Chemotherapy For Esophageal Cancer Research Articles

Fragmented care, Commission on Cancer accreditation, and overall survival in patients receiving surgery and chemotherapy for esophageal cancer

BackgroundIncreasing regionalization for esophagectomy for cancer may lead patients to travel for surgery at one institution and receive chemotherapy at another closer to home. We explore the effects on survival for care fragmentation, the Commission on Cancer status of secondary institutions providing chemotherapy, and the type of institution performing surgery. MethodsWe queried the National Cancer Database to identify all patients who underwent esophagectomy for esophageal cancer and received perioperative chemotherapy between 2006 and 2019. Patients were divided into single-center care, fragmented–to–Commission on Cancer care, or fragmented–to–non–Commission on Cancer care. We identified associations using multivariable logistic regression, Kaplan-Meier survival analyses, and Cox proportional hazards models. ResultsA total of 18,502 patients met the criteria for inclusion: 8,290 (44.8%) received single-center care; 3,414 (18.5%) fragmented–to–Commission on Cancer care; and 6,798 (36.4%) fragmented–to–non–Commission on Cancer care. Fragmented care was more likely in White patients (adjusted odds ratio = 1.25; P < .001) and in patients nonadjacent to a metropolitan area (adjusted odds ratio = 1.36; P < .001). Overall survival was equivalent between single-center and fragmented care, but undergoing an esophagectomy at an academic center was associated with improved survival (adjusted hazard ratio = 0.82; P = .016). In patients with an esophagectomy at a nonacademic center, overall survival was best if perioperative chemotherapy was administered at Commission on Cancer–accredited facilities compared with chemotherapy at fragmented–to–non–Commission on Cancer centers (P = .022). ConclusionMost of the esophageal cancer care in the US is fragmented at multiple institutions. When care is fragmented, it is most commonly at non–Commission on Cancer centers for perioperative chemotherapy. Overall survival is best when esophagectomy is performed at an academic center, and perioperative therapy is administered at Commission on Cancer–accredited facilities.

18. ASSOCIATION OF TUMOR PATHOLOGICAL COMPLETE RESPONSE WITH THE USE OF METFORMIN DURING NEOADJUVANT CHEMORADIOTHERAPY IN ESOPHAGEAL CANCER PATIENTS: RETROSPECTIVE STUDY

Abstract Background Metformin is a standard treatment for type 2 diabetes mellitus (DM). Previous in vitro and in vivo studies have reported the association of metformin’s additive anticancer response with chemotherapy in esophageal cancer. However, no clinical studies have been reported. Therefore, this study is to aim the administration of metformin use can improve clinical outcomes of esophageal cancer patient with neoadjuvant combined chemotherapy and radiation (CCRT). Methods A total of 209 patients with esophageal cancer and underlying DM who underwent neoadjuvant CCRT before surgical resection were included from 1998 to 2022. There were 22 patients with metformin medication (10.5%) and 186 patients without metformin (89%). Univariable and multivariable regression analysis were done for complete response effect of metformin medication. Moreover, early clinical outcomes such as, overall survival and disease free survival were compared between the two groups. Results The complete response rate was higher for the metformin group (45.5% vs 22.6%; p = 0.019) and the recurrence rate was significantly lower (21.1% vs 45.7%, p = 0.040). The metformin group was associated with complete response rate in univariate logistic regression analysis (odds ratio [OR] = 2.86 [1.15–7.08], p = 0.023) and multivariable analysis (odds ratio [OR] = 2.84 [1.12–7.23], p = 0.028). Median follow-up duration was 19.8 months for metformin group, 17.3 months for non-metformin group. Overall 2-year survival rate and disease free survival was higher for metformin group than non-metformin group, (40% vs 26.5%, p = 0.380, 31.6% vs 24.3%, p = 0.095), however, not significant. Conclusion An association of metformin use with complete response rate in neoadjuvant CCRT esophageal cancer patients has been shown. The potential of metformin’s tumor response after neoadjuvant CCRT for esophageal cancer has been demonstrated in our study. Further prospective study should be needed for clinical evidence.

Effect of sequential vs. non-sequential early enteral nutrition therapy on nutritional status, recovery, and quality of life of patients with esophageal cancer.

