Tumor Downstaging Research Articles

Comparison of neoadjuvant chemoimmunotherapy and neoadjuvant chemotherapy for resectable esophageal squamous cell carcinoma: a retrospective study with 3-year survival analysis

BackgroundNeoadjuvant chemoimmunotherapy (nCIT) for locally advanced esophageal squamous cell cancer (ESCC) has shown short-term benefits, but long-term survival outcomes are unclear. This study compares nCIT and neoadjuvant chemotherapy (nCT) in resectable ESCC.Patients and methodsA retrospective analysis was conducted on ESCC patients who underwent nCT or nCIT followed by esophagectomy. Propensity score matching (PSM) with a caliper of 0.02 was employed to minimize bias. The primary endpoints included disease-free survival (DFS) and overall survival (OS).ResultsA total of 131 comparable pairs of ESCC patients receiving nCT and nCIT were selected for the final analysis. The nCIT had higher rates of pathological complete response (pCR) and major pathological response (mPR) compared to nCT. Additionally, nCIT led to significant tumor down-staging, higher rates of R0 resection, and increased lymph node clearance during surgery. Patients who received nCIT exhibited improved disease-free survival (DFS) and overall survival (OS) at the 3-year follow-up. The incidence of distant and mixed relapses was lower in the nCIT group compared to the nCT group. However, the risk of locoregional relapse was comparable between the two groups. Subgroup analyses showed that the benefits of nCIT were generally observed across most patient subgroups. Interestingly, in patients without pCR or mPR, nCIT still demonstrated better survival benefits than nCT.ConclusionnCIT demonstrated superior pathological response rates and improved 3-year DFS and OS compared to nCT alone in locally advanced ESCC, but long-term survival validation is needed.

Short-Course TNT Improves Rectal Tumor Downstaging in a Retrospective Study of the US Rectal Cancer Consortium.

The RAPIDO trial showed promising rates of pathologic complete response (pCR) after neoadjuvant short-course radiation with consolidation chemotherapy (total neoadjuvant therapy [SC TNT]) for rectal cancer. Only single-center reviews comparing tumor downstaging between SC TNT and long-course chemoradiation (LCRT) have been published in the United States. We reviewed our multi-institutional experience with both. The US Rectal Cancer Consortium database (2007-2018) including data from six high-volume rectal cancer care centers was reviewed. Patients with nonmetastatic, rectal adenocarcinoma who had neoadjuvant LCRT alone or SC TNT before excision or definitive nonoperative management were included. The primary outcome was the rate of complete response (CR), including pCR or durable (12 month) clinical complete response. Of 857 included patients, 175 (20%) received SC TNT and 682 (80%) received LCRT. The LCRT group had more low tumors (51.8% vs. 37.1%, p < 0.0001) and more clinically node-negative disease (31.8% vs. 22.3%, p < 0.0001). The CR rate was higher after SC TNT (34.1% vs. 20.3%, p = 0.0001). SC TNT was a predictor of CR (OR: 2.52, CI: 1.68-3.78). SC TNT patients completing 5-6 months of consolidation chemotherapy had a CR rate of 42.9%. There was no difference in 3-year PFS. SC TNT increases CR rate when compared to LCRT. For patients seeking nonoperative options or fewer radiation treatments, SC TRT should be preferred over LCRT alone.

The Impact of Combined Chemotherapy and Intra-Tumoural Injection of Phosphorus-32 Microparticles on Vascularity in Locally Advanced Pancreatic Carcinoma.

Poor intra-tumoural vascularity contributes to a lack of response to chemotherapy in pancreatic cancers. Preliminary data suggest that the addition of endoscopic ultrasound (EUS)-guided intra-tumoural injection of phosphorus-32 (32P) microparticles to standard chemotherapy is potentially beneficial in locally advanced pancreatic cancer (LAPC). We aimed to assess changes in pancreatic tumour vascularity following 32P implantation, using contrast-enhanced EUS (CE-EUS). This was a prospective single-centre trial from January 2022 to 2024 of patients with unresectable, non-metastatic LAPC undergoing standard FOLFIRINOX chemotherapy and 32P implantation. We performed CE-EUS pre-implantation after two chemotherapy cycles and 4 and 12 weeks after implantation. Time-intensity curves were analysed for 90 s after IV contrast bolus to ascertain peak intensity and intensity gain. A total of 20 patients underwent 32P implantation, with 15 completing 12-week follow-up. The technical success of 32P implantation was 100%. The median primary tumour size reduced from 32 mm (IQR 27.5-38.75) pre-implantation to 24 mm (IQR 16-26) 12 weeks post-implantation (p < 0.001). Five patients (25%) had tumour downstaging, and four underwent resections. The baseline (pre-implantation, post-chemotherapy) median intensity gain of contrast enhancement within the tumour was 32.15 (IQR 18.08-54.35). This increased to 46.85 (IQR 35.05-76.6; p = 0.007) and 66.3 (IQR 54.7-76.3; p = 0.001) at 4 weeks and 12 weeks post-implantation, respectively. Over a median follow-up of 11.2 months (IQR 7.8-12.8), 15/20 (75%) of patients remained alive, with 3/20 (15%) demonstrating local disease progression. Overall survival was not significantly different between patients with or without an increased intensity of 10 a.u. or more at 12 weeks post-implantation. This is the first clinical study to demonstrate treatment-induced increased vascularity within pancreatic primary tumours, which followed 32P implantation and FOLFIRINOX chemotherapy. Larger comparative trials are warranted.

