Rectal adenocarcinoma: Ex vivo 9.4T MRI-correlation with histopathologic treatment response to neoadjuvant chemoradiotherapy.

OBJECTIVES: To determine the imaging details and diagnostic information of the treatment response to neoadjuvant chemoradiotherapy (nCRT) of rectal adenocarcinoma at 9.4T magnetic resonance imaging (MRI) by ex vivo. METHODS: Fifteen cases with locally advanced rectal cancer (LARC) followed by radical surgery after nCRT between September 2022 and February 2023 were recruited. Resected specimens were fixed in a perfluoropolyether-filled test tube and scanned with a 3.0T and 9.4T MRI system ex vivo. The residual tumor depth and MRI-based tumor regression grade (TRG) were subjectively assessed and then compared with the pathological findings. RESULTS: The ex vivo 9.4T T2WI without fat suppression clearly differentiated tumor tissue, fibrosis and normal rectal wall, which clearly corresponded to the pathologic tissues of the rectal specimens. The TRG could be accurately assessed on ex vivo 9.4T images in 13/15 specimens (86.7%), while in 11/15 specimens (73.3%) on ex vivo 3.0T images. CONCLUSION: Ex vivo 9.4T MR imaging clearly displayed the components of rectal wall and proved excellent diagnostic performance for evaluating the treatment response to nCRT, which allow radiologists to understand and then assess more accurately the TRG of LARC after nCRT.

Immune checkpoint regulation is critically involved in canine cutaneous histiocytoma regression.

Introduction: Canine cutaneous histiocytoma (CCH) is a benign tumor frequently occurring in young dogs which is derived from Langerhans cells (LC). Distinguishing features of this tumor are its spontaneous regression following a rapid tumor growth. Impaired control of immune checkpoints during tumor development and progression is a widespread phenomenon which may result in an absent or ineffective immune response. The interaction between the inflammatory response and the expression of immune checkpoint molecules is only partially described in this tumor type. The aim of this study was to identify immune checkpoint molecules and molecules from the interferon-mediated immune response that are involved in the regression of CCH. Methods: Forty-eight CCH derived from dogs ≤ 4 years of age were assigned to one of four groups according to the severity and distribution of lymphocyte infiltration. Using immunohistochemistry and whole-slide image scans of consecutive sections the expression of programmed death protein ligand 1 (PD-L1), CD80, CD86, Survivin, forkhead box protein 3, Ki-67, cleaved caspase-3, CD3, and mx1 were investigated. RNA in-situ hybridization was performed for transcripts of mx1 and interferon-γ. Results: Neoplastic cells showed an expression of PD-L1, CD80, CD86, and Survivin. The density of CD80 expressing cells was negatively correlated with regression while the density of cleaved caspase-3 positive cells increased with regression. Mx1 transcripts and protein were predominantly localized in neoplastic cells while interferon-γ transcripts were most frequently detected in T-cells. Conclusion: The expression of the immune checkpoint molecules CD86 and PD-L1 and particularly the reduced expression of CD80 in groups 3 and 4 indicate an influence of the investigated immune checkpoints on tumor regression. In parallel an activation of the apoptotic cascade during regression is suggested. Finally, the detection of mx1 within the neoplasm pinpoints to a yet undisclosed role of anti-cellular signaling in tumor immunity.

Regression of cardiac angiosarcoma in a 17-year-old: a percutaneous biopsy effect.

BACKGROUND: Cardiac angiosarcoma is a very rare and aggressive primary cardiac tumor associated with poor prognosis. Diagnosis is often delayed due to non-specific symptoms, with most cases involving metastases at the time of diagnosis. We describe a unique case of apparent tumor regression of cardiac angiosarcoma post percutaneous biopsy. CASE PRESENTATION: A young male was admitted with suspected pericarditis. Echocardiogram revealed a pericardial mass. Cardiovascular magnetic resonance (CMR) suggested primary cardiac malignancy. Percutaneous biopsy was inconclusive, with subsequent CMR demonstrating apparent tumor regression. Interval imaging revealed further tumor growth, and surgical biopsy revealed primary cardiac angiosarcoma (PCAS). Causes of tumor regression following percutaneous biopsy are discussed. CONCLUSIONS: Cases of suspected primary cardiac malignancy require careful follow up with serial multimodality imaging. Percutaneous biopsy effects should be considered in cases of tumor regression, and serial imaging should be planned afterwards.

