Prediction, prevention and management of gastroesophageal reflux after per-oral endoscopic myotomy: An update.

Achalasia cardia, the most prevalent primary esophageal motility disorder, is predominantly characterized by symptoms of dysphagia and regurgitation. The principal therapeutic approaches for achalasia encompass pneumatic dilatation (PD), Heller's myotomy, and the more recent per-oral endoscopic myotomy (POEM). POEM has been substantiated as a safe and efficacious modality for the management of achalasia. Although POEM demonstrates superior efficacy compared to PD and an efficacy parallel to Heller's myotomy, the incidence of gastroesophageal reflux disease (GERD) following POEM is notably higher than with the aforementioned techniques. While symptomatic reflux post-POEM is relatively infrequent, the significant occurrence of erosive esophagitis and heightened esophageal acid exposure necessitates vigilant monitoring to preclude long-term GERD-related complications. Contemporary advancements in the field have enhanced our comprehension of the risk factors, diagnostic methodologies, preventative strategies, and therapeutic management of GERD subsequent to POEM. This review focuses on the limitations inherent in the 24-h pH study for evaluating post-POEM reflux, potential modifications in the POEM technique to mitigate GERD risk, and the strategies for managing reflux following POEM.

Long-term outcomes of laparoscopic Heller's myotomy with angle of His accentuation in patients of achalasia cardia.

BACKGROUND: Laparoscopic Heller's myotomy (LHM) is an established treatment for achalasia cardia. Anti-reflux procedures (ARP) are recommended with LHM to reduce the post-operative reflux though the optimal anti-reflux procedure is still debatable. This study reports on the long-term outcomes of LHM with Angle-of-His accentuation (AOH) in patients of achalasia cardia. METHODS: One hundred thirty-six patients of achalasia cardia undergoing LHM with AOH between January 2010 to October 2021 with a minimum follow-up of one year were evaluated for symptomatic outcomes using Eckardt score (ES), DeMeester heartburn (DMH) score and achalasia disease specific quality of life (A-DsQoL) questionnaire. Upper gastrointestinal endoscopy, high resolution manometry (HRM) and timed barium esophagogram (TBE) were performed when feasible and rates of esophagitis and improvement in HRM and TBE parameters evaluated. Time dependent rates of success were calculated with respect to improvement in ES and dysphagia-, regurgitation- and heartburn-free survival using Kaplan-Meier analysis. RESULTS: At a median follow-up of 65.5 months, the overall success (ES ≤ 3) was 94.1%. There was statistically significant improvement in ES, heartburn score and A-DsQoL score (p < 0.00001, p = 0.002 and p < 0.00001). Significant heartburn (score ≥ 2) was seen in 12.5% subjects with 9.5% patients reporting frequent PPI use (> 3 days per week). LA-B and above esophagitis was seen in 12.7%. HRM and TBE parameters also showed a significant improvement as compared to pre-operative values (IRP: p < 0.0001, column height: p < 0.0001, column width: p = 0.0002). Kaplan-Meier analysis showed dysphagia, regurgitation, and heartburn free survival of 75%, 96.2% and 72.3% respectively at 10 years. CONCLUSIONS: LHM with AOH gives a lasting relief of symptoms in patients of achalasia cardia with heartburn rates similar to that reported in studies using Dor's or Toupet's fundoplication with LHM. Hence, LHM with AOH may be a preferred choice in patients of achalasia cardia given the simplicity of the procedure.

Proton therapy (PT) combined with concurrent chemotherapy for locally advanced non-small cell lung cancer with negative driver genes.

