Local Advanced Esophageal Carcinoma Research Articles

Evaluating the Impact of Age and G8 Assessment on Definitive Treatment Strategies in Elderly Patients with Local Advanced Esophageal Carcinoma

Introduction: While chemoradiotherapy (CRT) is commonly employed as a curative approach for esophageal cancer, administering standard CRT to elderly patients often presents challenges in practical settings. The objective of this study was to compare treatment tolerance and survival outcomes between younger and elderly patients (aged ≥65 years) diagnosed with locally advanced esophageal cancer receiving curative-intent treatment. Additionally, it aimed to assess the impact of the Geriatric-8 Health Status Screening Tool (G8 score) on treatment decisions in elderly patients. Methods: Ninety-seven patients treated with neoadjuvant or definitive CRT for locally advanced esophageal cancer were retrospectively evaluated at two centers from 2013 to 2023. We divided the patients by age (<65 and ≥65 years) and assessed their demographic, clinical, and treatment data, including pre- and post-treatment G8 scores. Radiotherapy (RT) was administered at a median dose of 50.4 Gy (45–66 Gy). Planned concurrent chemotherapy was completed in 73 (75.3%) of the patients. Results: In the comparative study of 97 esophageal cancer patients, 48 geriatric (aged ≥65 years) and 49 younger individuals were followed up for a median of 20 and 21 months, respectively. No significant statistical differences were noted between the groups concerning baseline and treatment characteristics. Surgical intervention rates were comparable, with 22.9% of geriatric and 36.7% of young patients undergoing surgery (p = 0.184). There were no significant differences in pathological complete response, local recurrence, distant metastasis, progression, or death rates. The median progression-free survival (PFS) for geriatric and younger patients was 31 months (95% CI, 13.6–48.4) and 19 months (95% CI, 0–39.4), respectively (p = 0.832). The median overall survival (OS) was 38 months (95% CI, 23.8–52.2) in geriatric patients, while it was not reached in younger patients (p = 0.745). There was no significant difference between the two groups. The pretreatment and post-treatment G8 values of the geriatric patients were 9.25 (6–13.5) and 9.5 (6–14), respectively. Patients with increased G8 scores were found to have significantly higher PFS (median 85 months vs. 11 months, p = 0.001) and OS (median 85 months vs. 14 months, p = 0.001) compared to those with unchanged or decreased G8 scores. Conclusion: Age alone should not be the determining factor in the treatment decision of elderly patients diagnosed with locally advanced esophageal cancer. Moreover, CRT could be safely performed even in patients with low G8 scores, and although the G8 score may not directly influence treatment decision, its enhancement during the treatment process holds significant prognostic value.

Pre-operative chemoradiotherapy with or without induction chemotherapy for operable locally-advanced esophageal cancer.

For patients with operable locally advanced esophageal carcinoma (LA-EC), we hypothesized that pre-operative induction chemotherapy followed by chemoradiotherapy (IC-CRT) would improve progression-free survival (PFS) and overall survival (OS) when compared to chemoradiotherapy (CRT). This was a single institution retrospective cohort study including patients with LA-EC who received preoperative-intent IC-CRT vs. CRT between 2013-2019. The Kaplan-Meier method was used to estimate OS and PFS. Cox proportional hazards regression was used to assess for variables associated with survival. The impact of treatment group on pathologic response was assessed by chi-square. Ninty-five patients were included for analysis (IC-CRT n=59; CRT n=36) and the median follow-up was 37.7 months (IQR: 16.8-56.1). There was no difference in median PFS or OS for IC-CRT or CRT, 22 months (95% CI: 12-59) vs. 32 months (95% CI: 10-57) (P=0.64) and 39 months (95% CI: 23-not reached) vs. 56.5 months (95% CI: 38-not reached) (P=0.36), respectively. Amongst the subset of patients with adenocarcinoma histology, there was no difference in median PFS or OS, nor was there when analyses were further restricted to those who received ≥3 cycles of induction 5-fluorouracil and platinum, or for those who underwent esophagectomy. Pathologic complete response occurred in 45% vs. 29% (P=0.24) and N-stage regression occurred in 72% vs. 58% (P=0.28) of patients in the IC-CRT and CRT cohorts, respectively. Distant metastasis occurred in 44% of patients in each treatment cohort. For patients with LA-EC, preoperative-intent IC-CRT was not associated with improved PFS or OS when compared with CRT.

The effect of gastric fundus radiation dose on postoperative anastomotic leakage in esophageal cancer.

