complete response (pCR) in TNBC patients treated with pembrolizumab-based neoadjuvant chemotherapy (NACT). Methods: We retrospectively analyzed 184 patients with stage II–III TNBC treated between 2021 and 2024 across eleven Italian oncology centers. All received pembrolizumab combined with platinum- and taxane-based NACT followed by anthracyclines, according to the KEYNOTE-522 regimen. Germline BRCA1/2 status was determined by next-generation sequencing. The primary endpoint was pCR, defined as ypT0/is ypN0. Fisher’s exact test and logistic regression models were used to assess associations between clinical–pathological variables and pCR. Results: Among 184 patients, 25 (13.6%) harbored BRCA1 mutations, 12 (6.5%) BRCA2 mutations, and 147 (79.9%) were wild-type. pCR was achieved in 80.0% of BRCA1-mutated, 75.0% of BRCA2-mutated, and 61.1% of wild-type tumors. When pooled, BRCA1/2-mutated cases showed a higher likelihood of achieving pCR (78.4% vs. 61.1%; odds ratio [OR] = 2.17; 95% CI 1.01–4.97; p = 0.056). High tumor-infiltrating lymphocytes (≥30%) were also associated with increased pCR rates. The frequency of BRCA mutations (20.1%) was consistent with that reported in major TNBC series. No comparative analysis of toxicity or survival outcomes was performed due to the retrospective design and limited follow-up. Conclusions: In this multicenter real-world cohort, TNBC patients carrying BRCA1/2 mutations exhibited a trend toward higher pCR rates with pembrolizumab-based NACT compared with wild-type tumors. These findings suggest enhanced chemosensitivity and immune responsiveness in BRCA-deficient disease, warranting further validation in larger prospective studies with survival endpoints. Full article
(This article belongs to the Section Oncology)
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11 pages, 502 KB  
Article
Impact of Chemotherapy Dose Intensity on Pathological Complete Response in Pembrolizumab-Treated Early Triple-Negative Breast Cancer: A Real-World Multicenter Analysis
by Palma Fedele, Stefania Luigia Stucci, Matteo Landriscina, Maria Morritti, Francesco Giuliani, Lucia Moraca, Giuseppe Cairo, Raffaele Ardito, Marianna Giampaglia, Domenico Bilancia, Assunta Melaccio, Antonella Terenzio, Antonio Gnoni, Antonella Licchetta, Federica Fumai, Laura Lanotte, Alessandro Rizzo and Gennaro Gadaleta-Caldarola
Cancers 2025, 17(21), 3554; https://doi.org/10.3390/cancers17213554 - 2 Nov 2025
Viewed by 1394
Abstract
Background: Pembrolizumab combined with neoadjuvant chemotherapy significantly improves pCR in early TNBC, but the effect of treatment intensity and baseline clinical factors has been insufficiently explored in real-world settings. Methods: We retrospectively included 169 consecutive patients with stage II–III TNBC treated across 11 [...] Read more.
Background: Pembrolizumab combined with neoadjuvant chemotherapy significantly improves pCR in early TNBC, but the effect of treatment intensity and baseline clinical factors has been insufficiently explored in real-world settings. Methods: We retrospectively included 169 consecutive patients with stage II–III TNBC treated across 11 Italian oncology centers (January 2022–January 2025) with the KEYNOTE-522 regimen. Clinical, pathological, and treatment data were collected, including relative dose intensity (RDI), dose modifications, and toxicities. The primary endpoint was pCR (ypT0/is ypN0). Results: The overall pCR rate was 65.7%, which is consistent with clinical trial data. Dose reductions occurred in 40% of patients and chemotherapy was discontinued in 18%. Patients maintaining RDI ≥85% achieved higher pCR (79.3% vs. 51.2%, p < 0.001). Similarly, patients without dose reductions (72.5% vs. 55.2%, p = 0.031) and those completing all cycles (73.1% vs. 41.0%, p < 0.001) had superior outcomes. Dose modifications occurred mainly during the taxane/carboplatin phase and were predominantly due to hematological toxicities (anemia 44%, neutropenia 30%, and thrombocytopenia 15%), neuropathy (18%), and gastrointestinal events (36%). Higher TILs correlated with increased pCR (70.6% vs. 60.7%, p = 0.049), while BRCA mutations showed a favorable trend. ECOG, BMI, pregnancy history, and comorbidities were not significantly associated with pCR. Conclusions: In this multicenter real-world cohort, maintaining chemotherapy dose intensity (RDI ≥ 85%) and completing all planned cycles were strongly associated with higher pCR rates, reinforcing the clinical importance of minimizing dose reductions and discontinuations during pembrolizumab-based neoadjuvant therapy for TNBC. Full article
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16 pages, 561 KB  
Article
Predictors of Pathologic Complete Response and Its Prognostic Value in Early Breast Cancer: A Real-World Cohort Study
by Selami Bayram, Ali Murat Tatli, Muharrem Okan Cakir and Mustafa Ozdogan
Curr. Oncol. 2025, 32(11), 603; https://doi.org/10.3390/curroncol32110603 - 28 Oct 2025
Viewed by 979
Abstract
Background: Pathologic complete response (pCR) after neoadjuvant systemic therapy (NAST) is a key prognostic marker in early breast cancer (EBC), particularly in triple-negative (TNBC) and HER2-positive subtypes. However, real-world data on predictors of pCR and their impact on survival remain limited. Methods: We [...] Read more.
