The efficacy and safety of short-course radiotherapy followed by sequential chemotherapy and Cadonilimab for locally advanced rectal cancer: a protocol of a phase II study.

BACKGROUND: For patients with locally advanced rectal cancer (LARC), total neoadjuvant therapy (TNT), namely, intensifying preoperative treatment through the integration of radiotherapy and systemic chemotherapy before surgery, was commonly recommended as the standard treatment. However, the risk of distant metastasis at 3 years remained higher than 20%, and the complete response (CR) rate was less than 30%. Several clinical trials had suggested a higher complete response rate when combining single-agent immunotherapy with short-course radiotherapy (SCRT). The CheckMate 142 study had shown encouraging outcomes of dual immunotherapy and seemingly comparable toxicity for CRC compared with single-agent immunotherapy in historical results. Therefore, dual immunotherapy might be more feasible in conjunction with the TNT paradigm of SCRT. We performed a phase II study to investigate whether the addition of a dual immune checkpoint inhibitor bispecific antibody, Cadonilimab, to SCRT combined with chemotherapy might further increase the clinical benefit and prognosis for LARC patients. METHODS: This single-arm, multicenter, prospective, phase II study included patients with pathologically confirmed cT3-T4N0 or cT2-4N + rectal adenocarcinoma with an ECOG performance score of 0 or 1. Bispecific antibody immunotherapy was added to SCRT combined with chemotherapy. Patients enrolled would be treated with SCRT (25 Gy in five fractions over 1 week) for the pelvic cavity, followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX and Cadonilimab. The primary endpoint was the CR rate, which was the ratio of the pathological CR rate plus the clinical CR rate. The secondary endpoints included local-regional control, distant metastasis, disease-free survival, overall survival, toxicity profile, quality of life and functional outcome of the rectum. To detect an increase in the complete remission rate from 21.8% to 40% with 80% power, 50 patients were needed. DISCUSSION: This study would provide evidence on the efficacy and safety of SCRT plus bispecific antibody immunotherapy combined with chemotherapy as neoadjuvant therapy for patients with LARC, which might be used as a candidate potential therapy in the future. TRIAL REGISTRATION: This phase II trial was prospectively registered at ClinicalTrials.gov, under the identifier NCT05794750.

Protocol of a pilot randomized clinical trial to evaluate nutritional support and rehabilitation on prevention of skeletal muscle mass loss during neoadjuvant chemotherapy in patients with esophageal cancer.

BACKGROUND: Subtotal esophagectomy with lymph node dissection followed by neoadjuvant chemotherapy (NAC) is the standard treatment for stage II-III esophageal cancer. Esophagectomy is still associated with high morbidity rates, and reducing these rates remains challenging. Among several complications, postoperative pneumonia (PP) is sometimes fatal, which has been reportedly caused by sarcopenia. Thus, nutritional support and rehabilitation may be promising for preventing skeletal muscle mass loss and reduce the incidence of PP. METHODS: This single-center, randomized, open-label, pilot trial will randomize a total of 40 patients with esophageal cancer in a 1:1 ratio either to ISOCAL Clear + rehabilitation arm or only rehabilitation arm. Although all patients will be educated about rehabilitation by a specialized physician and will be asked to undergo the prespecified rehabilitation program, patients treated with ISOCAL Clear + rehabilitation arm will be supplemented by 400 mL of ISOCAL Clear (Nestlé Japan Ltd, Tokyo, Japan) per day during two courses of NAC with docetaxel, cisplatin, and fluorouracil. Body composition will be assessed using Inbody (Inbody Co., Ltd., Tokyo, Japan) just before starting NAC and surgery. The primary endpoint is the change of skeletal muscle index (SMI) during NAC. Secondary endpoints include (i) body weight, total skeletal muscle mass, appendicular skeletal muscle mass, and lean body mass index changes; (ii) the percentage of ISOCAL Clear continuation; (iii) appetite evaluation; (iv) the percentage of targeted calorie achievement; (v) adverse events of NAC; (vi) postoperative complication rates; and (vii) postoperative hospital stay. DISCUSSION: This prospective trial assesses the efficacy of nutritional support in addition to rehabilitation during NAC for patients with esophageal cancer. The results will be utilized in assessing whether the effects of nutritional support by ISOCAL Clear are promising or not and in planning future larger clinical trials.

