Inoperable Esophageal Cancer Research Articles

Impaired liver function: effect on paclitaxel toxicity, dose modifications and overall survival

BackgroundThe anticancer drug paclitaxel is primarily metabolized in the liver. Previous studies have indicated a correlation between impaired liver function and paclitaxel toxicity, which may indicate dose reduction. Since the evidence is limited, the aim of this study was to investigate the effect of impaired liver function on the hematological toxicity of paclitaxel, dose modifications and overall survival (OS).MethodsFor this single-center retrospective observational study, patients treated with paclitaxel for breast, esophageal and ovarian cancer at the University Medical Centre Utrecht between 2011 and 2022 were identified from the Utrecht Patient Oriented Database (UPOD). Based on regression analysis, the risk of developing Grade 3/4 hematological toxicity was compared between patients with normal and impaired (based on the NCI criteria for bilirubin and ASAT (aspartate aminotransferase) concentrations) liver function. Additionally, differences in the occurrence of toxicity-related dose modifications and OS were evaluated between the two groups.ResultsA total of 569 patients were included. Breast cancer patients who were receiving advanced treatment and had mildly impaired liver function (ASAT ≤ 2x ULN, bilirubin ≤ ULN) had an increased risk of developing grade 3/4 neutropenia (HR = 4.39, 95% CI 1.20-16.02; p = 0.03). In addition, patients with impaired liver function treated according to the advanced ovarian cancer regimen had an increased risk of developing grade 3/4 leukopenia (HR = 12.64, 95% CI 2.12–75.22, p = 0.01) and dose modification (treatment discontinuation) (HR = 3.91, 95% CI 1.74–8.79, p < 0.01). Impaired liver function was also associated with decreased OS in inoperable esophageal and advanced ovarian cancer patients (HR = 7.65, 95% CI 2.54–23.1, p < 0.01 and HR = 2.98, 95% CI 1.36–6.54, p < 0.01, respectively). The risk of developing grade 3/4 hematological toxicity during lower-dose paclitaxel treatment protocols was not significantly different in patients with impaired liver function.ConclusionsThis study revealed that patients with impaired liver function treated with paclitaxel for breast and ovarian cancer in an advanced setting are at greater risk of developing hematological toxicity than patients with normal liver function at the start of therapy. Furthermore, in patients with ovarian (advanced) or inoperable esophageal cancer, impaired liver function is associated with decreased OS. Within these groups of patients, it is important to weigh the risk of upfront paclitaxel dose modifications versus an adaptive strategy.

The experiences of patients with oesophageal cancer receiving chemoradiotherapy treatment: a qualitative study embedded in the SCOPE2 trial

ObjectivesThis qualitative study explored patients’ experiences and perceptions of the SCOPE2 trial. SCOPE2 examined radiotherapy dose escalation in patients with inoperable oesophageal cancer treated with definitive chemoradiotherapy (dCRT).SettingRecruitment at five...

ENDOSCOPIC BOUGIENAGE AS PALLIATIVE TREATMENT FOR INOPERABLE ESOPHAGEAL CANCER: A CASE SERIES

Relevance: Esophageal cancer is one of the most aggressive tumors of the digestive tract, with a 5-year survival rate of only 10%. Given the global aging of the population and consequently the increase in the number of patients who will not undergo surgery, chemotherapy, andradiation, or the fact that they do not want it, especially due to deficiencies and concomitant pathology, endoscopic methods for palliative treatment are an alternative. The article aimed to report the results using distal caps to treat esophageal stenosis in inoperable esophageal cancer. Methods: The article describes cases of endoscopic cap bougienage in patients with inoperable cancerous esophageal stenosis at the National Scientific Cancer Center (Astana, Kazakhstan). Results: All 5 patients had inoperable cancerous esophageal stenosis and endoscopically installed percutaneous gastrostomy. All patients refused to eat through gastrostomy and wanted to take food physiologically orally while preserving the perception of food taste. Sessions of distal esophageal bougienage with distal caps were performed outpatiently and without sedation; the intervals between sessions ranged from 7 to 20 days and the number of bougees ranged from 4 to 11. Conclusions In our clinic, distal cap bougienage has been successfully used in patients with benign strictures for a long time, and in this article we present cases of bougienage in 5 patients with malignant stenoses. Further investigation of the effectiveness of cap bougienage of malignant stenoses requires a more extensive sample of patients and longer follow-ups. However, we decided to publish our preliminary results since we were the first in Kazakhstan to use them in inoperable cancer patients. Bougie, as a palliative treatment for inoperable esophageal cancer, is a method to improve food passage and a more physiological meal, which, according to taste preferences, is more psychologically demanded by patients, compared to eating through gastrostomy. Bougie caps are a safe method since the Bougie Cap is transparent and the bougie is performed under the visual supervision of an endoscopist. This bougie technique can be recommended for widespread use in clinics as the safest bougie method not only for malignant stenoses but also for benign strictures of the esophagus.

