Neoadjuvant Treatment Research Articles

To evaluate the efficacy and safety of a chemotherapy-free regimen consisting of monoclonal antibody trastuzumab, tyrosine kinase inhibitor pyrotinib and CDK4/6 inhibitor dalpiciclib in patients with hormone receptor-negative/HER2-positive (HR-HER2+) early breast cancer (EBC). This open-label, single-arm, phase II study was designed using the Simon two-stage method (Chi-CTR-2200060748). Patients with operable HR-HER2+EBC (T1-3 and N0-2) were enrolled. Eligible patients received trastuzumab (HLX02, 8mg/kg loading dose, followed by 6mg/kg every 3weeks intravenously), pyrotinib (400mg daily orally) and dalpiciclib (125mg daily orally for 3weeks, followed by 1week off) for 16weeks. Surgery was performed 3-6weeks after the completion of drug treatment. The primary endpoint was total pathological complete response (tpCR, ypT0/Tis, ypN0) rates at surgery, and secondary endpoints included breast pCR (bpCR) rates (ypT0/Tis), residual cancer burden (RCB), objective response rate (ORR), change of Ki-67 scores, survival and safety. Between Jun, 2022, and Jun, 2024, a total of 34 patients with a median age of 55years (range: 35-67) were enrolled. 30 patients received all cycles of treatment and underwent surgery with a median follow-up of 20months. The tpCR was achieved in 19 patients (63.3%; 95% CI, 45.5-78.1%). The bpCR was 66.7% (20/30). The number of patients with RCB-0 or RCB-I was 22 (73.3%). The most common Grade 3 treatment-related adverse events were diarrhea (50.0%), neutropenia (20.6%), and leukopenia (17.7%). No Grade 4 events or treatment-related deaths occurred. In patients with HR-HER2+EBC, the neoadjuvant therapy with trastuzumab, pyrotinib and dalpiciclib has promising activity and manageable toxicity. Further investigation is needed.

Introduction: Colorectal carcinoma is the third most common malignancy worldwide. The main challenge in the surgical treatment of low rectal cancer is achieving optimal oncological and functional outcomes while minimizing complications such as anastomotic leakage, stenosis, local recurrence, and low anterior resection syndrome (LARS). Aim: The aim of this article is to analyze the incidence of complications following low anterior resection of the rectum and the impact of surgical technique, tumor distance from the distal resection margin, neoadjuvant treatment, and the presence of a protective ileostomy. Materials and Methods: Between 2019 and 2025, a total of 51 patients with low anterior resection for rectal carcinoma were studied. Complication rates were compared based on the use of a mechanical stapler, administration of neoadjuvant therapy, creation of a protective ileostomy, and tumor distance from the distal resection margin. Results: A higher incidence of stenosis was observed in patients with coloanal anastomosis, those who underwent neoadjuvant therapy, and in cases with a distal resection margin of 2 cm. Anastomotic leakage occurred more frequently when a mechanical stapler was used, in the absence of a protective ileostomy, and when the distal resection margin was 2 cm from the tumor. Discussion and Conclusion: Low anterior resection of the rectum is an organ-preserving procedure that allows patients to maintain a good quality of life while achieving oncological radicality and satisfactory 5-year survival. Despite advances in surgical techniques and the implementation of a multimodal approach, complications such as stenosis and anastomotic leakage remain significant challenges without a universally accepted management strategy. This topic continues to be the focus of numerous studies aimed at improving treatment outcomes and patients’ quality of life.