PURPOSE: To discuss the optimal treatment modality for inoperable locally advanced Non-Small Cell Lung Cancer patients with poor physical status, impaired cardio-pulmonary function, and negative driver genes, and provide clinical evidence. MATERIALS AND METHODS: Retrospective analysis of 62 cases of locally advanced non-small cell lung cancer patients with negative driver genes treated at Tsukuba University Hospital(Japan) and Qingdao University Affiliated Hospital(China).The former received proton therapy with concurrent chemotherapy, referred to as the proton group, with 25 cases included; while the latter underwent X-ray therapy with concurrent chemoradiotherapy followed by 1 year of sequential immunomodulatory maintenance therapy, referred to as the X-ray group, with 37 cases included.The treatment response and adverse reactions were assessed using RECIST v1.1 criteria and CTCAE v3.0, and radiotherapy planning and evaluation of organs at risk were performed using the CB-CHOP method.All data were subjected to statistical analysis using GraphPad Prism v9.0, with a T-test using P < 0.05 considered statistically significant. RESULTS: (1)Target dose distribution: compared to the X-ray group, the proton group exhibited smaller CTV and field sizes, with a more pronounced bragg peak.(2)Organs at risk dose: When comparing the proton group to the X-ray group, lung doses (V5, V20, MLD) and heart doses (V40, Dmax) were lower, with statistical significance (P < 0.05), while spinal cord and esophagus doses showed no significant differences between the two groups (P > 0.05).(3)Treatment-related toxicities: The incidence of grade 3 or higher adverse events in the proton group and X-ray group was 28.6% and 4.2%, respectively, with a statistically significant difference (P < 0.05). In terms of the types of adverse events, the proton group primarily experienced esophagitis and pneumonia, while the X-ray group primarily experienced pneumonia, esophagitis, and myocarditis. Both groups did not experience radiation myelitis or esophagotracheal fistula.(4)Efficacy evaluation: The RR in the proton group and X-ray group was 68.1% and 70.2%, respectively (P > 0.05), and the DCR was 92.2% and 86.4%, respectively (P > 0.05), indicating no significant difference in short-term efficacy between the two treatment modalities.(5)Survival status: The PFS in the proton group and X-ray group was 31.6 ± 3.5 months (95% CI: 24.7 ~ 38.5) and 24.9 ± 1.55 months (95% CI: 21.9 ~ 27.9), respectively (P > 0.05), while the OS was 51.6 ± 4.62 months (95% CI: 42.5 ~ 60.7) and 33.1 ± 1.99 months (95% CI: 29.2 ~ 37.1), respectively (P < 0.05).According to the annual-specific analysis, the PFS rates for the first to third years in both groups were as follows: 100%, 56.1% and 32.5% for the proton group vs. 100%, 54.3% and 26.3% for the X-ray group. No statistical differences were observed at each time point (P > 0.05).The OS rates for the first to third years in both groups were as follows: 100%, 88.2%, 76.4% for the proton group vs. 100%, 91.4%, 46.3% for the X-ray group. There was no significant difference in the first to second years (P > 0.05), but the third year showed a significant difference (P < 0.05). Survival curve graphs also depicted a similar trend. CONCLUSION: There were no significant statistical differences observed between the two groups in terms of PFS and OS within the first two years. However, the proton group demonstrated a clear advantage over the X-ray group in terms of adverse reactions and OS in the third year. This suggests a more suitable treatment modality and clinical evidence for populations with frail health, compromised cardio-pulmonary function, post-COVID-19 sequelae, and underlying comorbidities.

Does One-Anastomosis Gastric Bypass Expose Patients to Gastroesophageal Reflux: a Systematic Review and Meta-analysis.

This systematic review and meta-analysis aimed to investigate the incidence of new-onset gastroesophageal reflux, reflux change, esophagitis, Barrett's esophagus, and revision due to reflux, gastritis, and marginal ulcer after one-anastomosis gastric bypass (OAGB). We performed subgroup analyses based on primary and revisional OAGB and time of follow-up. Meta-analysis of 87 studies with 27,775 patients showed a 6% rate of new-onset reflux after OAGB. Preoperative reflux status did not change significantly after OAGB. The rate of esophagitis and Barrett's esophagus was 15% and 1%, respectively. The new-onset reflux rate after OAGB was significantly higher than gastric bypass but not different with sleeve gastrectomy. The current study showed a relatively low rate of reflux and its complications after OAGB, but it was significantly higher than Roux-en-Y gastric bypass.

Model development of dose and volume predictors for esophagitis induced during chemoradiotherapy for lung cancer as a step towards radiobiological treatment planning.

BACKGROUND: Currently, radiation therapy treatment planning system intends biological optimization that relies heavily upon plan metrics from tumor control probability (TCP) and normal tissue complication probability (NTCP) modeling. Implementation and expansion of TCP and NTCP models with alternative data is an important step towards reliable radiobiological treatment planning. In this retrospective single institution study, the treatment charts of 139 lung cancer patients treated with chemo-radiotherapy were reviewed and correlated dosimetric predictors with the incidence of esophagitis and established NTCP model of esophagitis grade 1 and 2 for lung cancer patients. METHODS: Esophagus is an organ at risk (OAR) in lung cancer radiotherapy (RT). Esophagitis is a common toxicity induced by RT. In this study, dose volume parameters Vx (Vx: percentage esophageal volume receiving ≥ x Gy) and mean esophagus dose (MED) as quantitative dose-volume metrics, the esophagitis grade 1 and 2 as endpoints, were reviewed and derived from the treatment planning system and the electronic medical record system. Statistical analysis of binary logistic regression and probit were performed to have correlated the probability of grade 1 and 2 esophagitis to MED and Vx. IBM SPSS software version 24 at 5% significant level (α = 0.05) was used in the statistical analysis. RESULTS: The probabilities of incidence of grade 1 and 2 esophagitis proportionally increased with increasing the values of Vx and MED. V20, V30, V40, V50 and MED are statistically significant good dosimetric predictors of esophagitis grade 1. 50% incidence probability (TD50) of MED for grade 1 and 2 esophagitis were determined. Lyman Kutcher Burman model parameters, such as, n, m and TD50, were fitted and compared with other published findings. Furthermore, the sigmoid shaped dose responding curve between probability of esophagitis grade 1 and MED were generated respecting to races, gender, age and smoking status. CONCLUSIONS: V20, V30, V40 and V50 were added onto Quantitative Analysis of Normal Tissue Effects in the clinic, or QUANTEC group's dose constrains of V35, V50, V70 and MED. Our findings may be useful as both validation of 3-Dimensional planning era models and also additional clinical guidelines in treatment planning and plan evaluation using radiobiology optimization.