Tumor regression following autologous tumor lysate-loaded dendritic cell vaccination immunotherapy: illustrative case.

BACKGROUND: Despite years of research, the standard of care (SOC) treatment for grade 4 glioma has remained virtually unchanged for the last 2 decades. Autologous tumor lysate-loaded dendritic cell vaccination (DCVax-L), a novel immunotherapy, has demonstrated a significant survival benefit in a phase 3 trial. OBSERVATIONS: A 34-year-old male presented with episodes of lightheadedness and was subsequently diagnosed with a large fronto-insulo-temporal tumor, likely to be high grade. He underwent an asleep craniotomy for debulking, with a residual tumor noted in the frontal lobe and amygdala. Tumor histopathology was reported as isocitrate dehydrogenase (IDH) mutant methylated grade 4 astrocytoma. He received SOC treatment, alongside a course of DCVax-L. Surveillance imaging showed cystic transformation followed by a reduction in size of the residual tumor in the frontal lobe; the residual in the amygdala had regressed entirely. The patient remained clinically well and had returned to his preoperative functionality. LESSONS: The authors report a patient with grade 4 astrocytoma who received DCVax-L treatment in addition to SOC adjuvant therapy. The pattern and extent of tumor regression are highly unusual and atypical for what is seen or expected with adjuvant SOC treatment alone. The addition of DCVax-L to SOC opens new avenues in the management of this difficult disease. https://thejns.org/doi/10.3171/CASE24112.

Nomograms to predict tumor regression grade (TRG) and ypTNM staging in patients with locally advanced esophageal cancer receiving neoadjuvant therapy.

BACKGROUND: Neoadjuvant therapy (NT) has increased survival rates for patients with locally advanced esophageal cancer (EC), but estimating the impact of NT treatment prior to surgery is still very difficult. METHODS: A retrospective study of the clinical information of 150 patients with locally advanced EC who got NT at Qilu Hospital of Shandong University between June 2018 and June 2023. Patients were randomized into training and internal validation groups at a 3:1 ratio. Furthermore, an external validation cohort comprised 38 patients who underwent neoadjuvant therapy at Qianfoshan Hospital in the Shandong Province between June 2021 and June 2023. Independent risk factors were identified using univariate and multivariate logistic regression (forward stepwise regression). Predictive models and dynamic web nomograms were developed by integrating these risk factors. RESULTS: A total of 188 patients with locally advanced EC were enrolled, of whom 118 achieved stage I of neoadjuvant pathologic TNM (ypTNM) after receiving NT and 129 achieved grades 0-1 in the tumor regression grade (TRG). Logistic regression analysis identified five independent predictors of TRG grades 0-1: pulmonary function tests (PFT), prognostic nutritional index (PNI), triglyceride (TG) levels, squamous cell carcinoma antigen (SCC-Ag) levels, and combination immunotherapy. The areas under the receiver operating characteristic (ROC) curves for the training, internal validation, and external validation groups were 0.87, 0.75, and 0.80, respectively. Meanwhile, two independent predictors of stage I of ypTNM were identified: prealbumin (PA) and SCC antigen. The areas under the ROC curves for the training, internal validation, and external validation groups were 0.78, 0.67, and 0.70, respectively. The Hosmer-Lemeshow test for both predictive models showed excellent calibration, with well-fitted calibration curves. Decision curve analysis (DCA) and clinical impact curves (CIC) have demonstrated that nomograms are of clinical utility. CONCLUSION: The nomograms performed well in predicting the likelihood of stage I of ypTNM and TRG grade 0-1 after NT in patients with locally advanced EC. It helps thoracic surgeons to predict the sensitivity of patients to NT before surgery, which enables precise treatment of patients with locally advanced EC.

Clinical and genetic characteristics of patients with TRG 0 and TRG III in esophageal squamous cell carcinoma after neoadjuvant therapy.

