Neoadjuvant Chemoradiotherapy Research Articles

Neoadjuvant chemoradiotherapy for thoracic esophageal squamous cell carcinoma: does everyone need it?

Objective. In accordance with clinical guidelines, neoadjuvant chemoradiotherapy (nCRT) is recommended as a beneficial option for treatment of thoracic esophageal squamous cell carcinoma (TESCC). However, some studies did not demonstrate potential benefits of nCRT. In this paper we compared treatment outcomes of surgery alone with preoperative CRT followed by surgery. Material and methods. Group 1 (n=147) consisted of patients who underwent surgery alone. Group 2 (n=3,337) was formed in the framework of the present systematic review and meta-analysis (15 publications captured 20 separate subgroups for analysis). Patients of group 2 received nCRT followed by esophagectomy. Overall survival (OS) and median OS were estimated. Results. The median OS was reached in group 1 and in 12 separate subgroups of group 2 (2310 of 3337 patients). In groups 1 and 2 the OS median estimates were 31.0 and 28.1, respectively (p=0.873). Respective 3-year and 5-year OS were 0.49 vs 0.48 (p=0.425) and 0.37 vs 0.41 (p=0.228). The median OS was not reached in 8 separate subgroups of group 2 (1027 of 3337 patients). In this case, group 2 patients had significantly higher 3- and 5-year OS compared to group 1 patients: 0.69 vs 0.49 (p=0.000) and 0.60 vs 0.37 (p=0.000), respectively. Pathological complete response to nCRT was associated with better survival. conclusion. nCRT is not appropriate for all patients with TESCC. Improved overall survival may be achieved in patients with a high grade of pathological tumor response to neoadjuvant treatment. Selective administration of nCRT based on highly probable prediction of complete tumor response seems promising. This concept needs further research.

Correlation of microscopic tumor extension with tumor microenvironment in esophageal cancer patients.

In the era of image-guided adaptive radiotherapy, definition of the clinical target volume (CTV) is achallenge in various solid tumors, including esophageal cancer (EC). Many tumor microenvironmental factors, e.g., tumor cell proliferation or cancer stem cells, are hypothesized to be involved in microscopic tumor extension (MTE). Therefore, this study assessed the expression of FAK, ILK, CD44, HIF-1α, and Ki67 in EC patients after neoadjuvant radiochemotherapy followed by tumor resection (NRCHT+R) and correlated these markers with the MTE. Formalin-fixed paraffin-embedded tumor resection specimens of ten EC patients were analyzed using multiplex immunofluorescence staining. Since gold fiducial markers had been endoscopically implanted at the proximal and distal tumor borders prior to NRCHT+R, correlation of the markers with the MTE was feasible. In tumor resection specimens of EC patients, the overall percentages of FAK+, CD44+, HIF-1α+, and Ki67+ cells were higher in tumor nests than in the tumor stroma, with the outcome for Ki67+ cells reaching statistical significance (p < 0.001). Conversely, expression of ILK+ cells was higher in tumor stroma, albeit not statistically significantly. In three patients, MTE beyond the fiducial markers was found, reaching up to 31 mm. Our findings indicate that the overall expression of FAK, HIF-1α, Ki67, and CD44 was higher in tumor nests, whereas that of ILK was higher in tumor stroma. Differences in the TME between patients with residual tumor cells in the original CTV compared to those without were not found. Thus, there is insufficient evidence that the TME influences the required CTV margin on an individual patient basis. BO-EK-148042017 and BO-EK-177042022 on 20.06.2022, DRKS00011886, https://drks.de/search/de/trial/DRKS00011886 .

Transcriptionally Active Human Papillomavirus Infection in a Minority of Esophageal Squamous Cell Carcinomas in North America.