Background: Pathologic complete response (pCR) after neoadjuvant systemic therapy (NAST) is a key prognostic marker in early breast cancer (EBC), particularly in triple-negative (TNBC) and HER2-positive subtypes. However, real-world data on predictors of pCR and their impact on survival remain limited. Methods: We retrospectively analyzed 200 patients with stage II–III EBC treated with NAST at a single institution (2015–2023). Clinicopathologic variables and treatment characteristics were evaluated for association with pCR (ypT0/is ypN0), and histological regression was additionally assessed using the Miller–Payne scoring system. Multivariable logistic regression identified independent predictors. Disease-free survival (DFS) and overall survival (OS) were estimated using Kaplan–Meier methods. Results: Overall, 36.0% achieved pCR, with the highest rates in HER2-positive (65%) and TNBC (56%) subtypes. Independent predictors of pCR included HER2 positivity (OR 4.21, 95% CI 1.83–9.67, p < 0.001), high Ki-67 > 47.5% (OR 3.62, 95% CI 1.68–7.80, p = 0.001), ER < 10% (OR 2.77, 95% CI 1.18–6.50, p = 0.019), and radiologic complete response (OR 10.03, 95% CI 2.91–34.60, p < 0.001). At a median follow-up of 75 months, compared with non-pCR, patients achieving pCR had a significantly lower risk of recurrence (HR 0.16, 95% CI 0.04–0.70, p = 0.014) with 5-year DFS rates of 91.5% vs. 72.8%. For OS, pCR patients showed a lower risk of death (HR 0.33, 95% CI 0.07–1.49, p = 0.150), corresponding to 5-year OS of 92.2% vs. 87.0%, although this difference was not statistically significant. Conclusions: HER2 positivity, high Ki-67, low ER expression, and radiologic complete response are independent predictors of pCR. Achieving pCR strongly correlates with improved DFS but not OS, likely due to limited sample size and event number. These findings reinforce pCR as a surrogate endpoint in TNBC and HER2-positive disease and highlight the need for post-neoadjuvant escalation in non-pCR patients. Full article
(This article belongs to the Section Breast Cancer)
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13 pages, 449 KB  
Article
TCF Plus Radiochemotherapy Versus Neoadjuvant Radiochemotherapy Versus Flot Perioperative Chemotherapy in Esophageal Adenocarcinoma: The Results of a Three-Cohort, Multi-Centric Comparison: The A4 Study
by Marco Lorenzo Bonù, Giulia Volpi, Gloria Zanni, Jacopo Balduzzi, Fabrizia Terraneo, Giusto Pignata, Giuseppina Arcangeli, Francesco Frassine, Paola Vitali, Eliana La Rocca, Simone Giacopuzzi, Jacopo Weindelmayer, Carlo Alberto De Pasqual, Martina Milazzo, Michele Pavarana, Valentina Zen, Stefano De Pascale, Uberto Fumagalli Romario, Michela Buglione and Giovanni De Manzoni
Biomedicines 2025, 13(9), 2236; https://doi.org/10.3390/biomedicines13092236 - 11 Sep 2025
Viewed by 766
Abstract
Introduction: Recent randomized evidence suggests that stage II–IV non metastatic esophageal adenocarcinoma is best managed with perioperative chemotherapy (CHT) and surgery. Intensification of neoadjuvant chemotherapy and radiochemotherapy are proposed before surgery in high-volume centers with the aim of increasing both systemic and locoregional [...] Read more.