Is Liver Resection Still Required for Patients Who Have Predictive Factors for Complete Pathologic Necrosis after Downstaging Treatments of Locally Advanced Hepatocellular Carcinoma?

BackgroundLiver resection can induce complete remission after tumor downstaging in patients with locally advanced hepatocellular carcinoma. However, additional benefits of liver resection have not been investigated in patients expected to have complete pathological necrosis (CPN) following HCC downstaging. MethodsBetween 2002 and 2019, 999 patients with locally advanced HCC underwent concurrent chemoradiotherapy (CCRT) (n=800) or transarterial radioembolization (TARE) (n=199). Among these patients, excluding those who underwent liver transplantation, 94 who underwent liver resection (OP group) and 867 who did not undergo surgical treatment (non-OP group) were included in this study. CPN predictive factors in the OP group were analyzed using logistic regression analysis. Long-term outcomes were compared between patients with CPN (op-CPN) and those with CPN predictive factors in the non-OP group (nop-CPNPF). ResultsOf the 94 patients in the OP group, 38 (40.4%) had CPN (CCRT, n=72; TARE, n=22). In the multivariate analysis, CPN predictive factors were complete radiologic response and tumor marker responders (odds ratio [OR] 18.468, p=0.006; OR 3.698, p=0.045). Among the non-OP group, 21 patients were in the nop-CPNPF group. There was no difference in DFS between the nop-CPNPF and op-CPN groups (40.0 ± 18.3 vs. 60.0 ± 14.0 months, p=0.838). The OS of the op-CPN group was not higher than that of the nop-CPNPF group (5-year OS: 39.4% vs. 33.3%, p=0.328). ConclusionsThe nop-CPNPF group showed long-term outcomes similar to those of the op-CPN group, suggesting that liver resection may not provide additional benefits for long-term outcomes in patients with CPN-PF after HCC downstaging.

A Meta-Analysis of Efficacy and Safety of Neoadjuvant Immunotherapy Plus Chemotherapy for Resectable Non-Small Cell Lung Cancer.

Neoadjuvant immunotherapy plus chemotherapy has ushered in a new era for surgical treatment for patients with NSCLC. This study aimed to examine the efficacy and safety of neoadjuvant immunotherapy plus chemotherapy in NSCLC. Eligible studies were identified from PubMed, Embase, Web of Science, Cochrane Library, ClinicalTrials.gov, and conference meeting abstracts. The endpoints included major pathological response (MPR), complete pathological response (pCR), surgical resection rate, R0 resection, treatment-related adverse events (TRAEs), severe adverse events (SAEs), surgical complications, treatment discontinuation, surgical delay, and treatment-related death. Stata 18 software was used for statistical analysis, and p < 0.05 was considered statistically significant. Twenty-two studies including a total of 1108 patients were eligible for this study. Among the patients who received neoadjuvant immunotherapy plus chemotherapy, the pooled MPR rate was 51% (95% CI [0.44-0.58]), and pCR rate was 34% (95% CI [0.28-0.40]). The pooled surgical resection rate was 85% (95% CI [0.81-0.89]), and the pooled R0 rate was 94% (95% CI [0.91-0.96]). The pooled rate of pathological tumor downstaging was 84% (95% CI [0.79-0.88]), and the pooled rate of pathological nodal downstaging was 38% (95% CI [0.23-0.57]). During the treatment of neoadjuvant immunotherapy plus chemotherapy with or without surgery, the pooled rate of TRAEs (any grade) was 84% (95% CI [0.73-0.91]), and the pooled rate of SAEs was 29% (95% CI [0.21-0.38]). Surgical complications pooled rate was 25% (95% CI [0.14-0.41]). The pooled rate of treatment discontinuation (11%, 95% CI [0.09-0.13]), surgical delay (3%, 95% CI [0.02-0.05]), and treatment-related death (2%, 95% CI [0.02-0.03]) were conducted. Neoadjuvant immunotherapy plus chemotherapy provides a high pathological response, surgical resection rate, R0 resection rate, and pathological downstage rate and has a low risk of increasing the incidence of SAEs, surgical complications, treatment discontinuation, surgical delay, and treatment-related death. The validation of prospective and large sample studies is needed to confirm this conclusion.

Optimal Sequence for Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer: An Evidence-Based Review.