The role of Human papillomavirus (HPV) infection in esophageal squamous cell carcinoma (ESCC) is a topic of ongoing debate. This study used two screening approaches to look for evidence of HPV infection in esophageal squamous cell carcinoma. We initially checked for HPV infection in a randomly selected group of 53 ESCC cases. We did not detect any tumors positive for high-risk HPV. However, during clinical practice, we identified an HPV-positive ESCC in the distal esophagus, which tested positive for HPV16. This index case was TP53 wild-type, as determined by next-generation DNA sequencing (NGS). Since TP53 mutations are rare in other HPV-driven cancers, we improved our screening method by limiting our screen to a subset of ESCC cases without TP53 mutations. A second screen of 95 ESCCs (from 93 patients) sequenced by NGS revealed an additional 7 ESCCs with TP53 wild-type status (7.3% of the total). Of the 7 cases, 2 cases were found to be high-risk HPV positive. Both patients also tested positive for circulating cell-free HPV DNA and had a complete response to neoadjuvant chemoradiation. The index patient had microscopic residual tumor following neoadjuvant therapy. The patient underwent adjuvant immunotherapy and remained disease free after 22 months of surveillance. This study affirms the transcriptionally active status of high-risk HPV in a minority of ESCC patients in North America.

Machine learning in predicting pathological complete response to neoadjuvant chemoradiotherapy in rectal cancer using MRI: A systematic review and meta-analysis.

To evaluate the performance of machine learning models in predicting treatment response to neoadjuvant chemoradiotherapy (nCRT) in rectal cancer using computed tomography (CT) and magnetic resonance imaging (MRI). We searched PubMed, Embase, Cochrane Library, and Web of Science for studies published before January 2023. The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) was used to assess the methodological quality of the included studies, random-effects models were used to calculate sensitivity and specificity, I2 values were used for heterogeneity measurements, and subgroup analyses were carried out to detect potential sources of heterogeneity. A total of 1690 patients from 24 studies were included. The meta-analysis calculated a pooled area under the curve (AUC) of 0.92 (95%CI-0.89-0.94), pooled sensitivity of 0.81 (95%CI-0.73-0.88), and pooled specificity of 0.88 (95%CI-0.82-0.92). We investigated 4 studies that mainly contributed to heterogeneity. After performing meta-analysis again excluding these 4 studies, the heterogeneity was significantly reduced. In subgroup analysis, the pooled AUC of the deep learning model was 0.95 and was 0.88 for the traditional statistical model; the pooled AUC of studies that used diffusion-weighted imaging (DWI) was 0.90, and was 0.92 in studies that did not use DWI; the pooled AUC of studies conducted in China was 0.94, and was 0.83 in studies conducted in other countries. Machine learning has promising potential in predicting tumor response to nCRT in patients with locally advanced rectal cancer. Together with clinical information, machine-learning based models may bring us closer toward precision medicine. Compared to traditional machine learning models, deep learning-based studies are able to obtain higher AUC, although they are less predominant and more heterogeneous. Together with clinical information, machine-learning based models may bring us closer toward precision medicine.

Comparison of neoadjuvant chemotherapy or chemoradiotherapy plus immunotherapy for locally resectable esophageal squamous cell carcinoma

BackgroundNeoadjuvant chemotherapy plus immunotherapy (nCT + ICIs) and neoadjuvant chemoradiotherapy plus immunotherapy (nCRT + ICIs) both induced favorable pathological response and tolerant toxicities for locally resectable esophageal squamous cell carcinoma (ESCC). However, few studies compared safety and efficacy between the two treatment strategies.MethodsThis retrospective study collected clinical data of locally resectable ESCC patients who underwent nCT + ICIs or nCRT + ICIs followed by esophagectomy from November 2019 to December 2022. The incidence of adverse events, surgical outcomes, short and long-term efficacy, and treatment costs were compared.ResultsA total of 206 patients were included, with a ratio of 158:48 between nCT + ICIs group and nCRT + ICIs group. The two groups exhibited well-balanced baseline characteristics. Most adverse events were grade 1-2 in both groups. The nCT + ICIs group had a longer operative time (334.00 ± 170.2 min vs 279.60 ± 88.31 min, P=0.020) than nCRT + ICIs group, but there were no differences in surgical complications. Although nCT + ICIs group had a lower pCR rate (32.3% vs 52.1%, P=0.004), the 2-year overall survival (84.42% vs 81.70%, P=0.860), 2-year disease-free survival (83.21% vs 80.47%, P=0.839), and recurrence patterns were similar to nCRT + ICIs group. In addition, nCT + ICIs group had significantly lower expenses (188796.00 ± 107704.00 RMB vs 231808.00 ± 48067.00 RMB, P=0.045).ConclusionOverall, nCT + ICIs have comparable safety and efficacy compared to nCRT + ICIs for locally resectable ESCC, but with lower hospitalization costs.

