This prospective, two-cohort phase 2 trial with random allocation was conducted to evaluate the safety and efficacy of neoadjuvant tislelizumab combined with nab-paclitaxel/paclitaxel and cisplatin (TP) in patients with esophageal squamous cell carcinoma (ESCC). Patients were enrolled and randomly assigned to the nab-paclitaxel or paclitaxel cohorts at a 1:1 ratio, and received intravenous tislelizumab (200 mg, day 1) combined with cisplatin (25 mg/m2, days 1-3) and either nab-paclitaxel (125 mg/m2, days 1 and 8) or paclitaxel (150 mg/m2, day 1) in a 21-day cycle for two cycles before surgery. The primary endpoint was the major pathological response (MPR) rate. From March 01, 2022 to April 10, 2023, 46 patients were enrolled (n = 23 in each cohort), with 42 patients receiving the full two-cycle treatments and undergoing surgery (n = 22 in the nab-paclitaxel cohort, n = 20 in the paclitaxel cohort). The MPR rate and the pCR rate in the total cohort were 44.2% (19/42) and 19.0% (8/42), respectively, with 59.1% (13/22) and 31.8% (7/22) in the nab-paclitaxel cohort and 30.0% (6/20) and 5.0% (1/20) in paclitaxel cohorts. The most common treatment-related adverse events (TRAEs) were anemia (89.1%) and alopecia (71.7%), and no significant difference in TRAEs was observed between the two cohorts. Up until March 28, 2024, the median follow-up time was 15.5 months (range of 6.0-24.3 months), and the survival analysis revealed that the patients in the nab-paclitaxel cohort had a higher event-free survival (p = .002). In conclusion, neoadjuvant tislelizumab combined with cisplatin and nab-paclitaxel, rather than cisplatin and paclitaxel, is a more effective neoadjuvant strategy for locally advanced thoracic ESCC.

To investigate the predictive value of 2-[18F]-fluoro-2-deoxy-D-glucose ([18F]FDG) PET/CT for evaluating primary tumor (PT) and lymph node (LN) responses after neoadjuvant programmed death-ligand 1 (PD-L1) blockade monotherapy in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC).

In the single-arm phase 1b NATION-1907 trial (NCT04215471), 23 patients with LA-ESCC received two cycles of neoadjuvant PD-L1 blockade Adebrelimab followed by surgery. Among these, 18 patients underwent [18F]FDG PET/CT scans both before immunotherapy and prior to surgery. Standardized uptake value corrected for lean body mass (SUL)-derived parameters, including SULmax and SULpeak, were documented for PTs and LNs. Lesions > 1cm3 were segmented using thresholds of 41% and 50% of SULmax, respectively, following European Association of Nuclear Medicine (EANM) guidelines, with metabolic tumor volume (MTV) and total lesion glycolysis (TLG) calculated. Percentage changes of all metabolic parameters were also recorded. Residual viable tumor ≤ 33% were classified as well-responders, whereas residual viable tumor > 33% were classified as poor-responders based on histological evaluation.

In the PT analysis, 10 patients were classified as PT well-responders and 8 as PT poor-responders. All post-treatment metabolic parameters, except MTV, were significantly lower in well-responders compared to poor-responders. The %ΔMTV, %ΔTLG were significantly higher in the poor-responder group (all P < 0.05). ROC curves indicated %ΔMTV41 exhibited optimum performance in predicting well-responders, with an AUC of 0.875 (cut-off: -31.01). Furthermore, %ΔMTV41 significantly predicted patients' recurrence-free survival (RFS) (P < 0.1). In the LN analysis, 7 LNs were classified as well-responders and 10 as poor-responders. Pre-treatment SULmax, SULpeak were significantly lower in poor-responders compared to well-responders. Post-treatment MTV50 and all percentage changes in parameters were significantly higher in the poor-responder group (all P < 0.05). Receiver operating characteristic curve (ROC) analysis indicated %ΔTLG50 had excellent predictive performance for well-responders, with an AUC of 1.000 (cut-off: -7.5). However, there was no significant correlation between the metabolic response evaluations for PTs and LNs.

The metabolic parameters of [18F]FDG PET/CT, particularly %ΔMTV and %ΔTLG, could effectively predict well-responders among both PTs and LNs to neoadjuvant PD-L1 blockade monotherapy in LA-ESCC, which may facilitate personalized immunotherapy and serve as a stratification tool in future larger-scale studies.

Knowledge on the incidence of surgical complications after oesophagectomy for oesophageal cancer in nationwide practice is scarce. The aim of this study was to assess complication trends after oesophagectomy in a nationwide, population-based, unselected cohort.

All patients undergoing oesophagectomy for oesophageal cancer in Finland in 1987-2016 were included. All complications defined by the Esophagectomy Complications Consensus Group (ECCG) were reported in three 10-year periods. Chi-square test and Kruskal-Wallis test were used to compare outcomes in these periods.

A total of 1493 patients were included. From 1987 to 1996 to 2007-2016, improvements were seen in the rate of major complications (49% vs. 43%, p = 0.039), length of hospital stay (19 vs. 14 days, median, p < 0.001), length of ICU-stay (3 vs. 2 days, median, p < 0.001) and 90-day mortality (17.9% vs. 5.4%, p < 0.001), while pneumonia (16% vs. 23%, p = 0.029) and anastomotic leak (8% vs. 12% in total leaks, p = 0.006 for type II leak) increased. The most common complications were pneumonia, pleural effusion requiring drainage (16% vs. 23%, p = 0.080), atrial dysrhythmia (16% vs. 15%, p = 0.464) and anastomotic leak. The most common complication categories defined by ECCG were pulmonary (36% vs. 42%, p = 0.151) and gastrointestinal (21% vs. 23%, p = 0.398) complications.

