Neoadjuvant Chemoradiotherapy Research Articles

Tumor microenvironment remodeling after neoadjuvant chemoradiotherapy in local advanced rectal cancer revealed by single-cell RNA sequencing

Tumor microenvironment remodeling after neoadjuvant chemoradiotherapy in local advanced rectal cancer revealed by single-cell RNA sequencing

Multimodality deep learning radiomics predicts pathological response after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma.

This study aimed to develop and validate a deep-learning radiomics model using CT, T2, and DWI images for predicting pathological complete response (pCR) in patients with esophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant chemoradiotherapy (nCRT). Patients with ESCC undergoing nCRT followed by surgery were retrospectively enrolled from three institutions and divided into training and testing cohorts. Both traditional and deep-learning radiomics features were extracted from pre-treatment CT, T2, and DWI. Multiple radiomics models were developed, both single modality and integrated, using machine learning algorithms. The models' performance was assessed using receiver operating characteristic curve analysis, with the area under the curve (AUC) as a primary metric, alongside sensitivity and specificity from the cut-off analysis. The study involved 151 patients, among whom 63 achieved pCR. The training cohort consisted of 89 patients from Institution 1 (median age 62, 73 males) and the testing cohort included 52 patients from Institution 2 (median age 62, 41 males), and 10 in a clinical trial from Institution 3 (median age 69, 9 males). The integrated model, combining traditional and deep learning radiomics features from CT, T2, and DWI, demonstrated the best performance with an AUC of 0.868 (95% CI: 0.766-0.959), sensitivity of 88% (95% CI: 73.9-100), and specificity of 78.4% (95% CI: 63.6-90.2) in the testing cohort. This model outperformed single-modality models and the clinical model. A multimodality deep learning radiomics model, utilizing CT, T2, and DWI images, was developed and validated for accurately predicting pCR of ESCC following nCRT. Our research demonstrates the satisfactory predictive value of multimodality deep learning radiomics for the response of nCRT in ESCC and provides a potentially helpful tool for personalized treatment including organ preservation strategy. After neoadjuvant chemoradiotherapy, patients with ESCC have pCR rates of about 40%. The multimodality deep learning radiomics model, could predict pCR after nCRT with high accuracy. The multimodality radiomics can be helpful in personalized treatment of esophageal cancer.

ASO Visual Abstract: Prediction of Pathologic Complete Response in Esophageal Squamous Cell Carcinoma Using Preoperative Serum Small Ribonucleic Acid Obtained After Neoadjuvant Chemoradiotherapy.

ASO Visual Abstract: Prediction of Pathologic Complete Response in Esophageal Squamous Cell Carcinoma Using Preoperative Serum Small Ribonucleic Acid Obtained After Neoadjuvant Chemoradiotherapy.

Primary dedifferentiated liposarcoma of the gallbladder: a case report and literature review

BackgroundLiposarcoma (LPS) is a kind of malignancy of soft tissue usually found in the retroperitoneal, limb, or neck region, and some may be detected with delayed symptoms (pain or palpable mass), and less frequently occurs in organs of the digestive system. In contrast, Dedifferentiated liposarcoma (DDLPS) is a common histological subtype of LPS. The present study reported a case of dedifferentiated liposarcoma originating in the gallbladder. Differentiated liposarcoma originating from the gallbladder is rarely reported.Case descriptionA 64-year-old female patient presented to our hospital with a painless abdominal mass. Abdominal computed tomography (CT) showed that the gallbladder had lost its normal shape, and a 9.1 cm × 7.1 cm × 12.1 cm mass was seen in the area of the gallbladder fossa and the right upper abdomen below it, which had an irregular morphology, inhomogeneous density, and nodular calcification, with marked inhomogeneous enhancement on enhancement scan. Preoperative tumor markers and liver function indicators were not abnormal. With suspicion of a giant malignant tumor of the gallbladder, she underwent a cholecystectomy combined with abdominal mass resection. After surgery, the tumor and gallbladder, were completely resected, and postoperative pathological results confirmed the diagnosis of dedifferentiated liposarcoma deriving from gallbladder. After surgery, the patient and his family refused to continue treatment. After 15 months follow-up, the patient remains asymptomatic and does not show any signs of recurrence. And she is now under continued follow - up.ConclusionsTreatment of dedifferentiated liposarcoma is still at exploratory stage, and a lack of clinical evidence for this condition might hinder access to clinical trials and studies. Currently, the treatment of choice for dedifferentiated liposarcoma remains radical resection. In the available clinical studies, there are no robust data to support clinical use of neoadjuvant and adjuvant radiochemotherapy. As with other diseases, the use of radiotherapy and chemotherapy before and after surgery may be a potential future treatment.