Effect of Tumor Regression Grade on Survival and Disease-Free Interval in Patients Operated on for Locally Advanced Rectal Cancer

Introduction: Colorectal cancer is the fourth leading cause of cancer-related death in both men and women in our population. In this regard, rectal cancer accounts for more than half of colorectal cancer deaths, and its incidence is expected to increase in the coming years. There have been significant changes in neoadjuvant therapy regimens, with promising results, as demonstrated by the recent RAPIDO and PRODIGE23 studies. Around 40% of patients diagnosed with locally advanced rectal cancer show some degree of response to neoadjuvant treatment, with complete tumor regression observed in up to one in five patients. Materials and Methods: Retrospective observational study. A total of 181 patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by surgery were analyzed. Clinical and pathological data were collected from the patients, including assessment of tumor regression through histopathological studies after surgery. The Mandard tumor regression grading system was used to categorize tumor response into different grades. Results: The results showed a significant association between the degree of tumor regression and several important clinical outcomes. Specifically, patients with higher tumor regression had significantly better disease-free survival than those with less regression (p = 0.004). In addition, tumor regression was also correlated with the incidence of local recurrence (p = 0.018) and distant metastasis (p = 0.032). These associations suggest that tumor responsiveness to neoadjuvant therapy may influence the long-term progression of the disease. Regarding tumor deposits and the presence of lymphadenopathy, these factors were also found to be significantly associated with clinical outcomes. Patients with tumor deposits had a higher incidence of local recurrence (p = 0.025) and distant metastases (p = 0.041), while the presence of lymphadenopathy increased the risk of local recurrence (p = 0.013). These findings highlight the importance of evaluating not only tumor regression but also other pathological markers to predict prognosis and guide clinical management. Conclusions: The degree of tumor regression was not an independent predictor of survival compared to other variables such as nodal stage and presence of tumor deposits. This indicates that while tumor regression is an important factor, other elements also play a crucial role in determining the prognosis of patients with locally advanced rectal cancer. This study provides additional evidence for the importance of tumor regression, tumor deposits, and lymphadenopathy as predictors of clinical outcomes in patients with rectal cancer treated with neoadjuvant chemoradiotherapy.

International Expert Consensus on Semantics of Multimodal Esophageal Cancer Treatment: Delphi Study.

Recent developments in esophageal cancer treatment, including studies exploring active surveillance following chemoradiotherapy, have led to a need for clear terminology and definitions regarding different multimodal treatment options. The aim of this study was to reach worldwide consensus on the definitions and semantics of multimodal esophageal cancer treatment. In total, 72 experts working in the field of multimodal esophageal cancer treatment were invited to participate in this Delphi study. The study comprised three Delphi surveys sent out by email and one online meeting. Input for the Delphi survey consisted of terminology obtained from a systematic literature search. Participants were asked to respond to open questions and to indicate whether they agreed or disagreed with different statements. Consensus was reached when there was ≥75% agreement among respondents. Forty-nine of 72 invited experts (68.1%) participated in the first online Delphi survey, 45 (62.5%) in the second survey, 21 (46.7%) of 45 in the online meeting, and 39 (86.7%) of 45 in the final survey. Consensus on neoadjuvant and definitive chemoradiotherapy with or without surgery was reached for 27 of 31 items (87%). No consensus was reached on follow-up after treatment with definitive chemoradiotherapy. Consensus was reached on most statements regarding terminology and definitions of multimodal esophageal cancer treatment. Implementing uniform criteria facilitates comparison of studies and promotes international research collaborations.

Pathological response to neoadjuvant chemoradiotherapy for oesophageal squamous cell carcinoma in Eastern versus Western countries: meta-analysis.