This study reports high postoperative morbidity after oesophagectomy in nationwide practice. Mortality has significantly improved during the years, and it appears that patients who would have died earlier, can now be rescued. While the relative occurrence of complications has remained constant, overall morbidity has decreased as the more severe outcomes have decreased.

Regional lymph node (LN) status is a key prognostic factor in oesophageal cancer (OeC). Tumour-derived antigens can activate immune reactions in LNs, potentially reflecting the host's anti-tumour immune response. It remains unclear whether this response is homogeneous across all tumour negative LNs (LNneg) within individual OeC patients.

To investigate the hypotheses: (1) the host anti-tumour immune response is similar in all LNneg from an individual OeC patient reflected in a similar microarchitecture in all LNneg; and (2) immune response measured in the largest LNneg can represent that of all LNnegs.

(y)pN0 patients from the Oe02 trial with at least two LNneg were included. Microarchitectural LN features (germinal centres (GermC), lymphocytes outside GermCs (lymphocytes), histiocytes) were morphometrically quantified. Linear mixed-effects models, intraclass correlation coefficients (ICC) and Bland-Altman plots were used to determine systematic bias, reliability/variability and agreement of LNneg microarchitecture measurements.

Linear mixed-effects models showed no systematic bias in LNneg microarchitectural features within a patient. The ICC revealed moderate variability for lymphocytes (ICC: 0.39; 95 %CI: 0.01- 0.61, p = 0.02)) and GermC (ICC: 0.50; 95 %CI: 0.22-0.68, p < 0.001), and high variability for histiocytes (ICC: 0.07 (95 %CI: -0.45-0.40, p = 0.38). Bland-Altman plots showed that 5.0 % of GermC, 5.0 % of histiocytes and 8.5 % of lymphocyte measurements were outside the 95 % limits of agreement.

This is the first study to systematically assess agreement of microarchitectural features in LNneg within an individual (y)pN0 OeC patient. The absence of systematic bias supports using largest LNneg as surrogate for OeC patient's overall anti-tumour immune response.

Standard neoadjuvant chemotherapy for locally advanced esophageal or gastroesophageal junction squamous cancer, 5-fluorouracil plus platinum, is toxic and logistically challenging; alternative regimens are needed.

This was a phase III randomized open-label noninferiority trial at Tata Memorial Center, India, in resectable locally advanced esophageal or gastroesophageal junction squamous cancer. Patients were randomly assigned 1:1 to 3 cycles of 3-weekly platinum (cisplatin 75 mg/m2 or carboplatin area under the curve 6) with paclitaxel 175 mg/m2 (day 1) or 5-fluorouracil 1000 mg/m2 continuous infusion (days 1-4), followed by surgery.

Between August 2014 and June 2022, we enrolled 420 patients; 210 to each arm. Statistically significantly more patients on paclitaxel plus platinum (n =194, 92.3%) received all 3 chemotherapy cycles than on 5-fluorouracil with platinum (n = 170, 85.9%; P = .009). 5-fluorouracil plus platinum caused more grade 3 or higher toxicities (n = 124, 69.7%) than paclitaxel plus platinum (n = 97, 51.9%; P = .001). Surgery was performed in 131 (62.4%) patients on 5-fluorouracil plus platinum vs 139 (66.2%) on paclitaxel plus platinum (P = .415). Paclitaxel plus platinum resulted in higher pathologic primary tumor clearance (n = 33, 25.8%, vs n = 17, 15%; P = .04) and pathologic complete responses in 21.9% compared with 12.4% from 5-fluorouracil plus platinum (P = .053). Median overall survival was 27.5 months (95% confidence interval [CI] = 18.6 to 43.5 months) from paclitaxel plus platinum, which was noninferior to 27.1 months (95% CI = 18.8 to 40.7 months) from 5-fluorouracil plus platinum (hazard ratio [HR] = 0.89, 95% CI = 0.72 to 1.09; P = .346).

Neoadjuvant paclitaxel plus platinum chemotherapy is safer and results in similar R0 resections, higher pathologic tumor clearance and noninferior survival compared with 5-fluorouracil plus platinum. Paclitaxel plus platinum should replace 5-fluorouracil plus platinum as neoadjuvant chemotherapy for resectable locally advanced esophagealor gastroesophageal junction squamous cancer.

CTRI/2014/04/004516.

As humans undergo the aging process, they become more vulnerable to various types of cancers, including gastric cancer (GC), which is frequently associated with aging. The senescent phenotype is closely linked to lysosomes, but research on the combined impact of senescence and lysosomes on GC prognosis is scarce.

To construct and validate a prognostic model for gastric cancer (GC), we obtained gene expression and clinical data of GC patients from Cancer Genome Atlas (TCGA) databases. We employed Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression for model construction and ConsensusClusterPlus R package for generating cluster heatmaps. The model's predictive ability was evaluated through Kaplan-Meier survival analysis and ROC curve analysis. Our analysis included an assessment of the senescence and lysosome state using expression profiles and immune infiltration analysis through CIBERSORT methods. Finally, we validated potential gene targets through cellular experiments.

"In this research, we discovered two subtypes of gastric cancer (GC), Cluster 1 and Cluster 2. These subtypes are characterized by the presence of lysosomes and senescence, and we have identified distinct molecular features unique to each subtype. We observed that Cluster 2 had a lower survival prognosis compared to Cluster 1. Additionally, we have developed a risk prediction model that takes into consideration the presence of lysosomes and senescence. Patients in the high-risk group, as predicted by our model, experienced shorter survival times. Further analysis included immune infiltration, immune checkpoint, and chemotherapy evaluation of GC patients. We have displayed the frequency of mutations and copy number variations (CNVs) in visual formats. Our cellular experiments demonstrated that the MMP12 gene serves as a protective factor in GC cells."