Introduction: Recent randomized evidence suggests that stage II–IV non metastatic esophageal adenocarcinoma is best managed with perioperative chemotherapy (CHT) and surgery. Intensification of neoadjuvant chemotherapy and radiochemotherapy are proposed before surgery in high-volume centers with the aim of increasing both systemic and locoregional control. However, few data comparing intensified RTCHT, CHT plus RTCHT and perioperative CHT with FLOT in real-life scenarios are available. Methods: This is a multicenter, retrospective series, including three cohorts of patients treated for esophageal adenocarcinoma: Cohort A: nRTCHT; Cohort B: TCF plus RTCHT, defined as triplet chemotherapy followed by dose-reduced triplet therapy + RT; Cohort C: perioperative chemotherapy with FLOT regimen. The primary endpoint was disease-free survival (DFS), and the secondary endpoints were pathologic complete response (pCR), pathologic lymph-node complete response (ypN0), overall survival (OS), and perioperative acute toxicity. Results: From January 2013 to December 2023, 142 patients were identified. All patients received multimodal therapy with radical esophagectomy. A total of 95% of patients were male; the majority of patients presented with stage cT3cN1. A total of 63 patients were treated in Cohort A (31 cases with doublet 5FU-CDDP concurrent to 50.4 Gy and 32 cases with CROSS regimen), 36 in Cohort B, and 43 in Cohort C. After a median FU of 36 months, the 3-year DFS resulted 58.6%. pCR occurred in 26 cases (18.6%). Three-year OS had a value of 72%. At univariate analysis, ypN0 was related to better DFS; cN+ disease was related with worse OS. The treatment cohort did not impact survival outcomes; however, an effect on CR was shown, with pCR in 15% (A), 36.3% (B), 11% (C) of cases, respectively (χ: 0.008). A total of 67% of patients in Cohort B experienced a ypN0. Two treatment-related deaths occurred (one in Cohort A and one in C) with a slight increase in G3 toxicity in cohort C. Conclusions: In this real-life multicenter series, oncological results were adequate for all three neoadjuvant strategies. TCF plus RTCHT guaranteed a higher pCR and ypN0 rate without increasing toxicity. An intensified neoadjuvant schedule, such as TCF plus RTCHT, may be useful in cases where higher tumor and nodal responses are needed. Taken together, our data highlight that further investigation is warranted before abandoning radiotherapy-based neoadjuvant approaches in esophageal and GEJ adenocarcinoma. Full article
(This article belongs to the Section Cancer Biology and Oncology)
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26 pages, 7367 KB  
Article
CD133 and CD166 Stem Cells Markers Expression, Clinicopathological Parameters, and Fragmentation Response Patterns of ypT3 Rectal Cancer Following Neoadjuvant Chemoradiotherapy
by Diana Lavinia Pricope, Adriana Grigoraș, Gabriel Mihail Dimofte, Cristina Terinte and Cornelia Amalinei
Biomedicines 2025, 13(6), 1300; https://doi.org/10.3390/biomedicines13061300 - 26 May 2025
Cited by 2 | Viewed by 1052
Abstract
Background: The effectiveness of neoadjuvant chemoradiotherapy (nCRT) is variable in locally advanced rectal cancer (LARC) patients, the ypT3 stage having a minimal or moderate response. The aim of our study was the evaluation of the association between CD133 (Prominin1) and CD166 (ALCAM) [...] Read more.
Background: The effectiveness of neoadjuvant chemoradiotherapy (nCRT) is variable in locally advanced rectal cancer (LARC) patients, the ypT3 stage having a minimal or moderate response. The aim of our study was the evaluation of the association between CD133 (Prominin1) and CD166 (ALCAM) expression, survival parameters, and clinicopathological characteristics of a subgroup of LARC patients who achieved ypT3, showing post-nCRT and TME tumor fragmentation response and the assessment of these CSCs biomarkers value as indicators of the nCRT tumor response. Methods: Our study group comprised 60 LARC patients who achieved ypT3 status and exhibited a tumor fragmentation pattern following nCRT. Clinicopathological parameter and survival evaluations, along with CD133 and CD166 immunohistochemistry and scoring, were performed and the associations between different parameters were tested. Results: High CD133 expression was significantly associated with ypN category (p = 0.018), lymphovascular invasion (LVI) (p = 0.009), perineural invasion (PnI) (p = 0.006), and tumor grading (p = 0.047), while high CD166 expression was significantly associated with LVI (p = 0.020) and PnI (p = 0.028). Tumors with high CD133 and CD166 expressions were associated with decreased overall survival (OS) (p = 0.004 and p = 0.006). Cox regression analysis identified high CD133 and CD166 expression as independent factors associated with reduced survival (HR = 3.237, p = 0.014 and HR = 2.866, p = 0.020). Conclusions: Our results support the hypothesis that CD133 and CD166 are putative CSC biomarkers associated with aggressive behavior and a poor prognosis in LARC, offering opportunities for personalized targeted therapies. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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21 pages, 1220 KB  
Article
Long-Term Outcomes of Patients Undergoing Conversion Surgery After Induction Chemotherapy: Turkish Oncology Group Study
by Furkan Ceylan, Selin Aktürk Esen, Olçun Ümit Ünal, Ferit Aslan, İlknur Deliktaş Onur, Öztürk Ateş, Erkut Demirciler, İlkay Tuğba Ünek, Ahmet Gülmez, Esra Özen Engin, Semra Taş, Gamze Gököz Doğu, Melih Şimşek, Hacı Mehmet Türk, Ali İnal, Gökhan Şahin, Haydar Çağatay Yüksel, Ateş Kutay Tenekeci, Mutlu Hızal, Mehmet Ali Nahit Şendur and Doğan Uncuadd Show full author list remove Hide full author list
Medicina 2025, 61(5), 776; https://doi.org/10.3390/medicina61050776 - 22 Apr 2025
Viewed by 1139
Abstract
Background and Objectives: Conversion surgery for liver metastatic colorectal cancer (mCRC) has been associated with prolonged survival. This study aimed to evaluate the efficacy and safety of integrating biological therapies with fluorouracil-based induction chemotherapy in patients with isolated liver mCRC who subsequently [...] Read more.