Neoadjuvant therapy (NAT) is an important treatment for patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC), but neoadjuvant resistance affects the overall treatment outcome. Therefore, it is particularly important to accurately screen the population for NAT and explore the mechanism of resistance. Usually, different chemotherapy regimens cause different drug resistance mechanisms. Prior to combining immunotherapy with chemotherapy, extensive research has been conducted on previous drug resistance mechanisms. Currently, the mainstream NAT for ESCC involves chemotherapy combined with immunotherapy. We have witnessed the remarkable effect of this combination therapy; however, there are still a considerable number of patients whose tumor tissues show no change or even progress after NAT, and their drug resistance mechanisms remain unclear. Hence, we aim to identify relevant evidence that can distinguish and predict the effectiveness of NAT from a clinical perspective in order to provide a clinical basis for future screening of suitable populations for NAT and discovery of drug resistance mechanisms. This study is based in China's high incidence area of esophageal cancer, where enrolled patients all receive the current mainstream NAT regimen resulting in more reliable outcomes.

Spontaneous Tumor Regression and Reversion: Insights and Associations with Reduced Dietary Phosphate.

Tumors that spontaneously shrink from unknown causes in tumor regression, and that return to normal cells in tumor reversion, are phenomena with the potential to contribute new knowledge and novel therapies for cancer patient survival. Tumorigenesis is associated with dysregulated phosphate metabolism and an increased transport of phosphate into tumor cells, potentially mediated by phosphate overload from excessive dietary phosphate intake, a significant problem in Western societies. This paper proposes that reduced dietary phosphate overload and reregulated phosphate metabolism may reverse an imbalance of kinases and phosphatases in cell signaling and cellular proliferation, thereby activating autophagy in tumor regression and reversion. Dietary phosphate can also be reduced by sickness-associated anorexia, fasting-mimicking diets, and other diets low in phosphate, all of which have been associated with tumor regression. Tumor reversion has also been demonstrated by transplanting cancer cells into a healthy microenvironment, plausibly associated with normal cellular phosphate concentrations. Evidence also suggests that the sequestration and containment of excessive phosphate within encapsulated tumors is protective in cancer patients, preventing the release of potentially lethal amounts of phosphate into the general circulation. Reducing dietary phosphate overload has the potential to provide a novel, safe, and effective reversion therapy for cancer patients, and further research is warranted.

Significance of Nutritional-Inflammatory Index as Predictors for Total Neoadjuvant Therapy-Induced Tumor Regression in Locally Advanced Rectal Cancer Patients.

Purpose: To evaluate the predictive capacity of the nutritional-inflammatory index and clinicopathological characteristics in patients with locally advanced rectal cancer (LARC) receiving total neoadjuvant therapy (TNT). Methods: Data from 127 patients with LARC receiving TNT from January 2017 to January 2021 were retrospectively analyzed. Clinicopathological characteristics with different TNT-induced responses were compared. The Chi-square test and the Mann-Whitney test were used to analyze the association between pre-TNT factors and TNT-induced responses. Multivariable logistic regression analysis was used to construct a predictive model. Results: In the cohort of 127 patients with LARC who underwent total neoadjuvant therapy (TNT), the mean age was 54.1 ± 11.4 years; 88 (69.3%) were male. Seventy patients (55.1%) exhibited a favorable response to TNT, while 57 patients (44.9%) demonstrated a poor response. Tumor characteristics, including diameter, distance from the anal verge, pre-TNT lymphocyte, pre-TNT hemoglobin, CA199, PLR, and HALP, exhibit correlations with TNT-induced tumor regression. Multivariate logistic regression analysis identified large tumor diameters (> 5.0 cm; p = 0.005, HR 2.958; 95% CI 1.382-6.335) and low HALP (≤ 40; p = 0.002, HR 0.261; 95% CI 0.111-0.612) as predictors of TNT-induced poor responses. Additionally, low levels of HALP were associated with an increased risk of recurrence in patients with LARC with TNT, but this was not statistically significant (p = 0.087, HR 2.008, 95% CI 0.906-4.447). Conclusion: A large tumor diameter and low HALP predict poor tumor regression induced by the CAPOX-based TNT regimen in patients with LARC.

Recent studies have shown that total neoadjuvant therapy (TNT) is becoming a key treatment for some people with advanced rectal cancer. However, there's still a lot we do not know about what affects how well patients respond to this treatment. The aim of this study was to see if certain nutritional and inflammatory measures, along with other clinic characteristics, can predict how well patients with advanced rectal cancer will respond to TNT. We looked back at medical records from 127 patients who received TNT between 2017 and 2021. We examined how certain pre-treatment factors were linked to patients' responses to the therapy. Certain tumor characteristics and blood test results were connected to how well the tumors responded to treatment. Specifically, patients with larger tumors (over 5 cm in diameter) and lower levels of a specific blood marker called HALP were more likely to have a poor response to treatment. Although low HALP was also linked to a higher chance of the cancer coming back, this result was not strong enough to be certain about.

