Stent Applications for Palliative Treatment in Advanced Stage Esophageal Cancers

Background and Aim. Endoscopic stenting is a generally safe and effective palliative treatment for esophageal malignancies. In this study, we aimed to present endoscopic stent applications, adverse events, and relative advantages of covered versus uncovered stents in our center. Methods. We examined cases of endoscopic stenting for palliative treatment of advanced stage esophageal cancers between January 2014 and July 2019. Age, gender, location of mass, adverse events, survival time, and stent type were evaluated. Outcomes of fully covered and uncovered self-expanding stents were compared with regard to adverse events, including stent migration and occlusion. Results. The mean age of the patients was 66.4 ± 1 , 52 were male, and 8 were female. Patients were followed up for a mean of 133 days. The most common complication due to stenting was migration. 13 patients developed adverse events. Migration was the most common adverse event, occurring in 8 (13%) patients. Although the migration rate of fully covered stents was higher than uncovered stents, there was no statistically significant difference ( p = 0.47 ). Stent occlusion was observed in 4 patients. In three cases, it was due to the tumor; an uncovered stent was placed again in these cases. Food-related occlusion developed in one patient. There was no statistical difference in terms of overall adverse event rate when comparing fully covered stents to uncovered stents ( p = 0.68 ). Conclusion. Endoscopic stenting is a viable palliative method with low morbidity and mortality in experienced centers. Though there are relative advantages with covered versus uncovered stents in individual cases, the overall adverse event rate is low and relatively similar.

287 OUTCOMES OF DEFINITIVE CHEMORADIOTHERAPY IN LONG SEGMENT ESOPHAGEAL CANCERS FROM A TERTIARY CANCER CENTRE IN INDIA

Definitive chemoradiotherapy (CTRT) is the standard of care for unresectable esophageal cancer. Long segment esophageal primary disease makes it challenging to deliver radiation doses needed to achieve good local control without exceeding normal tissue tolerance to the surrounding organs at risk (OAR). We report our experience and outcomes of such patients where the RT doses were reduced from our institutional standard of 63Gy to 50.4Gy. Methods Between Jan 2017 and Dec 2019, 30/232 consecutive esophageal cancer patients were identified with long segment disease that required dose reduction from 63 to 50.4Gy and were included in this analysis. For this study, we divided nodal regions by their location into cervical, mediastinal, and gastro-hepatic. We generated and compared dosimetric parameters of the standard dose (63Gy) plan with that of treated low-dose plan (50.4Gy) using paired t-test. We also evaluated the patterns of recurrence and have reported them as local relapse (LR), loco-regional relapse (LRR), and distant metastases (DM). Results The median age was 55.5 years; 16 (53.3%) were males and 28 (93.3%) had squamous carcinoma. Single nodal site was involved in 6(20%), 2 sites in 20(66.7%) and 3 sites in 4 (13.3%). Median GTV and PTV length were 7.9 cm (IQR:6.4–9.7 cm) and 18.8 cm (IQR:14.08–22.31 cm) respectively. Median OAR doses with standard Vs treated plan achieved were: Total lung V20 and V5:28 Vs 22.14% (p = 0.00), and 81 Vs 70.5% (p = 0.005) respectively, and heart V20:70.92% Vs 64.7% (p = 0.000). No patients experienced ≥grade2 lung toxicity. After a median follow up of 8.4 months, 3 patients experienced LRR and 1 developed DM. Conclusion Treatment of long segment esophageal cancers warrants dose reduction to avoid higher doses to OAR like lung and heart. Early loco-regional and distant failures suggest need for improved treatment strategies or dose escalation with more conformal techniques like proton therapy. Longer follow-up is necessary to assess the median LR, LRR rates and overall survival for this reduced dose group as compared to the standard dose group.