In conclusion, we have clarified the extensive relationship between lysosomes and senescence in GC and developed a risk signature to forecast the prognosis of GC patients. MMP12 could be a promising protective factor for GC patients and might present a novel concept for anticipating the efficacy of targeted therapies and immunotherapies in GC patients.

Minimally invasive esophagectomy (MIO) offers a less traumatic resection for cancer patients resulting in improved quality of life. Concerns about the oncological efficacy of the procedure and potential impact on survival may have limited its wider adoption. This study reports survival outcomes fifteen years after patients underwent a total MIO for esophageal cancer.

A single-centre analysis of survival outcomes was conducted on all patients who underwent MIO between 2004 and 2010 and had completed at least 15-years follow-up. Actual overall survival (OS) and disease-free survival (DFS) were evaluated with the Kaplan-Meier method. The pattern of association of patient factors with survival was assessed with the Cox regression analysis.

A total of 121 patients underwent resection, with 4 (3.3%) in-patient deaths. With a median follow-up time of 15.2 years, the median OS was 41 months. At 15-years there were 20 survivors (17.1%), with numbers at 10 and 5 years being 34 (29.1%) and 45 (38.5%) respectively. Median DFS was 27 months, with 19 (16.2%) patient disease free at 15 years, and 32 (27.4%) and 38 (32.5%) at 10 and 5 years respectively. Predictors of poor survival were the intracorporeal fashioning of the gastric conduit, perioperative blood transfusions, advanced disease stage and recurrence.

Long term survival outcomes following MIO support its increasing recognition as the standard of care as for curative resection in esophageal cancer.

Esophageal cancer remains a significant global health challenge. Several treatment modalities were explored in randomized controlled trials (RCTs) in recent decades. This study evaluates the robustness of RCTs focusing on esophageal cancer treatment using the fragility index (FI) and reverse fragility index (RFI).

A systematic review of RCTs studying different treatment modalities for esophageal cancer from 2000 to 2023 was conducted. The FI and RFI were utilized to gauge the robustness of statistically significant and non-significant outcomes, respectively. The FI represents the minimal number of patient outcomes that would need to alter to overturn a trial's statistical significance, while RFI indicates the minimal changes required to achieve significance in non-significant results.

Out of 4028 studies retrieved, 21 RCTs were included for final analysis. The studies spanned 2001 to 2023 with a mean followup of 66 months (range, 29-108 months) and median number of patients of 194 (range, 45-802). The most common treatment modalities examined in these studies were neoadjuvant chemoradiotherapy (n = 7, 33.3%), neoadjuvant chemotherapy (n = 4, 19.0%), and neoadjuvant immunotherapy (n = 2, 9.5%). Only 5 studies (23.8%) had a statistically significant primary outcome result with a median FI of 6 (IQR, 2.5-8.5). Non-significant primary outcomes were seen in 16 studies (76.2%) with a median RFI of 4 (IQR 1-11) and lost to followup of 0 (IQR 0-4). In the study with the highest FI (10), the FI was lower than the number of patients lost to followup (13).

Our findings demonstrate that most RCTs on esophageal cancer treatments did not report significant primary outcomes. The few studies that reported significant results had a low fragility index, suggesting a vulnerability in their findings.

Patients with supraclavicular lymph node (SLN) metastasis from esophageal cancer encounter significant variations in treatment approaches due to differences in pathological subtypes and the lack of a unified regional staging system between East Asian and Western countries. The Tiger study aims to develop an internationally recognized staging system and to delineate the extent of regional lymph node dissection. In the context of esophageal squamous cell carcinoma (SCC) with SLN metastasis, the treatment paradigms from East Asia offer valuable insights. The Japan Esophageal Society (JES) 12th edition staging system guides a tailored comprehensive treatment strategy, emphasizing either radiotherapy and chemotherapy or surgical intervention. In contrast, esophageal adenocarcinoma (AC) predominates in Western countries, where the 8th edition of the American Joint Committee on Cancer (AJCC) staging system classifies SLN metastasis as a distant metastasis, advocating for systemic therapy as the primary treatment modality. Nonetheless, compelling evidence suggests that a multidisciplinary treatment approach, incorporating either radiotherapy and chemotherapy or surgery as the initial treatment, can yield superior outcomes for these patients compared to chemotherapy alone.

Multimodal therapy regimens became the standard of care for patients with esophageal cancer, whereas surgical resection remains at the center of curative treatment modalities. Current guidelines provide no recommendations on the extent of the oral resection margin, especially in the era of neoadjuvant therapy. Therefore, this study aimed to evaluate the relationship between the oral tumor-free resection margin and overall survival.

Retrospective study with 382 1:1 propensity-matched patients out of 660 patients, operated between 2013 and 2019, with an Ivor-Lewis-esophagectomy for adenocarcinoma and squamous cell carcinoma of the esophagus or esophagogastric junction after neoadjuvant therapy. Independent pathologists measured the oral resection margin after formalin fixation.

The mean oral tumor-free resection margin was 37.2 ± 0.6 mm. The ideal cut-off for survival differences was determined for 33 mm. Patients with an oral resection margin of more than 33 mm had a better median overall survival (≤33 mm: 45.0 months, 95% confidence interval: 22.4-67.6 months, >33 mm: not reached, P = .005). An oral resection margin of more than 33 mm proved to be an independent favorable prognostic factor for patients' overall survival in multivariate Cox regression analyses (P = .049).

This study analyzed a patient cohort retrospectively after curative intended Ivor-Lewis-esophagectomy after neoadjuvant therapy. An oral resection margin of more than 33 mm is a factor for improved overall survival. Therefore, a minimum resection margin of 34 mm after fixation could be suggested.