Historically, multimodal therapeutic strategies involving preoperative chemoradiotherapy (CRT), surgery, and adjuvant chemotherapy (CT) have been employed to treat locally advanced rectal cancer (LARC). Total Neoadjuvant Therapy (TNT) is showing promise in improving outcomes. Despite its benefits, the optimal sequencing within TNT-whether induction chemotherapy should precede or follow chemoradiotherapy-remains a critical question. This study endeavors to explore the effects of different TNT sequencing strategies on patient outcomes, including tumor downstaging, pathological response, organ preservation, and the balance between efficacy and tolerability. Our methodology entailed a comprehensive literature review conducted on Medline, focusing on recent research, including retrospective studies, systematic reviews, and clinical trials. The review emphasized the comparison of induction chemotherapy versus consolidation chemotherapy within TNT regimens, assessing outcomes such as pathological response, organ preservation rates, and adverse effects. To ensure the selection of appropriate and high-quality studies, specific inclusion and exclusion criteria were applied. The analysis revealed that induction chemotherapy might lead to decreased adherence to subsequent chemoradiotherapy while offering an early intervention against micrometastasis and potentially improving overall chemotherapy compliance. Conversely, consolidation chemotherapy has been associated with higher pathological complete response (pCR) rates and improved tolerability, indicating its potential for patients requiring local symptom relief or those eligible for a nonoperative management approach. Comparative studies like CAO/ARO/AIO-12 and the OPRA trials have significantly contributed to our understanding, suggesting that while both strategies have distinct advantages, the choice between induction and consolidation chemotherapy should be tailored based on individual patient profiles and tumor characteristics. This narrative review underscores the importance of a nuanced approach to TNT sequencing in locally advanced rectal cancer, highlighting the need for further research to refine treatment strategies.

Evidence for the evolving role of neoadjuvant and perioperative immunotherapy in resectable non-small cell lung cancer.

The treatment of early-stage non-small cell lung cancer (NSCLC) is becoming increasingly complex. Standard of care management for the past decade has been adjuvant chemotherapy following curative intent resection regardless of nodal status or tumour profile. With the increased incorporation of immunotherapy in NSCLC, especially in the locally advanced, unresectable, or metastatic settings, multiple studies have sought to assess its utility in early-stage disease. While there are suboptimal responses to neoadjuvant chemotherapy alone, there is a strong rationale for the use of neoadjuvant immunotherapy in tumour downstaging, based upon the concept of enhanced T cell priming at the time of a high tumour antigen burden, and demonstrated clinically in other solid tumours, such as melanoma. In the NSCLC cancer setting, currently over 20 combinations of chemoimmunotherapy in the neoadjuvant and perioperative setting have been studied with results variable. Multiple large phase III studies have demonstrated that neoadjuvant chemoimmunotherapy combinations result in significant advances in pathological response, disease free and overall survival which has led to practice change across the world. Currently, combination immunotherapy regimens with novel agents targeting alternate immunomodulatory pathways are now being investigated. Given this, the landscape of treatment in resectable early-stage NSCLC has become increasingly complex. This review outlines the literature of neoadjuvant and perioperative immunotherapy and discusses its potential benefits and complexities and ongoing considerations into future research.

Predictive value of mono-exponential and multiple mathematical models in locally advanced rectal cancer response to neoadjuvant chemoradiotherapy.

This prospective study aimed to assess the predictive value of mono-exponential and multiple mathematical diffusion-weighted imaging (DWI) models in determining the response to neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC). The study included 103 LARC patients scheduled for preoperative chemoradiotherapy between December 2021 and June 2023 Magnetic resonance imaging (MRI) scans were performed using a 3.0-T MR scanner, encompassing sagittal, axial, and oblique coronal T2-weighted images without fat saturation, along with DWI perpendicular to the rectum's long axis. Various DWI parameters, including apparent diffusion coefficient (ADC), stretched exponential model (SEM), continuous-time random-walk model (CTRW), and fractional-order calculus model (FROC), were measured. The pathologic complete response (pCR) rate and tumor downstaging (T-downstage) rate were determined. After nCRT, SEM-α, SEM-DDC, CTRW-α, CTRW-β, CTRW-D, FROC-β, and ADC values were significantly higher in the pCR group compared to the non-pCR group (all P < 0.05). SEM-DDC, CTRW-α, CTRW-D, FROC-β, FROC-µ, and ADC values were significantly higher in the T-downstage group (ypT0-1) than in the non-T-downstage group (ypT2-4) (P < 0.05). The combination of CTRW (α + β + D) exhibited the best diagnostic performance for assessing pCR after nCRT (AUC = 0.840, P < 0.001). Pre-nCRT CTRW (α + β) demonstrated a predictive AUC of 0.652 (95%CI: 0.552-0.743), 90.3% sensitivity, and 43.1% specificity for pCR. Regarding T-downstage assessment after nCRT, the combination of CTRW (α + D) yielded the best diagnostic performance (AUC = 0.877, P = 0.048). In LARC patients, imaging markers derived from CTRW show promise in predicting tumor response before nCRT and assessing pCR after nCRT.