Efficacy and safety of PD-1 inhibitors as first- and second- line treatments for advanced gastroesophageal cancers: A network meta-analysis of phase III clinical trials.

e16032 Background: Advanced gastroesophageal tumors are among the most prevalent and burdensome cancers worldwide. They have a poor prognosis and limited treatment options. Recent studies show that PD-1/PD-L1 inhibitors can improve outcomes, but the results are inconsistent across trials. Herein, we compare the effectiveness and safety of PD-1/PD-L1 inhibitors with chemotherapy in patients with ERBB2 negative advanced/metastatic gastric and esophageal cancers. Methods: We searched bibliographic databases (PubMed, Embase, Cochrane Central, Web of Science, Medline, Scopus) and ClinicalTrials.gov from January 1, 2010, to November 23, 2020. We included phase III randomized clinical trials comparing anti-PD-1/PD-L1 single-agent or in combination with chemotherapy (chemoimmunotherapy) for advanced gastric or esophageal cancers in the first- or second-line settings. We performed a network meta-analysis with a frequentist approach and a random-effects model using the package ‘netmeta’ for R statistical software. A prospective protocol was uploaded to PROSPERO (CRD42020221822). Results: The final analysis included a total of 8 trials that compared different anti-PD-1 agents; none of them involved anti-PD-L1 agents. The four first-line studies involved 3817 patients. Chemoimmunotherapy improved OS and PFS with no significant safety difference: Nivolumab + chemotherapy, OS (HR, 0.83; 95% CI, 0.75-0.92), PFS (HR, 0.68; 95% CI, 0.57-0.81), SAE (OR 0.54; 0;95% CI, 0.1-2.92); Pembrolizumab + chemotherapy: OS (HR, 0.77; 95% CI, 0.67-0.88), PFS (HR, 0.72; 95% CI, 0.60-0.85), SAE (OR, 1.31; 0;95% CI, 0.23-7.35). Pembrolizumab monotherapy was the safest first-line treatment, SAE (OR, 0.02; 95% CI, 0.00-0.2), but did not improve survival, OS (HR, 0.91; 95% CI, 0.71-1.16), PFS (HR, 1.62; 95% CI, 1.23-2.14). The four second-line studies totalized 2087 individuals. Anti-PD-1 drugs were significantly safer but did not significantly improve survival: camrelizumab, OS (HR 0.71; 95% CI, 0.54-0.93), PFS (HR 0.69; 95% CI, 0.45-1.06), SAE (OR, 0.37; 95% CI, 0.24-0.56); nivolumab, OS (HR 0.77; 95% CI, 0.58-1.02), PFS (HR 1.08; 95% CI, 0.77-1.66), SAE (OR, 0.13; 95% CI, 0.08-0.2) pembrolizumab, OS (HR 0.86; 95% CI, 0.72-1.04), PFS (HR 1.28; 95% CI, 0.96-1.71), SAE (OR, 0.4; 95% CI, 0.30-0.53). Conclusions: the combination of PD-1 inhibitors with chemotherapy improves OS and PFS in previously untreated gastroesophageal cancers. Single-agent anti-PD-1 drugs improve safety in refractory disease, with no significant change in OS and PFS.

Gastric and Esophageal Cancers: Guidelines Updates

For the treatment of gastric and esophageal cancers, several pivotal trials—especially those evaluating immune checkpoint inhibitors (ICIs)—have altered the treatment landscape and led to changes in the NCCN Guidelines. In addition to pembrolizumab and nivolumab, new treatment options include trastuzumab-deruxtecan (T-DXd), ramucirumab, and trifluridine/tipiracil. These agents convey varying degrees of benefit depending on treatment line, PD-L1 expression, HER2 expression, and tumor histology. Recently, ICIs have been incorporated into the first-line treatment of HER2-negative advanced esophageal, gastroesophageal junction (GEJ), and gastric cancers, in addition to second-line treatment of advanced esophageal and GEJ cancer of squamous histology. T-DXd is another new second-line option for HER2-positive esophageal, GEJ, and gastric adenocarcinomas. ICIs are now moving into the adjuvant setting as well, and a new recommendation is nivolumab use after preoperative chemoradiation and surgery in patients who have residual disease identified at the time of their R0 resections.