Efficacy of Oesophageal self expandable metal stent placement for palliation of dysphagia in inoperable oesophageal cancer patients: A low-income country perspective

Efficacy of Oesophageal self expandable metal stent placement for palliation of dysphagia in inoperable oesophageal cancer patients: A low-income country perspective

Initial safety assessment of the endoscopically injected oncolytic virus OBP-301 in medically inoperable esophageal cancer: NRG-GI007.

341 Background: Definitive chemoradiation (CRT) is a standard-of-care for patients (Pts) with medically inoperable esophageal cancer (EC). The NRG/RTOG 0436 study of cisplatin/paclitaxel and RT (+/- cetuximab) as definitive therapy showed that about half of Pts have locally persistent disease. OBP-301 is a conditionally restricted, replication-competent adenovirus derived from human adenovirus type 5 that adds a human Telomerase Reverse Transcriptase (hTERT) gene promoter, replicating only in tumor cells to cause lysis. It may cause immunogenic cell death, enhance RT, and improve local control. OBP-301 was previously studied with RT in Japanese esophageal cancer Pts and shown to be safe and has promising activity.1 Methods: In NRG-GI007, a phase 1 study (NCT04391049), OBP-301 is added to weekly carboplatin/paclitaxel and RT (50.4 Gy/28 fractions) for Pts with medically inoperable EC. Pts receive 1-2mL of intratumoral OBP-301 1×1012virus particles/ml via endoscopy 3 days prior to and then at days 12 and 26 of CRT. The primary endpoint is dose-limiting toxicity (DLT), defined as adverse events (AEs, by CTCAE v5) definitely or probably attributed to OBP-301 that meet either of the following: (1) leading to a &gt;14-day cumulative delay in CRT or (2) any grade ≥ 3 AE EXCEPT: grade 3 nausea/vomiting, grade 3 esophagitis or dehydration, first occurrence of grade 3/4 neutropenia, or grade 3/4 lymphopenia. Initially, 6 evaluable Pts (eligible and started protocol treatment) are enrolled. If protocol defined DLT occurs in ≤1 of 6 Pts, the dose will be deemed safe and an expansion cohort of 9 more will be enrolled to further assess safety and obtain a preliminary assessment of clinical complete response. If ≥2 Pts have a DLT then one de-escalated OBP-301 dose will be assessed. Results: From June 2020 to April 2023, 6 evaluable Pts were enrolled. Median age was 73.5 years, all male. Five Pts had adenocarcinoma and 1 had squamous cell carcinoma; 3 Pts had node-positive disease. All Pts received all planned OBP-301 injections, along with 50.4 Gy RT. Four out of 6 Pts received all 5 weekly doses of chemo for &gt; 85% of planned total dose, and 2 got 4 weekly doses for &gt; 70% of planned total dose. No Pt experienced ³7 day treatment delay. The following treatment-related (attributed as definitely, probably, or possibly related to CRT and/or OBP-301) grade 3 AEs were reported across 5 Pts: decreased neutrophil count (3 Pts), decreased lymphocyte count (2 Pts), decreased WBC (2 Pts), and fever and fatigue (1 Pt each). There were 4 Pts with AEs reported as definitely or probably related to OBP-301, all grade ≤2. No DLT occurred. Conclusions: No DLTs in the 6 evaluable Pts were observed and it is concluded that the initial OBP-301 dose level is safe. NRG-GI007 was reopened on August 7, 2023 to the expansion cohort. Full toxicity and treatment data will be presented. 1. Eur J Cancer 2021;153:98. Clinical trial information: NCT04391049 .