Evaluation of Volumetric Magnetic Resonance Imaging in Determining the Indication for Total Neoadjuvant Therapy in Rectal Cancer.

This study aims to evaluate the relationship between volumetric measurements of residual tumor via magnetic resonance imaging (MRI) and pathologic complete response (pCR) in rectal cancer patients undergoing neoadjuvant chemoradiotherapy (nCRT). Patients with locally advanced rectal cancer who had pelvic MRI for clinical staging and completed nCRT followed by radical resection were included. Two experienced radiologists measured tumor volume on MRI obtained before and after nCRT. We compared the pre- and post-CRT tumor volume and measured tumor volume reduction rates. The median value of tumor volume reduction rate in all patients was 64.7% (min-max - 81.1-98.1%). When the relationship between tumor volume and tumor regression grade (TRG) after nCRT was assessed, it was found that 18 of 21 (86%) patients with a good response (TRG 1) had a post-CRT tumor volume of ≤ 8 cm3 (p = 0.001). While 9 of 10 patients with pCR after nCRT had a tumor volume of ≤ 8 cm3, one patient had pCR despite having a tumor volume greater than 8 cm3 (p = 0.015). The correlation between post-nCRT residual tumor volume and pCR underscores the potential of volumetric MRI as a predictive tool in tailoring rectal cancer treatment. For patients with residual tumor volumes greater than 8 cm3, extending neoadjuvant chemotherapy as part of TNT may enhance the likelihood of achieving pCR. This approach advocates for a more personalized treatment strategy, potentially optimizing outcomes for rectal cancer patients.

Neuroendocrine differentiation and serotonin expression in oesophageal adenocarcinomas after neoadjuvant therapy: correlation with clinicopathological features and outcome.

Oesophageal adenocarcinoma (EAC) is a glandular or mucinous epithelial malignancy that can show immunohistochemical evidence of neuroendocrine differentiation (NED) and express the hormone serotonin. The objective of this study was to correlate the presence of NED and serotonin with clinicopathological characteristics and patient outcome after neoadjuvant chemoradiation. A retrospective cohort of patients treated between 2002 and 2021 was established and included 218 oesophagectomy specimens with residual tumour. Representative full-face sections of tumour were stained for synaptophysin, chromogranin-A and serotonin by immunohistochemistry, and staining results were correlated with disease-free survival (DFS) and overall survival (OS). In total, 129 (59%) tumours showed evidence of NED, defined as immunohistochemical expression of synaptophysin or chromogranin-A, while 40 (18%) showed evidence of NED and expressed serotonin. Patients with neuroendocrine-positive tumours had significantly shorter median OS compared to those with neuroendocrine-negative tumours (22.5 versus 48.8 months, P = 0.006), but similar median DFS (13.3 versus 17.8 months, P = 0.34). Using Cox regression, the association between NED and OS was significant in univariate [hazard ratio (HR) = 1.68, 95% confidence interval (CI) = 1.16-2.45] and multivariate (HR = 1.65, 95% CI = 1.08-2.52) analysis. Patients with serotonin-expressing tumours had similar median OS (21.7 versus 25.9 months, P = 0.24) and DFS (7.3 versus 15.6 months, P = 0.12) compared to those with NED but lacking serotonin. Using Cox regression, serotonin expression was associated with reduced OS in univariate (HR = 1.62, 95% CI = 1.06-2.47) but not multivariate (HR = 1.03, 95% CI = 0.64-1.65) analysis. Our findings support NED as independent predictor of OS in EAC after neoadjuvant chemoradiation. While a subset of tumours with NED expressed serotonin, this did not provide additional prognostic information.

Roles of MRI evaluation of pelvic recurrence in patients with rectal cancer.

