Neoadjuvant Therapy In Patients Research Articles

Survival benefit and impact of adjuvant chemotherapy following neoadjuvant therapy in patients with locally advanced rectal cancer.

The controversy surrounding the continuation of postoperative adjuvant chemotherapy (AC) for locally advanced rectal cancer patients who underwent neoadjuvant therapy (NAT) still existed. The study aimed to identify the individuals that would benefit from AC from those with stage ypII/III rectal cancer. Data for this retrospective study were obtained from the Surveillance, Epidemiology, and End Results (SEER) database and the local database. Subgroup differentiation of the beneficiary population by classification and regression tree analysis. The primary endpoint was overall survival (OS). 15,671 patients were included from the SEER database and 508 patients from local database. The proportions receiving AC were 41.9% in the SEER database and 77.6% in local database, respectively. Analysis results illustrated that the AC benefited population in the SEER database was characterized as: stage ypT4/N + patients (HR 0.75, 95% CI 0.69-0.82, p < 0.001); stage ypT3N0 patients aged 70years or older (HR 0.69, 95% CI 0.56-0.83, p < 0.001). Moreover, stage ypT4/N + patients also significantly benefited from AC in local database (HR 0.48, 95% CI 0.31-0.74, p < 0.001). The analysis of the two databases showed that stage ypT3N0 patients aged < 70years could not significantly benefit from AC (HR 0.90, p = 0.114 in the SEER database; HR 0.90, p = 0.960 in local database). Postoperative adjuvant chemotherapy provides a significant benefit in patients with stage ypT4/N + rectal cancer following neoadjuvant therapy. Our study discovered that locally advanced rectal cancer patients with aggressive tumors might benefit from postoperative adjuvant chemotherapy and prolonged the survival.

1P Multimodal integration of radiology, pathology and transcriptomics for prediction of response to neoadjuvant therapy in patients with retroperitoneal liposarcoma

1P Multimodal integration of radiology, pathology and transcriptomics for prediction of response to neoadjuvant therapy in patients with retroperitoneal liposarcoma

Neoadjuvant therapy-induced remodeling of tumor immune microenvironment in pancreatic ductal adenocarcinoma: a spatial and digital pathology analysis.

Neoadjuvant therapy (NAT) is the standard of care for borderline-resectable and locally advanced pancreatic ductal adenocarcinoma (PDAC). It can be used to treat resectable PDAC. This study aimed to investigate how NAT remodels the tumor immune microenvironment (TIME) and whether this remodeling translates into survival benefits. We performed spatial and digital pathology analysis of 27 upfront resection patients (naïve group) and 39 age-, gender-, and stage-matched patients who had surgery after NAT (NAT group). AI-assisted digital pathology was used to annotate cancer cells and CD8 + T lymphocytes. Spatial correlation between CD8 + T lymphocytes and cancer cells for each case was assessed using spatial point pattern analysis, followed by generalized linear modeling (GLM) of quadrat counts of CD8 + T cells, with the quadrat counts of cancer cells as the independent variable. The regression coefficient was used to quantify the strength of their spatial correlation and then further assessed for association with patient survival. The analyses showed that the NAT group, compared with the naïve group, had increased spatial correlation of CD8 + T cells with cancer cells, suggesting enhanced effector T cell-cancer cell engagement in the NAT patients. Additionally, patients with a higher degree of spatial correlation between the two cells showed improved after-surgery survival. Through a new methodological framework that takes advantage of AI-assisted digital pathology and spatial point pattern analysis, our study has successfully captured the subtle effects of NAT-induced TIME remodeling and assessed its impact on prognosis of PDAC patients.

Study on pathological factors affecting the sensitivity of neoadjuvant therapy in hypopharyngeal cancer