To study the effects of early sequential enteral nutrition (ESEN) therapy and early non-sequential enteral nutrition (EN) therapy on the nutritional status, recovery, and quality of life of patients who undergo postoperative chemotherapy for esophageal cancer. The data of 90 patients who underwent postoperative chemotherapy for esophageal cancer in Gansu Provincial Cancer Hospital from January 2018 to June 2020 were analyzed retrospectively. Patients were divided the Test group and the Control group (n=45 each) based on the method of nutritional support. Patients in the Control group were treated with non-sequential early enteral nutrition and the Test group treated with sequential early enteral nutrition until the discharge. Nutritional status, recovery, and quality of life of the chemotherapy patients in the two groups were compared. After the intervention, the pre-protein, albumin and hemoglobin levels were higher in the Test group than in the control group (p<0.05). Postoperative exhaustion, incision healing and length of hospital stay were significantly lower in the Test group than in the Control group (p<0.05), while the scores on all dimensions of the short-form 36 health survey scale (SF-36) and the total score were higher than in the Control group (p<0.05). Sequential early enteral nutrition may be used for patients who undergo chemotherapy after esophageal cancer surgery to promote their early recovery and improve their quality of life and nutritional status.

Thoracoscopic esophageal drainage for tracheal compression due to mucocele after esophagogastric bypass: a case report

BackgroundEsophagogastric bypass is performed for esophageal strictures. Mucus retention, known as mucocele, sometimes occurs at the stricture oral side of the remnant esophagus. It is often asymptomatic and is expected to be naturally decompressed, but it may cause respiratory failure depending on the case. Herein, we report a case in which we successfully performed thoracoscopic esophageal drainage as emergency airway management due to tracheal compression by a mucocele after esophagogastric bypass for unresectable esophageal cancer with esophagobronchial fistula.Case presentationA 56-year-old man underwent esophageal bypass surgery for an unresectable esophageal carcinoma with an esophagobronchial fistula following chemotherapy and radiation therapy. Nine months after bypass surgery, he experienced severe dyspnea due to tracheal compression caused by mucus retention on the oral side of the esophageal tumor. We planned thoracoscopic surgery for mucus retention drainage through the right thoracic cavity to secure the airway as an emergency procedure under general anesthesia. Intubation can be performed safely by guiding bronchoscopy in the semi-supine position. Upper esophageal dilation was observed on the cranial side of the azygos arch. We dissected the mediastinal pleura of the upper thoracic esophagus and exposed its wall. A 12-Fr silicone drain was placed in the esophagus through the right chest wall and 120 ml of white fluid was aspirated. He was discharged 9 days after surgery without complications and resumed treatment with an immune checkpoint inhibitor 23 days after surgery. Thereafter, he continued chemotherapy for esophageal cancer, but died of tumor progression and lung metastasis 35 months after bypass surgery and 25 months after thoracoscopic surgery.ConclusionsThoracoscopic esophageal drainage could be performed safely as emergency airway management, shorten the period of discontinuance, and allow cancer treatment to be resumed promptly. We believe that this thoracoscopic procedure is an effective and less invasive method if the percutaneous approach is difficult.

CLINICAL OUTCOME OF HIGH DOSE RADIOTHERAPY WITH OR WITHOUT CONCURRENT CHEMOTHERAPY IN ESOPHAGEAL CANCER (EC): A STUDY FROM NORTH – EAST INDIA