Prognostic analysis of rectal cancer patients after neoadjuvant chemoradiotherapy: different prognostic factors in patients with different TRGs.

PURPOSE: The extent of tumor regression varies widely among locally advanced rectal cancer (LARC) patients who receive neoadjuvant chemoradiotherapy (NCRT) followed by total mesorectal excision (TME). The purpose of this retrospectively study is to assess prognostic factors in LARC patients with NCRT, and further to analyze survival outcomes in patients with different tumor regression grades (TRGs). METHODS: This study includes LARC patients who underwent NCRT and TME at our institution. We retrospectively analyzed the clinicopathological characteristics and survival of all patients, and performed subgroup analysis for patients with different TRGs. Survival differences were compared using the Kaplan-Meier method and the log rank test. Additionally, a multiple Cox proportional hazard model was used to identify independent prognostic factors. RESULTS: The study included 393 patients, with 21.1%, 26.5%, 45.5%, and 6.9% achieving TRG 0, TRG 1, TRG 2, and TRG 3, respectively. The overall survival (OS) rate and disease-free survival (DFS) rate for all patients were 89.4% and 70.7%, respectively. Patients who achieved TRG 0-3 had different 5-year OS rates (96.9%, 91.1%, 85.2%, and 68.8%, P = 0.001) and 5-year DFS rates (80.8%, 72.4%, 67.0%, 55.8%, P = 0.031), respectively. Multivariate analyses showed that the neoadjuvant rectal (NAR) score was an independent prognostic indicator for both overall survival (OS) (HR = 4.040, 95% CI = 1.792-9.111, P = 0.001) and disease-free survival (DFS) (HR = 1.971, 95% CI = 1.478-2.628, P ˂ 0.001). In the subgroup analyses, the NAR score was found to be associated with DFS in patients with TRG 1 and TRG 2. After conducting multivariate analysis, it was found that ypT stage was a significant predictor of DFS for TRG 1 patients (HR = 4.384, 95% CI = 1.721-11.168, P = 0.002). On the other hand, ypN stage was identified as the dominant prognostic indicator of DFS for TRG 2 patients (HR = 2.795, 95% CI = 1.535-5.091, P = 0.001). However, none of these characteristics was found to be correlated with survival in patients with TRG 0 or TRG 3. CONCLUSION: NAR score, in particular, appears to be the most powerful prognostic factor. It is important to consider various prognostic predictors for patients with different TRGs.

Prognostic value of tumor regression grade (TRG) after oncological gastrectomy for gastric cancer.

PURPOSE: Perioperative chemotherapy combined with surgical resection represent the gold standard in the treatment of locally advanced gastric cancer. The Mandard tumor regression score (TRG) is widely used to evaluate pathological response to neoadjuvant treatment. The aim of this study was to assess the prognostic value of TRG in terms of overall survival (OS) and disease-free (DFS). METHODS: Retrospective analysis of all consecutive patients who underwent oncological gastrectomy after neoadjuvant chemotherapy from January 2007 to December 2019 for gastric adenocarcinoma was performed. Based on their TRG status they were categorized into two groups: good responders (TRG 1-2) and poor responders (TRG 3-5). Subsequent multivariable analyses were conducted. RESULTS: Seventy-four patients were included, whereby 15 (20.3%) were TRG 1-2. Neoadjuvant regimens for TRG 1-2 vs. TRG 3-5 were similar: MAGIC (53% vs. 39%), FLOT (40% vs. 36%), FOLFOX (7% vs. 15%, p = 0.462). Histologic types according to Lauren classification for TRG 1-2 vs. TRG 3-5 were: 13% vs. 29% intestinal, 53% vs. 44% diffuse and 34% vs. 27% indeterminate (p = 0.326). TRG 1-2 group exhibited significantly less advanced ypT (46% vs. 10%, p = 0.001) and ypN stages (66% vs. 37%, p = 0.008), alongside a diminished recurrence rate (20% vs. 42%, p = 0.111). The 3-year DFS was significantly better in this group (81% vs. 47%, p = 0.041) whereas the disparity in three-year OS (92% vs. 55%, p = 0.054) did not attain statistical significance. CONCLUSIONS: TRG 1-2 was associated with less advanced ypT and ypN stage and better DFS compared to TRG 3-5 patients, without a significant impact on OS.