Depth of Radiographic Response as an Independent Prognostic Factor for Patients with Initially Unresectable Hepatocellular Carcinoma Receiving Hepatectomy following Targeted Therapy plus Immunotherapy

Introduction: Surgical resection following systemic therapy is feasible in patients with initially unresectable hepatocellular carcinoma (HCC). However, postoperative tumor recurrence is common after surgery, and the factors affecting this recurrence remain unclear. This study aimed to assess factors influencing postoperative outcomes in patients with initially unresectable HCC undergoing hepatectomy after systemic therapy. Methods: This study retrospectively enrolled patients with initially unresectable HCC who underwent hepatectomy after targeted therapy plus immunotherapy (with or without locoregional therapy). Multivariate Cox regression analyses were used to identify the independent prognostic factors for recurrence-free survival (RFS) and overall survival (OS). Machine learning was used to determine the RFS rates at different intervals for different radiographic responses. Results: Eighty-one patients who underwent R0 hepatectomy after systemic therapy were included. With a median follow-up of 17.4 (interquartile range: 7.2–22.3) months, median RFS and OS were not reached. Preoperative tumor downstaging and achieving pathological complete response were associated with improved RFS and OS. Multivariate Cox analyses identified radiographic response as an independent prognostic factor for RFS and OS. Furthermore, a radiographic response >40% (assessed using the Response Evaluation Criteria in Solid Tumors, version 1.1) or >50% (assessed using the modified Response Evaluation Criteria in Solid Tumors) was associated with a longer RFS (p = 0.006 and 0.003, respectively). Conclusion: Radiographic response depth was an independent prognostic factor in patients with initially unresectable HCC who underwent hepatectomy following targeted therapy plus immunotherapy, and the response to systemic therapy may be the determining factor for patient prognosis after surgery.

Neoadjuvant chemoradiotherapy for T3N0M0 esophageal squamous cell carcinoma

The optimal treatment for patients with pretreatment T3N0M0 (pre-T3N0M0) esophageal squamous cell carcinoma (ESCC) remains controversial. This study evaluated the impact of neoadjuvant chemoradiotherapy (NCRT) on the survival outcomes of individuals diagnosed with pre-T3N0M0 ESCC. A total of 443 patients with pre-T3N0M0 ESCC who underwent either NCRT plus surgery (NCRT + S) or surgery alone were included in the study. In the surgery group, patients with post-operative staging of pathological T3N0M0 (pT3N0M0) were classified as pre-T3N0M0. In the NCRT + S group, due to tumor downstaging after NCRT, patients with pre-treatment clinical T3 and post-operative pathology indicating lymph nodes without evidence of tumor involvement or regression were considered to have pre-T3N0M0. Univariate and multivariate Cox analyses were conducted to identify independent prognostic factors influencing overall survival (OS) in pre-T3N0M0 patients. Kaplan&amp;ndash;Meier curves were employed to assess disparities in OS and disease-free survival (DFS) between the two groups. Compared to surgery alone, NCRT + S significantly enhanced the OS (Hazard ratio [HR] = 0.572, 95% Confidence interval [CI] = 0.407 &amp;ndash; 0.804; P = 0.0059); however, it did not show a significant benefit in DFS (HR = 0.784, 95% CI = 0.564 &amp;ndash; 1.09; P = 0.17). Compared with the surgery group, patients who achieved a pathologically complete response (pCR) after NCRT showed significantly improved OS (HR = 0.522, 95% CI = 0.339 &amp;ndash; 0.804; P = 0.019). The overall and locoregional recurrence rates were significantly lower in the NCRT + S group than in the surgery group. Compared with surgery alone, NCRT + S significantly improved OS in patients with pre-T3N0M0 stage disease, especially in those who achieved pCR after NCRT.

Physical activity at diagnosis is associated with tumor downstaging after neoadjuvant chemoradiotherapy in patients with rectal cancer

BackgroundPatients with rectal cancer are often treated with neoadjuvant chemoradiotherapy, followed by a waiting period and surgical resection. Good or complete response to neoadjuvant chemoradiotherapy might enable organ preservation, which highlights the need to increase response rates. Pre-clinical studies suggest that physical activity during neoadjuvant chemoradiotherapy may improve tumor downstaging. PurposeTo investigate whether physical activity and physical functioning of patients with rectal cancer at diagnosis are associated with tumor downstaging after neoadjuvant chemoradiotherapy. Materials and methodsPatients were included if they participated in the Dutch Prospective ColoRectal Cancer Cohort, a nationwide cohort providing an infrastructure for scientific research, and received neoadjuvant chemoradiotherapy for rectal cancer. Tumor downstaging was dichotomized into good/complete or moderate/poor downstaging. Physical activity (total physical activity, moderate-to-vigorous physical activity (MVPA), and Dutch physical activity guideline adherence) and physical functioning were assessed using questionnaires. Logistic regression analyses were performed to examine associations of physical activity and physical functioning with tumor downstaging, adjusted for relevant confounders. Results268 patients (aged 62 ± 11 years, 33 % female) with rectal cancer were included. Patients with moderate (OR = 2.07; 95%CI = 1.07 – 4.07; p = 0.03) or high (OR = 2.05; 95%CI = 1.05 – 4.07; p = 0.04) levels of MVPA were more likely to have good/complete tumor downstaging than patients with low levels. No significant associations with tumor downstaging were found for total physical activity, Dutch physical activity guideline adherence, and physical functioning. ConclusionsWe found augmented tumor downstaging in patients with rectal cancer with moderate or high levels of self-reported MVPA before the start of neoadjuvant chemoradiotherapy compared to patients with low levels.