Personalising management of primary oesophageal adenocarcinoma requires better risk stratification. Lack of independent validation of proposed imaging biomarkers has hampered clinical translation. We aimed to prospectively validate previously identified prognostic grey-level co-occurrence matrix (GLCM) CT features for 3-year overall survival.

Following ethical approval, clinical and contrast-enhanced CT data were acquired from participants from five institutions. Data from three institutions were used for training and two for testing. Survival classifiers were modelled on prespecified variables ('Clinical' model: age, clinical T-stage, clinical N-stage; 'ClinVol' model: clinical features + CT tumour volume; 'ClinRad' model: ClinVol features + GLCM_Correlation and GLCM_Contrast). To reflect current clinical practice, baseline stage was also modelled as a univariate predictor ('Stage'). Discrimination was assessed by area under the receiver operating curve (AUC) analysis; calibration by Brier scores; and clinical relevance by thresholding risk scores to achieve 90% sensitivity for 3-year mortality.

A total of 162 participants were included (144 male; median 67 years [IQR 59, 72]; training, 95 participants; testing, 67 participants). Median survival was 998 days [IQR 486, 1594]. The ClinRad model yielded the greatest test discrimination (AUC, 0.68 [95% CI 0.54, 0.81]) that outperformed Stage (ΔAUC, 0.12 [95% CI 0.01, 0.23]; p = .04). The Clinical and ClinVol models yielded comparable test discrimination (AUC, 0.66 [95% CI 0.51, 0.80] vs. 0.65 [95% CI 0.50, 0.79]; p > .05). Test sensitivity of 90% was achieved by ClinRad and Stage models only.

Compared to Stage, multivariable models of prespecified clinical and radiomic variables yielded improved prediction of 3-year overall survival.

Previously identified radiomic features are prognostic but may not substantially improve risk stratification on their own.

• Better risk stratification is needed in primary oesophageal cancer to personalise management. • Previously identified CT features-GLCM_Correlation and GLCM_Contrast-contain incremental prognostic information to age and clinical stage. • Compared to staging, multivariable clinicoradiomic models improve discrimination of 3-year overall survival.

In the era of immunotherapy, neoadjuvant immunochemotherapy (NAIC) for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC) is used clinically but lacks of high-level clinical evidence. This study aimed to compare the safety and long-term efficacy of NAIC followed by minimally invasive esophagectomy (MIE) with those of neoadjuvant chemotherapy (NAC) followed by MIE.

A prospective, single-center, open-label, randomized phase III clinical trial was conducted at Henan Cancer Hospital, Zhengzhou, China. Patients were randomly assigned to receive either neoadjuvant toripalimab (240 mg) plus paclitaxel (175 mg/m2) + cisplatin (75 mg/m2) (toripalimab group) or paclitaxel + cisplatin alone (chemotherapy group) every 3 weeks for 2 cycles. After surgery, the toripalimab group received toripalimab (240 mg every 3 weeks for up to 6 months). The primary endpoint was event-free survival (EFS). The pathological complete response (pCR) and overall survival (OS) were key secondary endpoints. Adverse events (AEs) and quality of life were also assessed.

Between May 15, 2020 and August 13, 2021, 252 ESCC patients ranging from T1N1-3M0 to T2-3N0-3M0 were enrolled for interim analysis, with 127 in the toripalimab group and 125 in the chemotherapy group. The 1-year EFS rate was 77.9% in the toripalimab group compared to 64.3% in the chemotherapy group (hazard ratio [HR] = 0.62; 95% confidence interval [CI] = 0.39 to 1.00; P = 0.05). The 1-year OS rates were 94.1% and 83.0% in the toripalimab and chemotherapy groups, respectively (HR = 0.48; 95% CI = 0.24 to 0.97; P = 0.037). The patients in the toripalimab group had a higher pCR rate (18.6% vs. 4.6%; P = 0.001). The rates of postoperative Clavien-Dindo grade IIIb or higher morbidity were 9.8% in the toripalimab group and 6.8% in the chemotherapy group, with no significant difference observed (P = 0.460). The rates of grade 3 or 4 treatment-related AEs did not differ between the two groups (12.5% versus 12.4%).

The interim results of this ongoing trial showed that in resectable ESCC, the addition of perioperative toripalimab to NAC is safe, may improve OS and might change the standard treatment in the future.

Radical surgery for esophageal cancer requires macroscopic and microscopic clearance of all malignant tissue. A critical element of the procedure is achieving a negative circumferential margin (CRM) to minimize local recurrence. The utility of minimally invasive surgery poses challenges in replicating techniques developed in open surgery, particularly for hiatal dissection in esophago-gastrectomy. In this study, the technical approach and clinical and oncological outcomes for open and laparoscopic esophago-gastrectomy are described with particular reference to CRM involvement.

This cohort study included all patients undergoing either open or laparoscopic esophago-gastrectomy between January 2004 and June 2022 in a single tertiary center. A standard surgical technique for hiatal dissection of the esophago-gastric junction developed in open surgery was adapted for a laparoscopic approach. Clinical parameters, length of stay (LOS), postoperative complications, and mortality data were collected and analyzed by a Mann-Whitney U or Fisher's exact method.

Overall 447 patients underwent an esophago-gastrectomy in the study with 219 open and 228 laparoscopic procedures. The CRM involvement was 18.8% in open surgery and 13.6% in laparoscopic surgery. The 90-day-mortality for open surgery was 4.1 compared with 2.2% for laparoscopic procedures. Median Intensive care unit (ITU), inpatient LOS and 30-day readmission rates were shorter for laparoscopic compared with open esophago-gastrectomy (ITU: 5 versus 8 days, P= 0.0004; LOS: 14 versus 20 days, P= 0.022; 30-day re-admission 7.46 versus 10.50%). Postoperative complication rates were comparable across both cohorts. The rates of starting adjuvant chemotherapy were 51.8 after open and 74.4% in laparoscopic esophago-gastrectomy.