Role of pathological tumor regression grade of lymph node metastasis following neoadjuvant chemotherapy in locally advanced gastric cancer.

AIMS: To confirm whether the pathological response of lymph node metastasis (LNM) to neoadjuvant chemotherapy (NCT) can predict the prognosis of patients with gastric cancer (GC). METHODS: A total of 979 patients with locally advanced GC were included. χ2 test was used to analyze the relationship between LNM TRG and clinicopathological factors. Cox proportional hazards model was used to analyze the relationship between LNM TRG, clinicopathological factors, and overall survival (OS). RESULTS: A total of 21,162 lymph nodes were evaluated, with 237 patients (35.4%) in the response group and 433 patients (64.6%) in the non-response group. The non-responsive group was strongly associated with higher ypT, ypN, ypTNM, primary tumor (PT) TRG (all p < 0.001), positive cancer nodules (p = 0.001), and more distant LNM location (p < 0.001). Patients with the same PT TRG but different LNM TRG had different prognosis. There was no difference in OS between the responding and non-responding groups of LNM at location 2, 3, and M. YpN, tumor location, and LNM location were independent prognostic factors. CONCLUSIONS: The combination of LNM TRG and PT TRG could better predict patient prognosis. Lymph node dissection should be routinely performed after NCT to provide the reference of radical resection.

Evaluation of the prognostic impact of pathologic tumor regression grade on patients with colorectal cancer after preoperative chemoradiotherapy.

BACKGROUND: The prognostic value of the pathological response to preoperative chemoradiotherapy (CRT) in rectal cancer (RC) remains unknown. OBJECTIVES: We aimed to assess the predictive value of the response to CRT that was derived from an evaluation of the histological findings (whole-section vs. representative-section sampling) and attempted to determine an objective cut-off value for the tumor regression grade (TRG). METHODS: We examined the association of the TRG with the outcomes (recurrence-free survival [RFS] and overall survival [OS]) of 78 patients with RC. Patients with RC treated with preoperative CRT were divided into development (30 cases) and validation (48 cases) cohorts. The TRG was classified as grades I (Ia, Ib), II, and III. The cut-off value was determined by receiver operating characteristic (ROC) curve analysis. RESULTS: The TRG determined from whole-section sampling versus representative-section sampling was more strongly correlated with patient survival. We found that in both cohorts, patients with a cut-off value of <73% had a poor prognosis. Finally, the cut-off value was found to be an independent predictive factor in both univariate and multivariate analysis. CONCLUSIONS: The TRG that was used to evaluate patients with RC who underwent preoperative CRT was an independent prognostic factor for outcome.

Machine learning-based response assessment in patients with rectal cancer after neoadjuvant chemoradiotherapy: radiomics analysis for assessing tumor regression grade using T2-weighted magnetic resonance images.

PURPOSE: This study aimed to assess tumor regression grade (TRG) in patients with rectal cancer after neoadjuvant chemoradiotherapy (NCRT) through a machine learning-based radiomics analysis using baseline T2-weighted magnetic resonance (MR) images. MATERIALS AND METHODS: In total, 148 patients with locally advanced rectal cancer(T2-4 or N+) who underwent MR imaging at baseline and after chemoradiotherapy between January 2010 and May 2021 were included. A region of interest for each tumor mass was drawn by a radiologist on oblique axial T2-weighted images, and main features were selected using principal component analysis after dimension reduction among 116 radiomics and three clinical features. Among eight learning models that were used for prediction model development, the model showing best performance was selected. Treatment responses were classified as either good or poor based on the MR-assessed TRG (mrTRG) and pathologic TRG (pTRG). The model performance was assessed using the area under the receiver operating curve (AUROC) to classify the response group. RESULTS: Approximately 49% of the patients were in the good response (GR) group based on mrTRG (73/148) and 26.9% based on pTRG (28/104). The AUCs of clinical data, radiomics models, and combined radiomics with clinical data model for predicting mrTRG were 0.80 (95% confidence interval [CI] 0.73, 0.87), 0.74 (95% CI 0.66, 0.81), and 0.75(95% CI 0.68, 0.82), and those for predicting pTRG was 0.62 (95% CI 0.52, 0.71), 0.74 (95% CI 0.65, 0.82), and 0.79 (95% CI 0.71, 0.87). CONCLUSION: Radiomics combined with clinical data model using baseline T2-weighted MR images demonstrated feasible diagnostic performance in predicting both MR-assessed and pathologic treatment response in patients with rectal cancer after NCRT.