Developments in the multidisciplinary treatment of rectal cancer with advances in preoperative magnetic resonance imaging (MRI), surgical techniques, neoadjuvant chemoradiotherapy, and adjuvant chemotherapy have had a significant impact on patient outcomes, increasing the rates of curative surgeries and reducing pelvic recurrence. Patients with pelvic recurrence have worse prognoses, with an impact on morbidity and mortality. Although local recurrence is more frequent within 2 years of surgical resection of the primary tumor, late recurrence may occur. Clinical manifestations can vary from asymptomatic, nonspecific symptoms, to pelvic pain, bleeding, and fistulas. Synchronous metastatic disease occurs in approximately 50% of patients diagnosed with local recurrence. MRI plays a crucial role in posttreatment follow-up, whether by identifying viable neoplastic tissues or acting as a tool for therapeutic planning and assessing the resectability of these lesions. Locally recurrent tissues usually have a higher signal intensity than muscle on T2-weighted imaging. Thus, attention is required for focal heterogeneous lesions, marked contrast enhancement, early invasive behavior, and asymmetric appearance, which are suspicious for local recurrence. However, postsurgical inflammatory changes related to radiotherapy and fibrosis make it difficult to detect initial lesions. This study therefore aimed to review the main imaging patterns of pelvic recurrence and their implications for the surgical decision-making process. CRITICAL RELEVANCE STATEMENT: MRI plays a crucial role in the posttreatment follow-up of rectal cancer, whether by identifying viable neoplastic tissues or by acting as a tool for therapeutic planning. This study reviewed the main imaging patterns of pelvic recurrence. KEY POINTS: MRI aids in surgical planning and the detection of pelvic recurrence and postoperative complications. Being familiar with surgical techniques enables radiologists to identify expected MRI findings. Patterns of rectal cancer recurrence have been categorized by pelvic compartments. Neoplastic tissue may mimic postsurgical and postradiotherapy changes. Resectability of pelvic recurrence is highly related to lesion location.

Active surveillance in patients with a complete clinical response after neoadjuvant chemoradiotherapy for esophageal- and gastroesophageal junction cancer

Abstract Neoadjuvant chemoradiotherapy in patients with esophageal- and gastroesophageal junction cancer induces tumor regression. In approximately one fourth of patients, this leads to a pathological complete response in the resection specimen. Hence, active surveillance may be an alternative strategy in patients without residual disease after neoadjuvant chemoradiotherapy. Previous studies have shown that the combination of esophagogastroduodenoscopy with bite-on-bite biopsies, endoscopic ultrasound with fine needle aspiration of suspected lymph nodes, and a PET-CT-scan can be considered adequate for the detection of residual disease. So far, it has been unclear whether active surveillance with surgery as needed is a safe treatment option and leads to non-inferior overall survival compared to standard esophagectomy after neoadjuvant chemoradiotherapy. This review will discuss the current status of active surveillance for esophageal and junctional cancer.

Final Results of the GRECCAR-6 Trial on Waiting Period Following Neoadjuvant Radiochemotherapy for Locally Advanced Rectal Cancer: 5 Years of Follow-up.

The potential oncological benefit of extending the waiting period between neoadjuvant radiochemotherapy and surgical resection for rectal cancer is debated. To evaluate the impact of prolonging this waiting period on the 5-year oncological prognosis and 2-year functional result of locally advanced rectal adenocarcinoma. Phase III, multicenter, randomized, open-label, parallel-group, controlled trial. Patients were enrolled from 24 colorectal centers. Patients with non-metastatic mid or lower cT3-4 or TxN+ rectal adenocarcinoma who had received radio-chemotherapy (45 to 50 Gy with fluorouracil or capecitabine). Patients were randomly assigned to undergo total mesorectal excision either 7 weeks (W7) or 11 weeks (W11) after radiochemotherapy. Overall survival and disease-free survival at 5 years of follow-up and low anterior resection syndrome score assessed after 2 years of follow-up. Among 265 patients enrolled, 133 were randomized in the 7-week group and 132 in the 11-week group. Twelve patients were excluded as they did not undergo resection. Among 253 patients analyzed, 5-year overall survival was not different between the two groups (81.6% in 7-week group versus 82.6% in 11-week group, p = 0.827), as well as for the 5-year disease-free survival (70.4% in 7-week group versus 69.5% in 11-week group, p = 0.856). No difference was observed between the two groups for distant recurrence (27.4% in 7-week group versus 25.7% in 11-week group, p = 0.777) or local recurrence (8.4% in 7-weeks group versus 10.2% in 11-week group, p = 0.543). Low anterior resection syndrome score was similar between the 7-week (25.0 IQR [15.0-34.0]) and 11-week groups (23.0 IQR[14.2-32.0], p = 0.743). The response rate to the LARS questionnaire was only 52%. Extending the waiting period between radiochemotherapy and resection from 7 to 11 weeks does not modify the 5-year oncological prognosis in rectal cancer and the 2-year low anterior resection occurrence.