[Neoadjuvant strategy for locally advanced colorectal cancer based organ preservation].

Neoadjuvant therapy for locally advanced colorectal cancer has made great progress in the past 20 years, but there are still limitations such as side effects, organ dysfunction and unsatisfactory control of metastasis. In recent years, with the improvement of surgical techniques and further development of molecular research, how to further improve local control, reduce distant metastasis, and even avoid surgery according to clinical remission to achieve organ preservation, is the current demand and research goal. With the advancement of molecular research, colorectal cancer has different treatment strategies based on microsatellite status. For patients with microsatellite instability locally advanced colorectal cancer, immune checkpoint inhibitor therapy significantly increased the pathologic complete response rate, reduced the incidence of adverse events and improved organ function compared with conventional chemoradiotherapy. For patients with microsatellite stable locally advanced colon cancer, neoadjuvant therapy is still in the exploratory stage. The standard of care is surgery combined with perioperative chemotherapy. For microsatellite stable locally advanced rectal cancer, the complete response rate is improved by enhancing neoadjuvant therapy, which helps to preserve organs. On the other hand, selective radiotherapy preserves organ function and improves quality of life. This article reviews the neoadjuvant treatment strategies for locally advanced colorectal cancer based on organ-sparing strategies.

Impact of neoadjuvant chemotherapy on the safety and long-term outcomes of patients undergoing immediate breast reconstruction after mastectomy.

BACKGROUND: In breast cancer patients receiving neoadjuvant chemotherapy (NAC), immediate breast reconstruction (IBR) as a breast cancer treatment option remains controversial. We assessed the impact of NAC on surgical and oncological outcomes of patients undergoing IBR. METHODS: This was a retrospective multicenter study of 4726 breast cancer cases undergoing IBR. The rate of postoperative complications and survival data were compared between IBR patients who received NAC and those who did not receive NAC. Propensity score matching analysis was performed to mitigate selection bias for survival. RESULTS: Of the total 4726 cases, 473 (10.0%) received NAC. Out of the cases with NAC, 96 (20.3%) experienced postoperative complications, while 744 cases (17.5%) without NAC had postoperative complications. NAC did not significant increase the risk of complications after IBR (Odds ratio, 0.96; 95%CI 0.74-1.25). At the median follow-up time of 76.5 months, 36 patients in the NAC group and 147 patients in the control group developed local recurrences. The 5-year local recurrence-free survival rate was 93.1% in the NAC group and 97.1% in the control group. (P < 0.001). After matching, there was no significant difference between the two groups. CONCLUSION: IBR after NAC is a safe procedure with an acceptable postoperative complication profile.

Associations of pre-diagnosis physical activity with treatment tolerance and treatment efficacy in breast cancer patients with neoadjuvant chemotherapy.

PURPOSE: Higher pre-diagnosis physical activity (PA) is associated with lower all-cause mortality in breast cancer (BCa) patients. However, the association with pathological complete response (pCR) is unclear. We investigated the association between pre-diagnosis PA level and chemotherapy completion, dose delay, and pCR in BCa patients receiving neoadjuvant chemotherapy (NACT). METHODS: 180 stage I-III BCa patients receiving NACT (mean [SD] age of diagnosis: 60.8 [8.8] years) in the Sister Study were included. Self-reported recreational and total PA levels were converted to metabolic equivalent of task-hours per week (MET-hrs/wk). The pCR was defined as no invasive or in situ residual in breast or lymph node (ypT0 ypN0). Multivariable logistic regression analyses estimated odds ratios (ORs) and 95% confidence intervals (CIs) for treatment outcomes. RESULTS: In this sample, 45 (25.0%) BCa patients achieved pCR. Higher pre-diagnosis recreational PA was not associated with lower likelihood of chemotherapy completion (highest vs. lowest tertile: OR = 0.87, 95% CI = 0.30-2.56; Ptrend = 0.84), greater dose delay (OR = 1.45, 95% CI = 0.54-3.92; Ptrend = 0.46), or greater odds of pCR (OR = 1.28, 95% CI = 0.49-3.34; Ptrend = 0.44). Associations were similar for pre-diagnosis total PA. Meeting the recommended level of recreational PA was not associated with pCR overall (≥ 7.5 vs. < 7.5 MET-hrs/wk: OR = 1.33, 95% CI = 0.59-3.01). CONCLUSIONS: Although small sample size and limited information on exercise closer to time of diagnosis limit interpretation, pre-diagnosis PA was not convincingly associated with treatment tolerance or treatment efficacy in BCa patients receiving NACT. Future investigations are needed to better understand the impact of pre-diagnosis PA on BCa treatment.