ObjectiveHypopharyngeal squamous cell carcinoma (HSCC) is a highly malignant tumor type in the head and neck region. In recent years, neoadjuvant therapy has significantly improved the laryngeal preservation rate among patients. However, there are variations in the efficacy of neoadjuvant therapy, and the identification of reliable predictive biomarkers for its efficacy remains a challenging research focus. This study aims to explore the correlation between the expression of P53, P16, and Ki67 and the response to neoadjuvant therapy.MethodsA retrospective analysis was conducted on 120 patients who underwent neoadjuvant therapy at Beijing Tongren Hospital, Capital Medical University, from January 2021 to June 2024. Patients were grouped based on their treatment response and the type of neoadjuvant therapy received. Group analysis were employed to assess the predictive value of P53, P16, and Ki67 for treatment efficacy across different neoadjuvant therapy groups.ResultsA total of 120 patients were included in the study, with 60 patients each in the good response and poor response groups. The study comprised three neoadjuvant therapy groups: neoadjuvant chemotherapy, neoadjuvant targeted therapy combined with chemotherapy, and neoadjuvant immunotherapy combined with chemotherapy. Each group had 20 patients with good and poor responses, respectively. Among patients with P53 positivity, the effective rate after neoadjuvant therapy was 35.94%, significantly lower than the 66.07% observed in P53negative patients (p = 0.0017). For P16 positivity, the effective rate was 28.57%, lower than the 52.83% in P16negative patients (p = 0.0880). For patients with Ki67 < 60%, the effective rate was 33.33%, significantly lower than the 66.67% in those with Ki67 ≥ 60% (p = 0.0005). Comprehensively evaluate confirmed that P53 positivity and Ki67 < 60% were associated with poor response to neoadjuvant therapy, while P53 negativity and Ki67 ≥ 60% were associated with good response.ConclusionOur findings suggest that the combination of P53 and P16 can be used as a preliminary tool to assess the efficacy of neoadjuvant therapy in patients with HSCC. Specifically, patients with P53 positivity and Ki67 < 60% tend to have lower sensitivity to neoadjuvant therapy. Further research may be needed to clarify the precise role of P16 in HSCC.

Phase II study of oral APL-1202 plus tislelizumab or tislelizumab alone as neoadjuvant therapy in patients with muscle-invasive bladder cancer (MIBC).

793 Background: Interim results of the randomized phase II trial of neoadjuvant tislelizumab +/- oral APL-1202 (nitroxoline) revealed promising pathological complete response (pCR) rates and met prespecified thresholds for study expansion (ASCO GU 2024). Here, we report the final primary endpoint analysis of this trial. Methods: Patients with cT2-T4aN0M0 urothelial cancer of the bladder based on local assessment, planned for radical cystectomy (RC), and ineligible for or refusing cisplatin-based chemotherapy were eligible. Patients were randomly assigned to APL-1202 plus tislelizumab (A+T) or tislelizumab (T), stratified by PD-L1 expression. Neoadjuvant tislelizumab was administered q3weeks for 3 cycles and APL1202 was administered orally tid. The primary endpoint was centrally assessed (pCR, pT0N0) rate and secondary endpoints included central pathologic response (PaR, &lt; ypT2N0) rate and safety. Results: A total of 103 patients were enrolled; 28 patients declined RC after neoadjuvant treatment (A+T=16, T=12). Consequently, 75 patients remained in the efficacy analysis set (EAS); RC was completed after A+T in 42/43 patients and after T in 31/32 patients. The pCR and PaR results in the EAS are presented in the table. On retrospective central pathology review of baseline TURBT specimens, a large subset of patients were determined to be ineligible due to &lt;cT2 disease (33/75). There was a numerically higher pCR rate in an exploratory analysis of this retrospectively defined ‘protocol eligible’ subset (A+T: 9/22, T: 4/20). Treatment related adverse events (TRAEs) occurred in 35 (59%) on the A+T arm and 19 (44%) on the T arm. TRAEs (94%) were predominantly ≤ CTCAE grade 2. Conclusions: Neoadjuvant A+T in cisplatin-ineligible patients prior to RC was safe. Evaluation of the efficacy in MIBC is complicated by the large subset of patients enrolled retrospectively determined to have &lt;cT2 disease but pCR rates were similar between groups in the EAS. A signal of higher activity of A+T may be present in PD-L1 “low” tumors supporting further exploration of the immunomodulatory effects of A+T. Evaluation of efficacy is further complicated by a large subset of patients declining RC after neoadjuvant treatment underlining the need for novel bladder-sparing approaches. Clinical trial information: NCT04813107 . pCR rate, pT0N0 PaR rate, &lt; ypT2N0 EAS (n=75) n(%) A+T (n=43) T (n=32) A+T (n=43) T (n=32) All evaluable patients 12 (33)* 7 (26)* 19 (44) 13 (41) PD-L1 h igh 5/18 (28) 4/16 (25) 7/18 (39) 8/16 (50) PD-L1 l ow 7/25 (28) 3/16 (19) 12/25 (48) 5/16 (31) *pCR rate is calculated using UMVUE method when the final sample size of Simon's two-stage is changed.