OBJECTIVE: The objective of this study is to evaluate the clinical outcomes of high dose radiotherapy 63 Gray (Gy) with or without concurrent chemotherapy in Esophageal Cancer (EC) patients of North-East, India.&#x0D; MATERIAL AND METHODS: All reported EC patients belonging to different states of North-East and treated with radical intent with high dose radiotherapy with or without concurrent chemotherapy during the period 2017-2018 (2 years) at State Cancer Institute (SCI),Gauhati Medical College (GMC), Assam, India were included in the study. This study was retrospective in nature and two years retrospective data were analyzed for clinical outcome. Statistical analysis of data was done using Statistical Packages for Social Sciences (SPSS) and Disease Free Survival (DFS) was calculated using Kaplan-Meier method.&#x0D; RESULTS: Total 105 patients were treated during the period. All patients received a total dose of 63 Gy radiation. Out of 105 patients, 76 patients (72.4%) received concurrent chemotherapy and 29 patients (27.6%) not received chemotherapy only due to co-morbidities. Here, at first follow up, 89 (84.8%) patients showed complete response, 10 (9.5%) showed partial response and 6 (5.7%) showed progressive disease. Treatment related toxicities were assessed. None of the patient developed &gt; Grade 2 toxicity.&#x0D; Further, Median Disease Free Survival (DFS) was 13 months with estimated mean was 16.98 months. Also, Standard Error (SE) =1.683, Confidence Interval (CI) =13.682-20.279.&#x0D; CONCLUSION: The high dose radiation (63 Gy) with concurrent chemotherapy as weekly regimen of Cisplatin or Paclitaxel plus Carboplatin is an effective definitive treatment of Stage I – IVA EC with acceptable toxicity. Median DFS is minimal in EC irrespective of the treatment. The rate of survival is decreasing rapidly before the median DFS and the rate of survival is constant after the Median DFS.

Mortality associated with the development of acute liver failure after a single dose of nivolumab

Immune-related adverse events (irAEs) caused by immune checkpoint inhibitors are reported in all organs; however, the frequency of liver injury is low compared to irAEs in other organs. We describe a case of fulminant hepatitis after administration of the first dose of nivolumab for the management of esophageal cancer. A man in his 80s was treated with nivolumab as a second-line therapy after his overall health worsened during preoperative chemotherapy for esophageal cancer. He was admitted to the hospital as an emergency case 30days later with complaints of vomiting, following which acute liver failure was diagnosed. The patient developed hepatic encephalopathy on the third day after admission and died on the seventh day. The pathological results showed sub-extensive spread hepatocellular necrosis throughout the liver, and immunostaining confirmed the presence of CD8-positive cells, which is consistent with irAEs. Immune checkpoint inhibitors have proven to be effective for the treatment of malignant tumors, and although fatalities due to acute liver failure are extremely rare, such cases have been reported previously. Among the immune checkpoint inhibitors, anti-programmed death-1 receptor is associated with less hepatotoxicity. However, even a single dose of this treatment can cause acute liver failure, which could be fatal.

Abstract 1688: Proton pump inhibitors as a potential combination therapy with existing chemotherapy for esophageal cancer

Abstract Introduction: V-ATPase is highly expressed in cancer cells and has been shown to be involved in the transformation of normal cells into cancer cells, invasion of tissues, survival of cancer cells, and the formation of drug resistance. The use of proton pump inhibitors (PPIs) as V-ATPase inhibitors has been shown to enhance the efficacy of chemotherapy in some cancers. Material and Method: We investigated the effect of proton pump inhibitors on esophageal squamous cell carcinoma, one of the major causes of cancer mortality in Japan. First, three PPIs at various concentrations (lansoprazole, esomeprazole, and bonoprazan) and pyrimidine fluoride (5-FU), a key drug in chemotherapy for esophageal cancer, were used as basic medical agents. Human esophageal squamous cell lines, KYSE50 and KYSE70, were prepared and treated with the above drugs, and cell viability assays were performed using Cell Counting Kit 8 for 72 hours. We then performed a retrospective clinical study of 40 patients with clinical stage IV esophageal squamous cell carcinoma treated with the drugs at Kyoto Prefectural University of Medicine Hospital in Japan. Result: In cell survival assays, PPIs showed significantly enhanced cytotoxic effects of pyrimidine fluoride on all cell lines compared with those not treated with PPIs. Clinical data showed no difference in the incidence of treatment-related adverse events between the PPI and non-PPI groups. The response rate after two courses of chemotherapy was 66.7% in the PPI group and 40.9% in the non-PPI group (p=0.102). Kaplan-Meier analysis showed improved OS in patients treated with PPIs (log rank test p=0.032), and multivariate analysis showed that PPI use was associated with a more favorable OS (p=0.009,HR 0.33,95% CI 0.12-0.76 ). Conclusion: In the chemotherapy of esophageal squamous cell carcinoma, the use of PPIs may enhance the cytotoxic effect of the key drug, pyrimidine fluoride, while ensuring safety, and may lead to better therapeutic efficacy. Citation Format: Ryuichi Morita, Takeshi Ishikawa, Shinya Matsumura, Tomoki Sakakida, Juichiro Yoshida, Toshifumi Doi, Ryohei Hirose, Ken Inoue, Osamu Dohi, Naohisa Yoshida, Kazuhiko Uchiyama, Tomohisa Takagi, Hideyuki Konishi, Yuji Naito, Yoshito Itoh. Proton pump inhibitors as a potential combination therapy with existing chemotherapy for esophageal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1688.