A phase II/III randomized clinical trial of CisPlatin plUs Gemcitabine and Nabpaclitaxel (GAP) as pReoperative chemotherapy versus immediate resection in patIents with resecTable BiliarY Tract Cancers (BTC) at high risk for recurrence: PURITY study.

BACKGROUND: Biliary tract cancers (BTCs) are rare and lethal cancers, with a 5-year survival inferior to 20%(1-3). The only potential curative treatment is surgical resection. However, despite complex surgical procedures that have a remarkable risk of postoperative morbidity and mortality, the 5-year survival rate after radical surgery (R0) is 20-40% and recurrence rates are up to ~ 75%(4-6). Up to ~ 40% of patients relapse within 12 months after resection, and half of these patient will recur systemically(4-6). There is no standard of care for neoadjuvant chemotherapy (NAC) in resectable BTC, but retrospective reports suggest its potential benefit (7, 8). METHODS: PURITY is a no-profit, multicentre, randomized phase II/III trial aimed at evaluating the efficacy of the combination of gemcitabine, cisplatin and nabpaclitaxel (GAP) as neoadjuvant treatment in patients with resectable BTC at high risk for recurrence. Primary objective of this study is to evaluate the efficacy of neoadjuvant GAP followed by surgery as compared to upfront surgery, in terms of 12-month progression-free survival for the phase II part and of progression free survival (PFS) for the phase III study. Key Secondary objectives are event free survival (EFS), relapse-free survival, (RFS), overall survival (OS), R0/R1/R2 resection rate, quality of life (QoL), overall response rate (ORR), resectability. Safety analyses will include toxicity rate and perioperative morbidity and mortality rate. Exploratory studies including Next-Generation Sequencing (NGS) in archival tumor tissues and longitudinal ctDNA analysis are planned to identify potential biomarkers of primary resistance and prognosis. DISCUSSION: Considering the poor prognosis of resected BTC experiencing early tumor recurrence and the negative prognostic impact of R1/R2 resections, PURITY study is based on the rationale that NAC may improve R0 resection rates and ultimately patients' outcomes. Furthermore, NAC should allow early eradication of microscopic distant metastases, undetectable by imaging but already present at the time of diagnosis and avoid mortality and morbidity associated with resection for patients with rapid progression or worsening general condition during neoadjuvant therapy. The randomized PURITY study will evaluate whether patients affected by BTC at high risk from recurrence benefit from a neoadjuvant therapy with GAP regimen as compared to immediate surgery. TRIAL REGISTRATION: PURITY is registered at ClinicalTrials.gov (NCT06037980) and EuCT(2023-503295-25-00).

Long survival after neoadjuvant and adjuvant camrelizumab plus chemotherapy and surgery in a patient with hepatoid adenocarcinoma of the lung: A case report.

Hepatoid adenocarcinoma of the lung (HAL) is a rare and aggressive subtype of lung cancer. The prognosis for patients with HAL is generally poor and currently, there are only limited treatment options. Here, we present a case of a 47-year-old male diagnosed with locally advanced-stage HAL who achieved a remarkably long disease-free survival after receiving neoadjuvant and adjuvant camrelizumab plus chemotherapy and surgery. This case highlights the potential of immunochemotherapy plus surgery in improving outcomes for patients with HAL.

Case report: Pathological complete response induced by immunochemotherapy in a case of Pulmonary Sarcomatoid Carcinoma staged IIIA-N2.

Pulmonary sarcomatoid carcinoma (PSC) represents a rare and highly aggressive variant of lung cancer, characterized by its recalcitrance to conventional therapeutic modalities and the attendant dismal prognosis it confers. Recent breakthroughs in immunotherapy have presented novel prospects for PSC patients; nevertheless, the utility of neoadjuvant/conversional immunotherapy in the context of PSC remains ambiguous. In this report, we present a middle-aged male presenting with Stage III PSC, notable for its high expression of the programmed death-ligand 1 (PD-L1), initially deemed as non-resectable for sizeable tumor mass and multiple lymph nodes metastases. The patient underwent a transformation to a resectable state after a regimen of three cycles of platinum-based chemotherapy plus immunotherapy. Following definitive surgical resection, the individual realized a pathological complete response (pCR), culminating in a significant prolongation of event-free survival (EFS). This case underscores the viability of employing immunochemotherapy as a neoadjuvant/conversional strategy for chosen cases of PSC.