Background and Objectives: Conversion surgery for liver metastatic colorectal cancer (mCRC) has been associated with prolonged survival. This study aimed to evaluate the efficacy and safety of integrating biological therapies with fluorouracil-based induction chemotherapy in patients with isolated liver mCRC who subsequently underwent curative resection of both the primary tumor and liver metastases. Materials and Methods: This multicenter, retrospective study, conducted by the Turkish Oncology Group (TOG), included 116 patients from 11 tertiary centers who underwent conversion surgery following induction chemotherapy between 2009 and 2024. Results: The median age was 57 years, with 62% male patients. The median follow-up period was 55.3 months. The median progression-free survival (PFS) and overall survival (OS) were 21.1 and 53.7 months, respectively. No significant differences in PFS or OS were observed based on biological therapy use or tumor localization. Among patients with RAS/RAF wild-type tumors, PFS and OS were comparable between those receiving Anti-EGFR and Anti-VEGF therapy. In RAS/RAF mutant tumors, the addition of Anti-VEGF therapy did not confer a survival benefit. Factors associated with shorter PFS included advanced tumor stage (ypT3-T4), lymph node metastasis, and multiple metastases, while shorter OS was linked to advanced tumor stage and lack of objective response. Conclusions: Surgical resection plays a pivotal role in improving survival outcomes in patients with potentially resectable liver mCRC. Optimizing induction chemotherapy regimens may enhance conversion rates and prolong long-term survival. Further studies are needed to refine treatment selection based on tumor localization, mutation status, and molecular biomarkers. Full article
(This article belongs to the Section Oncology)
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18 pages, 1641 KB  
Article
Large Unstained Cells: A Predictive Biomarker for Recurrence and Survival in Resected Gastric Cancer
by Furkan Ceylan, Ateş Kutay Tenekeci, Burak Bilgin, Mehmet Ali Nahit Şendur, Mutlu Hızal, Fahriye Tuba Köş and Didem Şener Dede
Medicina 2025, 61(2), 208; https://doi.org/10.3390/medicina61020208 - 24 Jan 2025
Viewed by 1756
Abstract
Background and Objectives: Despite advances in surgery and perioperative chemotherapy, locally advanced gastric cancer continues to pose significant challenges, creating a pressing need for biomarkers capable of predicting therapeutic efficacy and survival outcomes. This study evaluates the prognostic and predictive significance of large [...] Read more.
Background and Objectives: Despite advances in surgery and perioperative chemotherapy, locally advanced gastric cancer continues to pose significant challenges, creating a pressing need for biomarkers capable of predicting therapeutic efficacy and survival outcomes. This study evaluates the prognostic and predictive significance of large unstained cells (LUCs), a morphologically distinct subset of white blood cells identified in peripheral blood that remain unstained by standard hematological dyes, as potential indicators of immune competence and treatment response. Materials and Methods: This retrospective analysis included patients diagnosed with locally advanced gastric cancer (cT2-4, N0-3) at Ankara Bilkent City Hospital between January 2018 and November 2024. Primary endpoints were overall survival (OS) and disease-free survival (DFS), stratified by LUC levels. The secondary endpoint was the association between LUC levels and pathological tumor response. Results: A total of 180 patients were analyzed, with a median age of 59 years; a total of 76% were male. The median follow-up period was 16.5 months, during which OS and DFS rates were 82% and 66%, respectively. Most patients were presented with advanced-stage disease, including T3–T4 tumors (91%) and nodal positivity (81%). Stratification by LUC levels revealed significantly shorter DFS (HR: 2.12; 95% CI: 1.12–4.01; p = 0.020) and OS (HR: 3.37; 95% CI: 1.26–9.03; p = 0.015) in the low-LUC group compared to the high-LUC group. Furthermore, the high-LUC group exhibited a significantly higher tumor shrinkage rate (ypN0: 60% vs. 44%; p = 0.020), although tumor regression scores were similar across groups. Advanced tumor stage and lack of pathological response were strongly associated with reduced DFS and OS, while poorly cohesive carcinoma histology emerged as a predictor of inferior OS. Conclusions: This study demonstrates that elevated LUC levels are significantly associated with improved DFS and OS, as well as enhanced tumor shrinkage, in patients with locally advanced gastric cancer. These findings show the potential of LUCs as a promising biomarker for prognostication and therapeutic stratification in this population, offering a novel avenue for refining clinical decision-making. Further validation through prospective investigations is warranted. Full article
(This article belongs to the Special Issue Insights and Advances in Cancer Biomarkers)
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10 pages, 217 KB  
Article
A Retrospective, Single-Center Study Comparing Neoadjuvant ACTHP vs. DCbHP in HER2-Positive Early Breast Cancer Patients
by Amit Itay, Opher Globus, Keren Levanon, Tal Sella, Rinat Bernstein-Molho, Tal Shapira, Cecilie Oedegaard, Dana Fourey and Einav Nili Gal Yam
Cancers 2025, 17(2), 250; https://doi.org/10.3390/cancers17020250 - 14 Jan 2025
Cited by 1 | Viewed by 2086
Abstract
Background: Neoadjuvant systemic therapy is the preferred treatment approach for stage II–III HER2-positive breast cancer (BC). Real-life data comparing regimens with or without anthracyclines combined with two HER2 drugs is lacking. We compared the efficacy and toxicity of two commonly used regimens. Methods: [...] Read more.