Effectiveness of S-1–Based Chemoradiotherapy in Patients 70 Years and Older With Esophageal Squamous Cell Carcinoma

Double-agent intravenous chemotherapy concurrent with radiotherapy is the standard of care for patients with inoperable esophageal cancer. However, patients tend to tolerate intravenous chemotherapy less well with age and comorbidities. It is essential to find a better treatment modality that improves survival outcomes without reducing the quality of life. To evaluate the effectiveness of simultaneous integrated boost radiotherapy (SIB-RT) with concurrent and consolidated oral S-1 chemotherapy for patients aged 70 years and older with inoperable esophageal squamous cell carcinoma (ESCC). This multicenter, phase III randomized clinical trial was conducted between March 2017 and April 2020 in 10 centers in China. Patients with inoperable, locally advanced, clinical stage II to IV ESCC were enrolled and randomized to receive SIB-RT concurrent with and followed by oral S-1 chemotherapy (CRTCT group) or SIB-RT alone (RT group). Data analysis was completed on March 22, 2022. In both groups, the planning gross tumor volume was administered with radiation dose of 59.92 Gy and the planning target volume was administered with radiation dose of 50.4 Gy, in 28 fractions each. In the CRTCT group, concurrent S-1 was administered on radiotherapy days, and consolidated S-1 was administered at 4 to 8 weeks after SIB-RT. The primary end point was overall survival (OS) of the intent-to-treat population. Secondary end points were progression-free survival (PFS) and toxicity profile. A total of 330 patients (median [IQR] age, 75.5 [72-79] years; 220 [66.7%] male patients) were included, with 146 patients randomized to the RT group and 184 randomized to the CRTCT group. A total of 107 patients (73.3%) in the RT group and 121 patients (67.9%) in the CRTCT group were clinically diagnosed with stage III to IV disease. At the time of analysis of the 330 patients in the intent-to treat-population (March 22, 2022), OS was improved in the CRTCT group compared with the RT group at 1 year (72.2% vs 62.3%) and 3 years (46.2% vs 33.9%; log-rank P = .02). PFS was similarly improved in the CRTCT group compared with the RT group at 1 year (60.8% vs 49.3%) and 3 years (37.3% vs 27.9%; log-rank P = .04). There was no significant difference in the incidence of treatment-related toxic effects higher than grade 3 between the 2 groups. Grade 5 toxic effects occurred in each group, including 1 patient who experienced myelosuppression and 4 patients with pneumonitis in the RT group and 3 patients with pneumonitis and 2 patients with fever in the CRTCT group. These findings suggest that oral S-1 chemotherapy administered with SIB-RT should be considered as an alternative treatment option for patients aged 70 years and older with inoperable ESCC, since it improved survival outcomes without additional treatment-related toxic effects compared with SIB-RT alone. ClinicalTrials.gov Identifier: NCT02979691.

Efficacy and safety of self-expanding metal stents in patients with inoperable esophageal cancer: a real-life study.

Dysphagia is the most frequent symptom in patients diagnosed with esophageal cancer. Self-expanding metal stents (SEMS) are the current palliative treatment of choice for dysphagia in patients with non-curable esophageal cancer. This study aimed to evaluate the efficacy and adverse events (AEs) of different types of SEMS for palliation of dysphagia. We performed a retrospective cohort study of patients with advanced esophageal cancer and SEMS placement for dysphagia palliation in a tertiary care center. The primary outcome was the clinical success defined as an improvement in dysphagia (reduction of at least 2 points in the Mellow-Pinkas scoring system for dysphagia) after SEMS placement. Between January 1999 and May 2020, 295 patients with esophageal cancer were identified. Among them, 75 had a SEMS placement for dysphagia palliation. The mean age of the patients was 61.3 years (standard deviation: 13.4), 69 patients (92%) were men, and the mean Mellow-Pinkas scoring for dysphagia pre- and post-SEMS placement were 3.1 and 1.4 (change from baseline -1.7), respectively. Technical success and clinical success were achieved in 98.6% and 58.9%, respectively. AEs were identified in 35/75 patients (46.7%), and SEMS migration was the most frequent AE in 22/75 patients (29.3%). There were no significant differences in improvement in dysphagia (p = 0.054), weight changes (p = 0.78), and AE (p = 0.73) among fully covered SEMS (fc-SEMS) and partially covered SEMS (pc-SEMS). The median follow-up was 89 days (interquartile range: 29-221). SEMS placement was associated with a rapid improvement in dysphagia, high technical success, and a modest improvement in dysphagia with no major AE among fc-SEMS and pc-SEMS.