Identifying Indications for Neoadjuvant Therapy in Cholangiocarcinoma.

The recent Hot Topics section focuses on survival rates for patients with cholangiocarcinoma.

Efficacy and safety of neoadjuvant immunotherapy plus chemotherapy followed by adjuvant immunotherapy in resectable non-small cell lung cancer: a meta-analysis of phase 3 clinical trials.

Objective: At present, several important trials have been published show that perioperative immunotherapy combined with chemotherapy can improve the prognosis of patients with resectable non-small cell lung cancer, which further optimizes treatment options. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of perioperative immunotherapy combined with chemotherapy in resectable non-small cell lung cancer. Methods: The following databases were searched for relevant studies: PubMed, EMBASE, Cochrane library (updated 12 October 2023). All randomized trials comparing perioperative immunotherapy combined with chemotherapy versus chemotherapy alone in resectable non-small cell lung cancer were eligible for inclusion. Data were analyzed using Review Manager 5.4.1 (Cochrane collaboration software). Primary outcomes and measures included overall survival (OS), event-free survival (EFS), pathological complete response (pCR), major pathological response (MPR), R0 resection rate, rate of underwent surgery and adverse events (AEs). Results: A total of 2912 patients (1453 receiving perioperative immunotherapy plus chemotherapy and 1459 receiving chemotherapy alone) were included in this systematic review and meta-analysis. The result showed that compared with chemotherapy alone, combined therapy significantly improved OS (HR = 0.68;95% CI: 0.56-0.83), EFS (HR = 0.58;95% CI: 0.51-0.65), pCR (OR = 7.53;95% CI: 4.63-12.26), MPR (OR = 5.03;95% CI: 3.40-7.44), R0 resection (OR = 1.58;95% CI: 1.152.18) and rate of underwent surgery (OR = 1.25;95% CI: 1.04-1.49). However, combination therapy was associated with higher risk of severe adverse event (OR = 1.46;95% CI: 1.19-1.78; P=0.0002), grade 3 and higher treatment-related adverse event (TRAE) (OR = 1.25;95% CI: 1.06-1.49; P=0.010), TRAE that led to interruption (OR = 1.90;95% CI: 1.34-2.68; P=0.0003) and immune-related adverse event (OR = 2.78;95% CI: 2.18-3.55; P<0.00001). Significant benefits were observed across most subgroups of EFS and pCR. However, no statistical differences were observed for EFS of never smoked (HR = 0.73;95% CI: 0.51-1.05) and EGFR-mutation positive (HR = 0.35;95% CI: 0.04-3.03). Conclusion: This systematic review and meta-analysis found superior efficacy associated with perioperative immunotherapy plus chemotherapy compared with chemotherapy alone in both tumor regression and prolonged survival in resectable NSCLC, but increased the risk of TRAE, so monitoring for adverse events is warranted. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier (CRD42023476786).

Neoadjuvant chemotherapy is associated with suppression of the B cell-centered immune landscape in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at advanced stages and associated with early distant metastasis and poor survival. Besides clinical factors, the tumor microenvironment (TME) emerged as a crucial determinant of patient survival and therapy response in many tumors, including PDAC. Thus, the presence of tumor-infiltrating lymphocytes and the formation of tertiary lymphoid structures (TLS) is associated with longer survival in PDAC. Although neoadjuvant therapy (NeoTx) has improved the management of locally advanced tumors, detailed insight into its effect on various TME components is limited. While a remodeling towards a proinflammatory state was reported for PDAC-infiltrating T cells, the effect of NeoTx on B cell subsets, including plasma cells, and TLS formation is widely unclear. We thus investigated the frequency, composition, and spatial distribution of PDAC-infiltrating B cells in primary resected (PR) versus neoadjuvant-treated patients using a novel multiplex immunohistochemistry panel. The NeoTx group displayed significantly lower frequencies of pan B cells, GC B cells, plasmablasts, and plasma cells, accompanied by a reduced abundance of TLS. This finding was supported by bulk RNA-sequencing analysis of an independent fresh frozen tissue cohort, which revealed that major B cell pathways were downregulated in the NeoTx group. We further observed that plasma cells frequently formed aggregates that localized close to TLS and that TLS+ patients displayed significantly higher plasma cell frequencies compared to TLS- patients in the PR group. Additionally, high densities of CD20+ intratumoral B cells were significantly associated with longer overall survival in the PR group. While CD20+ B cells held no prognostic value for NeoTx patients, an increased frequency of proliferating CD20+Ki67+ B cells emerged as an independent prognostic factor for longer survival in the NeoTx group. These results indicate that NeoTx differentially affects PDAC-infiltrating immune cells and may have detrimental effects on the existing B cell landscape and the formation of TLS. Gaining further insight into the underlying molecular mechanisms is crucial to overcome the intrinsic immunotherapy resistance of PDAC and develop novel strategies to improve the long-term outcome of PDAC patients.