Postoperative tumor bed radiation versus T-shaped field radiation in the treatment of locally advanced thoracic esophageal squamous cell carcinoma: a phase IIb multicenter randomized controlled trial

BackgroundPostoperative radiotherapy (PORT) is crucial for patients with thoracic locally advanced esophageal squamous cell carcinoma (LA-ESCC, pT3-4aN0-3M0) following esophagectomy. However, the appropriate radiation volume has not been well established. This study aimed to determine the optimal PORT volume for LA-ESCC patients.MethodsLA-ESCC patients post-esophagectomy were randomly assigned to either the large-field irradiation (LFI, primary lesion and lymph node tumor bed plus elective nodal irradiation) group or the small-field irradiation (SFI, primary lesion and lymph node tumor bed alone) group. Stratification was based on T stage and the number of lymph node metastases. The primary endpoint was disease-free survival (DFS), while the secondary endpoints included overall survival (OS), adverse events, and patterns of initial failure.ResultsA total of 401 patients were randomly assigned to the intention-to-treat analysis(LFI group, n = 210; SFI group, n = 191). The median DFS of patients in the LFI group was 47.9 months and 48.1 months in the SFI group (HR = 0.87, 95%CI, 0.65 to 1.16; p = 0.32). The estimated one-year and three-year OS rates were 89.2% and 63.2% for patients in the LFI group, compared to 86.6% and 60.7% for the SFI group, respectively. The difference of OS between the two groups was not significant (HR = 0.86, 95%CI, 0.63 to 1.16; p = 0.35). Fewer patients in the LFI group experienced locoregional recurrence compared to the SFI group (12.9% vs 20.4%, p = 0.013). Additionally, locoregional recurrence-free survival of the LFI group was significantly longer than that of SFI group (HR = 0.54, 95%CI, 0.34–0.87; p = 0.01). The most common toxicity was grade 2 esophagitis, observed in 22.9% of the LFI group and 16.8% of the SFI group. Grade 3 adverse events occurred in 6.7% of the LFI group and 2.6% of the SFI group. No grade 4 or 5 toxicities were observed. Adverse events did not significantly differ between the two groups.ConclusionsPostoperative radiotherapy, with the specified radiation volume shows encouraging survival outcomes that are comparable to those of neoadjuvant chemoradiotherapy in patients with thoracic LA-ESCC. Both postoperative irradiation fields were found to be feasible and safe.

Dynamics of cell-free tumor DNA correlate with early MRI response during chemoradiotherapy in rectal cancer

BackgroundIn locally advanced rectal cancer, the prediction of tumor response during and after neoadjuvant treatment remains challenging. In terms of organ preservation, adaptive radiotherapy, and intensified (total) neoadjuvant therapies, biomarkers are desirable for patient stratification.MethodsIn 16 patients, weekly blood samples (n = 86) to detect cell-free tumor DNA (ctDNA) during long-course neoadjuvant chemoradiotherapy were analyzed. Data were correlated with initial tumor volumes, MRI response in week 2 and 5 of radiotherapy as well as with pathologic tumor response after resection and outcome parameters.ResultsMost patients showed decreasing ctDNA during the course of radiochemotherapy. However, we found heterogenous dynamics of ctDNA and could identify three groups: (1) decline (2) no clear decline and/or late shedding (3) persistence of ctDNA. In seven patients we could detect significant amounts of ctDNA in week 5 or week 6 of treatment. In our pilot cohort, we did not find significant correlations of ctDNA dynamics with pathologic response or outcome parameters. However, patients with distinct decline of ctDNA had larger tumor volumes prior to treatment, and MRI imaging in week 2 and 5 revealed bigger absolute decrease of tumor volumes. If significant levels of ctDNA were found in week 5 and / or 6, patients showed less absolute tumor volume decrease in week 2 and 5.ConclusionsWeekly measurement of ctDNA during radiochemotherapy is feasible and might represent a promising biomarker. Bigger initial primary tumors showed different ctDNA shedding profiles compared with smaller primary tumors and correlations of ctDNA dynamics with early imaging response were found.

Contemporary role of the plastic and reconstructive surgeon in the outcome of female peripelvic defects after oncologic extirpation.