Locally advanced oesophageal squamous cell carcinoma can be treated with neoadjuvant chemoradiotherapy or chemotherapy followed by oesophagectomy. Discrepancies in pathological response rates have been reported between studies from Eastern versus Western countries. The aim of this study was to compare the pathological response to neoadjuvant chemoradiotherapy in Eastern versus Western countries. Databases were searched until November 2022 for studies reporting pCR rates after neoadjuvant chemoradiotherapy for oesophageal squamous cell carcinoma. Multi-level meta-analyses were performed to pool pCR rates separately for cohorts from studies performed in centres in the Sinosphere (East) or in Europe and the Anglosphere (West). For neoadjuvant chemoradiotherapy, 51 Eastern cohorts (5636 patients) and 20 Western cohorts (3039 patients) were included. Studies from Eastern countries included more men, younger patients, more proximal tumours, and more cT4 and cN+ disease. Patients in the West were more often treated with high-dose radiotherapy, whereas patients in the East were more often treated with a platinum + fluoropyrimidine regimen. The pooled pCR rate after neoadjuvant chemoradiotherapy was 31.7% (95% c.i. 29.5% to 34.1%) in Eastern cohorts versus 40.4% (95% c.i. 35.0% to 45.9%) in Western cohorts (fixed-effect P = 0.003). For cohorts with similar cTNM stages, pooled pCR rates for the East and the West were 32.5% and 41.9% respectively (fixed-effect P = 0.003). The pathological response to neoadjuvant chemoradiotherapy is less favourable in patients treated in Eastern countries compared with Western countries. Despite efforts to investigate accounting factors, the discrepancy in pCR rate cannot be entirely explained by differences in patient, tumour, or treatment characteristics.

Predictive value of FCGBP expression for treatment response and survival in rectal cancer patients undergoing chemoradiotherapy.

Despite neoadjuvant chemoradiotherapy (CRT) being the established standard for treating advanced rectal cancer, clinical outcomes remain suboptimal, necessitating the identification of predictive biomarkers for improved treatment decisions. Previous studies have hinted at the oncogenic properties of the Fc fragment of IgG binding protein (FCGBP) in various cancers; however, its clinical significance in rectal cancer remains unclear. In this study, we first conducted an analysis of a public transcriptome comprising 46 rectal cancer patients. Focusing on cell adhesion during data mining, we identified FCGBP as the most upregulated gene associated with CRT resistance. Subsequently, we assessed FCGBP immunointensity using immunohistochemical staining on 343 rectal cancer tissue blocks. Elevated FCGBP immunointensity correlated with lymph node involvement before treatment (p = 0.001), tumor invasion, and lymph node involvement after treatment (both p < 0.001), vascular invasion (p = 0.001), perineural invasion (p = 0.041), and reduced tumor regression (p < 0.001). Univariate analysis revealed a significant association between high FCGBP immunoexpression and inferior disease-specific survival, local recurrence-free survival, and metastasis-free survival (all p ≤ 0.0002). Furthermore, high FCGBP immunoexpression independently emerged as an unfavorable prognostic factor for all three survival outcomes in the multivariate analysis (all p ≤ 0.025). Enriched pathway analysis substantiated the role of FCGBP in conferring resistance to radiation. In summary, our findings suggest that elevated FCGBP immunoexpression in rectal cancer significantly correlates with a poor response to CRT and diminished patient survival. FCGBP holds promise as a valuable prognostic biomarker for rectal cancer patients undergoing CRT.

Interrater Agreement of Height Assessment by Rigid Proctoscopy/ Rectoscopy for Rectal Carcinoma.