Neoadjuvant camrelizumab followed by concurrent camrelizumab plus chemotherapy for locally advanced esophageal squamous cell carcinoma: a single-arm, phase II study.

Neoadjuvant therapy combining camrelizumab with chemotherapy has emerged as a promising approach for treating locally advanced esophageal squamous cell carcinoma (ESCC). However, the optimal strategy for integrating immunotherapy with chemotherapy remains to be fully defined. This single-arm phase II study aimed to evaluate the efficacy and safety of neoadjuvant therapy with camrelizumab induction followed by camrelizumab plus chemotherapy in locally advanced ESCC. Patients with clinical stage cT2-4N0M0 or cTxN1-3M0 ESCC were enrolled in the study. Patients received one dose of camrelizumab (200 mg) followed by docetaxel (75 mg/m2) and nedaplatin (75 mg/m2) plus camrelizumab (200 mg) every 3 weeks for two cycles, and then underwent surgery within 3-4 weeks. The primary endpoint was the major pathological response (MPR) rate. The secondary endpoints included the pathological complete response (pCR) rate, R0 resection rate, downstaging rate, disease-free survival (DFS), overall survival (OS), and safety. In total, 55 patients were enrolled in the study between 16 April 2020 and 30 October 2021. Of these 55 patients, 53 (96.4%) completed neoadjuvant therapy, and 48 (87.3%) underwent surgery. The MPR rate was 77.1% [37/48, 95% confidence interval (CI): 62.7-88.0%]. The pCR (ypT0N0) rate was 39.6% (19/48, 95% CI: 25.8-54.7%). All the patients had R0 resections. Primary tumor downstaging occurred in 44 (91.7%) patients, and nodal downstaging occurred in 19 (39.6%) patients. The 2-year DFS rate was 68.9% (95% CI: 53.0-80.4%), and the 2-year OS rate was 74.7% (95% CI: 60.2-84.6%). Grade ≥3 treatment-related adverse events (TRAEs) were observed in 7 (12.7%) patients. In conclusion, neoadjuvant camrelizumab followed by camrelizumab plus chemotherapy showed promising efficacy in treating locally advanced ESCC and had a manageable safety profile.

The predicting value of post neoadjuvant treatment magnetic resonance imaging: a meta-analysis.

Neoadjuvant therapy has become standard of care for locally advanced rectal cancer patients. It is correlated with improved clinical and pathological outcomes, including significant tumor downstaging and organ preservation in certain patients. Magnetic resonance imaging (MRI), which has become the standard for pre-operative staging, is also used for clinical and pre-operative restaging following pre-operative treatment. In this meta-analysis, we aimed to evaluate the concordance between restaging MRI (following the completion of neoadjuvant therapy) and postoperative pathology result. We conducted a meta-analysis following the PRISMA 2020 guidelines. Two independent reviewers searched PubMed and Google Scholar for studies reporting restaging MRI results compared to pathological outcomes. Outcomes included tumor and nodal staging, circumferential resection margin (CRM) and pathological complete response (pCR). Out of 25,000 studies found on the initial search; 33 studies were included. The studies were published between 2005 and 2023 and included 4100 patients (57.14% males). The median age was 62.45 years. The median interval between the conclusion of neoadjuvant treatment and the subsequent restaging MRI was 6 weeks (range 4.14-8.8 weeks). The pooled concordance rates between the restaging MRI and the pathological outcomes for ypT stage and ypN stage were 63.9% (54.5%-73.3%, I2 = 96.02%) and 60.9% (42.9%-78.9%, I2 = 98.96%), respectively. The pooled concordance for predicting pathological complete response was 70.4% (53.6%-87.1%, I2 = 98.21%). As for the circumferential resection margin (CRM), the pooled concordance was 78.2.% (71.6%-84.8%, I2 = 83.76%). Our findings suggest that the concordance rates between restaging MRI and pathological outcomes in rectal cancer patients following neoadjuvant therapy are limited. Caregivers should take these results into consideration when making clinical decisions about these patients. More data should be gathered about the predictive value of MRI after total neoadjuvant therapy as well as immunotherapy in rectal cancer patients.