Background/Objectives: Management of cancer treatment-induced bone loss (CTIBL) is essential for preserving quality of life among breast cancer (BC) patients receiving endocrine therapy. However, bone-modifying agents (BMAs) remain underused and delayed. In 2014, IRST launched the first bone health outpatient service in Romagna (the eastern area of the Emilia-Romagna region). A multi-centre, retrospective observational study with propensity score matching (PSM) was conducted to evaluate the impact of the IRST organisational model on bone health. Methods: The PSM matched the Emilia-Romagna patients who underwent BC surgery between 2014 and 2022 and were in follow-up in the Romagna area. Patients were grouped as follows: (1) IRST and (2) other Romagna hospitals (without bone health service, i.e., the control group). The matching was based on age, in situ/invasive cancer, and type of early-stage treatment (hormone treatment vs. chemotherapy). Logistic regression and Cox proportional-hazard models assessed factors associated with bone care treatment initiation and timings, respectively. Results: After PSM, we matched 3112 of the 8021 eligible patients into the two cohorts. IRST patients were 39% more likely to receive BMAs (OR: 1.393; 95% CI: 1.236–1.571) and initiated treatment approximately 12 months earlier. We observed that patients with invasive tumours were 77% more likely to initiate bone therapy than those with in situ tumours (OR: 1.766; 95% CI: 1.237–2.585). The early initiation of bone health therapy was influenced by age (p < 0.001) and neoadjuvant chemotherapy treatment (p < 0.001). Conclusions: The IRST model demonstrates responsiveness to bone health needs in BC patients and may be implemented elsewhere to support integrated CTIBL care.

Long-term Results from the LEA Randomized Trial: Extended Versus Standard Lymph Node Dissection in Patients with Bladder Cancer Undergoing Radical Cystectomy.

To predict histologic grade of soft tissue sarcoma (STS) with preoperative ultrasound images, aiding in the selection of personalized treatment plans and improving long-term prognosis. In total, 238 patients with histologically proven STS were retrospectively enrolled from April 2016 to December 2023 and divided into the training and internal validation cohorts. 70 patients were prospectively enrolled from three centers between January 2024 and December 2024 as the external validation cohort. Radiomics features were extracted from preoperative grayscale ultrasound images. The dynamic nomogram (DynNom) was developed by using multivariable logistic regression analysis. Predictive performance was evaluated with the receiving operating characteristic curve, calibration curve, Hosmer-Lemeshow test, decision curve analysis (DCA), and clinical impact curve (CIC). The DynNom based on clinical-US characteristics (metastasis status, echogenicity, fascia layer, and vascularity) and radiomics features yielded an optimal AUC of 0.915 (95% CI, 0.873-0.947), 0.87 (95% CI, 0.79-0.93), and 0.90 (95% CI, 0.80-0.96) for predicting the STS histologic grade in the training, internal and external validation cohorts, respectively. The DynNom outperformed the conventional model and radiomics model (P < 0.05). Calibration curves and Hosmer-Lemeshow tests indicated its satisfactory calibration ability. DCA confirmed that the DynNom outperformed other models in overall net benefit, meanwhile CIC suggested that the DynNom had great clinical applicability in predicting histologic grade. The dynamic nomogram is a practical tool that could predict the histologic grade of STS, which might help clinicians to screen histologic high-grade STSs as neoadjuvant treatment candidates. The dynamic nomogram had the potential to accurately predict histologic grade in STS patients before surgery. High-risk patients defined by the dynamic nomogram were potential candidates for preoperative radiotherapy and neoadjuvant chemotherapy.

Patients with HER2-low breast cancer (BC) may be eligible for trastuzumab-deruxtecan (T-DXd) treatment. However, studies have shown that different HER2 antibodies vary in their sensitivity for low HER2 expression, potentially impacting HER2-low BC diagnosis and patient selection for T-DXd. We investigated the frequency of HER2-low BC in relation to the HER2-antibody used across Dutchpathology laboratories. Patients with primary BC without neoadjuvant treatment, diagnosed between 2013 and 2024, were included. HER2-low frequencies from 34 laboratories were obtained from the Dutch Nationwide Pathology Databank (Palga). Additional information (e.g., type of HER2 antibody, staining protocol) was obtained through a questionnaire. A total of 88,713 patients were included, representing 103,505 tumors, of which 94,934 had a conclusive HER2 status. Among non-amplified cases, HER2-low frequencies varied widely across laboratories (33.4%-94.5%), with a gradual increase since 2022. The most commonly used antibody clones were 4B5 (n = 21), DG44 (n = 7), A0485 (n = 4), and SP3 (n = 2). HER2-low proportions were highest with A0485 (71.5%), followed by DG44 (66.7%), SP3 (60.1%), and 4B5 (59.1% with Ultraview, 57.0% with Optiview). Substantial inter-laboratory variation was observed even within the same antibody group (4B5/Ultraview: 40.5%-80.4%; 4B5/Optiview: 37.3%-68.4%; DG44: 40.6%-95.4%; A0485: 62.3%-94.7%; SP3: 31.6%-78.6%). Our data showed a notable variation in HER2-low BC frequency across Dutch pathology laboratories, even among those using the same antibody and detection system. These differences may influence patient eligibility for T-DXd.