Some guidelines for rectal carcinoma consider 12 cm, measured by rigid endoscopy to be the cutoff tumor height for optional neoadjuvant chemoradiation. Measuring differences of only a few centimeters may therefore predetermine choice of further therapy. However, rigid endoscopy may exhibit similar operator dependence as do most other clinical examination methods. Evaluation of concordance of rigid rectoscopic tumor height measurements performed by 4 experienced examiners, 2 in lithotomy and 2 in left lateral position. Assessment of tumor palpability and distance of the anal verge to the anocutaneous line were also evaluated. Prospective observational study. Academic teaching hospital, referral center for colorectal surgery. There were 50 patients, of whom were 35 males (70%). The median age was 72.5 years (53-88 years). Interrater agreement of tumor height assessment and tumor allocation beneath or beyond the 12-cm height limit. With an intraclass correlation coefficient of 0.947 (95% CI: 0.918-0.967, p < 0.001), interrater reliability of tumor height assessment was statistically rated "excellent." Despite this, in 26% of patients, there was no agreement regarding the allocation of the tumor beneath or beyond the 12-cm height limit. Furthermore there was also considerable disagreement concerning tumor palpability and the distance of the anal verge to the anocutaneous line. Patient positioning was not found to influence results. Single center study. Rigid rectal endoscopy may not be a sound pivotal basis for the consideration of optional chemoradiation in rectal carcinoma. Application of a universally valid height limit obviously ignores biological variability in body frame, gender, and acquired pelvic descent. Eligibility for neoadjuvant therapy should not rely on height measurements alone. Uniform MRI or CT imaging protocols, based on agreed terminology, including factors such as tumor height relative to pelvic frame and peritoneal reflection, may be an important diagnostic addition for such decision. See Video Abstract . DRKS00012758 (German National Study Registry), ST-D 406 (German Cancer Society).

Impact of change in the Naples prognostic score after neoadjuvant chemoradiotherapy on survival in esophageal squamous cell carcinoma patients.

To assess the clinical relevance and prognostic value of changes in the Naples prognostic score (NPS) after neoadjuvant chemoradiotherapy (NACR) among esophageal squamous cell carcinoma (ESCC) patients. We studied 232 locally advanced ESCC patients who received NACR before undergoing esophagectomy retrospectively. Categorizing individuals into the elevated NPS group and the non-elevated NPS group based on the change in NPS after NACR (ΔNPS > 0 or ∆NPS ≤ 0), we examined and compared the clinicopathological characteristics, survival rates, and postoperative complications between these 2 groups (∆NPS = post-NACR NPS - pre-NACR NPS). Results: Out of the 232 patients enrolled, 105 exhibited elevated NPS levels, while 127 showed non-elevated NPS levels. Survival analyses indicated inferior overall survival (OS) (p=0.024) and recurrence-free survival (RFS) (p=0.047) in the elevated NPS cohort compared to the non-elevated NPS cohort. Subsequent cox regression analyses identified the post-NACR change in NPS as an independent prognostic indicator for RFS (p=0.029) and OS (p=0.036). Elevated NPS post-NACR emerged as a significant indicator of worse prognosis for locally advanced ESCC patients who underwent NACR. This finding has great potential to be useful for recognizing high-risk ESCC patients who received NACR before undergoing esophagectomy and making individualized subsequent therapeutic decisions in clinical practice.

GATA6 identifies an immune-enriched phenotype linked to favorable outcomes in patients with pancreatic cancer undergoing upfront surgery.

This study underscores GATA6's role in distinguishing classical and basal-like pancreatic ductal adenocarcinoma (PDAC) phenotypes. Retrospective studies associate GATA6 immunohistochemistry (IHC) expression with survival outcomes, warranting prospective validation. In a prospective treatment-naive cohort of patients with resected PDAC, GATA6 IHC proves a prognostic discriminator, associating high GATA6 expression with extended survival and the classical PDAC phenotype. However, GATA6's prognostic significance is numerically lower after gemcitabine-based neoadjuvant chemoradiotherapy compared to its significance in patients treated with upfront surgery. Furthermore, GATA6 is implicated in immunomodulation, although a comprehensive investigation of its immunological role is lacking. Treatment-naive PDAC tumors with varying GATA6 expression yield distinct immunological landscapes. Tumors highly expressing GATA6 show reduced infiltration of immunosuppressive regulatory Tcells and M2 macrophages but increased infiltration of immune-stimulating, antigen-presenting, and activated Tcells. Our findings caution against solely relying on GATA6 for molecular subtyping in clinical trials and open avenues for exploring immune-based combination therapies.

Prognostic value of neutrophil-to-lymphocyte ratio (NLR) and platelet-neutrophil (PN) index in locally advanced rectal cancer patients: a retrospective cohort study.