Case Report: The molecular fingerprint and the clinical implication of an exceptional response to neoadjuvant therapy in a metastatic cardia adenocarcinoma.

Background: Globally, gastric cancer holds the fifth position in terms of prevalence among malignant tumors and is the fourth leading cause of cancer-related mortality. Particular attention should be paid to cardia adenocarcinoma (CA) due to its increasing incidence and poor prognosis. Diagnosis of CA frequently occurs in advanced stages because of its late symptoms. In such cases, neoadjuvant chemotherapy is the primary treatment option. The response to chemotherapy depends on multiple variables including the tumor's molecular profile, the patient's performance status, and the feasibility of using targeted therapy. Patients exhibiting an exceptional response, defined as a complete response to medical therapy lasting more than 1 year, or a partial response or stable disease lasting more than 2 years, are rarely described. This case report presents one of the longest-lasting exceptional responses to chemotherapy in metastatic cardia adenocarcinoma and discusses its clinical implications. Case presentation: A 49-year-old male patient presented with cardia adenocarcinoma (human epidermal growth factor receptor 2 negative, mismatch repair proficient) and liver metastases. Molecular profiling identified a pathogenic mutation in the TP53 gene (R123W; Arg123Trp) as the sole alteration found. Five months after initiating the neoadjuvant chemotherapy with fluorouracil-leucovorin-oxaliplatin-docetaxel, the patient achieved a complete clinical response. The molecular profile was compared with others previously documented in an international data portal, revealing a similar pattern. At 4 years and 3 months from diagnosis, the exceptional response was still confirmed. The patient underwent a cumulative number of 33 cycles of chemotherapy, leading to chemotherapy-induced liver damage. Conclusions: Exceptional responses to neoadjuvant chemotherapy in cardia adenocarcinomas are rarely reported. The documentation of exceptional responses to cancer therapies should be included in large data repositories to explore the molecular fingerprint of these tumors. In such cases, the clinical implications of long-term chemotherapy should always be taken into account.

Tumor regression and safe distance of distal margin after neoadjuvant therapy for rectal cancer.

Neoadjuvant therapy has been widely employed in the treatment of rectal cancer, demonstrating its utility in reducing tumor volume, downstaging tumors, and improving patient prognosis. It has become the standard preoperative treatment modality for locally advanced rectal cancer. However, the efficacy of neoadjuvant therapy varies significantly among patients, with notable differences in tumor regression outcomes. In some cases, patients exhibit substantial tumor regression, even achieving pathological complete response. The assessment of tumor regression outcomes holds crucial significance for determining surgical approaches and establishing safe margins. Nonetheless, current research on tumor regression patterns remains limited, and there is considerable controversy surrounding the determination of a safe margin after neoadjuvant therapy. In light of these factors, this study aims to summarize the primary patterns of tumor regression observed following neoadjuvant therapy for rectal cancer, categorizing them into three types: tumor shrinkage, tumor fragmentation, and mucinous lake formation. Furthermore, a comparison will be made between gross and microscopic tumor regression, highlighting the asynchronous nature of regression in the two contexts. Additionally, this study will analyze the safety of non-surgical treatment in patients who achieve complete clinical response, elucidating the necessity of surgical intervention. Lastly, the study will investigate the optimal range for safe surgical resection margins and explore the concept of a safe margin distance post-neoadjuvant therapy.

Safety and efficacy of a programmed cell death 1 inhibitor combined with oxaliplatin plus S-1 in patients with Borrmann large type III and IV gastric cancers.