Implications of Neoadjuvant Therapy on Prognostic Factors in Pancreatic Ductal Adenocarcinoma: A Path Towards Personalized Prognostication.

The aim of the study was to investigate prognostic factors in context of neoadjuvant therapy (NAT) and develop tools that can allow for accurate and personalized patient prognostication. NAT might impact the prognostic ability of well-established clinicopathological factors in resected pancreatic ductal adenocarcinoma (PDAC). Patients after resection for PDAC were identified from the Dutch Pancreatic Cancer Group Recurrence Database and institutional databases at NYU Langone Health and the Johns Hopkins Hospital (2014-2019). Patients were stratified into NAT and chemo-naïve groups. Overall survival (OS), calculated from the time of resection, was estimated using Kaplan-Meier and compared using log-rank tests. Prognostic factors associated with OS were assessed in both groups using univariable and multivariable Cox-regression analyses and presented using hazard ratios (HR) with corresponding 95% confidence intervals (95%CI). Predictive models were developed and an interactive tool was created to predict survival independently in both groups. Of 2,760 patients with resected PDAC, 778 patients (28%) received NAT. Independent predictors for worse OS in chemo-naïve patients included age ≥65 years, markedly elevated CA19-9 (≥500 U/mL) at diagnosis, higher AJCC-T stage (T3/4 vs T1/2), worsening AJCC N-stage (N2 vs. N1 vs. N0), poor tumor differentiation, perineural invasion, and microscopically positive resection margin (R1 vs. R0). Contrastingly, predictors for worse OS in NAT patients included non-normalization of CA19-9 after NAT (<37 U/mL), presence of nodal disease (N1/2 vs. N0 given no statistical difference between N1 and N2 disease), and grade of treatment response (moderate/poor vs. complete/near complete). Prognostic factors for OS in patients with resected PDAC differ between chemo-naïve and NAT patients. Personalized prediction tools for OS in resected PDAC based on these specific factors are available online (www.pancpals.com/tools).

Prehabilitation during neoadjuvant therapy in patients with cancer of the upper gastrointestinal tract and rectum-the study protocol.

The concept of prehabilitation, defined as interventions aimed at enhancing a patient's functional capacity prior to an impending physiological stressor, may contribute to reduced postoperative morbidity and mortality. The study's goal is to verify or refute the feasibility of a prehabilitation programme for two diagnostic patient groups during neoadjuvant chemo(radio)therapy, which is prescribed before the scheduled surgical procedure. This is a single group study design, with all patients enrolled receiving the intervention. This is an interventional feasibility study of a prehabilitation programme in the form of physical training conducted at home. The training consists of progressively dosed walking and strength exercises for selected muscle groups. Data will be monitored telemetrically and also through telephone contact with participants. Primary outcomes include: the percentage of patients interested in participating in the study out of all patients indicated for neoadjuvant therapy at University Hospital Ostrava during the observed period, the percentage of patients who complete the prehabilitation programme until the date of surgery and individual patient compliance. Secondary outcomes include physical fitness parameters obtained from cardiopulmonary exercise testing, grip strength measured by a dynamometer, changes in body composition, EORTC QLQ-C30 quality of life questionnaire, and a questionnaire on the subjective perception of the exercise programme. Both primary and secondary outcomes will be compared between study arms (two diagnostic groups). The study is registered at ClinicalTrials.gov, ID: NCT05646043. The results of this study can serve as a foundation for larger, multicentre, controlled studies in the future.

Neoadjuvant adebrelimab plus chemotherapy for resectable locally advanced esophageal squamous cell carcinoma: A phase 2 trial.