A case report of esophageal cancer in a patient with pemphigus vulgaris: A coincidence or something beyond that?

BACKGROUND: Pemphigus is a group of rare but serious autoimmune blistering disorders, affecting skin and mucus membrane. Different reports have been published in respect to the coexistence of pemphigus with neoplasms, especially lympho-proliferative ones. CASE: Here, we have reported a patient previously diagnosed with pemphigus vulgaris (PV) who developed esophageal squamous cell carcinoma (SCC). CONCLUSION: Dyspepsia and dysphagia in patients with PV might not be merely due to pemphigus erosions or simply an adverse effect of systemic corticosteroid such as irritant or candidal esophagitis and should raise the suspicion of more serious conditions in case of resistant symptoms without appropriate response to treatment.

GERD-screening before bariatric surgery: the predictive value of the GERD-HRQL questionnaire score compared with preoperative EGD findings.

BACKGROUND: There is an ongoing debate on how to best identify patients with gastroesophageal reflux disease (GERD) before bariatric surgery. The value of routine preoperative esophagogastroduodenoscopy (EGD) is questioned, and patient reported symptoms are commonly used for screening. The goal of this study is to determine if patient reported symptoms using a validated questionnaire correlate with preoperative EGD findings. METHODOLOGY: A prospective cohort study at a single institution was performed. Patients undergoing bariatric surgery between December 2020 and March 2023 were required to report symptoms of reflux by completing a preoperative GERD. Health-Related Quality of Life (GERD-HRQL) questionnaire and undergo a mandatory preoperative screening EGD. Patients were stratified into two cohorts: (group A) asymptomatic (score = 0) and (group B) symptomatic (score > 0). Statistical analysis was conducted using Pearson's chi-squared test and Wilcoxon rank-sum test in RStudio version 4.2.2. The predictive value of the GERD-HRQL score was analyzed using Areas Under the Curve (AUC; AUC = 0.5 not predictive, 0.5 < AUC ≥ 6 poor prediction & AUC > 0.9 excellent prediction) calculated from Receiver Operating Characteristic (ROC) curves. RESULTS: 200 patients were included; median age was 42.0 years (IQR 36.0 to 49.2). There were 79 patients (39.5%) in Group A and 121 patients (60.5%) in Group B. There was no difference in the frequency esophagitis (27.8% vs 32.2%, p = 0.61) or hiatal hernias (49.4% vs 47.1%, p = 0. 867) between group A and group B, respectively. ROC analysis revealed that the total GERD HRQL scores, heartburn only scores and regurgitation only scores, were poor predictors of esophagitis found on EGD (AUC 0.52, 0.53, 0.52), respectively. In asymptomatic patients, higher BMI was significantly associated with esophagitis (OR 1.15, 95% CI 1.06-1.27, p = 0.002). CONCLUSION: Symptoms, identified through the GERD-HRQL questionnaire, are a poor indicator of esophagitis or its severity in patients undergoing workup for bariatric surgery. Therefore, liberal screening upper endoscopy is recommended for pre-bariatric surgery patients to guide appropriate procedure selection.

Natural Language Processing to Automatically Extract the Presence and Severity of Esophagitis in Notes of Patients Undergoing Radiotherapy.