BACKGROUND: Gastric cancer (GC) is the fifth most common and the fourth most lethal malignant tumour in the world. Most patients are already in the advanced stage when they are diagnosed, which also leads to poor overall survival. The effect of postoperative adjuvant chemotherapy for advanced GC is unsatisfactory with a high rate of distant metastasis and local recurrence. AIM: To investigate the safety and efficacy of a programmed cell death 1 (PD-1) inhibitor combined with oxaliplatin and S-1 (SOX) in the treatment of Borrmann large type III and IV GCs. METHODS: A retrospective analysis (IRB-2022-371) was performed on 89 patients with Borrmann large type III and IV GCs who received neoadjuvant therapy (NAT) from January 2020 to December 2021. According to the different neoadjuvant treatment regimens, the patients were divided into the SOX group (61 patients) and the PD-1 + SOX (P-SOX) group (28 patients). RESULTS: The pathological response (tumor regression grade 0/1) in the P-SOX group was significantly higher than that in the SOX group (42.86% vs 18.03%, P = 0.013). The incidence of ypN0 in the P-SOX group was higher than that in the SOX group (39.29% vs 19.67%, P = 0.05). The use of PD-1 inhibitors was an independent factor affecting tumor regression grade. Meanwhile, the use of PD-1 did not increase postoperative complications or the adverse effects of NAT. CONCLUSION: A PD-1 inhibitor combined with SOX could significantly improve the rate of tumour regression during NAT for patients with Borrmann large type III and IV GCs.

The ypT may better predict the efficacy of neoadjuvant chemoradiotherapy than tumor regression grade in locally advanced rectal cancer patients diagnosed ypT1-4N0 / El ypT puede predecir mejor la eficacia de la quimiorradioterapia neoadyuvante que el grado de regresión tumoral en pacientes con cáncer de recto localmente avanzado diagnosticados ypT1-4N0

Purpose: This study aimed to assess the impact of ypT stage and tumor regression grade (TRG) on the long-term prognosis of patients with locally advanced rectal cancer (LARC) stage ypT1-4N0 after neoadjuvant chemoradiotherapy (NCRT). Methods: We retrospectively analyzed 585 patients with histologically diagnosed middle-low LARC (cT3-4 or cN + by pelvic MRI) from 2014 to 2019. All patients underwent NCRT, followed by total mesorectal excision. Disease-free survival (DFS) rates were compared among patients with different ypT stages and TRGs by Kaplan–Meier survival analysis. The chi-square test was used to analyze the relationship between clinicopathological or therapeutic factors and ypT stage. Results: The median follow‐up was 35.8 months (range 2.8–71.8 months). The 3-year DFS was 79.5%. A better 3-year DFS was achieved in patients with a pathologic complete response (94.0% vs. 74.3%, p < 0.001) and those in the ypT0-2 (86.5% vs. 66.6%, p < 0.001), ypN0 (85.0% vs. 60.2%, p < 0.001), and TRG0 + 1 (83.1% vs. 73.0%, p = 0.004) subgroups. A total of 309 patients (52.8%) achieved stage ypT1-4N0 after surgery. Among these patients, the ypT1-2N0 subgroup achieved a significantly higher 3-year DFS than the ypT3-4N0 subgroup (85.4% vs. 72.8%, p = 0.018); in contrast, the 3-year DFS did not significantly differ between the TRG1 and TRG2 + 3 subgroups (79.9% vs. 81.1%, p = 0.833). In the ypT1-2N0 or ypT3-4N0 subgroup, different TRG had no significant effect on failure patterns. Conclusions: For LARC patients with a ypT1-4N0 status after NCRT, ypT stage may be a more effective predictor of long-term prognosis than TRG.(AU)

Value of perfusion parameters from golden-angle radial sparse parallel dynamic contrast-enhanced magnetic resonance imaging in predicting pathological complete response after neoadjuvant chemoradiotherapy for locally advanced rectal cancer