443 Background: Several clinical trials have demonstrated the enhanced pathological response with the addition of immune checkpoint inhibitor to neoadjuvant chemotherapy in patients with resectable esophageal squamous cell carcinoma (ESCC), including the phase 3 ESCORT-NEO trial. Adebrelimab, an anti-programmed cell death-ligand 1 antibody, has shown potential as neoadjuvant monotherapy in the phase 1b NATION-1907 trial of resectable ESCC, with a 2-year overall survival rate of 92% in 30 patients. This study evaluated the efficacy and safety of adebrelimab plus chemotherapy as neoadjuvant therapy in patients with resectable locally advanced ESCC. Methods: In this single-center phase 2 trial (NCT06178211), patients aged 18-75 years with stage II-III (cT2N1-2M0 or cT3N0-2M0) ESCC received adebrelimab (1200 mg, day 1) plus albumin-bound paclitaxel (100 mg/m 2 , days 1, 8, and 15) and carboplatin (area under the curve of 5 mg/mL/min, day 1) every 3 weeks for 2 cycles. Esophagectomy was performed 4-6 weeks after neoadjuvant therapy. The primary endpoint was pathological complete response (pCR; ypT0N0) rate. Secondary endpoints were clinical complete response (cCR) rate (defined as no residual tumor after neoadjuvant therapy, based on computed tomography, positron emission tomography-computed tomography [PET-CT], endoscopic biopsy, and endoscopic ultrasound-guided fine-needle aspiration [EUS-FNA]), margin-free (R0) resection rate, major pathological response (MPR; ≤10% residual tumor cells) rate, event-free survival, overall survival, and safety. Results: Between January 2024 and May 2024, a total of 36 patients were enrolled. Most patients (75.0%) had clinical stage III ESCC. Thirty-five patients completed 2 cycles of neoadjuvant therapy, while one patient refused the last dose of albumin-bound paclitaxel. Two patients refused surgery while 34 underwent esophagectomy. The pCR rate was 38.9% (95% confidence interval [CI], 23.1-56.5) in all patients and 41.2% (95% CI, 24.6-59.3) in the surgery set; the R0 resection rate was 94.4% (95% CI, 81.3-99.3) and 100% (95% CI, 89.7-100), and the MPR rate was 63.9% (95% CI, 46.2-79.2) and 67.6% (95% CI, 49.5-82.6), respectively. The cCR rate was 47.2% (95% CI, 30.4-64.5) in all patients. Of 36 patients, grade ≥3 treatment-emergent adverse events during neoadjuvant therapy included decreased neutrophil count (2 [5.6%]), decreased white blood cell (2 [5.6%]), decreased platelet count (1 [2.8%]), impaired hearing (1 [2.8%]), hyponatremia (1 [2.8%]), immune-mediated hepatitis (1 [2.8%]), intestinal obstruction (1 [2.8%]), and esophageal ulcer (1 [2.8%]). Surgical complications occurred in 17 (50%) of 34 patients. Conclusions: Neoadjuvant adebrelimab plus chemotherapy shows promising pathological response and favorable safety profile in patients with resectable locally advanced ESCC. Survival follow-up is ongoing. Clinical trial information: NCT06178211 .

Does the Presence of Ductal Carcinoma in situ Affect Prognostic Outcomes After Neoadjuvant Therapy in Invasive Ductal Carcinoma of the Breast?

Does the Presence of Ductal Carcinoma in situ Affect Prognostic Outcomes After Neoadjuvant Therapy in Invasive Ductal Carcinoma of the Breast?

Short-course radiation(SCRT) followed by 6 cycles of cadonilimab plus mFOLFOX6 as neoadjuvant therapy for patients with locally advanced rectal cancer (LARC): A multicenter, single arm, phase II trial (NeoCaCRT).