The cisplatin-induced acute kidney injury is a novel risk factor for postoperative complications in patients with esophageal cancer: a retrospective cohort study

BackgroundCisplatin-induced acute kidney injury (AKI) is common during preoperative chemotherapy for esophageal cancer. The purpose of this study was to investigate the association between AKI after preoperative chemotherapy and postoperative complications in patients with esophageal cancer.MethodsIn this retrospective cohort study, we included patients who had received preoperative chemotherapy with cisplatin and underwent surgical resection for esophageal cancer under general anesthesia from January 2017 to February 2022 at an education hospital. A predictor was stage 2 or higher cisplatin-induced AKI (c-AKI) defined by the KDIGO criteria within 10 days after chemotherapy. Outcomes were postoperative complications and length of hospital stays. Associations between c-AKI and outcomes including postoperative complications and length of hospital stays were examined with logistic regression models.ResultsAmong 101 subjects, 22 developed c-AKI with full recovery of the estimated glomerular filtration (eGFR) before surgery. Demographics were not significantly different between patients with and without c-AKI. Patients with c-AKI had significantly longer hospital stays than those without c-AKI [mean (95% confidence interval (95%CI)) 27.6 days (23.3–31.9) and 43.8 days (26.5–61.2), respectively, mean difference (95%CI) 16.2 days (4.4–28.1)]. Those with c-AKI had higher C-reactive protein (CRP) levels and prolonged weight gain after surgery and before the events of interest despite having comparable eGFR trajectories after surgery. c-AKI was significantly associated with anastomotic leakage and postoperative pneumonia [odds ratios (95%CI) 4.14 (1.30–13.18) and 3.87 (1.35–11.0), respectively]. Propensity score adjustment and inverse probability weighing yielded similar results. Mediation analysis showed that a higher incidence of anastomotic leakage in patients with c-AKI was primarily mediated by CRP levels (mediation percentage 48%).Conclusionc-AKI after preoperative chemotherapy in esophageal cancer patients was significantly associated with the development of postoperative complications and led to a resultant longer hospital stay. Increased vascular permeability and tissue edema due to prolonged inflammation might explain the mechanisms for the higher incidence of postoperative complications.

Efficacy and safety of neoadjuvant immunotherapy combined with chemoradiotherapy or chemotherapy in esophageal cancer: A systematic review and meta-analysis.

Significant progress has been made in the investigation of neoadjuvant immune-chemoradiotherapy (NICRT) and neoadjuvant immune-chemotherapy (NICT) on the outcomes of esophageal cancer patients. To summarize the current developments, a systematic review and meta-analysis were conducted to evaluate the efficacy and safety of neoadjuvant immunotherapy combined with chemoradiotherapy or chemotherapy. A search strategy of prospective studies on esophageal cancer receiving neoadjuvant immunotherapy was predefined to scan PubMed, Embase, Cochrane, and additional major conferences for prospective studies. Efficacy was assessed by pathological complete response (pCR), major pathological response (MPR), and R0 resection rates. Safety was evaluated based on the incidence of grade ≥ 3 treatment-related adverse events (TRAEs), neoadjuvant therapy completion rate, surgical resection rate, and surgical delay rate. Differences between the NICRT and NICT groups were also analyzed. A total of 38 studies qualified for the analysis. The pooled pCR, MPR, and R0 resection rates were 30, 58, and 99%, respectively. The pCR and MPR in the NICRT vs. NICT group were 38% vs. 28% (p=0.078) and 67% vs. 57% (p=0.181), respectively. The pooled incidence of grade ≥ 3 TRAEs was 24% (NICRT,58%, I2 = 61% vs. NICT,18%, I2 = 79%; p<0.001). In addition, the pooled neoadjuvant therapy completion and surgical resection rates were 92% and 85%, respectively; the difference was not statistically significant between the NICRT and NICT groups. Neoadjuvant immunotherapy combined with chemoradiotherapy or chemotherapy is effective and safe in the short term for locally advanced esophageal cancer. However, further randomized trials are needed to confirm which combined model is more favorable. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021284266, identifier CRD42021284266.