This study presents a standardized surgical approach to hiatal dissection for esophageal cancer. The authors present equivalence between open and laparoscopic esophago-gastrectomy in clinical, oncological, and survival outcomes with similar rates of CRM involvement. The authors also observe a significantly shorter hospital length of stay with the minimally invasive approach.

This study aims to analyze the efficacy and safety of neoadjuvant programmed cell death-1 (PD-1) blockade plus chemotherapy in real-world applications. Additionally, we report survival outcomes with a median follow-up of 40.1 months.

From January 2018 to October 2022, we retrospectively recruited patients with esophageal squamous cell carcinoma (ESCC) who underwent surgery after receiving PD-1 blockade (immunotherapy) plus chemotherapy at Jiangsu Cancer Hospital.

A total of 132 eligible ESCC patients were included, and R0 resection was achieved in 131 cases (99.2 %). A complete pathological response rate (ypT0N0) was observed in 32 patients (24.2 %), and the objective response rate was 59.1 %. The most common grade 3-4 treatment-related adverse events (TRAEs) were leukopenia (18.2 %) and neutropenia (15.9 %). Three cases (2.3 %) of grade 3 immune-related AEs were observed, including increased ALT (0.8 %), rash (0.8 %), and encephalitis (0.8 %). The 1-year disease-free survival (DFS) and overall survival (OS) rates were 68.2 % and 89.4 %, respectively, and the 2-year DFS and OS rates were 55.1 % and 78.6 %, respectively. The pathological responses of 103 cases (94.5 % of 109) of the index lymph node (ILN) were categorized as the worst regression subgroup. In these cases, using the pathological response of the ILN to indicate the status of other lymph nodes would not result to a missed therapeutic lymph node dissection.

Neoadjuvant immunotherapy plus chemotherapy is safe and effective for ESCC, with observable survival benefits. The pathological response of the ILN after neoadjuvant therapy may have important value in guiding therapeutic lymph node dissection.

The role of neoadjuvant chemotherapy (NAC) in colon cancer remains unclear. This trial investigated whether 3 months of modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or capecitabine and oxaliplatin (CAPOX) as NAC could improve outcomes in patients with locally advanced colon cancer versus upfront surgery.

OPTICAL was a randomized, phase III trial in patients with clinically staged locally advanced colon cancer (T3 with extramural spread into the mesocolic fat ≥5 mm or T4). Patients were randomly assigned 1:1 to receive six preoperative cycles of mFOLFOX6 or four cycles of CAPOX, followed by surgery and adjuvant chemotherapy (NAC group), or immediate surgery and the physician's choice of adjuvant chemotherapy (upfront surgery group). The primary end point was 3-year disease-free survival (DFS) assessed in the modified intention-to-treat (mITT) population.

Between January 2016 and April 2021, of the 752 patients enrolled, 744 patients were included in the mITT analysis (371 in the NAC group; 373 in the upfront surgery group). At a median follow-up of 48.0 months (IQR, 46.0-50.1), 3-year DFS rates were 82.1% in the NAC group and 77.5% in the upfront surgery group (stratified hazard ratio [HR], 0.74 [95% CI, 0.54 to 1.03]). The R0 resection was achieved in 98% of patients who underwent surgery in both groups. Compared with upfront surgery, NAC resulted in a 7% pathologic complete response rate (pCR), significantly lower rates of advanced tumor staging (pT3-4: 77% v 94%), lymph node metastasis (pN1-2: 31% v 46%), and potentially improved overall survival (stratified HR, 0.44 [95% CI, 0.25 to 0.77]).

NAC with mFOLFOX6 or CAPOX did not show a significant DFS benefit. However, this neoadjuvant approach was safe, resulted in substantial pathologic downstaging, and appears to be a viable therapeutic option for locally advanced colon cancer.

The higher pathologic complete response (pCR) after neoadjuvant chemoradiotherapy compared with neoadjuvant chemotherapy for locally advanced esophageal squamous cell carcinoma (ESCC) has not translated into significant gains in overall survival. Data on the long-term survival of patients who obtained a pCR after neoadjuvant chemotherapy are scarce. Therefore, this study aimed to evaluate the long-term prognosis and recurrence patterns in these patients.

The study enrolled patients with locally advanced ESCC after neoadjuvant chemotherapy followed by surgery in the authors' hospital between January 2007 and December 2020. The factors predictive of pCR were analyzed. Furthermore, propensity score-matching was performed for those who did and those who did not have a pCR using 1:5 ratio for a long-term survival analysis. Finally, the survival and recurrence patterns of patients obtaining pCR after neoadjuvant chemotherapy were analyzed.

A pCR was achieved for 61 (8.70%) of the 701 patients in the study. Univariate analysis showed that the patients without alcohol drinking had a higher possibility of obtaining a pCR, although multivariate analysis failed to confirm the difference as significant. After propensity score-matching, the 5-year overall survival was 84.50% for the patients who had a pCR and 52.90% for those who did not (p < 0.001). Among the 61 patients with a pCR, 9 patients (14.80%) experienced recurrence, including 6 patients with locoregional recurrence and 3 patients with distant metastasis.

Advanced ESCC patients with pCR after neoadjuvant chemotherapy had a favorable prognosis, yet some still experienced recurrence, particularly locoregional recurrence. Therefore, for this group of patients, regular follow-up evaluation also is needed.