In locally advanced rectal cancers (LARC), tumour node metastasis (TNM) staging is far from optimal. The authors aimed to investigate the value of previously described circulating biomarkers as predictors of prognosis. Retrospective analysis of 245 LARC patients diagnosed between January 2010 and December 2022, who underwent neoadjuvant chemoradiotherapy and surgery at two centres. A Cox regression and Kaplan-Meier analysis were performed. Post-treatment platelet-to-lymphocyte ratio (PLR) predicted pathological complete response. The neutrophil-to-lymphocyte ratio (NLR) in two timepoints of the treatment significantly predicted overall survival, whereas the platelet-neutrophil (PN) index significantly predicted disease-free survival. In pathological stage II, the PN index predicted patients with a higher risk of disease-free survival. Blood parameters might allow the definition of subgroups of risk beyond TNM for the application of different therapeutic strategies.

Adjuvant Pembrolizumab in Patients with Stage IIIA/N2 Non-Small Cell Lung Cancer Completely Resected after Neoadjuvant Concurrent Chemoradiation: A Prospective, Open-Label, Single-Arm, Phase 2 Trial.

Optimal treatment for stage IIIA/N2 non-small cell lung cancer (NSCLC) is controversial. We aimed to assess the efficacy and safety of adjuvant pembrolizumab for stage IIIA/N2 NSCLC completely resected after neoadjuvant concurrent chemoradiation therapy (CCRT). In this open-label, single-center, single-arm phase 2 trial, patients with stage IIIA/N2 NSCLC received adjuvant pembrolizumab for up to two years after complete resection following neoadjuvant CCRT. The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS) and safety. As an exploratory biomarker analysis, we evaluated the proliferative response of blood CD39+PD-1+CD8+ T cells using fold changes in the percentage of proliferating Ki-67+ cells from days 1 to 7 of cycle 1 (Ki-67D7/D1). Between October 2017 and October 2018, 37 patients were enrolled. Twelve (32%) and three (8%) patients harbored EGFR and ALK alterations, respectively. Of 34 patients with programmed cell death ligand 1 assessment, 21 (62%), 9 (26%), and 4 (12%) had a tumor proportion score of <1%, 1-50%, and ≥50%, respectively. The median follow-up was 71 months. The median DFS was 22.4 months in the overall population, with a five-year DFS rate of 29%. The OS rate was 86% at two years and 76% at five years. Patients with tumor recurrence within six months had a significantly lower Ki-67D7/D1 among CD39+PD-1+CD8+ T cells than those without (p=0.036). No new safety signals were identified. Adjuvant pembrolizumab may offer durable disease control in a subset of stage IIIA/N2 NSCLC patients after neoadjuvant CCRT and surgery.

ASO Visual Abstract:Impact of Skeletal Muscle Loss and Sarcopenia on Outcomes of Locally Advanced Esophageal Cancer During Neoadjuvant Chemoradiation.

ASO Visual Abstract:Impact of Skeletal Muscle Loss and Sarcopenia on Outcomes of Locally Advanced Esophageal Cancer During Neoadjuvant Chemoradiation.

Contemporary outcomes of left thoraco-abdominal esophagectomy due to cancer in the esophagus or gastroesophageal junction, a multicenter cohort study.