LBA210 Background: Preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME) is recommended for mismatch repair-proficient (pMMR) or microsatellite stability(MSS) LARC. Recent studies have shown that anti-PD-1/PD-L1 in combination with CRT can improve pathological complete response (pCR) compared to CRT in the neoadjuvant setting. This trial aims to investigate the efficacy and safety of SCRT followed by cadonilimab, a first-in-class anti-PD-1/CTLA-4 bispecific antibody, plus mFOLFOX6 in patients (pts) with LARC. Methods: Eligible pts aged 18-79 years with pMMR/MSS, nonmetastatic, stage cT3-4N0 or cT1-4N1-2 rectal adenocarcinoma located below the peritoneal reflection were enrolled and given SCRT (25Gy/5F) followed by 6 cycles of cadonilimab (6mg/kg, q2w) plus mFOLFOX6. The primary endpoint was pCR. Secondary endpoints included clinical complete response (cCR), major pathological response (MPR), disease-free survival (DFS), overall survival (OS), safety and quality of life. The exploratory endpoint explored potential biomarkers related to response. Results: From April 2023 to May 2024, 27 pts were enrolled and received at least 1 dose of treatment. As of data cutoff date of October 20, 2024,median follow-up was 9.7 months (IQR 5.4–18·8)，and all pts received study treatment, and 24/27(88.9%) underwent R0 resections (one delayed surgery due to chemotherapy-related pneumonia, while the other two were assessed unresectable). The primary endpoint was met with a pCR of 37%(10/27)(95% CI, 19.4%–57.6%) and MPR of 55.6%. A cCR of 22.2%(6/27) was observed, and among them, 83.3%(5/6) still received local excisions. The T downstaging was observed in 59.3%(16/27) while N downstaging in 66.7%(18/27). Grade 3–5 adverse events occurred in 5 (18.5%) of 27 pts; the most common were diarrhea (ten [37%]),nausea (ten [37%]) and fatigue (ten [37%]), and neutropenia (seven [26%]). Drug-related serious adverse events occurred in eight (30%) of 27 patients. No new safety signal was identified. Conclusions: In pts with pMMR/MSS LARC, neoadjuvant SCRT with cadonilimab plus mFOLFOX6 resulted in promising pCR rates with intolerable toxicities. Follow up continues. These data deserve further investigations in a phase III randomized trial. Clinical trial information: NCT05792735 .

Clinical Impact of Neoadjuvant Therapy for Resectable Pancreatic Ductal Adenocarcinoma: A Single-Center Retrospective Study

BackgroundNeoadjuvant therapy is recommended for treating resectable pancreatic ductal adenocarcinoma (PDAC); however, its appropriate use in patients with resectable PDAC remains debatable.ObjectiveThis study aimed to identify independent poor prognostic factors and evaluate the clinical significance of neoadjuvant therapy in patients with resectable PDAC.MethodsWe retrospectively reviewed consecutive patients diagnosed with resectable PDAC at our institute between January 2003 and December 2022. We analyzed poor prognostic factors at the time of diagnosis in patients who underwent upfront surgery using the Cox proportional hazards model for overall survival (OS). The prognostic score was calculated by adding the individual prognostic factor scores.ResultsOverall, 359 patients were included in this study, with 308 patients undergoing upfront surgery and the remaining 51 patients receiving neoadjuvant therapy. The R0 resection rate was significantly higher in the neoadjuvant therapy group (70.6%) than in the upfront surgery group (64.0%). Multivariate analysis in the upfront surgery group revealed the following independent poor prognostic factors: tumor size ≥ 35 mm, serum albumin level ≤ .5 g/dL, neutrophil-to-lymphocyte ratio ≥ 3.5, carbohydrate antigen 19-9 level ≥ 250 U/mL, and Duke pancreatic monoclonal antigen type 2 level ≥ 750 U/mL. Among patients with prognostic scores of 0–1 (n = 263), the intention-to-treat OS did not significantly differ between the neoadjuvant therapy and upfront surgery groups. Among those patients with a prognostic score of ≥ 2 (n = 96), the neoadjuvant therapy group had significantly longer intention-to-treat OS than the upfront surgery group.ConclusionsPrognostic score-based stratification can help identify patients who could benefit from neoadjuvant therapy.

Role of MRI in evaluation of residual tumor burden following neoadjuvant therapy in patients with breast cancer

Objectives To correlate the accuracy of MRI with pathology in assessing the response of neoadjuvant chemotherapy (NACT) in patients with breast cancer and assessment of factors affecting the accuracy of MRI. Materials and Methods Twenty-five patients (with 33 tumors) having biopsy-proven breast cancer were included to undergo dynamic contrast-enhanced MRI, mammography, and ultrasound prior to NACT and after completion of NACT before undergoing surgery. Tumor morphological features and receptor subtypes were compared between complete and non-complete responders, and the accuracy of MRI in estimating residual disease was assessed with respect to histopathology. The performance of MRI was also compared with ultrasound and mammography, wherever feasible. Results The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of MRI for predicting pathological complete response (pCR) were 100%, 70%, 83.3%, 100%, and 88%, respectively, which were significantly better (p = 0.02) in the triple-negative subtype. Size measured in preoperative MRI had a significant positive correlation with pathological size (r = 0.76, p &lt; 0.001) with the lowest mean size difference in triple negative subtype and in tumors showing a concentric pattern of shrinkage. Among the baseline morphological features on MRI, significant difference was seen in the shape (p = 0.02) and enhancement (p = 0.036) of the tumors between complete and non-complete responders. Also, MRI had the highest overall accuracy in predicting pCR and residual tumor size as compared to mammography and ultrasound. Conclusion MRI is a sensitive modality for predicting pCR and residual tumor size with better accuracy for triple-negative tumors as compared to other subtypes.