Locally advanced colon cancer (LACC) can be cured under an appropriate treatment strategy, but the decision on the treatment strategy is also important in terms of long-term prognosis. In cases with extensive abdominal wall involvement, it is especially important to secure adequate margins and repair abdominal wall defects. Recently, neoadjuvant chemotherapy (NAC) for LACC has shown promise in improving the chance of cure with tumor shrinkage. Herein, we report a case of curative surgery after NAC for locally advanced sigmoid colon cancer with extensive abdominal wall invasion. A 50-year-old woman visited our hospital with anemia and an abdominal mass. The diagnosis was LACC of the sigmoid colon with abdominal wall invasion (maximum size, 12 cm), and the clinical stage was stage IIIc (T4b[skin]N1bM0). Resection of the involved skin was expected to cause an extensive abdominal wall defect. At first, a colostomy was performed, followed by NAC with leucovorin, 5-fluorouracil, and oxaliplatin (FOLFOX). Ten cycles of chemotherapy were completed without severe adverse events, and the tumor shrank in size by approximately 39%. We performed a curative sigmoidectomy combined with abdominal wall resection with adequate margins. We reconstructed the abdominal wall defect using a left anterolateral thigh skin flap. Pathological examination revealed mucinous carcinoma involving the transverse colon and abdominal wall, with luminal narrowing in the sigmoid colon. The surgical margins were negative, and the tumor was considered to have had a pathological partial response to NAC. Herein, we report a rare case of curative surgery after NAC with FOLFOX for LACC in the sigmoid colon with extensive invasion of the abdominal wall. We reconstructed the extensive abdominal wall defect with a free anterolateral thigh flap. One of the optional treatment strategies for LACC with extensive abdominal wall invasion was reported in our report.

Neoadjuvant therapy (NT) has increased survival rates for patients with locally advanced esophageal cancer (EC), but estimating the impact of NT treatment prior to surgery is still very difficult.

A retrospective study of the clinical information of 150 patients with locally advanced EC who got NT at Qilu Hospital of Shandong University between June 2018 and June 2023. Patients were randomized into training and internal validation groups at a 3:1 ratio. Furthermore, an external validation cohort comprised 38 patients who underwent neoadjuvant therapy at Qianfoshan Hospital in the Shandong Province between June 2021 and June 2023. Independent risk factors were identified using univariate and multivariate logistic regression (forward stepwise regression). Predictive models and dynamic web nomograms were developed by integrating these risk factors.

A total of 188 patients with locally advanced EC were enrolled, of whom 118 achieved stage I of neoadjuvant pathologic TNM (ypTNM) after receiving NT and 129 achieved grades 0-1 in the tumor regression grade (TRG). Logistic regression analysis identified five independent predictors of TRG grades 0-1: pulmonary function tests (PFT), prognostic nutritional index (PNI), triglyceride (TG) levels, squamous cell carcinoma antigen (SCC-Ag) levels, and combination immunotherapy. The areas under the receiver operating characteristic (ROC) curves for the training, internal validation, and external validation groups were 0.87, 0.75, and 0.80, respectively. Meanwhile, two independent predictors of stage I of ypTNM were identified: prealbumin (PA) and SCC antigen. The areas under the ROC curves for the training, internal validation, and external validation groups were 0.78, 0.67, and 0.70, respectively. The Hosmer-Lemeshow test for both predictive models showed excellent calibration, with well-fitted calibration curves. Decision curve analysis (DCA) and clinical impact curves (CIC) have demonstrated that nomograms are of clinical utility.

The nomograms performed well in predicting the likelihood of stage I of ypTNM and TRG grade 0-1 after NT in patients with locally advanced EC. It helps thoracic surgeons to predict the sensitivity of patients to NT before surgery, which enables precise treatment of patients with locally advanced EC.

Esophageal cancer is the seventh most common malignancy worldwide, with over 470 000 new cases diagnosed each year. Two distinct histological subtypes predominate, and should be considered biologically separate disease entities.1 These subtypes are esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). Outcomes remain poor regardless of subtype, with most patients presenting with late stage disease.2 Novel strategies to improve early detection of the respective precursor lesions, squamous dysplasia, and Barrett's esophagus offer the potential to improve outcomes. The introduction of a limited number of biologic agents, as well as immune checkpoint inhibitors, is resulting in improvements in the systemic treatment of locally advanced and metastatic esophageal cancer. These developments, coupled with improvements in minimally invasive surgical and endoscopic treatment approaches, as well as adaptive and precision radiotherapy technologies, offer the potential to improve outcomes still further. This review summarizes the latest advances in the diagnosis and management of esophageal cancer, and the developments in understanding of the biology of this disease.

Neoadjuvant chemotherapy (NCT) is the standard preoperative treatment for resectable locally advanced esophageal squamous cell carcinoma (ESCC). Some studies reported neoadjuvant immunochemotherapy (NICT) could improve pathological response with manageable safety. However, few studies have compared the efficacy and safety of NICT and NCT, especially survival outcomes. In this study, we compared the efficacy and safety of NICT and NCT after a median follow-up of 36.0 months.

This was a retrospective study with a 1:1 propensity score matching (PSM). Locally advanced ESCC patients treated with neoadjuvant sintilimab plus chemotherapy or chemotherapy followed by esophagectomy were reviewed. The primary outcome was recurrence-free survival (RFS).

Forty-five patients were identified in each group by PSM. The pathological complete response (pCR) rate in NICT and NCT group were 28.9% and 8.9% (P = 0.02). The hazard ratio (HR) was 0.396 (95% CI 0.171-0.919, p = 0.025) for RFS and 0.377 (95% CI 0.145-0.981, p = 0.038) for overall survival (OS), 3-year RFS was 80.6% and 62.1%, 3-year OS was 86.2% and 68.1%. Patients with pCR, MPR or downstaging had better 3-year RFS and 3-year OS. The incidences of postoperative complications and treatment-related adverse events (TRAEs) were similar.

This trial preliminarily shows that NICT improves pathological and survival outcomes over NCT for resectable locally advanced ESCC, with acceptable and manageable safety.