PURPOSE: Radiotherapy (RT) toxicities can impair survival and quality of life, yet remain understudied. Real-world evidence holds potential to improve our understanding of toxicities, but toxicity information is often only in clinical notes. We developed natural language processing (NLP) models to identify the presence and severity of esophagitis from notes of patients treated with thoracic RT. METHODS: Our corpus consisted of a gold-labeled data set of 1,524 clinical notes from 124 patients with lung cancer treated with RT, manually annotated for Common Terminology Criteria for Adverse Events (CTCAE) v5.0 esophagitis grade, and a silver-labeled data set of 2,420 notes from 1,832 patients from whom toxicity grades had been collected as structured data during clinical care. We fine-tuned statistical and pretrained Bidirectional Encoder Representations from Transformers-based models for three esophagitis classification tasks: task 1, no esophagitis versus grade 1-3; task 2, grade ≤1 versus >1; and task 3, no esophagitis versus grade 1 versus grade 2-3. Transferability was tested on 345 notes from patients with esophageal cancer undergoing RT. RESULTS: Fine-tuning of PubMedBERT yielded the best performance. The best macro-F1 was 0.92, 0.82, and 0.74 for tasks 1, 2, and 3, respectively. Selecting the most informative note sections during fine-tuning improved macro-F1 by ≥2% for all tasks. Silver-labeled data improved the macro-F1 by ≥3% across all tasks. For the esophageal cancer notes, the best macro-F1 was 0.73, 0.74, and 0.65 for tasks 1, 2, and 3, respectively, without additional fine-tuning. CONCLUSION: To our knowledge, this is the first effort to automatically extract esophagitis toxicity severity according to CTCAE guidelines from clinical notes. This provides proof of concept for NLP-based automated detailed toxicity monitoring in expanded domains.

[Analysis of risk factors of radiation-induced toxicity in limited-stage small cell lung cancer treated with hypofractionated intensity-modulated radiotherapy].

Objective: To compare the incidence of radiation-related toxicities between conventional and hypofractionated intensity-modulated radiation therapy (IMRT) for limited-stage small cell lung cancer (SCLC), and to explore the risk factors of hypofractionated radiotherapy-induced toxicities. Methods: Data were retrospectively collected from consecutive limited-stage SCLC patients treated with definitive concurrent chemoradiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from March 2016 to April 2022. The enrolled patients were divided into two groups according to radiation fractionated regimens. Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) was used to evaluate the grade of radiation esophagus injuries and lung injuries. Logistic regression analyses were used to identify factors associated with radiation-related toxicities in the hypofractionated radiotherapy group. Results: Among 211 enrolled patients, 108 cases underwent conventional IMRT and 103 patients received hypofractionated IMRT. The cumulative incidences of acute esophagitis grade ≥2 [38.9% (42/108) vs 35.0% (36/103), P=0.895] and grade ≥ 3 [1.9% (2/108) vs 5.8% (6/103), P=0.132] were similar between conventional and hypofractionated IMRT group. Late esophagus injuries grade ≥2 occurred in one patient in either group. No differences in the cumulative incidence of acute pneumonitis grade ≥2[12.0% (13/108) vs 5.8% (6/103), P=0.172] and late lung injuries grade ≥2[5.6% (6/108) vs 10.7% (11/103), P=0.277] were observed. There was no grade ≥3 lung injuries occurred in either group. Using multiple regression analysis, mean esophageal dose ≥13 Gy (OR=3.33, 95% CI: 1.23-9.01, P=0.018) and the overlapping volume between planning target volume (PTV) and esophageal ≥8 cm(3)(OR=3.99, 95% CI: 1.24-12.79, P=0.020) were identified as the independent risk factors associated with acute esophagitis grade ≥2 in the hypofractionated radiotherapy group. Acute pneumonitis grade ≥2 was correlated with presence of chronic obstructive pulmonary disease (COPD, P=0.025). Late lung injuries grade ≥2 was correlated with tumor location(P=0.036). Conclusions: Hypofractionated IMRT are tolerated with manageable toxicities for limited-stage SCLC patients treated with IMRT. Mean esophageal dose and the overlapping volume between PTV and esophageal are independently predictive factors of acute esophagitis grade ≥2, and COPD and tumor location are valuable factors of lung injuries for limited-stage SCLC patients receiving hyofractionated radiotherapy. Prospective studies are needed to confirm these results.

Full Dose SBRT in Combination With Mediastinal Chemoradiation for Locally Advanced, Non-Small Cell Lung Cancer: A Practical Guide for Planning, Dosimetric Results From a Phase 2 Study, and a Treatment Planning Guide for the Phase 3 NRG Oncology LU-008 Trial.