Efficacy and safety of neoadjuvant therapy for hepatocellular carcinoma with portal vein thrombosis: A meta‑analysis.

Hepatocellular carcinoma (HCC) with coexisting portal vein tumor thrombus (PVTT) is associated with poor patient outcomes. The efficacy and safety of neoadjuvant therapy in patients with HCC with PVTT remain a subject of debate. In the present study, a comprehensive search of electronic databases, including PubMed, Web of Science, Embase and the Cochrane Library, was conducted to identify studies evaluating the outcomes of neoadjuvant therapy in patients with HCC and PVTT. The primary outcomes assessed were overall survival (OS) and relapse-free survival (RFS), with complication rates as a secondary outcome. A total of six studies comprising 750 patients were included in the present meta-analysis. The neoadjuvant therapy group exhibited significantly superior OS [hazard ratio (HR), 0.39; P<0.001] and RFS (HR, 0.31; P<0.001) compared with the primary hepatectomy control group. Compared with the control group, neoadjuvant radiotherapy improved OS (HR, 0.34; P<0.001) and RFS (HR, 0.24; P=0.004). While the neoadjuvant intervention subgroup exhibited an improved OS compared with controls (HR, 0.37; P=0.001), no significant difference in RFS was observed (HR, 0.11; P=0.095). Geographical analysis revealed that the Chinese subgroup demonstrated a significantly improved OS and RFS (HR, 0.41 for both; P<0.001), compared with the control group. However, the Japanese and Korean subgroups showed no improvement in OS (HR, 0.25; P=0.057) compared with the control group, and the results did not reach statistical significance. There were no significant differences between the groups in terms of blood transfusion, blood loss, operation time, bile leakage, ascites, peritoneal infection, postoperative bleeding, complications or mortality (all P>0.05). Overall, neoadjuvant therapy significantly improved survival outcomes in patients with HCC and PVTT without increasing complication rates, supporting its efficacy and manageable safety profile.

Immunonutrition to improve the quality of life of upper gastrointestinal cancer patients undergoing neoadjuvant treatment prior to surgery (NEOIMMUNE): double-blind randomized controlled multicenter clinical trial.

Malnutrition is common with esophagogastric cancers and is associated with negative outcomes. We aimed to evaluate if immunonutrition during neoadjuvant treatment improves patient's health-related quality of life (HRQOL) and reduces postoperative morbidity and toxicities during neoadjuvant treatment. A multicenter double-blind randomized controlled trial (RCT) was undertaken. Included patients had untreated nonmetastatic esophagogastric tumor, aged 18 ≥ years with a life expectancy of >3months. The study was powered for 80% power to detect a clinically relevant difference in EORTC-QLQC30 with standard deviation of 15 between groups. Primary end point was the quality of life as measured by the global health status at 30days after surgery. An intention-to-treat analysis was employed. The study was terminated at the interim analysis stage. About 300 patients were randomized: 149 to the IMPACT group and 151 to the control-formula group. Patient groups were well-balanced in terms of age, sex, body mass index, WHO performance status, and clinical tumor stage. Analysis of the primary end point for the study of global health status at 30-day postoperatively failed to show any significant differences between the groups (55.4 ± 18.6 [IMPACT] vs. 55.9 ± 19.8 [control]; P = 0.345). No significant differences between the groups were detected in the majority of domains from EORTC QLQC30 and OG25 tools after neoadjuvant therapy and 30 days postoperatively. Finally, no significant differences were seen between groups in neoadjuvant therapy or postoperative complications, or tumor response. The results of this multicenter double-blind RCT fail to demonstrate any HRQOL benefits to the utilization of immunonutrition during neoadjuvant therapy in patients with esophagogastric cancer.

The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study.

The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study.