ASO Visual Abstract: Accuracy of PET-CT to Assess the Extent of Nodal Disease in Patients with Clinical Stage III Melanoma Following Neoadjuvant Treatment.

Neoadjuvant systemic therapy may enhance ocular and visual preservation, also prolonging life in patients with choroidal melanoma. We investigated how many choroidal melanomas would be eligible for such treatment to enable Ruthenium-106 brachytherapy. The cohort comprised 5859 patients treated for choroidal melanoma at the Liverpool Ocular Oncology Centre between 1993 and 2023. If the objective is ocular conservation, then, after excluding tumors > 16 mm in diameter, involving disc and/or more than two clock hours of angle or iris, and/or extending extraocularly, approximately 60.5%, 65.1%, and 67.6% of patients would remain eligible for neoadjuvant systemic therapy, according to whether the maximum allowable tumor thickness is 8 mm, 10 mm or 12 mm, respectively. If the objective is preservation of 20/80 vision, and if exclusion criteria also include vision worse than 20/80 and tumor extension to within 3 mm of optic disc and/or fovea, then 31.0%, 33.2% and 34.1% of tumors would remain in the three tumor-thickness groups, respectively. Chromosome 3 loss would be found in approximately 33%, 52% and 56% of tumors measuring 11-12 mm, 13-14 mm and >14 mm, respectively. Based on the provided data and with effective neoadjuvant treatment, approximately two thirds of subjects with choroidal melanoma requiring enucleation could potentially become candidates for ruthenium-106 brachytherapy and as many as one third could also have the potential for preservation of useful vision.

Breast cancer remains a significant public health concern, and neoadjuvant therapy has significantly reconfigured the landscape of its clinical management. The intricate characteristics of the tumor microenvironment (TME) have profound implications for tumor development and therapeutic responses. Thus, understanding the dynamics of the TME during treatment is crucial. Advancements in molecular biology research, such as single-cell analysis and spatial omics technologies, provide valuable tools for investigating the complexities of the breast cancer microenvironment. These innovative approaches facilitate the identification of cellular heterogeneity, spatial interactions, and altered signaling pathways, illuminating the TME's adaptive mechanisms in response to neoadjuvant therapy. In this review, we first elucidate the current status of neoadjuvant therapy in breast cancer. Subsequently, we outline cutting-edge molecular biology research methods and their applications within the breast cancer microenvironment. Finally, we provide an overview of the alterations in the components of the tumor microenvironment during neoadjuvant treatment for breast cancer, focusing on insights gained from single-cell analysis and spatial pathology.

Background: Breast cancer screening and effective neoadjuvant treatments have increased surgeries for nonpalpable tumors, often requiring preoperative localization. The wire-guided method, performed on the same day as surgery, has limitations, prompting interest in wire-free alternatives like magnetic seed devices.Methods: A retrospective single-center study (November 2020–March 2024) compared magnetic seed and wire-guided localization in 558 patients. The primary aim was to assess localization and retrieval success, resection margins, and reoperation rates. Secondary endpoints included the interval between localization and surgery, operative time, incision site selection, and volume excised.Results: Among 558 patients, 188 underwent magnetic seed and 370 wire-guided localizations. Both groups were similar in BMI, breast size, and lesion characteristics. Complications in the wire-guided group included device migration (0.5%) and hematoma (1.3%). Success rates were comparable (98.9% vs. 99.7%), as were positive margins (5.3% vs. 6.7%) and reoperation rates (6.9% vs. 7.8%). Excised volume was significantly lower in the magnetic seed group (24.2 [range 6.5–48.0 cm3] vs. 41.5 cm3 [range 16.0–68.0 cm3], p < 0.001). The magnetic seed group had an average localization-to-surgery interval of 1 day (range 0–160 days).Conclusions: Magnetic seed localization is as safe and effective as wire-guided localization, with comparable success rates and resection margins adequacy. Its primary advantage is scheduling flexibility, offering a longer interval between localization and surgery.