Surgery for cancer of the esophagus or gastro-esophageal junction can be performed with a variety of minimally invasive and open approaches. The left thoracoabdominal esophagectomy (LTE) is an open technique that gives an opportunity to operate in the chest and abdomen with excellent exposure of the gastro-esophageal junction through a single incision, and there is currently no equivalent minimally invasive technique available. The aim of this multi-institutional review was to study a large contemporary international study cohort of patients treated with LTE. An international multicenter cohort study was performed including all patients treated with LTE at six high-volume centers for gastro-esophageal cancer surgery between 2012 and 2022. Patient data were prospectively collected in each participating centers' institutional database. Information about patient, tumor, and treatment details were collected. The study cohort included a total of 793 patients treated with LTE during the study period. The most frequently observed complications were pneumonia in 185/727 (25.5%) patients and atrial fibrillation in 91/727 (12.5%). Anastomotic leak occurred in 35/727 (4.8%) patients; no patient suffered from conduit necrosis. Thirty-day mortality occurred in 15/785 (1.9%) patients and 90-day mortality in 39/785 (5.0%) patients. Factors with statistically significant association with survival were American Society for Anesthesiologists-score, tumor location, tumor stage, and tumor free resection margins. Neoadjuvant therapy was not associated with increased survival compared to surgery alone but neoadjuvant chemoradiotherapy compared to neoadjuvant chemotherapy showed statistically significant improved survival with hazard ratio 0.60 (95% confidence intervals:0.44-0.80, P = 0.001) in a multivariable adjusted model. This study demonstrates that LTE can be applied in selected patients with results that are comparable to other large studies of open and minimally invasive surgery for esophageal or gastro-esophageal cancer at high-volume centers.

Serum Cytokines Correlate with Pretreatment Body Mass Index-adjusted Body Weight Loss Grading and Cancer Progression in Patients with Stage III Esophageal Squamous Cell Carcinoma Undergoing Neoadjuvant Chemoradiotherapy Followed by Surgery.

Serum Cytokines Correlate with Pretreatment Body Mass Index-Adjusted Body Weight Loss Grading and Cancer Progression in Patients with Stage III Esophageal Squamous Cell Carcinoma Undergoing Neoadjuvant Chemoradiotherapy Followed by Surgery. Circulating cytokines have been linked to the development of esophageal squamous cell carcinoma (ESCC) and its associated malnutrition process. Nonetheless, given the varied disease stages and treatment modalities in previous studies, the clinical relevance of their findings is limited. We retrospectively studied 52 patients with stage III ESCC who underwent neoadjuvant chemoradiotherapy and curative-intent surgery. We investigated the association of clinicopathological features, pretreatment laboratory data, and pretreatment inflammatory status, as indicated by the levels of albumin, C-reactive protein, and 10 circulating cytokines, namely tumor necrosis factor-alpha (TNF-α), interferon-gamma, interleukin-1-beta (IL-1β), IL-4, IL-6, IL-8, IL-12, IL-13, IL-17A, and IL-23, with malnutrition, as shown by body mass index-adjusted body weight loss (BMI-BWL) grading, cancer progression. Half the patients showed severe malnutrition and high BMI-BWL grades (3 and 4). Multivariate analysis revealed an independent association between the levels of three cytokines (TNF-α, ≤ 5.8 pg/ml; IL-1β, > 0.4 pg/ml; IL-6, ≤ 12.4 pg/ml) and high BMI-BWL grades and between IL-4 levels > 22.5 pg/ml and cancer progression. All 10 cytokines were closely correlated with each other. In conclusion, TNF-α, IL-1β, and IL-6 were independent markers of malnutrition status and IL-4 was a prognostic factor for cancer progression in this patient population.

Effect of neoadjuvant concurrent three-dimensional conformal chemoradiotherapy with conventional two-dimensional chemoradiotherapy in locally advanced rectal cancer