Intensified total neoadjuvant therapy in patients with locally advanced rectal cancer: long-term results of a prospective phase II study

AimsTo analyze the long-term results of a prospective phase II trial testing intensified total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer (LARC). Materials and methodsPatients with histologically confirmed LARC adenocarcinoma were enrolled. Intensified TNT consisted of targeted agent (bevacizumab or panitumumab/cetuximab) plus FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) induction chemotherapy followed by intensified (oxaliplatin and 5-fluorouracil) chemoradiotherapy (CRT) and surgical resection. Follow-up data were collected for all patients included in the trial. Survival outcomes were calculated using the Kaplan-Meier method and curves were compared by the log-rank test. ResultsBetween October 2015 and September 2019, 28 LARC patients were enrolled. Follow-up data were available for all included patients. In total, 11 (39.3%) patients had a complete response (CR). At 6.3 years (median follow-up), 5-year OS and DFS were 74.6% and 57.1%, respectively. Five-year OS was 80.8% for CR patients and 70.1% in no-CR patients (p-value 0.07). Those patients with CR after TNT treatment had a 5-year DFS of 81.8% versus 41.2% for those with no-CR (p-value 0.015). ConclusionThe addition of targeted agent to induction FOLFOXIRI and of oxaliplatin to 5-fluorouracil-based CRT, with the doses and intensities as used in this study, resulted in high CR rates. Patients who achieve a CR demonstrate superior DFS compared to patients without CR. Intensified TNT may have the potential to increase survival outcomes. Further research of TNT strategies in LARC is encouraged.

Efficacy and safety of S-1 plus oxaliplatin combined with apatinib and camrelizumab as neoadjuvant therapy for patients with locally advanced gastric or gastroesophageal junction adenocarcinoma: a protocol for a single-arm phase II trial.

Gastric cancer, as the fifth most diagnosed malignancy and the fourth leading cause of cancer-related death globally, remains a significant health concern. The potential effect of the programmed death-1 (PD-1) inhibitor, when used alongside chemotherapy and antiangiogenic agents in neoadjuvant therapy for gastric cancer, has yet to be explored in the published literature. This study aims to evaluate the efficacy and safety of the S-1 plus oxaliplatin (SOX) regimen when combined with apatinib and camrelizumab (SOXAC) as neoadjuvant therapy for patients with locally advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. A single-arm, open-label, single-center phase II clinical trial has been designed to evaluate the safety and efficacy of the SOXAC regimen as neoadjuvant therapy for patients diagnosed with locally advanced gastric or GEJ adenocarcinoma (cT2-3N + M0 or T4NxM0). Eligible patients are to receive 2 cycles of SOXAC and 1 cycle of SOX regimen with camrelizumab (SOXC) as neoadjuvant therapy prior to radical surgery, and 3 cycles of SOXC as postoperative adjuvant therapy. The primary endpoint is major pathological remission (MPR), while secondary endpoints include pathological complete response (pCR) rate, R0 resection rate, objective response rate (ORR), operation-related outcomes, and safety. The SOX regimen remains a leading choice for neoadjuvant chemotherapy in Eastern countries. Recent studies suggest that combining chemotherapy, targeted agents, and immune checkpoint inhibitors can enhance the antitumor immune response. This phase II clinical trial seeks to assess the safety and efficacy of the SOXAC regimen as neoadjuvant therapy for patients with locally advanced resectable gastric or GEJ adenocarcinoma, while also exploring the correlation between biomarkers and efficacy.Trial Registration Chinese Clinical Trial Registry (ChiCTR): ChiCTR2200062285 ( https://www.chictr.org.cn/ ).

Do socioeconomic factors impair uptake of neoadjuvant therapy for patients with locoregional oesophageal cancer?