Patterns of Treatment and Outcome in Patients with Unresectable or Inoperable Esophageal Cancer: A Real-World Data

Background: Esophageal cancer is the eighth most common cancer in the world with high morality. Our study provides real world data on patterns of treatment and outcome in patients with unresectable or inoperable esophageal cancer. Materials and Methods: This is a retrospective analysis of all consecutive esophageal cancer patients treated with radical radiotherapy at a tertiary cancer center from January 2016 to December 2017. Data regarding patients’ age, histology, location, pre-treatment imaging, disease stage, treatment details, compliance and response to treatment and status at last follow-up were retrieved from their file. Continuous and categorical variables were summarized by descriptive statistics. Results: A total of 100 patients, mean age of 60.24 years, were included in the study. 60% of the patients were male and upper one-third was the most common site involved. Squamous cell carcinoma was reported in 83% of the patients. About 70% of the patients had a T3/T4 disease, 44% also had nodal metastasis. Radiation dose ranged from 45Gy – 63Gy. 15% and 54% of the patients received neoadjuvant and concurrent chemotherapy respectively. With a median follow-up of 7 months (range 3-58 months), 80% of the patients were alive with 32.22% having no evidence of disease. Univariate analyses showed no significant predictor of loco-regional control. Distant metastases and loco regional failure were seen in 32.22% and 28% of the patients respectively. Conclusion: Our study showed that esophageal cancer is more common in elderly males. Both distant metastases and loco regional failure continues to be a matter of concern.

Self-Expanding Metallic Stents for Palliation of Esophageal Cancer: A Single Center Experience From Saudi Arabia.

Self-expanding metallic stents (SEMSs) are increasingly used as a non-surgical alternative for the palliation of advanced esophageal cancer (EC). However, there is a scarcity of real-life experience with the use of these stents exclusively in EC. The aim of this study is to evaluate the efficacy of SEMS in inoperable ECs in the western region of Saudi Arabia. A retrospective review of SEMS placed in a tertiary referral hospital for histologically proven inoperable EC from 2016 to 2019. Demographics data, procedure success, complication, re-intervention, and mortality were analyzed. Forty-eight SEMS placed in 35 patients for palliation of dysphagia. The median age of patients was 68 years (range 31-95). 69% (24) patients have a lower third of EC and the rest have a middle third. SEMSs were placed successfully in all cases with symptomatic improvement. No major stent-related complication was seen. 28% (13) patients required re-intervention with additional SEMS placement, nine of which were for tissue in growth and four for distal migration. Median survival was 114 days (range 30-498). Most of the complications seen in fully covered SEMS compared to the partially covered 50% (8/16) vs 17% (5/30), respectively, p = 0.04. Chemo and/or radiotherapy were given to 51% (18) of the patients without any significant benefit on survival (p = 0.79) or re-intervention rate (p = 0.47) compared to those who did not. SEMSis effective in palliating dysphagia in inoperable EC without major complications. Rates of tumors in growth and migration were comparable to other studies. SEMS provides long-term palliation.

Optimal Management of Dysphagia in Patients with Inoperable Esophageal Cancer: Current Perspectives.

The majority of patients with esophageal cancer are diagnosed at an advanced, incurable stage. Palliation of symptoms, specifically dysphagia, is a crucial component to improve quality of life and optimize nutritional status. Despite multiple available treatment modalities, there is not one accepted or recommended to be the preferred treatment option. Palliative management is often decided by a multidisciplinary team considering factors including local availability, preference, patient life expectancy, and symptom severity. Systemic therapies such as chemotherapy are the most commonly used palliative modalities. Oncologists are most familiar with radiation for dysphagia palliation, especially for advanced metastatic cancer patients with good performance status. One common approach used by endoscopist is self-expandable metal stents. This is preferred for patients with short-term survival and poor functional status as it provides rapid relief of dysphagia. Cryotherapy is a relatively new endoscopic ablative modality and appears to be a promising option for dysphagia palliation, but more data is needed for wider adoption. This review summarizes the current literature on endoscopic and non-endoscopic treatment options for malignant dysphagia.