Perioperative 5-FU, leucovorin, oxaliplatin, and docetaxel (FLOT) is recommended in resectable esophagogastric adenocarcinoma based on randomised trials. However, the effectiveness of FLOT in routine clinical practice remains unknown as randomised trials are subject to selection bias limiting their generalisability. The aim of this study was to evaluate the implementation of FLOT in real-world patients.

Retrospectively collected data were analysed in consecutive patients treated before or after the implementation of FLOT. The primary endpoint was complete pathological response (pCR) and secondary endpoints were margin-free resection (R0), overall survival (OS), relapse-free survival (RFS) tolerability of chemotherapy and surgical complications.

Mean follow-up time for patients treated with FLOT (n = 205) was 37.7 versus 47.0 months for epirubicin, cis- or oxaliplatin, and capecitabine (ECX/EOX, n = 186). Surgical resection was performed in 88.0% versus 92.0%; pCR were observed in 3.8% versus 2.4%; and R0 resections were achieved in 78.0% versus 86.0% (p = 0.03) in the ECX/EOX and FLOT cohorts, respectively. Survival analysis indicated no significant difference in RFS (p = 0.17) or OS (p = 0.37) between the cohorts with a trend towards increased OS in performance status 0 (hazard ratio [HR] = 0.73, 95% confidence interval [CI]: 0.50-1.04). More patients treated with ECX/EOX completed chemotherapy (39% vs. 28%, p = 0.02). Febrile neutropenia was more common in the FLOT cohort (3.8% vs. 11%, p = 0.0086). 90-days mortality (1.2% vs. 0%) and frequency of anastomotic leakage (8% vs. 6%) were equal and low.

Patients receiving FLOT did not demonstrate improved pCR, RFS or OS. However, R0 rate was improved and patients in good PS trended towards improved OS.

Venous thrombosis (VT) after esophagectomy for esophageal cancer is an important complication, potentially leading to pulmonary embolism. However, there are few available information about the risk for the postsurgical VT.

This study included 271 patients who underwent esophagectomy for esophageal cancer between 2006 and 2019. Contrast-enhanced computed tomography (CT) was performed for all patients on the seventh postoperative day to survey complications, including VT.

VT was radiologically visualized in 48 patients (17.7%), 8 of whom (16.7%) had pulmonary embolism. The thrombus disappeared in 42 patients, the thrombus size was unchanged in 5 patients, and 1 patient died. Multivariate analysis was performed on factors clinically considered to have a significant influence on thrombus formation. The analysis showed that CVC insertion via the femoral vein (odds ratio, 7.67; 95% CI, 2.64-22.27; P < 0.001), retrosternal reconstruction route (odds ratio, 3.94; 95% CI, 1.90-8.17; P < 0.001) and intraoperative fluid balance < 5 ml/kg/hr (odds ratio, 0.38; 95% CI, 0.17-0.85; P = 0.019) were independently related to VT.

Intraoperative fluid balance < 5 ml/kg/hr, along with CVC insertion via the femoral vein and retrosternal reconstruction may be potential risk factors for VT after esophagectomy.

The role of neoadjuvant chemotherapy (NAC) in advanced sigmoid colon carcinoma remains to be further characterized. Rationale for NAC includes downstaging on final pathology and optimization of microscopically negative margins (R0 resection). We investigated rates of neoadjuvant chemotherapy use in advanced sigmoid colon cancer at academic cancer centers and assessed factors associated with likelihood of NAC administration.

The National Cancer Database was queried from 2004 to 2017 for patients with clinical T3 or T4, N0-2, M0 sigmoid colon cancer who underwent surgical resection. Those with neoadjuvant radiation or metastatic disease were excluded. The outcomes of patients who did and did not receive neoadjuvant chemotherapy were evaluated for this retrospective cohort study.

There were 23,597 patients of whom 364 (1.5%) received NAC. More patients received NAC at academic (41%, P < .001) and high-volume centers (27%, P < .001). Patients with Medicare/Medicaid (39%) and private insurance (52%) were more likely to receive NAC (P < .001). There was a significantly higher rate of N2 to N1 downstaging in the NAC group. Propensity-score matching demonstrated comprehensive community cancer programs (CCCP) were less likely to provide NAC (OR 0.4; 95% CI 0.23, 0.70, P < .001). There was no difference in survival (P = .20), R0 resection (P = .090), or 30-day readmission rates (P = .30) in the NAC cohort compared to the non-NAC cohort.

Access to centers offering multi-disciplinary care with NAC prior to surgical resection is important. This care was associated with academic and high-volume centers and private or government-sponsored insurance. There was no difference in survival between NAC and non-NAC cohort.

Diagnosis and therapy of esophageal carcinoma is challenging and requires a multidisciplinary approach. The purpose of the updated German guideline "Diagnosis and Treatment of Squamous Cell Carcinoma and Adenocarcinoma of the Esophagus-version 3.1" is to provide practical and evidence-based advice for the management of patients with esophageal cancer. Recommendations were developed by a multidisciplinary expert panel based on an extensive and systematic evaluation of the published medical literature and the application of well-established methodologies (e.g. Oxford evidence grading scheme, grading of recommendations). Accurate diagnostic evaluation of the primary tumor as well as lymph node and distant metastases is required in order to guide patients to a stage-appropriate therapy after the initial diagnosis of esophageal cancer. In high-grade intraepithelial neoplasia or mucosal carcinoma endoscopic resection shall be performed. Whether endoscopic resection is the definitive therapeutic measure depends on the histopathological evaluation of the resection specimen. Esophagectomy should be performed minimally invasive or in combination with open procedures (hybrid technique). Because the prognosis in locally advanced esophageal carcinoma is poor with surgery alone, multimodality therapy is recommended. In locally advanced adenocarcinomas of the esophagus or esophagogastric junction, perioperative chemotherapy or preoperative radiochemotherapy should be administered. In locally advanced squamous cell carcinomas of the esophagus, preoperative radiochemotherapy followed by complete resection or definitive radiochemotherapy without surgery should be performed. In the case of residual tumor in the resection specimen after neoadjuvant radiochemotherapy and R0 resection of squamous cell carcinoma or adenocarcinoma, adjuvant immunotherapy with nivolumab should be given. Systemic palliative treatment options (chemotherapy, chemotherapy plus immunotherapy, immunotherapy alone) in unresectable or metastastic esophageal cancer depend on histology and are stratified according to PD-L1 and/or Her2 expression.