PURPOSE: Stereotactic body radiation therapy (SBRT) has been used with high effectiveness in early-stage non-small cell lung cancer (NSCLC) but has not been studied extensively in locally advanced NSCLC. We conducted a phase 2 study delivering SBRT to the primary tumor followed by conventionally fractionated chemoradiation to the involved lymph nodes for patients with node-positive locally advanced NSCLC. This manuscript serves as both a guide to planning techniques used on this trial and the subsequent phase 3 study, NRG Oncology LU-008, and to report patient dosimetry and toxicity results. METHODS AND MATERIALS: We initiated a phase 2 multicenter single arm study evaluating SBRT to the primary tumor (50-54 Gy in 3-5 fractions) followed by conventionally fractionated chemoradiation to 60 Gy in 2 Gy fractions with doublet chemotherapy to the involved lymph nodes for patients with stage III or unresectable stage II NSCLC. Patients eligible for adjuvant immunotherapy received up to 12 months of durvalumab. We report a detailed guide for the entire treatment process from computed tomography simulation through treatment planning and delivery. The dosimetric outcomes from the 60 patients who completed therapy on study are reported both for target coverage and normal structure doses. We also report correlation between radiation-related toxicities and dosimetric parameters. RESULTS: Sixty patients were enrolled between 2017 and 2022. Planning techniques used were primarily volumetric modulated arc therapy for SBRT to the primary tumor and conventionally fractionated radiation to the involved nodes, with a minority of cases using dynamic conformal arc technique or static dynamic multileaf collimator intensity modulated radiation therapy. Grade 2 or higher pneumonitis was associated with lung dose V5 Gy > 70% and grade 2 or higher pulmonary toxicity was associated with lung dose V10 Gy > 50%. Only 3 patients (5%) experienced grade 3 or higher pneumonitis. Grade 2 or higher esophagitis was associated with esophageal doses, including mean dose > 20 Gy, V60 Gy > 7%, and D1cc > 55 Gy. Only 1 patient (1.7%) experienced grade 3 esophagitis. CONCLUSIONS: SBRT to the primary tumor followed by conventionally fractionated chemoradiation to the involved lymph nodes is feasible with planning techniques as described. Radiation-related toxicity on this phase 2 study was low. This manuscript serves as a guideline for the recently activated NRG Oncology LU-008 phase 3 trial evaluating this experimental regimen.

Role of Preoperative High-Resolution Manometry in the Identification of Patients at High Risk of Postoperative GERD Symptoms 1 Year After Sleeve Gastrectomy.

PURPOSE: Sleeve gastrectomy (SG) has become the most common bariatric procedure, but it is often characterized by the onset of postoperative gastroesophageal reflux disease (GERD). High-resolution manometry (HRM) is a useful tool to detect risk factors for GERD. The aim of this study was to evaluate preoperative manometric parameters as possible predictors of postoperative GERD. MATERIALS AND METHODS: This was a monocentric retrospective study. We analyzed 164 patients, with preoperative esophagitis/GERD symptoms who underwent preoperative HRM and were submitted to SG (July 2020-February 2022). RESULTS: Postoperative GERD was observed in 60 patients (36.6%): 41 of them (68%) already had preoperative GERD symptoms, whereas the remaining 19 patients (32%) developed postoperative symptoms. Female patients developed postoperative GERD in a significantly higher fraction of cases as compared to male patients (82% versus 18%; p < 0.001). DCI (distal contractile integral) was identified as the only HRM parameter correlating with the presence of GERD. Patients with DCI ≤ 1623 mmHg*cm*s developed postoperative GERD in 46% of cases (n = 43/94), as compared to 24% of cases (n = 17/70) among patients with DCI > 1623 mmHg*cm*s (p = 0.005). At multivariable analysis, female sex (OR 3.402, p = 0.002), preoperative GERD symptoms (OR 2.489, p = 0.013), and DCI ≤ 1623 mmHg*s*cm (OR 0.335, p = 0.003) were identified as independent determinants of postoperative GERD. CONCLUSION: All the patients with preoperative risk factors for reflux, such as GERD symptoms or esophagitis on EGDS (esophagogastroduodenoscopy), should be considered for an HRM. Moreover, when a DCI ≤ 1623 mmHg*s*cm is found, a bariatric procedure different from SG might be considered.

Effects of PEG in patients with esophageal squamous cell carcinoma during concurrent chemoradiotherapy: a prospective study.