Rectal cancer radiotherapy: 2025 update.

To evaluate the association between the KRAS mutational load and the histologic tumor response in patients with resectable pancreatic ductal adenocarcinoma (PDAC) who received neoadjuvant treatment (NAC) with pegylated liposomal irinotecan in combination with oxaliplatin, 5-fluorouracil, and leucovorin (NALIRIFOX). This was a multicenter, single-arm, interventional, open-label, phase 2 trial in patients 18 years or older who had histologically or cytologically confirmed PDAC and were candidates for surgery and received neoadjuvant NALIRIFOX. The primary outcome was determination of the association between the KRAS mutational load and the histologic tumor response after chemotherapy. Twenty patients were included in the study. Before initiating NAC, 11 patients were KRAS+, 6 were KRAS-, and 3 were not evaluable for KRAS mutation status. Eight of the 11 (72.7%) patients changed from KRAS+ at baseline to KRAS- after treatment, and none of the 6 (0.0%) patients changed from KRAS- at baseline to KRAS+ after treatment. A good histopathologic response after NAC was observed in 3 (15%) of the 20 patients, with a greater proportion of good responses among patients who were KRAS- (3 out of 16 [18.8%]) than among those who were KRAS+ (0 out of 1 [0.0%]) after NAC, although the differences were not statistically significant (P=0.633). Our results indicate that patients with potentially resectable PDAC tend to have detectable KRAS in the blood if the disease is locally more advanced and that most patients who are treated with neoadjuvant NALIRIFOX are negative for KRAS at the end of therapy.

Background: Multidisciplinary Tumor Councils (MDTs) are vital platforms that provide tailored treatment plans for cancer patients by combining expertise from various medical disciplines. Recently, Artificial Intelligence (AI) tools have been investigated as decision-support systems within these councils. Methods: In this prospective study, the compatibility of AI (ChatGPT-4.0) with MDT decisions was evaluated in 100 cancer patients presented to the tumor council between November 2024 and January 2025. AI-generated treatment recommendations based on anonymized, detailed clinical summaries were compared with real-time MDT decisions. Cohen’s Kappa and Spearman correlation tests were used for statistical analysis. Results: Neoadjuvant treatment (45%) and surgery (36%) were the most frequent MDT decisions. AI recommended surgery (39%) and neoadjuvant treatment (37%) most frequently. A high concordance rate of 76.4% was observed between AI and MDT decisions (κ = 0.764 [95% CI; 0.658–0.870] p < 0.001, ρ = 0.810 [95% CI; 0.729–0.868], p < 0.001). Most inconsistencies arose in cases requiring individualized decisions, indicating AI’s current limitations in incorporating contextual clinical judgment. Conclusion: AI demonstrates substantial agreement with MDT decisions, particularly in cases adhering to standardized oncological guidelines. However, for AI integration into clinical workflows, it must evolve to interpret real-time patient data and function transparently within ethical and legal frameworks.