Consolidation Chemotherapy Rather than Induction Chemotherapy Can Prolong the Survival Rate of Inoperable Esophageal Cancer Patients Who Received Concurrent Chemoradiotherapy.

Concurrent chemoradiotherapy (CRT) is regarded as the standard treatment for inoperable esophageal cancers (EC). It is still controversial whether consolidation chemotherapy (CCT) or induction chemotherapy (IC) is beneficial for the patients who received CRT. Therefore, we carried out a retrospective analysis at our institution. A total of 186 inoperable EC patients from 20 October 2017 to 7 June 2021 who have previously received CRT were included in our study. The patients were divided into IC + CRT (n = 52), CCRT (n = 64), and CRT + CCT (n = 70) groups according to whether they received induction chemotherapy, consolidation chemotherapy, or not. We used Kaplan–Meier statistics to analyze their 1-, 2-, and 3-year OS. The median follow-up time for the whole group was 14.15 months. The 1-, 2-, 3- year overall survival (OS) for the CCRT group were 72.2%, 52.5%, and 29.5%, and 50.9%, 37.5%, and 25% for the IC + CRT group (p > 0.05). For the CRT + CCT group,1-, 2-, and 3-year OS were 89.8%, 59.0%, and 42.5% (p < 0.05). Adverse reactions in the three groups were mainly graded 0–3. The difference between the three groups was not statistically significant (p > 0.05). For non-surgical EC patients who received CRT, CCT after CRT but not IC before CRT can improve 1-, 2-, and 3-year OS with a low incidence of associated severe adverse effects. As a result, the addition of consolidation chemotherapy to chemoradiotherapy has significant prognostic advantages for inoperable EC patients.

Intensity modulated radiation therapy for elderly patients with esophageal cancer: Our experience.

The aim of this study was to discuss the treatment mode of radical radiotherapy for elderly patients with esophageal cancer. The clinical data of 136 elderly patients (≥60 years old) with esophageal cancer (EC) who received radical intensity-modulated radiotherapy in the Second Affiliated Hospital of Xi'an Jiaotong University from January 2015 to December 2019 were retrospectively analyzed. Cox risk model was used for multivariate prognostic analysis, and Kaplan Meier method was used to calculate progression free survival (PFS) and overall survival (OS). Cox regression analysis showed that ECOG score, basic diseases, T stage, radiation dose, radiation injury and chemotherapy were the prognostic factors of elderly patients. The median OS of the radiotherapy group, concurrent chemoradiotherapy group and sequential chemoradiotherapy group were 17, 41 and 10 months (p=0.009), respectively. The 3-year OS and PFS of concurrent intravenous chemotherapy and oral chemotherapy were 50%, 42.9% and 34.1%, 28.6% (p=0.641, p=0.702), respectively. The median OS of IFI and ENI were 23 and 24 months (p=0.219) and the local recurrence rate were 59.8% and 43.2% (p=0.069), respectively, but the incidence and mortality of radiation pneumonia and esophagitis in ENI were higher. The 3-year OS and PFS the low-dose group (≤60Gy) and high-dose group (>60Gy) were 19.1%, 40.4% and 14.9%, 29.2% (p=0.012, p=0.049), respectively. In conclusion, for elderly patients with inoperable EC, radical chemoradiotherapy should be considered a preferable selection. Among them, oral drugs and high-dose involved field irradiation exhibited better curative effects and safety.

148 Migrated Esophageal Stent Causing Imminent Ischemia. a Case Report

Abstract Introduction Esophageal stents are being used more frequently for maintaining esophageal lumen patency in benign as well as malignant conditions. But the stents do not come without complications. The most common complication is stent migration. It can go unnoticed in asymptomatic individuals whereas timely exclusion of more urgent complications associated with migration is necessary to avoid morbidity and mortality. Case presentation We present the case of a 58-year-old patient with inoperable esophageal cancer. He underwent esophageal stenting twice, for palliation, and on both occasions, the stents did not maintain its position. He presented with abdominal pain, abdomen was peritonitic on examination and computerised tomography (CT) scan showed that the esophageal stent had migrated into his ileum. Upon laparoscopy, stent was found lodged in distal ileum causing ischemia and imminent perforation. We found the radiology and per-operative images interesting and are sharing herewith. Conclusion With the growing use of esophageal stents, it is important to recognize the possible immediate and delayed complications to manage them effectively. Surgeons need to be aware of the possible complications and have a high index of suspicion to diagnose and treat these.