BACKGROUND AND AIMS: This prospective study aimed to compare the changes in nutritional status and adverse events among patients with esophageal squamous cell carcinoma who received enteral nutrition through oral intake, PEG, and an enteral nasogastric tube (NGT) during concurrent chemoradiotherapy (CCRT). METHODS: Of 141 included patients, 38, 74, and 29 patients were fed through oral intake, PEG, and NGTs, respectively. The clinical characteristics and baseline nutritional status of the 3 groups were recorded and analyzed. The Patient-Generated Subjective Global Assessment score, skeletal muscle index, and quality of life were evaluated before and after CCRT; the incidence of adverse events during feeding using PEG and NGTs was also recorded. The correlations among the different nutritional pathways and the CCRT-related adverse events (eg, radiation esophagitis and myelosuppression) were assessed. RESULTS: At baseline, the oral intake group had a significantly better nutritional status and lower disease stage than those in the PEG and NGT groups. However, during CCRT, the oral intake group exhibited the most significant decreases in weight and skeletal muscle index. The synchronous chemotherapy completion rate was the highest in the PEG group. Multivariate analysis showed that the planning tumor volume and oral intake and NGT feeding pathways were associated with radiation esophagitis of at least grade 2. CONCLUSIONS: We found that PEG effectively maintained the body weight and skeletal muscle index of patients with esophageal cancer during CCRT. PEG also improved the synchronous chemotherapy completion rate and reduced the occurrence of at least grade 2 radiation esophagitis. (Clinical trial registration number: NCT04199832.).

Toxic Effects of Volume-modulated Arc Therapy for Esophageal Squamous Cell Cancer: Preliminary Clinical Results.

BACKGROUND/AIM: To evaluate the toxic effects associated with various factors, including the presence or absence of concurrent chemotherapy with volume-modulated arc therapy (VMAT) and dose parameters for esophageal cancer (EC), and to assess the safety and feasibility of the VMAT protocol. PATIENTS AND METHODS: Patients with EC who received definitive VMAT between December 2016 and December 2020 were retrospectively analyzed. VMAT plans were designed to deliver 60 Gy to the primary tumor, 54 Gy to high-risk sites, and 51.3 Gy to regional lymph node sites. Toxic effects were evaluated for esophagitis, neutropenia, esophageal stricture, pericardial effusion, radiation-associated pneumonia. RESULTS: Forty-five patients received concurrent chemoradiotherapy (CCRT), while 29 were treated with radiation therapy (RT) alone. The following grade 3 complications were detected: Neutropenia in four patients (5.4%), esophagitis in two (2.7%), and esophageal stricture in one (1.4%). Grade 4 or more complications were not observed. The median age of the CCRT group (67 years) was significantly lower than that of the RT-alone group (77 years) (p<0.0001). The incidence of esophagitis was significantly higher in the CCRT group (75.5%) than in the RT group (48.3%) (p=0.033). The univariate analysis identified increasing mean dose to the pericardium as a significant risk factor for pericardial effusion, and CCRT and performance status ≥1 as significant for radiation-associated pneumonia. These factors were not significant in the multivariate analysis. Neutropenia and esophageal stricture were not associated with any factor examined. CONCLUSION: VMAT alone and in CCRT performed with our protocol was safe and feasible in patients with esophageal squamous cell cancer.

Hypofractionated Radiotherapy followed by Hypofractionated Boost with weekly concurrent chemotherapy for Unresectable Stage III Non-Small Cell Lung Cancer: Results of A Prospective Phase II Study (GASTO-1049).

PURPOSE: We launched a prospective phase 2 clinical trial to explore the safety and efficacy of hypofractionated radiation therapy (hypo-RT) followed by hypofractionated boost (hypo-boost) combined with concurrent weekly chemotherapy in patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC). METHODS AND MATERIALS: Patients with newly diagnosed LA-NSCLC with unresectable stage III disease were recruited between June 2018 and June 2020. Patients were treated with hypo-RT (40 Gy in 10 fractions) followed by hypo-boost (24-28 Gy in 6-7 fractions) combined with concurrent weekly chemotherapy (docetaxel 25 mg/m2 and nedaplatin 25 mg/m2). The primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints included overall survival (OS), locoregional failure-free survival (LRFS), distant metastasis-free survival (DMFS), objective response rate (ORR), and toxicities. RESULTS: From June 2018 to June 2020, 75 patients were enrolled with a median follow-up duration of 28.0 months. The ORR of the whole cohort was 94.7%. Disease progression or death was recorded in 44 (58.7%) patients, with a median PFS of 21.6 months (95% confidence interval [CI], 15.6-27.6 months). The 1- and 2-year PFS rates were 81.3% (95% CI, 72.5%-90.1%) and 43.3% (95% CI, 31.5%-55.1%), respectively. The median OS, DMFS, and LRFS had not been reached at the time of the last follow-up. The 1- and 2-year OS rates were 94.7% (95% CI, 89.6%-99.8%) and 72.4% (95% CI, 62.0%-82.8%), respectively. The most frequent acute nonhematologic toxicity was radiation esophagitis. Grade (G) 2 and G3 acute radiation esophagitis were observed in 20 (26.7%) and 4 (5.3%) patients, respectively. Thirteen patients (13/75, 17.3%) had G2 pneumonitis and no G3-G5 acute pneumonitis occurred during follow-up. CONCLUSIONS: Hypo-RT followed by hypo-boost combined with concurrent weekly chemotherapy could yield satisfactory local control and survival outcomes with moderate radiation-induced toxicity in patients with LA-NSCLC. The new potent hypo-CCRT regimen significantly shortened treatment time and provided the potential opportunity for the combination of consolidative immunotherapy.