To further standardize lung cancer prevention and treatment measures in China, enhance the quality of diagnosis and treatment, improve patient prognosis, and provide evidence-based medical guidance for clinicians at all levels, the Chinese Medical Association convened experts from respiratory medicine, oncology, thoracic surgery, radiotherapy, imaging, and pathology to develop the Chinese Medical Association's Clinical diagnosis and treatment guidelines for lung cancer (2025 edition). This consensus resulted in several updates from the 2024 version. In the screening section, a new recommendation has been added to specify populations not advised to undergo lung cancer screening. It also emphasizes that individuals at high risk for lung cancer should be fully informed of the potential benefits and risks of low-dose CT (LDCT) screening before undergoing the examination. With the advancement of treatment options, updates have been made to the recommended genetic testing for patients with early-and mid-stage postoperative and advanced non-small cell lung cancer (NSCLC). For patients with advanced EGFR mutations, in addition to a broader range of monotherapy options, the application of combination therapies may offer better disease control for certain patients. Furthermore, more treatment options have been approved for patients undergoing immunotherapy-based neoadjuvant treatment and for those who develop resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI). For patients with previously limited treatment options, such as those with KRAS G12C mutations, HER2 mutations, or small cell lung cancer after resistance develops, the approval of novel drugs has brought significantly improved efficacy and prognosis. These recommendations are based on State-approved drug applications, international guidelines, and current clinical practices in China, integrating the latest evidence-based medical research in screening, diagnosis, pathology, genetic testing, immune molecular marker detection, treatment methods, and follow-up care. The goal is to provide comprehensive and reasonable recommendations for clinicians, imaging specialists, laboratory technicians, and other medical staff at all levels.

BackgroundOur study represents the first effort in the Eastern Mediterranean Region to identify disparities in the quality of colorectal cancer (CRC) care in Iran.MethodsWe established a collaborative registry program for non-metastatic CRC patients to evaluate survival rates between teaching cancer centers (TCCs) and a high-volume, non-teaching, non-cancer center (NTNC). The study included a diverse patient population and considered various factors such as cancer stage, margin involvement, adherence to guidelines for adjuvant and neoadjuvant treatments, emergency surgeries, socioeconomic status, and risk of surgery. We utilized a multivariate Cox regression model and the targeted maximum likelihood estimator (TMLE) to analyze survival disparities in colorectal cancer between TCCs and the NTNC.ResultsWe recruited 668 CRC patients, including 320 with colon cancer and 298 with rectal cancer. Patients who underwent surgery at teaching cancer centers (TCCs) displayed significantly higher quality of care and better outcomes than those treated at the non-teaching, non-cancer center (NTNC). The adjusted hazard ratios (HR) were 1.97 (95% CI 1.21–3.21) for colon cancer and 1.54 (95% CI 1.01–2.55) for rectal cancer. Additionally, we observed significant causal mortality risk ratios (RR) based on hospital type for overall colorectal cancer (RR = 1.42, 95% CI 1.12–1.81) and specifically for colon (RR = 1.48, 95% CI 1.04–2.11) and rectum cancer (RR = 1.39, 95% CI 1.01–2.02).ConclusionThe survival disparities in colon and rectal cancers between TCCs and NTNCs highlight a significant gap in CRC care in Iran. It is essential to expand this study nationally and implement the knowledge and experiences from TCCs in other hospitals to improve the quality of care and enhance patient outcomes.

ObjectiveThe present research aimed to evaluate the diagnostic performance of a magnetic resonance imaging (MRI)-based radiomics model for predicting lymph node staging in patients with stage T3 rectal cancer (RC).MethodsThis retrospective study included 225 patients with RC who underwent surgical resection without neoadjuvant therapy treatment. Radiomics features were extracted from high-resolution T2-weighted imaging (T2WI) of primary tumor. Feature selection was performed using the least absolute shrinkage and selection operator (LASSO) algorithm. Five machine learning classifiers were employed to construct radiomics signatures differentiating between N0/N1 (low nodal burden) and N2 (high nodal burden) stages prediction in the training cohort. The predictive performance of each classifier was evaluated using receiver operating characteristic curve analysis, with area under the curve (AUC) comparisons conducted via DeLong’s test. Decision curve analysis (DCA) and calibration curves were utilized to assess the clinical utility and calibration performance of the developed models, respectively.ResultsA total of 1,746 radiomics features were extracted from the imaging data, of which 16 features were selected to construct a radiomics signature for lymph node staging in RC. The logistic regression classifier demonstrated the best predictive performance, achieving an AUC of 0.900 [95% confidence interval (CI), 0.848–0.952] in the training cohort. The model’s robustness was further validated in the test cohort, with an AUC of 0.876 (95% CI, 0.765–0.986). DCA confirmed the clinical utility of the model.ConclusionsThe radiomics model based on high-resolution T2WI provided an effective and noninvasive approach for preoperatively differentiating between N0/1 and N2 stages in stage T3 RC.