Reconstruction of female oncologic peripelvic defects is challenging due to complex anatomy, neoadjuvant chemoradiation, operative resection margins, and wound healing risks. Functional restoration requires thoughtful management focused on defect reconstruction and patient-reported outcomes. A retrospective chart review of peripelvic reconstruction in female patients at MD Anderson Cancer Center from 2016 to 2023. Data collected included the patient'scomorbidities, tumor characteristics, and reconstructive details. Complications were classified as nonoperative or operative within 30 days. Patient outcomes included hernia rates, sexual activity, and revision needs. In the study period, 164 patients underwent peripelvic defect reconstruction. Most had colorectal (57%), anal (17%), or gynecologic malignancies (10%). 83% had prior radiation. 33.3% had Class II or III obesity. The most common resection was open colorectal resection with partial vaginectomy (66%). Pedicled flaps (93%) were frequently used, mainly vertical rectus abdominis muscle (65%) and gracilis (11%). For multi-visceral resections, abdominal-based flaps were used in 95% of open casesand thigh-based flaps in 88.9% of robotic cases. 51% had formal abdominal wall repair. Complications occurred in 47%, with 9.1% needing surgery. Postoperative hernias were reported in 4.9%, with 3% requiring repair. Approximately 11% reported being sexually active at the last follow-up. Of those instructed on vaginal dilator therapy (42%), 24.6% were sexually active. Peri-pelvic soft tissue reconstruction in the oncologic population is safe. Operative complications and hernia rates are low. In robotic surgery, thigh-based flaps are increasingly used to reconstruct the peripelvic region. Return to sexual activity is higher in patients when given dilator therapy instruction.

The Ongoing Development of Watch and Wait

AbstractThe nonoperative management of rectal cancer, known as watch and wait (W&W), has gained increasing acceptance in recent years. This approach is based on using complete clinical response (cCR) as a marker for complete pathological response (pCR) following neoadjuvant chemoradiation (nCRT). Advances in nCRT regimens have resulted in higher tumor regression rates, making W&W a viable option for selected patients. This study presents the historical evolution and efficacy of the W&W strategy and offers modern recommendations based on recent clinical findings. Key findings include an 85 to 92% 5-year disease-free survival rate in patients achieving cCR, highlighting the potential for improved quality of life and reduced morbidity without compromising survival outcomes.

Perianal leiomyosarcoma as a rare sequela of rectal cancer radiotherapy: a case report

Radiation-induced sarcomas (RIS) are iatrogenic malignancies that arise following high-dose radiotherapy, posing a significant clinical challenge due to their poor prognosis and resistance to conventional treatments. The incidence of RIS is increasing with advancements in radiotherapy techniques. This report presents a case of a 71-year-old male diagnosed with stage III rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy and curative surgery. Three years postoperatively, he developed a low-grade radiation-induced leiomyosarcoma in the perianal region. Histopathological examination confirmed a spindle cell neoplasm with notable immunohistochemical markers. RIS often presents as aggressive high-grade tumors resistant to radiotherapy and chemotherapy, necessitating surgical resection as the primary treatment. This case underscores the importance of long-term surveillance post-radiotherapy and highlights the need for innovative therapeutic strategies, including immunotherapy. Despite being rare, RIS poses a significant risk following cancer treatment, making early detection through vigilant monitoring and advancements in therapeutic approaches crucial for improving patient outcomes.

Laparoscopic pancreatoduodenectomy is safe for the treatment of pancreatic ductal adenocarcinoma treated by chemoradiotherapy compared with open pancreatoduodenectomy: A matched case-control study