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

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

Safety and efficacy of percutaneous arterial port Implantation for Hepatic Arterial Infusion Chemotherapy.

Approximately 40% of patients with colorectal cancer will develop liver metastases. Hepatic arterial infusion chemotherapy (HAIC) represents a valuable treatment option, with curative, palliative, or adjuvant intent. The aim of our study was to describe technical considerations, safety, and oncological outcomes of patients receiving HAIC. All patients who underwent percutaneous hepatic arterial port placement in our institution between 2004 and 2021 were included in this retrospective analysis. Demographic, anatomical and technical data were collected. Tumor response was assessed using RECIST 1.1. Kaplan-Meier estimates were used for overall survival (OS) and hepatic progression-free survival (PFS). Adverse events (AEs) were graded using the Clavien-Dindo classification. A total of 360 patients (median age, 58.6 years [interquartile range (IQR): 49.5-65.4]; 208 men [57.8%]) were included. Percutaneous hepatic arterial port placement was successful in 87.9% of cases, resulting in 379 port placements (431 attempts). Overall, 394 HAIC courses were delivered, mostly oxaliplatin-based (94.7%), with a median of 6 cycles per course (IQR: 3-8). AEs (all grades) were observed in 42.0% of ports (grade IIIb-V: 1.1%). Most port dysfunctions could be resolved, resulting in a 73.1% rate of HAIC resumption, without impact on OS. Median OS was 22 months (IQR: 18-24), and median hepatic PFS was 11 months (IQR: 9.5-13). Tumor downstaging allowed surgery in 35.6% of patients, with significantly longer median OS than non-operated patients (39 months [IQR: 33-79] versus 14 months [IQR: 12-16], p < 0.001). This retrospective cohort study demonstrates the feasibility, safety, and efficacy of percutaneous hepatic arterial port placement with an impact on survival for selected patients. Percutaneous hepatic arterial port placement is feasible, safe and effective with an impact on the survival of selected patients. Hepatic arterial infusion chemotherapy provides promising tumor response and overall survival, especially in cases of resection/ablation. Total complication rate of hepatic arterial infusion chemotherapy port use is high, but serious complications are rare. Port revision is often necessary but allows the resumption of hepatic arterial infusion chemotherapy without affecting overall survival.

Perioperative chemotherapy and immunotherapy to optimize cystectomy outcomes in the curative intent of non-metastatic muscle-invasive bladder cancer: A systematic review and meta-analysis

IntroductionPerioperative systemic treatments play a crucial role in the comprehensive management of muscle-invasive bladder cancer. While neoadjuvant platinum-based chemotherapy has a proven efficacy, administering adjuvant chemotherapy can be challenging in patients with multiple comorbidities. Although immunotherapy has shown success in metastatic settings, its effectiveness in both neoadjuvant and adjuvant settings remains under investigation. This study aims to conduct a systematic literature review and meta-analysis to assess the impact of chemotherapy and/or immunotherapy in neoadjuvant and/or adjuvant settings. MethodsA systematic review and meta-analysis were conducted by consulting the PubMed, Scopus, and ClinicalTrial.gov databases for the period from 1994 to 2023. The analysis utilized Forest Plots for key points of interest: overall survival/pathologic response for neoadjuvant chemotherapy (NAC) and overall survival/disease-free survival for adjuvant chemotherapy (AC), employing random or fixed models. ResultsThe systematic review included 26 articles, and 14 were incorporated into the meta-analysis. For NAC, five studies assessed overall survival, yielding an overall hazard ratio (HR) of 0.84 [0.75–0.94]; P=0.002. Pathologic response under NAC was evaluated in five studies, resulting in an overall odds ratio (OR) of 0.3 [0.2–0.4]; P<0.001 compared to cystectomy and 0.86 [0.65–1.13]; P=0.28 for MVAC vs. GC. Regarding AC, six studies investigated overall survival, revealing an overall HR of 0.93 [0.77–1.12]; P=0.46. Disease-free survival under AC was examined in seven studies, with an overall OR of 0.58 [0.44–0.78]; P<0.001. Meta-analysis was not conducted for immunotherapy due to limited phase II studies in the neoadjuvant setting and only two available studies in the adjuvant setting. ConclusionThis study reaffirms the efficacy of platinum-based chemotherapy in neoadjuvant and adjuvant scenarios, enhancing overall survival in muscle-invasive bladder cancer patients. Immunotherapy exhibits promising outcomes in tumor downstaging in the neoadjuvant setting and in disease-free survival, in the adjuvant setting.

Clinical outcomes with perioperative nivolumab (NIVO) by nodal status among patients (pts) with stage III resectable NSCLC: Results from the phase 3 CheckMate 77T study.