Prognostic factors for very early recurrence after neoadjuvant treatment and curative resection in pancreatic ductal adenocarcinoma.

In patients scheduled for breast-conserving surgery (BCS) after neoadjuvant chemotherapy, the primary mass is marked with a metallic clip. A comparative study was conducted to determine the efficacy and safety of tattoo application as an alternative to this invasive procedure. Forty patients (clip: 20, tattoo: 20) after neoadjuvant chemotherapy, in the group marked with clips, nonpalpable patients were marked with wire, and BCS was performed; in the tattoo group, BCS was performed with the skin containing the tattoo. All statistical analyses was performed using Statistical Package for the Social Sciences version 25.0 (IBM Corp., Armonk). The study was ultimately completed with a total of 40 patients, comprising 20 patients in each group. In comparison to the standard method, the effect size of our study in reducing complications was d = 0.5, and the power was 88%. This power analysis demonstrates that the necessary number of targeted patients has been successfully reached. There were no significant differences between the groups in terms of demographic and clinicopathological features in the 40 patients included in the study (P > .05). The radiological distance of the tumor to the skin was significantly lower in the group of patients who were marked with the tattoo technique than in the group of patients who underwent clipping (tattoo: 15.7 ± 7.4 vs clip: 20.7 ± 9.5) (P = .045). Reexcision requirement was lower in the tattoo group (35% vs 15%, P = .273). All 4 patients whose surgical margin closeness of the tumor was found to 1 to 2 mm, were in the clip group (P = .106). Complications (hematoma/ecchymosis) were observed in 6 (15%) patients in the clip group, and pain was observed in 5 (12.5%) patients. All patients with complications were included in the clip-marked group. Clip migration was observed in 3 (15%) of the patients. No complications were observed in the tattoo group. Tattooing, which is an alternative to the method of marking the mass with metallic clips (accepted as the standard today) before neoadjuvant treatment, is an easy and inexpensive method with fewer complications.

The presence of androgen receptor (AR) as a marker can be detected in all breast cancer subtypes, and it may provide information on treatment response and prognosis. This study aimed to examine the correlation between AR expression and treatment response in patients diagnosed with human epidermal growth factor receptor 2 (HER2) positive breast cancer who were undergoing neoadjuvant therapy (NAT). The evaluation included breast cancer patients who received NAT and underwent surgery at Weifang People's Hospital's Department of Breast Surgery between October 2019 and October 2022. We examined and compared the clinical and pathological factors between patients who achieved a pathological complete response (pCR) and those who did not. Statistical methods: The statistical analysis was conducted utilizing SPSS 17.0 software. Univariate and multivariable analyses were employed to establish the association between each variable and pCR. Independent variables included in the multivariable analyses were those factors deemed significant (P < .05) in the chi-square test of univariate analysis. Variables with a P-value < 0.05 were regarded as being independent influencing factors. Survival curves were generated using the Kaplan-Meier method. A total of 63 patients were included, all of whom had received NAT, with an overall pCR rate of 31.7%. pCR was positively correlated with AR positivity (OR = 0.105 [95% CI = 0.012~0.939], P = .044) and high density of tumor-infiltrating lymphocytes (TILs) (OR = 0.134 [95% CI = 0.031~0.586], P = .008). Receiver operating characteristic (ROC) curves had been plotted to assess the predictive value of AR expression and the density of TILs for pCR, with areas under the curves being 0.661 (95% CI = 0.573-0.749, P = .044) and 0.716 (95% CI = 0.606-0.825, P = .008), respectively. Potential biomarkers for pCR in HER2-positive breast cancer patients receiving NAT may include the expressions of AR and TILs.

The association of preneoadjuvant maximal standardized uptake value (SUVmax) and postneoadjuvant change in maximal standardized uptake value on 18-fluorodeoxyglucose positron emission tomography with survival after esophagectomy for cancer.