BackgroundFew studies compared laparoscopic and open pancreatoduodenectomy for pancreatic ductal adenocarcinoma after neoadjuvant chemoradiotherapy. MethodsRetrospective cohort of patients who underwent laparoscopic or open pancreatoduodenectomy for resectable or borderline resectable pancreatic ductal adenocarcinoma after chemoradiotherapy between 2012 and 2023 was analyzed. Open pancreatoduodenectomy patients could theoretically benefit from the laparoscopic approach. We used a 1:2 (laparoscopic-to-open pancreatoduodenectomy) propensity score matching analysis stratified on age, gender, and body mass index. ResultsWe included 128 patients (33 laparoscopic and 95 open pancreatoduodenectomy), and after propensity score matching, 33 laparoscopic pancreatoduodenectomy and 66 open pancreatoduodenectomy were compared. There was no difference in demographic data except for lower tobacco use in laparoscopic pancreatoduodenectomy group (9% vs 30%, P = .023) with similar clinical presentation. Laparoscopic pancreatoduodenectomy compared to open pancreatoduodenectomy showed a longer median operative duration (380 vs 255 minutes, P < .001), shorter median length of resected vein (15 vs 23 mm, P = .01), longer median venous clamping time (29 vs 15 minutes, P = .005), similar median blood loss (300 vs 300 mL, P = .223), similar rate of hard pancreas (97% vs 85%, P = .094), and a larger median size of Wirsung duct (5 vs 4 mm, P = .02). Postoperative outcomes showed similar 90-day mortality rates (3% vs 3%, P > .99), Clavien-Dindo III-IV complications (6% vs 14%, P = .158), median lengths of hospital stay (12 vs 13 days, P = .409), and readmission rates (9% vs 18%, P = .366). Pathologic data showed similar R0 resection rates (88% vs 82%, P = .568). With a similar rate of adjuvant chemotherapy (P = .324) and shorter median follow-up with laparoscopic pancreatoduodenectomy (18 vs 34 months, P = .004), 3-year overall (P = .768) and disease-free (P = .839) survival rates were similar. ConclusionIn selected patients, laparoscopic pancreatoduodenectomy for pancreatic ductal adenocarcinoma after neoadjuvant chemoradiotherapy appears to be safe and feasible when performed in experienced centers.

A phase III randomized trial on the addition of a contact x-ray brachytherapy boost to standard neoadjuvant chemo-radiotherapy for organ preservation in early rectal adenocarcinoma: 5 year results of the OPERA trial

The OPERA trial has shown that a contact X Ray Brachytherapy 50kV (CXB) boost with neoadjuvant chemoradiotherapy (NCRT) can increase organ preservation (OP) rate for early rectal adenocarcinoma (ADK) of low-mid rectum. We report the results after 5 years of follow-up. OPERA was a multicenter, phase III trial that included operable patients (pts), with cT2-cT3b low-mid rectal ADK, tumors <5 cm, cN0 or cN1 <8 mm. All pts received external beam radiotherapy (EBRT): 45Gy in 25 fractions with concurrent capecitabine. Pts were randomly assigned (1:1) to receive a boost of EBRT in group A (9Gy/5 fractions) or a boost with CXB (90Gy/3 fractions) in group B. The primary end point was OP rate. Out of 148 patients randomized, 141 were eligible. Between week 14-24, a clinical complete (or near) response was observed in 44 pts in group A (64%) vs 66 in group B (92%); p<0.001. The 3-year OP rate was 59% in group A vs 81% in group B (p=0.003). After update the median follow-up was 61.1 months [56.8-64.5]. The 5-year local regrowth was 39% in group A and 17% in group B (p=0.1). The difference in OP was still highly significant between both groups: A 56% vs B 79% (p=0.004). The difference was more significant if tumors < 3cm, with an OP rate of 93% in group B compared to 54% in group A. Of the 28 local regrowths, 3 occurred after 3 years of follow-up. Rectal bleeding (grade 1-2), which was the most prevalent toxicity during follow-up, disapeared most of the time after three years. Bowel function was not worsened by the CXB boost. The OPERA trial was the first trial to demonstrate that CXB dose escalation was increasing the OP rate with good bowel function at 3 years. At 5 years, these results are sustained, specially in small early-stage tumors. The occurrence of some local regrowth after 3 years necessitates close surveillance of these pts during the 5-year period.

Neoadjuvant chemoradiotherapy in locally advanced and locally recurrent colon cancer

Neoadjuvant chemoradiotherapy in locally advanced and locally recurrent colon cancer

Metagenomic analysis reveals effects of gut microbiome in response to neoadjuvant chemoradiotherapy in advanced rectal cancer

Neoadjuvant chemoradiotherapy can enhance survival rate of patients with advanced rectal cancer, but its effectiveness varies considerably. Previous studies have indicated that gut microbes may serve as biomarkers for predicting treatment efficacy. However, the specific roles of the gut microbiome in patients who have good response to nCRT remains unclear. In this study, shotgun metagenomic sequencing technology was used to analyze the fecal microbiome of patients with varying responses to nCRT. Our findings revealed that beneficial intestinal bacteria and genes from different metabolic pathways (carbohydrate metabolism, amino acid metabolism, and sulfur metabolism) were significantly enriched in patients with good response. Additionally, causal relationship in which microbial-derived GDP-D-rhamnose and butyrate could influence the response to nCRT was clarified. Our results offered new insights into the different response to nCRT, and provided valuable reference points for improving the effectiveness of nCRT in patients with advanced colorectal cancer.