PURPOSE: Non-invasive methods for predicting pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) can provide distinct leverage in the management of patients with locally advanced rectal cancer (LARC). This study aimed to investigate whether including the golden-angle radial sparse parallel (GRASP) dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) perfusion parameter (Ktrans), in addition to tumor regression grading (TRG) and apparent diffusion coefficient (ADC) values, can improve the predictive ability for pCR. METHODS: Patients with LARC who underwent nCRT and subsequent surgery were included. The imaging parameters were compared between patients with and without pCR. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive ability of these parameters for pCR. RESULTS: A total of 111 patients were included in the study. A pCR was obtained in 32 patients (28.8%). MRI-based TRG (mrTRG) showed a negative correlation with pCR (r = -0.61, P < 0.001), and the average ADC value showed a positive correlation with pCR (r = 0.62, P < 0.001). Before nCRT, Ktrans in the pCR group was significantly higher than in the non-pCR group (1.30 ± 0.24 vs. 0.88 ± 0.34, P < 0.001), but no difference was identified after nCRT. Following ROC curve analysis, the area under the curve (AUC) of mrTRG (level 1-2), average ADC value, and Ktrans value for predicting pCR were 0.738 [95% confidence interval (CI): 0.65-0.82], 0.78 (95% CI: 0.69-0.86), and 0.84 (95% CI: 0.77-0.92), respectively. The model combining the three parameters had significantly higher predictive ability for pCR (AUC: 0.94, 95% CI: 0.88-0.98). CONCLUSION: The use of a combination of the GRASP DCE-MRI Ktrans with mrTRG and ADC can lead to a better pCR predictive performance.

Complete regression of intrahepatic cholangiocarcinoma after right portal vein ligation. Case report.

INTRODUCTION: Spontaneous tumor regression is an extremely rare phenomenon in the oncology field. PRESENTATION OF CASE: We present the case of a 72-years-old male patient presenting with a bulky hepatic tumor mass located in segment V and extending into segments IVb and VI with MRI features of atypical cholangiocarcinoma with a liver metastasis in segment III. In first surgical step, excision of the metastasis, and ligation of the right portal vein was done. A new MRI examination performed 5 weeks later shows significant tumor regression, and 2 weeks later, during the second surgery, the tumor was not found. Under these conditions we performed a limited segment V liver resection, in the area indicated by the radiologist as the site of the tumor. No viable malignant cells existed in the tumor specimen, and a third MRI examination didn't identify any residual tumor. DISCUSSION: From our literature study this is the only case of complete tumor regression of an intrahepatic cholangiocarcinoma following portal vein ligation. We believe the portal vein ligation resulted in a marked regression/deficiency in the tumor blood supply. CONCLUSION: Serial MRI examinations demonstrated the regression of intrahepatic cholangiocarcinoma after portal vein ligation. Intrahepatic cholangiocarcinoma should be included in the tumors that could extremely rarely spontaneously regress.

Context-Responsive Nanoparticle Derived from Synthetic Zwitterionic Ionizable Phospholipids in Targeted CRISPR/Cas9 Therapy for Basal-like Breast Cancer.

The majority of triple negative breast cancers (TNBCs) are basal-like breast cancers (BLBCs), which tend to be more aggressive, proliferate rapidly, and have poor clinical outcomes. A key prognostic biomarker and regulator of BLBC is the Forkhead box C1 (FOXC1) transcription factor. However, because of its functional placement inside the cell nucleus and its structural similarity with other related proteins, targeting FOXC1 for therapeutic benefit, particularly for BLBC, continues to be difficult. We envision targeted nonviral delivery of CRISPR/Cas9 plasmid toward the efficacious knockdown of FOXC1. Keeping in mind the challenges associated with the use of CRISPR/Cas9 in vivo, including off-targeting modifications, and effective release of the cargo, a nanoparticle with context responsive properties can be designed for efficient targeted delivery of CRISPR/Cas9 plasmid. Consequently, we have designed, synthesized, and characterized a zwitterionic amino phospholipid-derived transfecting nanoparticle for delivery of CRISPR/Cas9. The construct becomes positively charged only at low pH, which encourages membrane instability and makes it easier for nanoparticles to exit endosomes. This has enabled effective in vitro and in vivo downregulation of protein expression and genome editing. Following this, we have used EpCAM aptamer to make the system targeted toward BLBC cell lines and to reduce its off-target toxicity. The in vivo efficacy, biodistribution, preliminary pharmacokinetics, and biosafety of the optimized targeted CRISPR nanoplatform is then validated in a rodent xenograft model. Overall, we have attempted to knockout the proto-oncogenic FOXC1 expression in BLBC cases by efficient delivery of CRISPR effectors via a context-responsive nanoparticle delivery system derived from a designer lipid derivative. We believe that the nonviral approach for in vitro and in vivo delivery of CRISPR/Cas9 targeted toward FOXC1, studied herein, will greatly emphasize the therapeutic regimen for BLBC.