Systematic review of targeted axillary dissection in node-positive breast cancer treated with neoadjuvant systemic therapy: variation in type of marker and timing of placement.

BACKGROUND: In node-positive (cN+) breast cancer treated with neoadjuvant systemic therapy, combining sentinel lymph node biopsy and targeted lymph node excision, that is targeted axillary dissection, increases accuracy. Targeted axillary dissection procedures differ in terms of the targeted lymph node excision technique. This systematic review aimed to provide an overview of targeted axillary dissection procedures regarding definitive marker type and timing of placement: before neoadjuvant systemic therapy (1-step procedure) or after neoadjuvant systemic therapy adjacent to a clip placed before the neoadjuvant therapy (2-step procedure). METHODS: PubMed and Embase were searched, to 4 July 2023, for RCTs, cohort studies, and case-control studies with at least 25 patients. Studies of targeted lymph node excision only (without sentinel lymph node biopsy), or where intraoperative localization of the targeted lymph node was not attempted, were excluded. For qualitative synthesis, studies were grouped by definitive marker and timing of placement. The targeted lymph node identification rate was reported. Study quality was assessed using a National Institutes of Health quality assessment tool. RESULTS: Of 277 unique records, 51 studies with a total of 4512 patients were included. Six definitive markers were identified: wire, 125I-labelled seed, 99mTc, (electro)magnetic/radiofrequency markers, black ink, and a clip. Fifteen studies evaluated one-step procedures, with the identification rate of the targeted lymph node at surgery varying from 8 of 13 to 47 of 47. Forty-one studies evaluated two-step procedures, with the identification rate of the clipped targeted lymph node on imaging after neoadjuvant systemic therapy varying from 49 to 100%, and the identification rate of the targeted lymph node at surgery from 17 of 24 to 100%. Most studies (40 of 51) were rated as being of fair quality. CONCLUSION: Various targeted axillary dissection procedures are used in clinical practice. Owing to study heterogeneity, the optimal targeted lymph node excision technique in terms of identification rate and feasibility could not be determined. Two-step procedures are at risk of not identifying the clipped targeted lymph node on imaging after neoadjuvant systemic therapy.

Lymph node volume predicts survival in esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy and surgery.

Large primary tumor volume has been identified as a poor prognostic factor of esophageal squamous cell carcinoma (ESCC) treated with definitive concurrent chemoradiotherapy (CCRT). However, when neoadjuvant CCRT and surgery are adopted, the prognostic impact of primary tumor and lymph node (LN) volume on clinical outcomes in ESCC remains to be elucidated. This study included 107 patients who received neoadjuvant CCRT and surgery for ESCC. The volume of the primary tumor and LN was measured using radiotherapy planning computed tomography scans, and was correlated with overall survival (OS), disease-free survival (DFS), and cancer failure pattern. The median OS was 24.2 months (IQR, 11.1-93.9) after a median follow-up of 18.4 months (IQR, 8.1-40.7). The patients with a baseline LN volume > 7.7 ml had a significantly worse median OS compared to those with smaller LN volume (18.8 vs. 46.9 months, p = 0.049), as did those with tumor regression grade (TRG) 3-5 after CCRT (13.9 vs. 86.7 months, p < 0.001). However, there was no association between OS and esophageal tumor volume (p = 0.363). Multivariate analysis indicated that large LN volume (HR 1.753, 95% CI 1.015-3.029, p = 0.044) and high TRG (HR 3.276, 95% CI 1.556-6.898, p = 0.002) were negative prognostic factors for OS. Furthermore, large LN volume was linked to increased locoregional failure (p = 0.033) and decreased DFS (p = 0.041). In conclusion, this study demonstrated that large LN volume is correlated with poor OS, DFS, and locoregional control in ESCC treated with neoadjuvant CCRT and esophagectomy.