Background: Neoadjuvant systemic therapy is the preferred treatment approach for stage II–III HER2-positive breast cancer (BC). Real-life data comparing regimens with or without anthracyclines combined with two HER2 drugs is lacking. We compared the efficacy and toxicity of two commonly used regimens. Methods: Retrospective data were collected on patients newly diagnosed with clinical stage II–III HER2-positive BC and treated at Sheba Medical Center, Israel, between September 2017 and June 2022 with either neoadjuvant DCbHP (docetaxel, carboplatin, trastuzumab, pertuzumab) or ACTHP (doxorubicin, cyclophosphamide, paclitaxel trastuzumab pertuzumab). PCR (pathological complete response) (ypT0/isN0) was evaluated in both cohorts and according to HER2 immunohistochemistry (IHC) staining (3+ or 2+ and fluorescence in situ hybridization [FISH] positive), estrogen receptor (ER), tumor size and nodal status. The toxicity indices evaluated were reductions in left ventricle ejection fraction (LVEF), dose reductions, hospitalizations and febrile neutropenia. Results: Here, 106 received ACTHP and 73 received DCbHP. Median age at diagnosis, ER status, HER2 IHC (2+/FISH pos or 3+) and nodal status were balanced. PCR occurred in 63.1% of patients, 67.0% and 57.5% in the ACTHP and DCbHP groups, respectively (p = 0.129). In patients with HER2 3+ IHC, pCR rates were significantly better with the ACTHP regimen than with DCbHP (83% vs. 62.9%, p < 0.039). No difference was observed among patients with HER2 +2 IHC FISH pos. Symptomatic LVEF decrease was observed in seven patients (6.6%) receiving ACTHP vs. none (0%) receiving DCbHP (p < 0.001). Conclusions: PCR rates were similar overall between ACTHP and DCbHP; however, in the HER2 3+ subgroup, ACTHP demonstrated increased efficacy. DCbHP was significantly less cardiotoxic. Full article
(This article belongs to the Special Issue Neo-Adjuvant Treatment of Breast Cancer)
17 pages, 1777 KB  
Article
Neoadjuvant Accelerated Methotrexate, Vinblastine, Doxorubicin, and Cisplatin Chemotherapy for Muscle-Invasive Urothelial Cancer: Large, Single-Center Analysis of Consecutive Patients’ Data
by Łukasz Kwinta, Kamil Konopka, Krzysztof Okoń, Mateusz Łobacz, Piotr Chłosta, Przemysław Dudek, Anna Buda-Nowak, Paweł Potocki and Piotr J. Wysocki
Cancers 2025, 17(2), 258; https://doi.org/10.3390/cancers17020258 - 14 Jan 2025
Cited by 1 | Viewed by 2027
Abstract
Background/Objectives: Bladder cancer is a significant clinical problem with approximately 500,000 new cases worldwide annually. In approximately 25% of cases, disease is diagnosed at a stage of invasion of the muscle layer of the bladder. The current standard approach in this disease [...] Read more.
Background/Objectives: Bladder cancer is a significant clinical problem with approximately 500,000 new cases worldwide annually. In approximately 25% of cases, disease is diagnosed at a stage of invasion of the muscle layer of the bladder. The current standard approach in this disease is preoperative chemotherapy followed by radical cystectomy. Dose-dense MVAC (ddMVAC), a two-day chemotherapy regimen, is the reference treatment protocol in this setting. The presented study evaluated the effectiveness and safety of accelerated MVAC (aMVAC) chemotherapy—a one-day regimen given before the resection of the bladder due to muscle-invasive disease. Methods: A retrospective analysis included 119 consecutive patients diagnosed with urothelial muscle-invasive bladder cancer (MIBC) who underwent preoperative chemotherapy with the aMVAC regimen. The planned treatment included 4–6 cycles of preoperative chemotherapy. The analysis of the degree of histopathological response to treatment was based on the three-grade TRG (tumor regression grade) classification. Results: A complete pathological response (TRG1) was observed in 44 patients (36.7%), and a major pathologic response (<ypT2) was achieved in 58 patients (48.7%). A reduction in the cisplatin dose was associated with a statistically significant decrease in the chance of achieving complete pathologic responses (46.1% vs. 10%, RR for TRG1 = 0.69, p = 0.00118). Patients who received at least 4 cycles (compared to ≤3 cycles) of neoadjuvant chemotherapy had a significantly higher chance of achieving a pathological response (partial or complete) to treatment (78.1% vs. 52.2%, RR 0.68, p = 0.0374). Administration of at least five cycles of chemotherapy was associated (compared to four cycles) with a significantly higher likelihood of achieving a complete pathological response (63.2% vs. 33.8%, RR = 1.71, p = 0.0221). The vast majority of adverse events were in grades 1 and 2, according to CTCAE version 5.0. Only five patients experienced grade 3–4 toxicities. The most common adverse event was anemia, which occurred in 66.3% of patients. Conclusions: Our real-world data analysis confirms the activity, safety, and feasibility of the aMVAC regimen as neoadjuvant chemotherapy in patients with urothelial MIBC. Full article
(This article belongs to the Special Issue New Insights into Urologic Oncology)
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12 pages, 1865 KB  
Article
The Association between Sampling and Survival in Patients with Pancreatic Ductal Adenocarcinoma Who Received Neoadjuvant Therapy and Pancreaticoduodenectomy
by Mehran Taherian, Matthew H. G. Katz, Laura R. Prakash, Dongguang Wei, Yi Tat Tong, Zongshan Lai, Deyali Chatterjee, Hua Wang, Michael Kim, Ching-Wei D. Tzeng, Naruhiko Ikoma, Robert A. Wolff, Dan Zhao, Eugene J. Koay, Anirban Maitra and Huamin Wang
Cancers 2024, 16(19), 3312; https://doi.org/10.3390/cancers16193312 - 27 Sep 2024
Cited by 1 | Viewed by 1602
Abstract
Adequate sampling is essential to an accurate pathologic evaluation of pancreatectomy specimens resected for pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy (NAT). However, limited data are available for the association between the sampling and survival in these patients. We examined the association of [...] Read more.