Pepsin in saliva for the diagnosis of erosive esophagitis post-sleeve gastrectomy: a prospective observational study.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has become the preferred bariatric procedure in many countries. However, new onset erosive esophagitis (EE) is a major shortcoming. Current recommendation is esophago-gastro-duodenoscopy (EGD) should be performed routinely at 1 year and subsequently every 2-3 years to enable the early detection of Barrett's or esophageal adenocarcinoma. This would put significant strains on resources and costs of bariatric program. Our study assesses the association between and diagnostic value of salivary pepsin concentration and endoscopically proven EE in post-LSG patients as a surrogate for EGD. METHODS: Twenty patients on routine post-LSG endoscopy between June and September 2022 were recruited for this correlational pilot study. Under supervision, fasting and post-prandial saliva sample was collected and analyzed by Peptest lateral flow device. EGD examinations were performed, and patients completed a validated 25-item QoLRAD questionnaire. RESULTS: We found a significant correlation between positive endoscopy findings of EE and salivary pepsin concentrations. The normal group had a lower mean fasting pepsin level (13.13 ng/mL ± 18.97) versus the EE-group (90.55 ng/mL ± 81.28, p = 0.009) and lower mean post-prandial pepsin level (30.50 ng/mL ± 57.72) versus the EE-group (135.09 ng/mL ± 130.17, p = 0.02). The predictive probabilities from the binary regression of fasting and post-prandial pepsin concentrations yield AUC of 0.955 ± 0.044 (95% CI 0.868 to 1.000, p < 0.001). CONCLUSION: Our study distinctively identified salivary pepsin to have excellent sensitivity and negative predictive value in EE, potentially useful to preclude the need for post-LSG EGD in asymptomatic patients with low salivary pepsin.

Multi-omics to predict acute radiation esophagitis in patients with lung cancer treated with intensity-modulated radiation therapy.

PURPOSE: The study aimed to predict acute radiation esophagitis (ARE) with grade ≥ 2 for patients with locally advanced lung cancer (LALC) treated with intensity-modulated radiation therapy (IMRT) using multi-omics features, including radiomics and dosiomics. METHODS: 161 patients with stage IIIA-IIIB LALC who received chemoradiotherapy (CRT) or radiotherapy by IMRT with a prescribed dose from 45 to 70 Gy from 2015 to 2019 were enrolled retrospectively. All the toxicity gradings were given following the Common Terminology Criteria for Adverse Events V4.0. Multi-omics features, including radiomics, dosiomics (including dose-volume histogram dosimetric parameters), were extracted based on the planning CT image and three-dimensional dose distribution. All data were randomly divided into training cohorts (N = 107) and testing cohorts (N = 54). In the training cohorts, features with reliably high outcome relevance and low redundancy were selected under random patient subsampling. Four classification models (using clinical factors (CF) only, using radiomics features (RFs) only, dosiomics features (DFs) only, and the hybrid features (HFs) containing clinical factors, radiomics and dosiomics) were constructed employing the Ridge classifier using two-thirds of randomly selected patients as the training cohort. The remaining patient was treated as the testing cohort. A series of models were built with 30 times training-testing splits. Their performances were assessed using the area under the ROC curve (AUC) and accuracy. RESULTS: Among all patients, 51 developed ARE grade ≥ 2, with an incidence of 31.7%. Next, 8990 radiomics and 213 dosiomics features were extracted, and 3, 6, 12, and 13 features remained after feature selection in the CF, DF, RF and DF models, respectively. The RF and HF models achieved similar classification performance, with the training and testing AUCs of 0.796 ± 0.023 (95% confidence interval (CI [0.79, 0.80])/0.744 ± 0.044 (95% CI [0.73, 0.76]) and 0.801 ± 0.022 (95% CI [0.79, 0.81]) (p = 0.74), respectively. The model performances using CF and DF features were poorer, with training and testing AUCs of 0.573 ± 0.026 (95% CI [0.56, 0.58])/ 0.509 ± 0.072 (95% CI [0.48, 0.53]) and 0.679 ± 0.027 (95% CI [0.67, 0.69])/0.604 ± 0.041 (95% CI [0.53, 0.63]) compared with the above two models (p < 0.001), respectively. CONCLUSIONS: In LALC patients treated with CRT IMRT, the ARE grade ≥ 2 can be predicted using the pretreatment radiotherapy image features. To predict ARE, the multi-omics features had similar predictability with radiomics features; however, the dosiomics features and clinical factors had a limited classification performance.