LBA8007 Background: In CheckMate 77T, perioperative NIVO showed statistically significant EFS improvement vs neoadjuvant (neoadj) chemo followed by adjuvant (adj) placebo (PBO) in pts with stage (stg) II or III resectable NSCLC. We report clinical outcomes by baseline (BL) stg III N2 status, a subgroup with poor historical 5 y survival (26%–36%; Goldstraw J Thorac Oncol 2016). Methods: Adults with resectable stg IIA–IIIB (N2; AJCC v8) NSCLC were randomized to neoadj NIVO 360 mg Q3W + chemo (4 cycles [cyc]) followed by adj NIVO 480 mg Q4W (13 cyc) or neoadj PBO Q3W + chemo (4 cyc) followed by adj PBO Q4W (13 cyc). Primary endpoint: EFS per BICR. Exploratory analysis: efficacy and safety in pts with BL clinical stg III N2 or non N2 disease (dz). Results: BL characteristics were generally similar between pts with stg III N2 (NIVO, 91; PBO, 90) and non N2 dz (55; 57), and between treatment (tx) arms, except a higher percent of pts with N2 dz had NSQ histology and ECOG PS 0 (both arms). Pts with N2 dz had improved EFS with NIVO vs PBO (HR 0.46; 1 y EFS 70% vs 45%) and higher pCR (22.0% vs 5.6%; median f/u 25.4 mo; Table). Pts with non N2 also had EFS benefit with NIVO vs PBO (HR 0.60; 1 y EFS 74% vs 62%) and higher pCR (25.5% vs 5.3%; Table). Surgical feasibility was similar between pts with N2 and non N2 dz and numerically higher with NIVO vs PBO. Of pts with N2 dz, 77% (NIVO) vs 73% (PBO) had definitive surgery (pneumonectomy 1% vs 14%; R0 resection 86% vs 86%); of pts with non N2 dz, 82% vs 79% had definitive surgery (pneumonectomy 13% vs 9%; R0 resection 84% vs 87%). Tumor downstaging postsurgery was seen in most pts with stg III dz and was deeper with NIVO vs PBO: 61% vs 50% (N2; 33% vs 14% to ypT0), 87% vs 76% (non N2; 27% vs 11% to ypT0). Of all pts with stg III dz, nodal downstaging postsurgery was 52% (NIVO) vs 45% (PBO); 46% vs 36% to ypN0. Grade 3–4 TRAEs occurred in 34% (NIVO) and 26% (PBO) of pts with N2; 29% and 21% of pts with non N2 dz. Conclusions: In this exploratory analysis, perioperative NIVO showed clinical benefit vs PBO in pts with stg III NSCLC, regardless of N2 status. Over half of pts with stg III dz had nodal downstaging with NIVO; majority downstaged to ypN0. This first comprehensive analysis by nodal status among pts with stg III dz from a global phase 3 study of perioperative immunotherapy further supports perioperative NIVO as a tx option for pts with resectable NSCLC. Clinical trial information: NCT04025879 . [Table: see text]

Prolonged interval to surgery following neoadjuvant chemoradiotherapy in locally advanced rectal cancer: A meta-analysis of randomized controlled trials

BackgroundLong-course neoadjuvant chemoradiotherapy (NCRT), followed by surgery after an interval of 6–8 weeks, represents standard of care for patients with locally advanced rectal cancer (LARC). Increasing this interval may improve rates of complete pathological response (pCR) and tumour downstaging. We performed a meta-analysis comparing standard (SI, within 8 weeks) versus longer (LI, after 8 weeks) interval from NCRT to surgery. MethodsPubMed, Embase, and Cochrane databases were searched up to 31 August 2022. Randomized controlled trials (RCTs) comparing SI with LI after NCRT for LARC were included. The primary endpoint was pCR rate. Secondary endpoints included rates of R0 resection, circumferential resection margin positivity (+CRM), TME completeness, lymph node yield (LNY), operative duration, tumour downstaging (TD), sphincter preservation, mortality, postoperative complications, surgical site infection (SSI) and anastomotic leak (AL). Random effects models were used to calculate pooled effect size estimates. ResultsFour RCTs encompassing 867 patients were included. There were 539 males (62.1%). LI was associated with a higher pCR rate (OR 0.61, 95%CI ​= ​0.39–0.95, p ​= ​0.03), and more TD (OR 0.60, 95%CI ​= ​0.37–0.97, p ​= ​0.04) compared to SI. However, there was no difference in rates of R0 resection (p ​= ​0.87), +CRM (p ​= ​0.66), sphincter preservation (p ​= ​0.26), incomplete TME (p ​= ​0.49), LNY (p ​= ​0.55), SSI (p ​= ​0.33), AL (p ​= ​0.20), operative duration (p ​= ​0.07), mortality (p ​= ​0.89) or any surgical complication (p ​= ​0.91). ConclusionsA LI to surgery after NCRT for LARC increases pCR and TD rates. Local recurrence or survival were not assessed due to unavailable data. We recommend deferring TME until after an interval of 8 weeks following completion of NCRT.