Adequate sampling is essential to an accurate pathologic evaluation of pancreatectomy specimens resected for pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy (NAT). However, limited data are available for the association between the sampling and survival in these patients. We examined the association of the entire submission of the tumor (ESOT) and the entire submission of the pancreas (ESOP) with disease-free survival (DFS) and overall survival (OS), as well as their correlations with clinicopathologic features, for 627 patients with PDAC who received NAT and pancreaticoduodenectomy. We demonstrated that both ESOT and ESOP were associated with lower ypT, less frequent perineural invasion, and better tumor response (p < 0.05). ESOP was also associated with a smaller tumor size (p < 0.001), more lymph nodes (p < 0.001), a lower ypN stage (p < 0.001), better differentiation (p = 0.02), and less frequent lymphovascular invasion (p = 0.009). However, since ESOP and ESOT were primarily conducted for cases with no grossly identifiable tumor or minimal residual carcinoma in initial sections, potential bias cannot be excluded. Both ESOT and ESOP were associated with less frequent recurrence/metastasis and better DFS and OS (p < 0.05) in the overall study population. ESOP was associated with better DFS and better OS in patients with ypT0/ypT1 or ypN0 tumors and better OS in patients with complete or near-complete response (p < 0.05). ESOT was associated with better OS in patients with ypT0/ypT1 or ypN0 tumors (p < 0.05). Both ESOT and ESOP were independent prognostic factors for OS according to multivariate survival analyses. Therefore, accurate pathologic evaluation using ESOP and ESOT is associated with the prognosis in PDAC patients with complete or near-complete pathologic response and ypT0/ypT1 tumor after NAT. Full article
(This article belongs to the Special Issue Histology and Pathology of Pancreatic Cancer)
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15 pages, 1810 KB  
Article
Retrospective Evaluation of the Efficacy of Total Neoadjuvant Therapy and Chemoradiotherapy Neoadjuvant Treatment in Relation to Surgery in Patients with Rectal Cancer
by Lucian Dragoș Bratu, Michael Schenker, Puiu Olivian Stovicek, Ramona Adriana Schenker, Alina Maria Mehedințeanu, Tradian Ciprian Berisha, Andreas Donoiu and Stelian Ștefăniță Mogoantă
Medicina 2024, 60(4), 656; https://doi.org/10.3390/medicina60040656 - 19 Apr 2024
Cited by 2 | Viewed by 2830
Abstract
Background and Objective: In the therapeutic strategy of rectal cancer, radiotherapy has consolidated its important position and frequent use in current practice due to its indications as neoadjuvant, adjuvant, definitive, or palliative treatment. In recent years, total neoadjuvant therapy (TNT) has been [...] Read more.
Background and Objective: In the therapeutic strategy of rectal cancer, radiotherapy has consolidated its important position and frequent use in current practice due to its indications as neoadjuvant, adjuvant, definitive, or palliative treatment. In recent years, total neoadjuvant therapy (TNT) has been established as the preferred regimen compared to concurrent neoadjuvant chemoradiotherapy (CRT). In relation to better outcomes, the percentage of patients who achieved pathological complete response (pCR) after neoadjuvant treatment is higher in the case of TNT. This study aimed to analyze the response to TNT compared to neoadjuvant CRT regarding pCR rate and the change in staging after surgical intervention. Materials and Methods: We performed a retrospective study on 323 patients with rectal cancer and finally analyzed the data of 201 patients with neoadjuvant treatment, selected based on the inclusion and exclusion criteria. Patients received CRT neoadjuvant therapy or TNT neoadjuvant therapy with FOLFOX or CAPEOX. Results: Out of 157 patients who underwent TNT treatment, 19.74% had pathological complete response, whereas in the group with CRT (n = 44), those with pCR were 13.64%. After neoadjuvant treatment, the most frequent TNM classifications were ypT2 (40.30%) and ypN0 (79.10%). The statistical analysis of the postoperative disease stage, after neoadjuvant therapy, showed that the most frequent changes were downstaging (71.14%) and complete response (18.41%). Only four patients (1.99%) had an upstaging change. The majority of patients (88.56%) initially presented clinical evidence of nodal involvement whereas only 20.9% of the patients still presented regional disease at the time of surgical intervention. Conclusions: By using TNT, a higher rate of stage reduction is obtained compared to the neoadjuvant CRT treatment. The post-neoadjuvant-treatment imagistic evaluation fails to accurately evaluate the response. A better response to TNT was observed in young patients. Full article
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14 pages, 3365 KB  
Review
The Role of Adjuvant Radiotherapy in the Treatment of Breast Cancer
by Iveta Kolářová, Bohuslav Melichar, Igor Sirák, Jaroslav Vaňásek, Jiří Petera, Kateřina Horáčková, Denisa Pohanková, Filip Ďatelinka, Zuzana Šinkorová and Milan Vošmik
Curr. Oncol. 2024, 31(3), 1207-1220; https://doi.org/10.3390/curroncol31030090 - 24 Feb 2024
Cited by 9 | Viewed by 12044
Abstract
The role of postmastectomy radiotherapy and regional nodal irradiation after radical mastectomy is defined in high-risk patients with locally advanced tumors, positive margins, and unfavorable biology. The benefit of postmastectomy radiotherapy in intermediate-risk patients (T3N0 tumors) remains a matter of controversy. It has [...] Read more.