The Efficacy and Safety of Oral Nutrient Solution Supplementation in Patients with Esophageal Cancer under Nutritional, Psychological, Physical, and Prognostic Survival Differences.

Inflammasomes are massive intracellular multiprotein signaling complexes produced in the cytosolic compartment. Tumor etiology involves dysregulation of NLRP3 inflammasome activation. Current studies are being conducted to ascertain the effectiveness and safety of oral nutrient solution supplementation in patients with esophageal cancer based on the current understanding of the role of the NLRP3 inflammasome in possible cancer promotion and therapy. This study examines how oral nutrient solution supplement therapy affects patients receiving radiotherapy and chemotherapy for esophageal cancer in terms of nutrition, physical composition, quality of life, psychology, prognosis, and survival. A total of 120 patients with esophageal cancer admitted to our hospital from March 2020 to January 2021 were selected for the current study. The selected 120 patients are divided into nutritional supplement and traditional groups according to the random number table method, with 60 cases in each group. The nutritional supplement group received an oral nutritional solution, whereas the conventional group received the ordinary dietary intervention. Since radiotherapy can potentially damage healthy tissue with short- and long-term negative effects. Inflammatory reactions are a common component of adverse effects of early and late ionizing radiation. Oral nutrient solution supplement therapy for patients with esophageal cancer after radiotherapy and chemotherapy can significantly improve the levels of blood nutrients, later physical components, and quality of life of patients.

A Case of Pegfilgrastim-induced Aortitis during Neoadjuvant Chemotherapy for Esophageal Cancer

A Case of Pegfilgrastim-induced Aortitis during Neoadjuvant Chemotherapy for Esophageal Cancer

Neoadjuvant Chemotherapy and Endoscopic Resection for Hypopharyngeal Cancer

A 79-year-old man was diagnosed with a cT2 hypopharyngeal cancer and cT2 esophageal cancer by upper gastrointestinal endoscopy. Computed tomography showed swelling of the thoracic paratracheal lymph nodes (cN1 for esophageal cancer). He first underwent neoadjuvant chemotherapy for esophageal cancer (2 courses of cisplatin 80 mg/m2/d on Day 1 and fluorouracil 800 mg/m2/d on Days 1–5) followed by esophagectomy with lymphadenectomy and reconstruction of the gastric tube. Before chemotherapy, the hypopharyngeal cancer extended from the aryepiglottic fold to the posterior cricoid region and right piriform sinus (Figure A).

STMO-4 INITIAL EXPERIENCE WITH BRAIN TUMOR SURGERY USING STEALTH AUTOGUIDE

Abstract Tissue sampling of brain tumors is generally performed by biopsy with large or small craniotomy and stereotaxic brain biopsy. Recently, Stealth Autoguide, a robotic system for stereotactic deep electrode implantation and brain tumor biopsy in epilepsy, has become available. We report the initial experience of brain tumor surgery using stealth Autoguide in our hospital.Case: A man in his 70s. Left paralysis occurred during chemotherapy for esophageal cancer. Magnetic resonance imaging (MRI) revealed a ring-enhanced lesion from the right basal ganglia to the coronal radiatum. Because he was under steroid administration, he was diagnosed with metastatic brain tumor, malignant lymphoma, malignant glioma, or demyelinating disease. Since paralysis was progressing and MRS was suspected to be a malignant tumor, a stereotactic biopsy using a stealth autoguide was performed. Biopsies were performed with skin incisions of 1 cm or less from two locations that were automatically positioned based on the preoperative planning, and a sufficient amount of tissue was collected from the lesions. No complications such as bleeding were observed. Since the histological diagnosis was glioblastoma, chemotherapy with temozolomide and radiotherapy were promptly started.Brain tumor biopsy using stealth Autoguide allows accurate tissue sampling in a short period of time, and is a very useful tool for brain tumor diagnosis in the future.