Programmed death-1/programmed death-ligand 1 (PD-L1) inhibitors have shown efficacy in metastatic esophageal squamous cell carcinoma (ESCC) therapy. However, data is still limited regarding neoadjuvant immunotherapy for operable ESCC.

Patients with clinical stage T2 or T3 and N0 ESCC received three cycles of nivolumab therapy every two weeks before surgical resection. The primary endpoint is major pathologic responses (MPR) rate (≤ 10% of residual viable tumor [RVT]).

Total 20 patients completed the planned nivolumab therapy. Among them, 17 patients underwent surgery as protocol, showing MPR in two patients (MPR rate, 11.8%), including one pathologic complete response, on conventional pathologic response evaluation. Pathologic response was re-evaluated using the immune-related pathologic response criteria based on immune-related RVT (irRVT). Three patients were classified as immunologic major pathologic response (iMPR; ≤ 10% irRVT, iMPR rate: 17.6%), five as pathologic partial response (> 10% and < 90% irRVT), and nine as pathologic nonresponse (≥ 90% irRVT). The combined positive score (CPS) for PD-L1 in the baseline samples was predictable for iMPR, with the probability as 37.5% in CPS ≥ 10 (3/8) and 0% in CPS < 10 (0/9).

Although the efficacy of neoadjuvant nivolumab therapy was modest in unselected ESCC patients, further researches on neoadjuvant immunotherapy are necessary in patients with PD-L1 expressed ESCC.

Real-world, long-term survival outcomes of neoadjuvant, docetaxel-based therapy for esophageal and junctional adenocarcinoma are lacking. This study describes the long-term survival outcomes of patients with esophageal and junctional adenocarcinoma treated with neoadjuvant docetaxel-based chemotherapy and en bloc transthoracic esophagectomy.

A retrospective cohort analysis of a prospectively maintained database from a regional upper gastrointestinal cancer network in Quebec, Canada, was performed. From January 2007 to December 2021, all patients with locally advanced (cT3 and/or N1) esophageal/Siewert I/II adenocarcinoma treated with neoadjuvant DCFx3 (Docetaxel/Cisplatin/5FU) or FLOTx4 (5FU/Leucovorin/Oxaliplatin/Docetaxel) and transthoracic en bloc esophagectomy were identified. Postoperative, pathological, and survival outcomes were compared.

Overall, 236 of 420 patients met the inclusion criteria. Tumor location was esophageal/Siewert I/Siewert II (118/33/85), most were cT3-4 (93.6%) and cN+ (61.0%). DCF and FLOT were used in 127 of 236 (53.8%) and 109 of 236 (46.2%). All neoadjuvant cycles were completed in 87.3% with no difference between the regimens. Operative procedures included Ivor Lewis (81.8%), left thoraco-abdominal esophagectomy (10.6%) and McKeown (7.6%) with an R0 resection in 95.3% and pathological complete response in 9.7% (DCF 12.6%/FLOT 6.4%, p = 0.111). The median lymph node yield was 32 (range 4-79), and 60.6% were ypN+. Median follow-up was longer for the DCF group (74.8 months 95% confidence interval [CI] 4-173 vs. 37.8 months 95% CI 2-119, p <0.001. Overall survival was similar between the groups (FLOT 97.3 months, 78.6-115.8 vs. DCF 92.9, 9.2-106.5, p = 0.420).

Neoadjuvant DCF and FLOT followed by transthoracic en bloc resection are both highly effective regimens for locally advanced esophageal adenocarcinoma with equivalent survival outcomes despite high disease load.

Esophageal squamous cell neoplasms (ESCNs) are common second primary tumors in patients with head and neck cancer. Image-enhanced endoscopy (IEE) with Lugol chromoendoscopy or magnifying narrow-band imaging both increase the detection of early ESCNs. No evidence-based ESCN surveillance program for head and neck cancer patients without a history of synchronous ESCNs exists. We aimed to evaluate the performance of an IEE surveillance program with magnifying narrow-band imaging endoscopy and Lugol chromoendoscopy.

From April 2016, we routinely used IEE with magnifying narrow-band imaging and Lugol chromoendoscopy to evaluate patients with head and neck cancer history. All patients who were negative for ESCNs at the first surveillance endoscopy and received at least 2 IEEs through December 2019 were included. Demographic profiles, clinical data, cancer characteristics, IEE results and pathology reports were analyzed.

A total of 178 patients were included. Only 4 patients (2.2%) developed metachronous ESCNs during follow-up, all of whom received curative resection treatment. The interval for the development of metachronous ESCNs was 477 to 717 days. In multivariate Firth logistic regression and Kaplan‒Meier survival curve analysis, Lugol's voiding lesion type C had an increased risk of esophageal cancer development (adjusted odds ratio = 15.71; 95% confidence interval, 1.33-185.87, p = 0.029). Eight patients died during the study period, and none of them had metachronous ESCNs.

IEE with magnifying narrow-band imaging and Lugol chromoendoscopy is an effective surveillance program in head and neck cancer patients without a history of ESCNs. Annual surveillance can timely detect early ESCNs with low ESCN-related mortality.