The role of postmastectomy radiotherapy and regional nodal irradiation after radical mastectomy is defined in high-risk patients with locally advanced tumors, positive margins, and unfavorable biology. The benefit of postmastectomy radiotherapy in intermediate-risk patients (T3N0 tumors) remains a matter of controversy. It has been demonstrated that radiotherapy after breast-conserving surgery lowers the locoregional recurrence rate compared with surgery alone and improves the overall survival rate. In patients with four or more positive lymph nodes or extracapsular extension, regional lymph node irradiation is indicated regardless of the surgery type (breast-conserving surgery or mastectomy). Despite the consensus that patients with more than three positive lymph nodes should be treated with radiotherapy, there is controversy regarding the recommendations for patients with one to three involved lymph nodes. In patients with N0 disease with negative findings on axillary surgery, there is a trend to administer regional lymph node irradiation in patients with a high risk of recurrence. In patients treated with neoadjuvant systemic therapy and mastectomy, adjuvant radiotherapy should be administered in cases of clinical stage III and/or ≥ypN1. In patients treated with neoadjuvant systemic therapy and breast-conserving surgery, postoperative radiotherapy is indicated irrespective of pathological response. Full article
(This article belongs to the Section Breast Cancer)
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14 pages, 1869 KB  
Article
Different Chemotherapy Regimens and Pathologic Complete Response in Triple-Negative Breast Cancer: An Updated Network Meta-Analysis of Phase 3 Trials
by Fausto Petrelli, Gianluca Tomasello, Maria Chiara Parati, Antonio Ghidini, Michele Ghidini, Karen Borgonovo, Mary Cabiddu, Mara Ghilardi, Roberto Reduzzi, Donatella Gambini, Alberto Zaniboni, Giovanni Faustinelli and Ornella Garrone
Medicina 2024, 60(2), 341; https://doi.org/10.3390/medicina60020341 - 19 Feb 2024
Cited by 2 | Viewed by 6096
Abstract
Background and Objectives: Currently, the standard treatment for non-metastatic triple-negative breast cancer (TNBC) consists of a systemic neoadjuvant (or perioperative) anthracycline plus taxane-based chemotherapy, delivered either sequentially or concomitantly. We performed a network meta-analysis (NMA) to compare the relative efficacy of different [...] Read more.
Background and Objectives: Currently, the standard treatment for non-metastatic triple-negative breast cancer (TNBC) consists of a systemic neoadjuvant (or perioperative) anthracycline plus taxane-based chemotherapy, delivered either sequentially or concomitantly. We performed a network meta-analysis (NMA) to compare the relative efficacy of different neoadjuvant treatments for TNBC in terms of pathologic complete response (pCR). Materials and Methods: The MEDLINE, Embase, and Cochrane databases were searched from database inception to 1 November 2023. Randomized clinical trials were used that enrolled adults with stage I-III TNBC and provided data on pCR defined as residual ypT0/TisN0M0. Between-group comparisons were estimated using risk ratios (RRs) with 95% credible intervals (95% CrIs). The primary outcome was the pCR rate. Results: 1129 citations were screened, and 12 randomized clinical trials were included. In Bayesian comparisons, all regimens, except anthracycline/taxanes plus gemcitabine or capecitabine, resulted in a higher pCR than the standard regimen in both direct and indirect comparisons. In particular, immunotherapy-based regimens resulted in more than double the pCR compared to historical regimens (RR = 2.3, 95% CI 1.9–2.9) and ranked as being the optimal regimen with a probability of 97%. Disease-free survival was better for immune checkpoint inhibitor-based chemotherapy (HR = 0.36, 95% 1.21–2.09) than for historical regimens. Conclusion: This meta-analysis confirmed that incorporating immunotherapy with neoadjuvant platinum-based chemotherapy is the best option to guarantee remarkable pathologic downstaging and improve clinical outcomes. Full article
(This article belongs to the Section Oncology)
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10 pages, 428 KB  
Article
Complete Primary Pathological Response Following Neoadjuvant Treatment and Radical Resection for Pancreatic Ductal Adenocarcinoma
by Kai Tai Derek Yeung, Joseph Doyle, Sacheen Kumar, Katharine Aitken, Diana Tait, David Cunningham, Long R. Jiao and Ricky Harminder Bhogal
Cancers 2024, 16(2), 452; https://doi.org/10.3390/cancers16020452 - 20 Jan 2024
Cited by 1 | Viewed by 2443
Abstract
Introduction: Neoadjuvant treatment (NAT) for borderline (BD) or locally advanced (LA) primary pancreatic cancer (PDAC) is now a widely adopted approach. We present a case series of patients who have achieved a complete pathological response of the primary tumour on final histology following [...] Read more.