Efficacy and Safety of Neoadjuvant Immunotherapy Combined with Chemoradiotherapy vs. Combined with Chemotherapy in Esophageal Cancer: A Systematic Review and Meta-Analysis

<h3>Purpose/Objective(s)</h3> Immunotherapy has showed promising clinical benefit in esophageal cancer. Both the neoadjuvant immunochemoradiotherapy (NICRT) and neoadjuvant immunochemotherapy (NICT) are making great progress. This meta-analysis was to evaluate the efficacy and safety of neoadjuvant immunotherapy combined with chemoradiotherapy versus combined with chemotherapy by synthesizing various trials. <h3>Materials/Methods</h3> A search of PubMed, Embase and Cochrane, in addition of major conferences, for clinical trials including single-arm trials, was conducted up to 30 August 2021. Efficacy was assessed by pathological complete response (pCR), major complete response (MPR) and R0 resection rate. Safety was evaluated by the incidence of ≥ grade 3 treatment-related adverse events (TRAEs), neoadjuvant therapy completion rate, surgical resection rate, and surgical delay rate. Difference between NICRT and NICT groups was tested by Chi-square. <h3>Results</h3> A total of 20 studies was included, including 5 with NICRT and 15 with NICT. The overall pooled pCR, MPR, and R0 resection rate was 32%, 55%, and 96%, respectively. The pCR and R0 resection rates in NICRT vs NICT were 41% vs 30% (p=0.16) and 96% vs 96% (p=0.75), respectively. Only 1 trial in NICRT group reported a MPR of 89%, while the pooled MPR in NICT was 54%. Incidence of ≥ grade 3 TRAEs in NICRT vs NICT was 52% vs 20% (p=0.03), with high heterogeneity in both groups (I²=62%, p=0.10 vs I²=83%, p<0.01). Besides, the overall pooled rates of neoadjuvant therapy completion and surgical resection were 91% and 87%, respectively, which were proved not statistically different between the NICRT vs NICT group. <h3>Conclusion</h3> Neoadjuvant immunotherapy combined with chemoradiotherapy or chemotherapy is effective and safe. NICRT may not achieve better efficacy than NICT, but with potential increase of toxicity. Large trials are needed to confirm whether NICRT or NICT is more suitable for resectable esophageal cancer.

P69-1 Advantages of using patient-reported outcomes (PROs) during chemotherapy for esophageal cancer

Although patient-reported outcomes (PROs) are gaining greater importance, few efforts have been made to assess PROs in the late line treatment of esophageal cancer. Thus, we evaluated the usefulness of a novel assessment tool - Integrated Palliative care Outcome Scale (IPOS) - in these patients.

Feasibility study of adjuvant chemotherapy with S-1 after curative esophagectomy following neoadjuvant chemotherapy for esophageal cancer

BackgroundDespite advances in surgical techniques, long-term survival after esophagectomy for esophageal cancer remains unacceptably low, and more effective perioperative chemotherapy is expected. However, an important concern regarding the application of postoperative adjuvant chemotherapy is treatment toxicity. We aimed to evaluate the feasibility of adjuvant chemotherapy with S-1 in patients after esophagectomy.MethodsWe investigated the tolerability of a 2-week administration followed by 1-week rest regimen of S1 as postoperative adjuvant therapy in 20 patients with esophageal squamous cell carcinoma who received neoadjuvant chemotherapy (NAC) and 22 patients who did not receive NAC during 2011–2020.ResultsIn the non-NAC group, the mean and median relative dose intensity (RDI) were 78.7% and 99.4%, respectively, and 11 patients (50%) had altered treatment schedules. The corresponding rates in the NAC group were 77.9% and 100%, respectively, and nine patients (45%) had altered treatment schedules, with no significant difference among the groups. Moreover, 17 patients (77.2%) in the non-NAC group and 16 patients (80.0%) in the NAC group continued S-1 treatment as planned for one year postoperatively, with no significant difference in the S-1 continuation rate (p = 0.500). Seventeen of 22 patients (77.3%) and 15 of 20 patients (75.0%) experienced several adverse events in the non-NAC and NAC groups, respectively. The frequency, severity, and type of adverse events were consistent among patients with and without NAC.ConclusionsS-1 could be safely and continuously administered as adjuvant chemotherapy for patients with esophageal cancer regardless of NAC. Long-term prognosis should be evaluated for S-1 to become the standard treatment after esophagectomy.