Chemotherapy combined with endocrine neoadjuvant therapy for hormone receptor-positive local advanced breast cancer: a case report and literature review.

Background: Early studies have revealed antagonistic effects associated with stacking chemotherapy (CT) and endocrine therapy (ET), thereby conventional wisdom does not advocate the simultaneous combination of these two treatment modalities. Limited clinical studies exist on the combined use of neoadjuvant CT (NACT) and neoadjuvant ET (NET), and there are no reported instances of concurrent neoadjuvant treatment for locally advanced breast cancer (LABC) using capecitabine and fulvestrant (FUL). Case presentation: We reported a 54-year-old woman who was diagnosed with hormone receptor-positive (HR+) LABC at our hospital. After neoadjuvant treatment involving two distinct CT regimens did not lead to tumor regression. Consequently, the patient was transitioned to concurrent capecitabine and FUL therapy. This change resulted in favorable pathological remission without any significant adverse events during treatment. Conclusions: A novel approach involving concurrent neoadjuvant therapy with CT and endocrine therapy may offer a potentially effective treatment avenue for some cases with HR+ LABC.

The role of neoadjuvant chemotherapy for patients with variant histology muscle invasive bladder cancer undergoing robotic cystectomy: Data from the International Robotic Cystectomy Consortium.

OBJECTIVE: To assess the role of neoadjuvant chemotherapy (NAC) before robot-assisted radical cystectomy (RARC) for patients with variant histology (VH) muscle-invasive bladder cancer (MIBC). METHODS: Retrospective review of 988 patients who underwent RARC (2004-2023) for MIBC. Primary outcomes included the utilization of NAC among this cohort of patients, frequency of downstaging, and discordance between preoperative and final pathology in terms of the presence of VH. Secondary outcomes included disease-specific (DSS), recurrence-free (RFS), and overall survival (OS). RESULTS: A total of 349 (35%) had VH on transurethral resection or at RARC. The 4 most common VH subgroups were squamous (n = 94), adenocarcinoma (n = 64), micropapillary (n = 34), and sarcomatoid (n = 21). There was no difference in OS (log-rank: P = 0.43 for adenocarcinoma, P = 0.12 for micropapillary, P = 0.55 for sarcomatoid, P = 0.29 for squamous), RFS (log-rank: P = 0.25 for adenocarcinoma, P = 0.35 for micropapillary, P = 0.83 for sarcomatoid, P = 0.79 for squamous), or DSS (log-rank P = 0.91 for adenocarcinoma, P = 0.15 for micropapillary, 0.28 for sarcomatoid, P = 0.92 for squamous) among any of the VH based on receipt of NAC. Patients with squamous histology who received NAC were more likely to be downstaged on final pathology compared to those who did not (P < 0.01). CONCLUSION: Our data showed no significant difference in OS, RFS, or DSS for patients with VH MIBC cancer who received NAC before RARC. Patients with the squamous variant who received NAC had more pathologic downstaging compared to those who did not. The role of NAC among patients with VH is yet to be defined. Results were limited by small number in each individual group and lack of exact proportion of VH.

Nomogram for predicting pathological response to neoadjuvant treatment in patients with locally advanced gastric cancer: Data from a phase III clinical trial.