Introduction: Neoadjuvant treatment (NAT) for borderline (BD) or locally advanced (LA) primary pancreatic cancer (PDAC) is now a widely adopted approach. We present a case series of patients who have achieved a complete pathological response of the primary tumour on final histology following neoadjuvant chemotherapy +/− chemoradiation and radical surgery. Methods: Patients who underwent radical pancreatic resection following neoadjuvant treatment between March 2006 and March 2023 at a single institution were identified by retrospective case note review of a prospectively maintained database. Results: Ten patients were identified to have a complete primary pathological response (ypT0) on postoperative histology. Before treatment, five patients were considered BD and five were LA according to National Comprehensive Cancer Network guidelines. All patients underwent staging Computed Tomography (CT) and nine underwent 18Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET/CT) imaging, with a mean maximum standardized uptake value (SUVmax) of the primary lesion at 6.14 ± 1.98 units. All patients received neoadjuvant chemotherapy, and eight received further chemoradiotherapy prior to resection. Mean pre- and post-neoadjuvant treatment serum Ca19-9 was 148.0 ± 146.3 IU/L and 18.0 ± 18.7 IU/L, respectively (p = 0.01). The mean duration of NAT was 5.6 ± 1.7 months. The mean time from completion of NAT to surgery was 13.1 ± 8.3 weeks. The mean lymph node yield was 21.1 ± 10.4 nodes, with one patient found to have 1 lymph node involved. All resections were reported to be R0. The mean length of stay was 11.8 ± 6.2 days. At the time of analysis, one death was reported at 35 months postoperatively. Two cases of recurrence were reported at 16 months (surgical bed) and 33 months (pulmonary). All other patients remain alive and under active surveillance. The current overall survival is 26.6 ± 20.7 months and counting. Conclusions: Complete primary pathological response is uncommon but possible following neoadjuvant treatment in patients with PDAC. Further work to identify the common denominator within this unique cohort may lead to advances in the therapeutic approach and offer hope for patients diagnosed with borderline or locally advanced pancreatic ductal adenocarcinoma. Full article
(This article belongs to the Section Clinical Research of Cancer)
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13 pages, 1268 KB  
Article
Independent Stage Classification for Gastroesophageal Junction Adenocarcinoma
by Yuki Hirata, Yi-Ju Chiang, Jeannelyn S. Estrella, Prajnan Das, Bruce D. Minsky, Mariela Blum Murphy, Jaffer A. Ajani, Paul Mansfield, Brian D. Badgwell and Naruhiko Ikoma
Cancers 2023, 15(21), 5137; https://doi.org/10.3390/cancers15215137 - 25 Oct 2023
Viewed by 2671
Abstract
In gastroesophageal junction (GEJ) adenocarcinoma cases, a prognosis based on ypTNM staging could be affected by preoperative therapy. Patients with esophageal adenocarcinoma and gastric adenocarcinoma who underwent preoperative therapy followed by surgical resection from 2006 through 2017 were identified in the National Cancer [...] Read more.
In gastroesophageal junction (GEJ) adenocarcinoma cases, a prognosis based on ypTNM staging could be affected by preoperative therapy. Patients with esophageal adenocarcinoma and gastric adenocarcinoma who underwent preoperative therapy followed by surgical resection from 2006 through 2017 were identified in the National Cancer Database. To enable stage-by-stage OS comparisons, tumors were classified into four gross ypTNM groups: ypT1/2, N-negative; ypT1/2, N-positive; ypT3/4, N-negative; and ypT3/4, N-positive. Prognostic factors were examined, and an OS prediction nomogram was developed for patients with abdominal/lower esophageal and gastric cardia adenocarcinoma, representing GEJ cancers. We examined 25,463 patient records. When compared by gross ypTNM group, the abdominal/lower esophageal and gastric cardia adenocarcinoma groups had similar OS rates, differing from those of other esophageal or gastric cancers. Cox regression analysis of patients with GEJ cancers showed that preoperative chemoradiotherapy was associated with shorter OS than preoperative chemotherapy after adjustment for the ypTNM group (hazard ratio 1.31, 95% CI 1.24–1.39, p < 0.001), likely owing to downstaging effects. The nomogram had a concordance index of 0.833 and a time-dependent area under the curve of 0.669. OS prediction in GEJ adenocarcinoma cases should include preoperative therapy regimens. Our OS prediction nomogram provided reasonable OS prediction for patients with GEJ adenocarcinoma, and future validation is needed. Full article
(This article belongs to the Special Issue Preoperative Chemoradiotherapy for Gastrointestinal Cancer)
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