CT radiomics to predict pathologic complete response after neoadjuvant immunotherapy plus chemoradiotherapy in locally advanced esophageal squamous cell carcinoma.

To develop and validate a CT-based radiomics model to predict pathologic complete response (pCR) after neoadjuvant immunotherapy plus chemoradiotherapy (NICRT) in locally advanced esophageal squamous cell carcinoma (ESCC). A total of 105 patients with locally advanced ESCC receiving NICRT from February 2019 to December 2023 were enrolled. Patients were randomly divided into the training cohort and the test cohort at a 3:1 ratio. Enhanced CT scans were obtained before NICRT treatment. The 2D and 3D regions of interest were segmented, and features were extracted, followed by feature selection. Six algorithms were applied to construct the radiomics and clinical models. These models were evaluated by area under curve (AUC), accuracy, sensitivity, and specificity, and their respective optimal algorithms were further compared. Forty-eight patients (45.75%) achieved pCR after NICRT. The AUC values of three algorithms in 2D radiomics models were higher than those in the 3D radiomics model and clinical model. Among these, the 2D radiomics model based on eXtreme Gradient Boosting (XGBoost) exhibited the best performance, with an AUC of 0.89 (95% CI, 0.81-0.97), accuracy of 0.85, sensitivity of 0.86, and specificity of 0.84 in the training cohort, and an AUC of 0.80 (95% CI, 0.64-0.97), accuracy of 0.77, sensitivity of 0.84, and specificity of 0.69 in the test cohort. Calibration curves also showed good agreement between predicted and actual response, and the decision curve analysis further confirmed its clinical applicability. The 2D radiomics model can effectively predict pCR to NICRT in locally advanced ESCC. Question Can CT-based radiomics predict pathologic complete response (pCR) after neoadjuvant immunotherapy plus chemoradiotherapy (NICRT) in locally advanced esophageal squamous cell carcinoma (ESCC)? Findings The model based on eXtreme Gradient Boosting (XGBoost) performed best, with an AUC of 0.89 in the training and 0.80 in the test cohort. Clinical relevance This CT-based radiomics model exhibits promising performance for predicting pCR to NICRT in locally advanced ESCC, which may be valuable in personalized treatment plan optimization.

Fecal Microbiome Composition Correlates with Pathologic Complete Response in Patients with Operable Esophageal Cancer Treated with Combined Chemoradiotherapy and Immunotherapy.

Background: Preclinical and clinical data indicate that chemoradiotherapy (CRT) in combination with checkpoint inhibitors may prime an anti-tumor immunological response in esophageal cancer. However, responses to neoadjuvant therapy can vary widely and the key biomarkers to determine response remain poorly understood. The fecal microbiome is a novel and potentially modifiable biomarker of immunotherapy response, and both fecal and tumor microbes have been found to associate with outcomes in esophageal cancer. Methods: Fecal and tumor samples were collected from patients with stage II-III resectable esophageal or gastroesophageal junction carcinoma treated with neoadjuvant immune checkpoint inhibitors (ICIs) plus CRT prior to surgical resection. Microbiome profiles were analyzed by 16S rRNA amplicon sequencing and taxonomic data were integrated with fecal metabolite analysis to assess microbial function. Results: The fecal microbiome of patients with pathological complete response (PCR) grouped in distinct clusters compared to patients with residual viable tumor (RVT) by Bray-Curtis diversity metric. Integrated taxonomic and metabolomic analysis of fecal samples identified a sphingolipid and primary bile acid as enriched in the PCR, the levels of which correlated with several bacterial species: Roseburis inulinivorans, Ruminococcus callidus, and Fusicantenibacter saccharivorans. Analysis of the tumor microbiome profiles identified several bacterial genera previously associated with esophageal tumors, including Streptococcus and Veillonella. Conclusions: These results further characterize the fecal and tumor microbiome of patients with operable esophageal cancer and identify specific microbes and metabolites that may help elucidate how microbes contribute to tumor response with neoadjuvant CRT combined with ICI.