EP-33 Migrated Esophageal Stent Causing Imminent Perforation. A Case Report

Abstract Introduction Esophageal stents are being used more frequently for maintaining esophageal lumen patency in benign as well as malignant conditions. But the stents do not come without complications. The most common complication is stent migration. It can go unnoticed in asymptomatic individuals whereas timely exclusion of more urgent complications associated with migration is necessary to avoid morbidity and mortality. Case Presentation We present the case of a 58-year old patient with inoperable esophageal cancer. He underwent esophageal stenting twice, for palliation, and on both occasions, the stents did not maintain its position. He presented with abdominal pain, abdomen was peritonitic on examination and computerised tomography (CT) scan showed that the esophageal stent had migrated into his ileum. Upon laparoscopy, stent was found lodged in distal ileum causing ischemia and imminent perforation. We found the radiology and per-operative images interesting and are sharing herewith. Conclusion With the growing use of esophageal stents, it is important to recognize the possible immediate and delayed complications to manage them effectively. Surgeons need to be aware of the possible complications and have a high index of suspicion to diagnose and treat these.

Cryotherapy’s impact on quality of life in inoperable esophageal cancer.

260 Background: dysphagia (dys) palliation in non-operable esophageal cancer (EC) continues to be a challenge. While chemotherapy and radiation help with dys, many patients require endoscopic interventions during their illness. Self-expanding metal stents have been the mainstay of endoscopic interventions but have a significant risk of severe adverse events and prevent the patient from being able to lie flat without severe reflux. Cryotherapy (cryo) is an emerging technique that can be used while the patient is receiving systemic therapy (ST). Previous retrospective studies showed improvement in dys with a favorable adverse event profile but did not report on quality of life (QOL) or reflux symptoms in patients receiving ST. Prospective studies have shown modest improvement in dys and QOL in patients not receiving ST. This prospective study reports the outcomes of cryo including dys, QOL, reflux symptoms and adverse events (AE) in patients receiving ST. Methods: A prospective multicenter cohort study of 35 adult inoperable EC patients undergoing cryo from Sep 2017 to Aug 2021. QoL was assessed using a modified EORTC QLQ-OES18 questionnaire (score 18 to 72, higher scores indicating worse QoL) while dys was measured using a 4-point Likert scale (0, no Dys; 1, Dys to solids; 2, Dys to semi-solids; 3, Dys to liquids; 4, Dys to saliva) at the start of cyro and 1-2 weeks post cryo. Paired t-test was used to evaluate changes in QoL and Dys between pre- and post-cryo. Results: There were 29 males and 6 females (30 stage IV and 5 stage III at diagnosis). Among 35 patients, a total of 104 cryo procedures were performed, with a mean of 3 per patient. The median number of tumor sites treated per cryo was 2 while the median number of cryo cycles delivered per tumor site was 3. The median total freeze time per tumor site was 60 seconds. The mean QoL score improved significantly from 31.8 pre-cryo to 28.2 with one cryo session (improvement of 3.6 points; p &lt; 0.001). The mean dysphagia score improved significantly from 1.42 to 1.05 per cryo session (improvement of 0.37 points; p = 0.002). The mean After a mean of 3 cryo sessions, QoL score improved significantly from 35.9 pre-cryo to 29.8 post-cryo (improvement of 6 points; p = 0.001) and the mean dysphagia score improved significantly from 1.97 pre-cryo to 1.25 post-cryo (improvement of 0.72 points; p = 0.004). 86.5% of patient were able to sleep lying flat without heartburn or regurgitation. 6 patients received another intervention (1 stenting, 3 radiation and 2 dilation) for Dys palliation. 8 patients underwent feeding tube placement. Cryotherapy related grade 3 or higher adverse events occurred after 3 cryo sessions. Conclusions: Cryotherapy for palliation in non operable esophageal cancer improved dysphagia and quality of life without causing reflux and had a favorable adverse event profile with most patients not needing another intervention for dysphagia palliation.