Background: Rectal carcinoma is a prevalent clinical condition, and treatment hinges on factors like tumor specifics, staging, grading, and histopathological characteristics. While surgery remains the primary treatment, neoadjuvant chemoradiotherapy, particularly using 3D-CRT, has proven effective in reducing local recurrence rates for locally advanced cases. Alternatively, 2D-RT is considered for neoadjuvant treatment. This study aimed to compare the impact of neoadjuvant concurrent three-dimensional conformal chemoradiotherapy with conventional two-dimensional chemoradiotherapy in the context of locally advanced rectal cancer. Methods: In this multicentre quasi-experimental study, 60 patients with biopsy-proven adenocarcinoma and clinically confirmed locally advanced rectal cancer, were divided into Group A (receiving oral capecitabine with three-dimensional conformal radiotherapy) and Group B (receiving the same capecitabine dose with 50 Gy two-dimensional radiotherapy). After surgery within 6-12 weeks, outcomes were analysed. Results: After neoadjuvant chemoradiotherapy, clinical complete response rates were 16.7% in Group A and 10.0% in Group B, with a higher pathological complete response in Group A (10.0% vs. 3.3%). Tumor downsizing occurred in 83.3% of Group A and 73.3% of Group B, and sphincter-sparing surgery was achieved in 73.3% of Group A and 56.7% of Group B. Grade 2 toxicities included anemia (10.0% vs. 13.3%), leucopenia (13.3% vs. 20.0%), diarrhoea (10.0% vs. 16.7%), proctitis (13.3% vs. 40.0%), and urinary toxicity (10.0% vs. 20.0%). Grade-1 toxicities were nausea (20.0% vs. 40.0%), vomiting (20.0% vs. 36.7%), mucositis (56.7% vs. 60.0%), hand-foot syndrome (33.3% vs. 40.0%), and urinary toxicity (43.3% vs. 56.67%), with significant proctitis in Group A (p=0.012). Other toxicities showed non-significant p-values (&gt;0.05). Conclusions: Tumour response was not statistically significant between the patients of concurrent 3D-CRT and 2D-RT Arms. But the patients of 3D-CRT arm showed better response arithmetically. Also, there was an observable significant reduction of toxicities (lower gastrointestinal) in the 3D-CRT arm.

A Re-Examination of Neoadjuvant Therapy for Thymic Tumors: A Long and Winding Road.

For most patients with advanced thymic epithelial tumors (TETs), a complete resection is a strong indicator of a better prognosis. But sometimes, primary surgery is unsatisfactory, and preoperative therapy is needed to facilitate complete resection. Neoadjuvant chemotherapy is the most used form of preoperative therapy. But studies on neoadjuvant chemotherapy have included mainly patients with thymoma; its efficacy in patients with thymic carcinoma is less known. Neoadjuvant chemoradiation has also been explored in a few studies. Novel therapies such as immunotherapy and targeted therapy have shown efficacy in patients with recurrent/metastatic TETs as a second-line option; their role as preoperative therapy is still under investigation. In this review, we discuss the existing evidence on preoperative therapy and the insight it provides for current clinical practice and future studies.

A prospective study on using shear wave elastography to predict the ypT0 stage of rectal cancer after neoadjuvant therapy: a new support for the watch-and-wait approach?

The diagnostic accuracy of traditional imaging examination in predicting ypT stage of rectal cancer after neoadjuvant therapy is significantly reduced, which would affect patients' subsequent treatment choices. This study aimed to investigate the use of endorectal shear wave elastography (SWE) for diagnosing ypT0 stage of rectal cancer after neoadjuvant chemoradiotherapy (nCRT). Sixty patients with rectal cancer were prospectively recruited in this study. Data on endorectal ultrasound (ERUS) and SWE parameters were collected before nCRT and 6-8 weeks after nCRT. Postoperative pathological results were the gold standard for evaluating the diagnostic accuracy of SWE and ERUS in predicting the ypT0 stage of rectal cancer after nCRT. Receiver operating characteristic (ROC) curve analysis was used to determine the cut-off values of the SWE parameters that best corresponded to the ypT0 stage and analyze the sensitivity, specificity, and accuracy. The diagnostic accuracies of using ERUS to predict the ypT and ypT0 stages of rectal cancer after nCRT were 58.1% (18/31) and 64.3% (9/14), respectively. The ROC curve was constructed with the lesion's Emean, Emean corrected (EC), Emean difference (ED), Emean corrected differencede (ECD), Emean descendding rate (EDR) and Emean corrected descendding rate (ECDR) values after nCRT, the cut-off values of diagnosing the ypT0 stage were 64.40kPa, 55.45kPa, 72.55kPa, 73.75kPa, 50.15%, and 55.93%, respectively; the area under the curve (AUC) for diagnosing the ypT0 stage was 0.924, 0.933, 0.748, 0.729, 0.857 and 0.861, respectively. The EC value showed the best diagnostic performance. SWE could improve the accuracy of conventional ERUS in diagnosing the ypT0 stage of rectal cancer after nCRT. It is expected to become a new method to help predict pathological complete responses in clinical practice and provide new evidence for the watch-and-wait approach.