Definitive chemoradiotherapy +/- induction chemotherapy in esophageal cancer: A real-world experience.

e16072 Background: The SEER 5-year overall survival rate for all stages of esophageal cancer (EC) was 25% in 2019. Definitive chemoradiation (CRT) remains the primary treatment approach for locally advanced EC in the US, however, there are data to support use of induction chemotherapy (CT) in addition to CRT, particularly in adenocarcinoma (AC) histology. The purpose of our study was to assess outcomes in EC patients treated with definitive CRT (+/- induction) to determine which prognostic factors predicted for better survival in a recent, real-world cohort of patients, including those with limited stage IV disease. Methods: This retrospective study included Stages II-IVB (AJCC 8th ed.) EC patients treated with definitive CRT (radiation dose of ≥40 Gy and at least two cycles of concurrent CT [+/- induction CT, +/- esophagectomy]) at our institution between 2008 and 2020. To analyze prognostic factors and estimate OS, univariate models (UVA) and a multivariate (MVA) Cox proportional hazards regression model including age, Stage (II, III, IVA, IVB), AC vs. SCC, esophagectomy, ECOG performance status (PS), and induction CT were performed. Results: Of the 183 patients treated with definitive CRT, 18 were stage II, 119 stage III, 21 stage IVA, and 25 stage IVB. There were 45 SCC and 138 AC patients (Table). Prognostic factors associated with prolonged OS on MVA included lower PS (p&lt;0.01) and esophagectomy (p = 0.05). Stage IVA was associated with shorter survival (p&lt;0.01). Induction CT (delivered in 53% of AC, 31% SCC) was associated with improved survival on UVA (p=0.04), but not MVA (p = 0.08). By histology, 5-year survival rate was 42.7% and 18.2% for AC and SCC, respectively. Conclusions: At our institution, those who received an esophagectomy and those with lower ECOG scores had better survival. The 5-year survival rate was higher for AC patients compared to SCC, with more AC patients receiving esophagectomy and induction CT (significant on UVA, but not MVA). The 5-year survival rate for AC in our study was nearly identical to that seen in the CROSS trial (Shapiro et al. 2015) AC cohort but included &gt;25% stage IV patients. This modern cohort also included poor PS (ECOG≥2) patients (9.2% AC and 13.6% SCC), suggesting induction CT, in addition to pre-operative CRT + surgery, may have added benefit in a real-world practice. Thus, further prospective study is needed.[Table: see text]

Phase II trial of perioperative chemotherapy of esophageal cancer: PIECE trial.

4038 Background: Neoadjuvant chemotherapy followed by surgery (NAC-S) is the standard therapy for locally advanced esophageal squamous cell cancer (ESCC) in Japan. The aim of this phase II trial was to assess the efficacy and safety of the addition of adjuvant S-1 after R0 resection in patients treated with NAC-S. Methods: Key eligibility criteria were as follows: ESCC of clinical stage IB-III (without T4 disease); aged 20 to 75 years; ECOG performance status 0 or 1; and performed neoadjuvant chemotherapy (5-FU + cisplatin). All patients registered before surgery. Patients received adjuvant therapy with 4 cycles of S-1 (80 mg/m2/day) that is administered orally for 4 weeks of a 6-weeks cycle. The primary endpoint was three-year relapse free survival (RFS). Results: A total of 52 patients were enrolled between January 2016 and January 2019. Two patients (one with small cell carcinoma and the other with synchronous malignancy) were excluded from analysis. Five patients were diagnosed as R1 or R2. Seven patients did not receive adjuvant S-1 due to adverse events of surgery in 5 patients, refusal to adjuvant S-1 in a patient, and forgot to start in a patient. Thirty-eight patients received adjuvant S-1, with 32 patients completing 4 cycles. The median relative dose intensity of adjuvant S-1 was 85.8%. Median follow-up time among survivors after surgery was 4.5 years (range 0.2-5.6). Three-year RFS in intention to treat population was 72.3% (90% confidence interval [CI] 59.9-81.5), suggesting that the primary endpoint was met, and 3-year overall survival was 85.0% (90% CI 73.9-91.6). Grade 3 or higher adverse event with an incidence 10% of greater were neutropenia (13.2%), anorexia (13.2%), and diarrhea (10.5%). There was no treatment-related death. Conclusions: Adjuvant S-1 showed promising efficacy with manageable safety profile for patients with resectable ESCC after NAC-S, and warrants further evaluation in larger studies. Clinical trial information: UMIN000020204.