Why is a very easy, useful, old technique underused? An overview of esophageal brachytherapy - interventional radiotherapy.

Endoesophageal brachytherapy (EBT) or endoesofageal interventional radiotherapy (EIRT) is an effective technique that has been used with varying frequency for many years. It is a very good technique in T1-T2 inoperable esophageal cancer and in the palliation of dysphagia. However, only some centers have access to this technique, and consequently, it is underused. Here, we discussed the indications and several technical aspects as well as the literature available. Also, why this technique is underused and how this can be overcome. We consider that EBT is a very effective technique that should be used whenever indicated.

Genomic Profiling Identified Prognostic Biomarkers of Definitive Chemo-Radiotherapy Response in Esophageal Carcinoma

Esophageal cancer (EC), especially esophageal squamous cell carcinoma is one of the most aggressive tumors in China with a five-year survival rate of approximately 40%. While definitive chemo-radiotherapy (CRT) remains the main treatment modality for EC, its clinical efficacy is largely limited by variations in individuals' radio-sensitivity. The ability to accurately and reliably identify poor CRT responders might be of great value for timely regimen adjustments.In this retrospective study, targeted next-generation sequencing using a 474-gene panel was performed on baseline tumors of 190 inoperable EC patients treated with CRT. Baseline clinical characteristics, genomic alterations and canonical oncogenic pathways were investigated for their associations with clinical outcomes.In this cohort, alterations in TP53 (94.2%), CDKN2A (51.1%), CCND1 (45.3%), MYC (34.2%), FGF19 (34.2%), CDKN1C (33.2%), NOTCH1 (30.5%), NFE2L2 (30.0%), FAT1 (25.8%) and PIK3CA (24.2%) were frequently observed. We revealed distinct genomic profiles between patients who achieved complete or partial response (CR/PR) and those with stable or progressive disease (SD/PD). Specifically, deletion of CDKN2B [29.59% vs. 16.48%, fisher's exact P = 0.039] and amplification of CDK6 [10.2% vs. 0%, fisher's exact P = 0.002] were significantly enriched in the SD/PD group comparing to CR/PR. Pathway analyses demonstrated that genetic alterations in the cell cycle regulation pathway were also more commonly identified in SD/PD than CR/PR group [22.22% vs. 17.83%, fisher's exact P = 0.025]. At baseline, clinical stage, the best response and level of reported radiation toxicity were significantly associated with PFS following CRT. Additionally, mutations in CHEK2 [PFS HR 3.81 (1.89-7.67), P < 0.0001; OS HR 2.44 (1.06-5.64), P = 0.031] and deletion of CDKN1C [PFS HR 1.63 (1.12-2.36), P = 0.009; OS HR 1.57 (0.984-2.5), P = 0.057], among others, could predict poor PFS and OS following CRT and remained meaningful after adjusting for clinical factors.We demonstrated here crucial prognostic factors and abnormal oncogenic pathways that were associated lesser clinical benefit of CRT-treated EC patients. Results from comprehensive pre-treatment genomic testing could provide guidance for future clinical management for inoperable EC patients.

The role of surgery after prolonged primary chemotherapy for advanced oesophageal adenocarcinoma.

Most patients presenting with oesophageal cancer do so with advanced disease not suitable for surgery. However, there are examples of encouraging survival following surgery in highly selected patients who respond well to chemotherapy. This was a retrospective cohort study of patients who presented with advanced but nonvisceral metastatic oesophageal cancer. Consecutive patients on a prolonged primary chemotherapy pathway who underwent surgical resection following a favourable response to chemotherapy were included. Survival and recurrence rates were analysed using Cox regression, providing hazard ratios (HRs) with 95% confidence intervals (CIs). A total of 57 patients included in the cohort operated between 2007 and 2015, the overall median survival was 44 months and the 5-year survival was 42%. Prechemotherapy cN0/cN1 (HR: 0.27, 95% CI: 0.12-0.62) conferred an independent survival advantage compared to cN2 and cN3 disease. Poor differentiation (HR: 2.46, 95% CI: 1.11-5.42), R1 resection (HR: 2.43, 95% CI: 1.14-5.19) and advanced nodal status (HR: 3.28, 95% CI: 1.44-7.47) predicted worse survival on univariable analysis. Poor differentiation (HR: 3.93, 95% CI: 1.62-9.56) was independently associated with poor survival when adjusted for other variables. Patients who present with advanced inoperable oesophageal cancer who have a favourable response to chemotherapy represent a limited group of patients who may benefit from surgery.