PURPOSE: This study aimed to establish a nomogram using routinely available clinicopathological parameters to predict the pathological response in patients with locally advanced gastric cancer (LAGC) undergoing neoadjuvant treatment. MATERIALS AND METHODS: We conducted this study based on the ongoing Neo-CRAG trial, a prospective study focused on preoperative treatment in patients with LAGC. A total of 221 patients who underwent surgery following neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) at Sun Yat-sen University Cancer Center between June 2013 and July 2022 were included in the analysis. We defined complete or near-complete pathological regression and ypN0 as good response (GR), and determined the prognostic value of GR by Kaplan-Meier survival analysis. Eventually, a nomogram for predicting GR was developed based on statistically identified predictors through multivariate logistic regression analysis and internally validated by the bootstrap method. RESULTS: GR was confirmed in 54 patients (54/221, 24.4%). Patients who achieved GR had a longer progression-free survival and overall survival. Then, five independent factors, including pretreatment tumor differentiation, clinical T stage, monocyte count, CA724 level, and the use of nCRT, were identified. Based on these predictors, the nomogram was established with an area under the curve (AUC) of 0.777 (95% CI, 0.705-0.850) and a bias-corrected AUC of 0.752. CONCLUSION: A good pathological response after neoadjuvant treatment was associated with an improved prognosis in LAGC patients. The nomogram we established exhibits a high predictive capability for GR, offering potential value in devising personalized and precise treatment strategies for LAGC patients.

Predicting pathological complete response to neoadjuvant chemotherapy in breast cancer patients: use of MRI radiomics data from three regions with multiple machine learning algorithms.

OBJECTIVE: To construct a multi-region MRI radiomics model for predicting pathological complete response (pCR) in breast cancer (BCa) patients who received neoadjuvant chemotherapy (NACT) and provide a theoretical basis for the peritumoral microenvironment affecting the efficacy of NACT. METHODS: A total of 133 BCa patients who received NACT, including 49 with confirmed pCR, were retrospectively analyzed. The radiomics features of the intratumoral region, peritumoral region, and background parenchymal enhancement (BPE) were extracted, and the most relevant features were obtained after dimensional reduction. Then, combining different areas, multivariate logistic regression analysis was used to select the optimal feature set, and six different machine learning models were used to predict pCR. The optimal model was selected, and its performance was evaluated using receiver operating characteristic (ROC) analysis. SHAP analysis was used to examine the relationship between the features of the model and pCR. RESULTS: For signatures constructed using three individual regions, BPE provided the best predictions of pCR, and the diagnostic performance of the intratumoral and peritumoral regions improved after adding the BPE signature. The radiomics signature from the combination of all the three regions with the XGBoost machine learning algorithm provided the best predictions of pCR based on AUC (training set: 0.891, validation set: 0.861), sensitivity (training set: 0.882, validation set: 0.800), and specificity (training set: 0.847, validation set: 0.84). SHAP analysis demonstrated that LZ_log.sigma.2.0.mm.3D_glcm_ClusterShade_T12 made the greatest contribution to the predictions of this model. CONCLUSION: The addition of the BPE MRI signature improved the prediction of pCR in BCa patients who received NACT. These results suggest that the features of the peritumoral microenvironment are related to the efficacy of NACT.

Does the time interval from neoadjuvant camrelizumab combined with chemotherapy to surgery affect outcomes for locally advanced esophageal squamous cell carcinoma?

BACKGROUND: There is currently no consensus on the optimal interval time between neoadjuvant therapy and surgery, and whether prolonged time interval from neoadjuvant therapy to surgery results in bad outcomes for locally advanced esophageal squamous cell carcinoma (ESCC). In this study, we aim to evaluate outcomes of time intervals ≤ 8 weeks and > 8 weeks in locally advanced ESCC. METHODS: This retrospective study consecutively included ESCC patients who received esophagectomy after neoadjuvant camrelizumab combined with chemotherapy at the Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine. The primary endpoints were disease-free survival (DFS) and overall survival (OS), while the secondary endpoints were pathological response, surgical outcomes, and postoperative complications. RESULTS: From 2019 to 2021, a total of 80 patients were included in our study and were divided into two groups according to the time interval from neoadjuvant immunochemotherapy to surgery: ≤ 8 weeks group (n = 44) and > 8 weeks group (n = 36). The rate of MPR in the ≤ 8 weeks group was 25.0% and 27.8% in the > 8 weeks group (P = 0.779). The rate of pCR in the ≤ 8 weeks group was 11.4%, with 16.7% in the > 8 weeks group (P = 0.493). The incidence of postoperative complications in the ≤ 8 weeks group was 27.3% and 19.4% in the > 8 weeks group (P = 0.413). The median DFS in the two groups had not yet reached (hazard ratio [HR], 3.153; 95% confidence interval [CI] 1.383 to 6.851; P = 0.004). The median OS of ≤ 8 weeks group was not achieved (HR, 3.703; 95% CI 1.584 to 8.657; P = 0.0012), with the > 8 weeks group 31.6 months (95% CI 21.1 to 42.1). In multivariable analysis, inferior DFS and OS were observed in patients with interval time > 8 weeks (HR, 2.992; 95% CI 1.306 to 6.851; and HR, 3.478; 95% CI 1.481 to 8.170, respectively). CONCLUSIONS: Locally advanced ESCC patients with time interval from neoadjuvant camrelizumab combined with chemotherapy to surgery > 8 weeks were associated with worse long-term survival.