The benefits of neoadjuvant therapy prior to surgery for patients with locally advanced oesophageal cancer have been well established by multiple trials. However, there may be socioeconomic barriers impacting equitable administration. We aim to identify whether disparities exist in the uptake of neoadjuvant therapy among patients with loco-regional oesophageal cancer. We queried the National Cancer Database to identify patients with clinical stage II-III oesophageal cancer who underwent surgical resection (2006-2020). Logistic regression was performed to identify associations between sociodemographic factors and uptake of neoadjuvant therapy. In propensity score-matched groups, survival was evaluated using the Kaplan-Meier method. Among 19748 clinical stage II-III patients, 85% (n = 16781) received neoadjuvant therapy and 15% (n = 2967) underwent upfront surgery. Rates of neoadjuvant uptake increased over time. On multivariable analysis after adjusting by clinical stage, factors associated with lower rates of neoadjuvant therapy included older age (age ≥70, adjusted odds ratio 0.52; 95% confidence interval 0.47-0.57; P < 0.001), female sex (0.76; 0.69-0.85; P < 0.001), Black race (0.77; 0.63-0.94; P = 0.009), more comorbidities (0.76; 0.65-0.85; P < 0.001) and government rather than private insurance (0.84; 0.76-0.93; P < 0.001). In a propensity-matched cohort accounting for these variables, neoadjuvant treatment was associated with improved 5-year overall survival compared to upfront surgery (41.1% vs 35.4%, P < 0.001). Several sociodemographic factors are associated with the delivery of neoadjuvant therapy in patients with oesophageal cancer, including age, sex, race, and insurance status. Interventions can be put into place to target vulnerable patients and ensure equitable delivery of care.

Narrative review of neoadjuvant therapy in patients with locally advanced colon cancer.

Colorectal cancer is a leading cause of cancer-related morbidity and mortality worldwide, with more than 1.9 million new cases reported in 2020, and is associated with major survival challenges, particularly in patients with locally advanced colon cancer (LACC). LACC often involves T4 invasion or extensive nodal involvement and requires a multidisciplinary approach for management. Radical surgery followed by adjuvant chemotherapy remains the primary treatment strategy for LACC. However, achieving complete tumor resection (R0) is challenging because locally advanced colon tumors typically infiltrate adjacent organs or nodes. Advancements in LACC treatment have involved neoadjuvant chemotherapy (NACT), neoadjuvant chemoradiotherapy (NACRT), and neoadjuvant immunotherapy (NAIT). Studies such as FOxTROT and PRODIGE 22 have demonstrated that NACT, particularly with FOLFOX or CAPOX, can lead to major tumor downstaging, improved survival rates, and increased R0 resection rates. Predictive biomarkers, such as mismatch repair (MMR) status and T stage, are crucial in identifying candidates who may benefit from NACT. NACRT has demonstrated promise in enhancing tumor regression, particularly in patients with rectal cancer, underscoring its potential for use with LACC. NAIT, particularly for deficient MMR tumors, has emerged as a novel approach, with studies such as NICHE-2 and NICHE-3 reporting excellent pathologic responses and pathologic complete responses. Integrating these therapies can enhance the surgical and survival outcomes of patients with LACC, highlighting the importance of personalized treatment strategies based on tumor characteristics and response to neoadjuvant interventions. This review discusses the evolving landscape of LACC management, focusing on optimizing treatment approaches for improved patient outcomes.

Association Between Change in Prognostic Nutritional Index During Neoadjuvant Therapy and Dental Occlusal Support in Patients with Esophageal Cancer Under Neoadjuvant Therapy: A Retrospective Longitudinal Pilot Study.

Background: A high prognostic nutritional index (PNI) is associated with good prognosis in patients with esophageal cancer. However, nutritional status often decreases during neoadjuvant therapy. Functional tooth units (FTUs) provide an index for the status of posterior occlusal support. We have previously reported that low PNI is related to low FTUs. Objectives: The purpose of this study was to retrospectively examine whether the status of occlusal support relates to changes in PNI during neoadjuvant therapy in patients with esophageal cancer. Methods: This study included 34 patients who underwent neoadjuvant therapy before esophagectomy (32 men, 2 women; age, 36-82 years) in 2012 at Okayama University Hospital. Patients were divided into the good occlusal support group (FTUs ≥ 11, n = 18) or poor occlusal support group (FTUs < 11, n = 16), and changes in PNI during neoadjuvant therapy were investigated. Results: PNI decreased significantly after neoadjuvant therapy, particularly in the good occlusal support group, and became more dispersed after neoadjuvant therapy. Decreases in PNI after neoadjuvant therapy showed a significant positive correlation with good occlusal support by multiple regression analysis (p = 0.03). The proportions of patients provided with nutritional intervention (p = 0.02) or early dental intervention (p = 0.04) were lower in the good occlusal support group than in the poor occlusal support group. Conclusions: Even in patients with esophageal cancer with good occlusal support experienced significant declines in PNI during neoadjuvant therapy, potentially due to delayed nutritional and dental interventions. Early multidisciplinary interventions are thus recommended for all patients, regardless of preoperative dental or nutritional status.