Surgical decision-making after neoadjuvant chemotherapy for breast cancer.

e23282 Background: Following neoadjuvant chemotherapy (NAC), a significant subset of breast cancer patients become candidates for breast conserving surgery (BCS) after tumor downstaging. Studies have shown there is no survival advantage between BCS and mastectomy after NAC and that patient prognosis is largely predicted by the pathologic response to treatment. While the literature highlights many aspects of surgical decision-making in breast cancer, there is little analysis of patient choice after NAC. The goal of this study is to investigate clinical and demographic factors that may associate with patients’ surgical decision-making after receiving NAC as well as related outcomes. Methods: A retrospective chart review was conducted on breast cancer patients at our institution who became BCS candidates after receiving NAC from 1/1/2010 to 9/30/2020. Patient demographics, clinical characteristics, choice of mastectomy versus BCS, and outcomes were compared. Exclusion criteria included inflammatory, recurrent, and bilateral breast cancers, and patients with genetic predisposition. T-tests and chi-squared tests of association were used for continuous and categorical variables respectively. Survival outcomes were reported using the log-rank test. The p-value threshold for significance was p &lt; 0.05. Statistical analysis was performed using R software version 4.2.3. Results: In this analysis, 244 patients met study criteria, of which 181 (74.2%) patients chose BCS and 63 (25.8%) patients elected mastectomy. Patients who chose mastectomy were younger at time of diagnosis than those who chose BCS: median age 48 years in mastectomy group versus 53 years in BCS group (p = 0.003). Regarding physical exam findings, while palpability of the primary breast tumor was not associated with choice of surgery (p = 0.271), presence of axillary lymphadenopathy was associated with a higher likelihood of choosing mastectomy (44.4% in mastectomy subgroup versus 29.3% in BCS subgroup, p = 0.041). Patient race, pre-treatment clinical stage, and doxorubicin-based chemotherapy were not associated with patients’ decisions for type of surgery. With respect to outcomes, follow-up time was similar between both groups with overall median of 5 years, and there was no significant difference in local or distant recurrence, and overall mortality (log-rank p = 0.3). Conclusions: The majority of breast cancer patients elect BCS after downstaging from NAC. Factors that are associated with choosing mastectomy include younger age at diagnosis and pre-treatment palpable axillary lymphadenopathy, which may be perceived as more advanced stage, despite no difference in stage between both groups. Regardless of surgical choice, both recurrence and mortality rates did not significantly differ between patients who chose BCS versus mastectomy, which is consistent with the literature.

The NEO-RT trial: A phase 3 randomized trial of neoadjuvant chemotherapy, excision and observation versus chemoradiotherapy for early rectal cancer, CCTG CO.32.

TPS3646 Background: There is significant interest in organ-sparing management of rectal cancer. Data from the National Cancer Database suggest that in 2020 only 20% of US patients with stage I rectal cancer are managed non-operatively. The phase II CCTG CO.28/NEO trial previously reported high rates of tumor downstaging, organ preservation and excellent rectal function among patients with T1-T3abN0 rectal adenocarcinoma treated with 3 months of FOLFOX/CAPOX followed by Transanal Endoscopic Surgery (TES). The phase III CO.32/NEO-RT trial (NCT06205485) will compare two organ sparing strategies for patients with stage I rectal cancer. Methods: Eligible patients with clinical stage T1/2 N0 adenocarcinoma with preserved mismatch repair (MMR) will be randomized 1:1 to ARM A, 3 months of FOLFOX or CAPOX versus ARM B, chemoradiation (54 Gy) followed by tumor restaging within 16 weeks of start of therapy. Patients with histological high grade, mucinous or deficient MMR and those that can be treated with tumor excision alone are excluded. The primary endpoint is tumor downstaging to clinical Complete Response (cCR) by pelvic MRI, endoscopy and digital rectal exam. Subsequent TES is recommended for all patients with tumor response and may be done within 24 weeks of treatment begin, followed by 5 years (y) of observation with serial MRI (q6m x 2y then annually) and endoscopy (q4m x 2y, then q6m during year 3, then annually). The co-primary endpoint is Quality Of Life (QOL) measured by the Low Anterior Resection Score (LARS). In a non-inferiority comparison between treatment arms, if the cCR is assumed to be 45% in ARM B and if there is no true difference between ARMS A and B, then 250 patients are required to be 80% sure that the upper limit of a one-sided 90% confidence interval will exclude a difference in favor of chemoradiation of more than 14%. Results: The approved CCTG CO.32 trial is expected to open February, 2024 at Canadian CCTG and US Alliance, ECOG-ACRIN, NRG, and SWOG NCTN sites with an estimated accrual duration of 4 years. Conclusions: The results of this study will have a major impact on the treatment of patients with stage I rectal cancer. Both arms offer the potential of organ preservation and results will inform whether induction chemotherapy is non-inferior to ChemoRT and compare patient QOL and functional outcomes. Clinical trial information: NCT06205485 .