Proton Pump Inhibitors Enhance the Antitumor Effect of Chemotherapy for Esophageal Squamous Cell Carcinoma.

Simple SummaryThe use of proton pump inhibitors (PPIs) as V-ATPase inhibitors has been reported to enhance the effectiveness of chemotherapy in some cancers. This study aimed to evaluate the effect of PPIs on 5-Fuorouracil (5-FU)-based therapy for advanced esophageal cancer based on in vitro experiments and a clinical study. In the present study, PPIs showed a dose-dependent antitumor effect on esophageal cancer cells and enhanced the sensitivity of esophageal cancer cells to 5-FU at sublethal concentrations. In the clinical setting, patients treated with oral PPIs showed a superior tumor response to 5-FU and better overall survival in comparison to the non-PPI group. These results indicate that PPIs can enhance chemosensitivity in esophageal cancer patients treated with 5-FU.Background: Vacuolar ATPase (V-ATPase) is involved in cancer development. The use of proton pump inhibitors (PPIs) as V-ATPase inhibitors has been reported to enhance the effectiveness of chemotherapy in certain cancers. This study aimed to evaluate the effect of PPIs on chemotherapy for esophageal cancer. Methods: To investigate the effects of PPIs on esophageal cancer cells, human KYSE50 and 70 cells were plated and 3 PPIs (lansoprazole, esomeprazole, vonoprazan) were added at various concentrations with 5-Fluorouracil (5-FU) to the corresponding cells for a cell viability assay. To investigate the effects of PPI treatment on patients undergoing 5-FU-based therapy in the clinical setting, we retrospectively analyzed the clinical outcomes and chemotherapy-related adverse events in 40 esophageal cancer patients who received 5-FU chemotherapy in our hospital between May 2013 and April 2017. Results: In the viability assays, all PPIs significantly enhanced the cytotoxic effect of 5-FU on the two esophageal cancer cell lines. In the clinical study, PPI-treated patients showed better overall survival (OS) than patients managed without PPI treatment. A multivariate analysis revealed that PPI treatment was independently associated with OS (p = 0.009, HR, 0.33; 95% CI, 0.12–0.76). Conclusions: PPI treatment may safely enhance chemosensitivity in esophageal cancer patients.

Tolerability of neoadjuvant chemotherapy for esophageal cancer in elderly patients over 76 years of age.

ABSTRACTAlthough the Japan Clinical Oncology Group trial demonstrated that neoadjuvant chemotherapy (NAC) with 5-fluorouracil plus cis-diamminedichloroplatinum had significant survival benefits, it excluded elderly patients aged ≥ 76 years. Therefore, our study aimed to evaluate the tolerability of NAC in elderly patients with esophageal cancer. Classified 174 patients with clinical stage II/III esophageal cancer who underwent esophagectomy from 2010 to 2020 into the E (aged ≥ 76 years; 55 patients) and Y (aged < 76; 119 patients) groups, and retrospectively investigated for clinicopathological findings, tolerability of NAC, relative dose intensity (RDI) and short- and long-term result. Patients who received NAC were fewer in the E group than in the Y group (51% vs 77%, p = 0.001). The E group had relatively lower completion rate of NAC (71% vs 85%, p = 0.116) and significantly lower mean RDI of 5-fluorouracil and cis-diamminedichloroplatinum than the Y group (73% vs 89%, p < 0.001). However, histological and radiological were comparable between both groups. Severe adverse events (grade ≥ 3) were relatively frequent (E, 42.9%; Y, 27.5%, p = 0.091), especially, neutropenia was significantly more frequent in the E group (25.0% vs 7.7%, p = 0.022). There were no differences in the incidence of postoperative complications between with and without NAC in both E and Y groups. Elderly patients with esophageal cancer might be more susceptible to toxicity of NAC. Hence, adequate case selection and careful of dose reduction are needed for elderly with esophageal cancer.