Immediate Results of Concurrent Chemoradiotherapy with Inoperable Esophageal Squamous Cell Carcinoma

Background: The incidence of esophageal cancer is increasing. In this connection, the search for the most effective methods of treating this disease continues. In most patients, esophageal cancer is diagnosed at III– IV stages of the disease. Currently, the standard of treatment for inoperable patients is chemo radiotherapy. Brachytherapy is one of the perspective methods of radiation therapy. Using of brachytherapy in the complex treatment of patients with esophageal cancer makes possible to increase the radiation dose without increasing the risk of complications after treatment.Methods: The study included 20 patients with inoperable esophageal cancer (most of them with III stages, 60 %). The age of the patients is from 51 to 89 years, ECOG performance status ½ (25 %/75 %), dysphagia score 1/2/3–4 (25 %,50 %, 25 %). All patients were diagnosed with esophageal squamous cell carcinoma. Most patients were with tumor in the middle third of the esophagus (70 %). The greatest length of the tumor was 10 cm. On the first stage of treatment patients underwent external-beam radiation therapy 46 Gy in 2 Gy fractions with simultaneous chemotherapy. After that, brachytherapy was performed (single dose of 5 Gy, 2 fractions with an interval of 6–7 days, 62,8 Gy (EQD2, α/β = 10 Gy).Results: Patients received therapy support for cardiovascular and lung diseases and nutritional support before, during and following chemoradiotherapy. There were no patients with hematological toxicity grade 3–4. Esophagitis grade 2 was noted in 40 % of patients, grade 1 in 60 % of patients. Esophagitis resolved on its own 2 weeks after completion of therapy. Complete tumor regression was observed in 10 % of patients, partial regression in 80 % of patients, stabilization of tumor process was observed in 10 % of patients. All patients have a poor QOL due to physical and psychological disorders. The general health situation and physical function after 3 months of treatment was improved compared to the prior to treatment period.

Definitive Chemoradiation with Concurrent Weekly Cisplatin in the Treatment of Esophageal Squamous Cell Carcinoma – A Simplistic Approach

Purpose: Chemoradiation is the standard of care in locally advanced/ inoperable esophageal squamous cell cancer (ESCC). Though combination chemotherapy with Cisplatin and 5-Fluorouracil is the standard, it has low compliance due to toxicities and prolonged treatment time. Hence there is a window of opportunity to explore a safer chemotherapy regimen without compromising the treatment outcome. Methods: 55 patients of ESCC who were treated with definitive External Beam Radiotherapy (EBRT) to a dose of 50.4 – 59.4 Gray and concurrent weekly Cisplatin (or Carboplatin) were retrospectively evaluated for treatment efficacy and outcomes. 2 year Overall Survival (OS) and Progression Free Survival (PFS) were evaluated. Prognostic variables were assessed with respect to OS in Univariate analysis. Results: Median age at presentation was 58 years. 29 (53%) had lesion in the upper third of esophagus. 40 (72%) had T3 disease and 31 (56%) were node positive. All patients (100%) completed planned radiotherapy dose. 54 (98%) received 4 or more cycles of weekly chemotherapy. Mean overall treatment time was 43 days. Only 7 patients (12.7%) had grade 3 or more acute toxicity. 36 (65.5%) had complete response. At median follow-up of 13.7 months, the median OS was 15.2 months and 2 year OS was 42.6%. On univariate analysis, patients with comorbidities and lower third lesion had poor OS (p=0.016 and p=0.002). Stage II disease and complete response to treatment showed better OS (p=0.02 and p=0.00). Conclusion: Radical chemoradiation with weekly Cisplatin in ESCC is a simple and effective regimen which needs to be explored in larger trials.