Dose-Volume Predictors for Radiation Esophagitis in Patients With Breast Cancer Undergoing Hypofractionated Regional Nodal Radiation Therapy.

PURPOSE: Our objective was to assess the incidence and dose-volume predictors of radiation esophagitis (RE) in patients with breast cancer undergoing hypofractionated regional nodal irradiation. METHODS AND MATERIALS: Eligible patients who received intensity modulated radiation therapy (RT) at the chest wall, the supraclavicular/infraclavicular fossa, level II axilla, and/or the internal mammary chain after mastectomy were included. The prescribed dose was 43.5 Gy in 15 fractions. RE was evaluated weekly during RT and at 1 and 2 weeks, followed by 3 and 6 months after RT, and was graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0. The esophagus was contoured from the lower border level of the cricoid cartilage to the lower margin of the aortic arch. Esophageal total volume, mean dose, maximum dose, and the relative volumes (RV) and absolute volumes (AV) receiving at least 5 to 45 Gy by 5-Gy increments (RV5-RV45 and AV5-AV45) were evaluated. Univariable and multivariable logistic regression analyses were performed to determine risk factors for RE, and receiver operating characteristic curves were obtained to identify the thresholds of esophageal dosimetric parameters. RESULTS: In total, 298 patients were included between May 8, 2020, and January 5, 2022 (minimum post-RT follow-up: 6 months). Grade 2 and 3 RE incidence was 40.9% (122/298) and 0.3% (1/298), respectively. No grade 4 or 5 RE was observed. Esophageal RV20-RV40 and AV35-AV40 were significantly associated with the risk of grade ≥2 RE after adjusting for tumor laterality and internal mammary nodal irradiation. RV25 and AV35 were optimum dose-volume predictors for grade ≥2 RE at thresholds 20% for RV25 (35.9% vs 60.9%; P = .04) and 0.27 mL for AV35 (31.0% vs 54.6%; P = .04). CONCLUSIONS: RE is common in patients with breast cancer undergoing hypofractionated regional nodal irradiation. Maintaining the upper esophageal V25 at <20% and V35 at <0.27 mL may decrease the risk of RE.

Transoral incisionless fundoplication for recurrent symptoms after laparoscopic fundoplication.

BACKGROUND: Revision of a failed laparoscopic fundoplication carries higher risk of complication and lower chance of success compared to the original surgery. Transoral incisionless fundoplication (TIF) may be an endoscopic alternative for select GERD patients without need of a moderate/large hiatal hernia repair. The aim of this study was to assess feasibility, efficacy, and safety of TIF 2.0 after failed laparoscopic Nissen or Toupet fundoplication (TIFFF). METHODS: This is a multicenter retrospective cohort study of patients who underwent TIFFF between September 2017 and December 2020 using TIF 2.0 technique (EsophyX Z/Z+) performed by gastroenterologists and surgeons. Patients were included if they had (1) recurrent GERD symptoms, (2) pathologic reflux based upon pH testing or Grade C/D esophagitis or Barrett's esophagus, and (3) hiatal hernia ≤ 2 cm. The primary outcome was improvement in GERD Health-Related Quality of Life (GERD-HRQL) post-TIFFF. The TIFFF cohort was also compared to a similar surgical re-operative cohort using propensity score matching. RESULTS: Twenty patients underwent TIFFF (median 4.1 years after prior fundoplication) and mean GERD-HRQL score improved from 24.3 ± 22.9 to 14.75 ± 21.6 (p = 0.014); mean Reflux Severity Index (RSI) score improved from 14.1 ± 14.6 to 9.1 ± 8.0 (p = 0.046) with 8/10 (80%) of patients with normal RSI (< 13) post-TIF. Esophagitis healed in 78% of patients. PPI use decreased from 85 to 55% with 8/20 (45%) patients off of PPI. Importantly, mean acid exposure time decreased from 12% ± 17.8 to 0.8% ± 1.1 (p = 0.028) with 9/9 (100%) of patients with normalized pH post-TIF. There were no statistically significant differences in clinical efficacy outcomes between TIFFF and surgical revision, but TIFFF had significantly fewer late adverse events. CONCLUSION: Endoscopic rescue with TIF is a safe and efficacious alternative to redo laparoscopic surgery in symptomatic patients with appropriate anatomy and objective evidence of persistent or recurrent reflux.