Radiomics-enhanced early regression index for predicting treatment response in rectal cancer: a multi-institutional 0.35 T MRI-guided radiotherapy study.

PURPOSE: The accurate prediction of treatment response in locally advanced rectal cancer (LARC) patients undergoing MRI-guided radiotherapy (MRIgRT) is essential for optimising treatment strategies. This multi-institutional study aimed to investigate the potential of radiomics in enhancing the predictive power of a known radiobiological parameter (Early Regression Index, ERITCP) to evaluate treatment response in LARC patients treated with MRIgRT. METHODS: Patients from three international sites were included and divided into training and validation sets. 0.35 T T2*/T1-weighted MR images were acquired during simulation and at each treatment fraction. The biologically effective dose (BED) conversion was used to account for different radiotherapy schemes: gross tumour volume was delineated on the MR images corresponding to specific BED levels and radiomic features were then extracted. Multiple logistic regression models were calculated, combining ERITCP with other radiomic features. The predictive performance of the different models was evaluated on both training and validation sets by calculating the receiver operating characteristic (ROC) curves. RESULTS: A total of 91 patients was enrolled: 58 were used as training, 33 as validation. Overall, pCR was observed in 25 cases. The model showing the highest performance was obtained combining ERITCP at BED = 26 Gy with a radiomic feature (10th percentile of grey level histogram, 10GLH) calculated at BED = 40 Gy. The area under ROC curve (AUC) of this combined model was 0.98 for training set and 0.92 for validation set, significantly higher (p = 0.04) than the AUC value obtained using ERITCP alone (0.94 in training and 0.89 in validation set). CONCLUSION: The integration of the radiomic analysis with ERITCP improves the pCR prediction in LARC patients, offering more precise predictive models to further personalise 0.35 T MRIgRT treatments of LARC patients.

Image-based artificial intelligence for the prediction of pathological complete response to neoadjuvant chemoradiotherapy in patients with rectal cancer: a systematic review and meta-analysis.

OBJECTIVE: Artificial intelligence (AI) holds enormous potential for noninvasively identifying patients with rectal cancer who could achieve pathological complete response (pCR) following neoadjuvant chemoradiotherapy (nCRT). We aimed to conduct a meta-analysis to summarize the diagnostic performance of image-based AI models for predicting pCR to nCRT in patients with rectal cancer. METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A literature search of PubMed, Embase, Cochrane Library, and Web of Science was performed from inception to July 29, 2023. Studies that developed or utilized AI models for predicting pCR to nCRT in rectal cancer from medical images were included. The Quality Assessment of Diagnostic Accuracy Studies-AI was used to appraise the methodological quality of the studies. The bivariate random-effects model was used to summarize the individual sensitivities, specificities, and areas-under-the-curve (AUCs). Subgroup and meta-regression analyses were conducted to identify potential sources of heterogeneity. Protocol for this study was registered with PROSPERO (CRD42022382374). RESULTS: Thirty-four studies (9933 patients) were identified. Pooled estimates of sensitivity, specificity, and AUC of AI models for pCR prediction were 82% (95% CI: 76-87%), 84% (95% CI: 79-88%), and 90% (95% CI: 87-92%), respectively. Higher specificity was seen for the Asian population, low risk of bias, and deep-learning, compared with the non-Asian population, high risk of bias, and radiomics (all P < 0.05). Single-center had a higher sensitivity than multi-center (P = 0.001). The retrospective design had lower sensitivity (P = 0.012) but higher specificity (P < 0.001) than the prospective design. MRI showed higher sensitivity (P = 0.001) but lower specificity (P = 0.044) than non-MRI. The sensitivity and specificity of internal validation were higher than those of external validation (both P = 0.005). CONCLUSIONS: Image-based AI models exhibited favorable performance for predicting pCR to nCRT in rectal cancer. However, further clinical trials are warranted to verify the findings.