Standard-of-care treatment for locally advanced esophageal carcinoma (LAEC) includes neoadjuvant chemoradiotherapy followed by esophagectomy. A potentially catastrophic surgical complication is the development of a postoperative anastomotic leak. To date, the association with radiation dose exposure had been inconclusive. We examined the correlation between radiation exposure to the gastric fundus and risk of postoperative leakage using contemporary radiation doses and fractionation. A total of 69 consecutive patients with LAEC who underwent neoadjuvant chemoradiotherapy followed by esophagectomy in our tertiary center were prospectively followed (median, 27 months). Neoadjuvant regimen included 50.4 Gy in 28 fractions with 5-fluorouracil and cisplatin and 41.4 Gy in 23 fractions with carboplatin and paclitaxel. The gastric fundus was contoured and dosimetric and radiation technique parameters were retrospectively evaluated. Of the total number of patients, 71% and 29% had esophageal and gastroesophageal junction (GEJ) tumors, respectively. Fourteen patients (20.3%) experienced anastomotic leaks within a median of 2 days postoperatively, 78.6% of whom had lower third esophagus or GEJ primaries. Mean and minimum fundus dose did not significantly differ between those with and those without leakage (p = 0.42, p = 0.51). Mean fundus V25, V30, and V35 doses were numerically but not statistically higher in those with anastomotic leak (p = 0.58, p = 0.39, and p = 0.30, respectively). No correlation with incidence of leakage was seen between 3D and IMRT treatment modalities. In our comparatively large prospectively collected series of patients treated for LAEC, radiation dose to the gastric fundus during neoadjuvant combination therapy prior to surgery did not correlate with the risk of postoperative anastomotic leak.

Converting borderline-resectable, locally-advanced esophageal carcinoma to resectability with neoadjuvant chemoradiotherapy.

160 Background: Treatment of T3-4/N+ esophageal cancer is challenging. Outcomes are suboptimal and patterns of care are not well defined for borderline-resectable esophageal cancer (BREC). We present our institutional experience using preoperative chemoradiotherapy (CRT) in the management of BREC. Methods: We identified 67 patients with T3-4/N+ BREC who were treated with concurrent CRT between 2009 and 2014. Survival was calculated with Kaplan-Meier curves and cohort comparisons were made with log-rank test and Cox regression. Results: We treated 67 patients (81% males, median age 61 years, and KPS of 80), primarily with T3N2 disease. Median follow-up was 16 months. The most common CRT regimen was 58.8Gy in 28 fractions with carboplatin and paclitaxel. Median survival was 16.5 months. Forty two (62.7%) patients underwent minimally invasive Ivor-Lewis esophagectomy within 100 days of CRT. Resected patients had a median survival of 30.6 vs. 6.4 months without surgery (p&lt;.001). Pathologic complete response and pN0 was 30.0% and 59.5%, respectively. Acute grade 3+ toxicity was seen in 34.3% and late grade 3+ toxicity in 49.3%. Three patients (4.5%) died during CRT or before surgery. Predictors of overall survival (OS) on univariate analysis included age, KPS, male gender, absence of radiographic progression and surgical resection (all p&lt;.05). Surgery remained significant on multivariate analysis (HR 0.215 [95%CI .114-.408, p&lt;.001]). For resected patients, survival was predicted by positive margins, pathologic N stage, and number of positive nodes (all p&lt;.05). The only predictor of OS on multivariate analysis was pathologic N stage, with actuarial 1- and 2-year OS for pN0 vs. pN+ of 96.2%/73.1% vs 53.3%/40.0% (p=.001). pN+ patients receiving adjuvant chemotherapy (53.3%) had improved survival of 26.7 vs 8.3 months without (p=.023). Conclusions: Preoperative CRT enabled a significant proportion of patients with BREC to proceed with a potentially curative resection. Further investigation with careful patient selection is warranted in incorporating a trimodality strategy to optimize outcomes and better define a treatment algorithm for this complex cohort of patients.

Relationship between expression of serum vascular endothelial growth factor and efficacy of local advanced esophageal carcinoma treated with intensity-modulated radiotherapy combined with chemotherapy

Objective To investigate the expression of serum vascular endothelial growth factor(VEGF) in local advanced esophageal carcinoma patients, and to explore the relationship between its change rule and the recent curative effect and significance. Methods The serum levels of VEGF in 46 patients with local advanced esophageal carcinoma were detected by ELISA before and after concurrent chemoradiotherapy, the serum levels of VEGF in 46 healthy people were detected at the same time. Results The serum VEGF levels of local advanced esophageal carcinoma patients before treatment and health control group were (264.66±62.11) ng/L and (101.96±39.53) ng/L, and the difference was statistically significant (t = 23.367, P = 0.000). After treatment, the serum VEGF level of patients with esophageal cancer was decreased to (127.50±49.07) ng/L (t = 19.086, P = 0.000). After the treatment, the serum VEGF levels of complete remission (CR) and partial remission (PR) patients were decreased [(94.03±38.86) ng/L vs (248.79±47.84) ng/L, (117.06±20.68) ng/L vs(295.26±67.20) ng/L, both P = 0.000], the level of the stable disease (SD) patients was decreased, too [(235.63±26.05) ng/L vs (385.67±26.50) ng/L, P = 0.017]. Conclusions The recent curative effects of docetaxel and nedaplatin chemotherapy combined with intensity-modulated radiotherapy for the local advanced esophageal carcinoma patients are significant. The levels of serum VEGF before and after treatment can be used as an important index to judge the treatment effect. Key words: Esophageal neoplasms; Drug therapy; Radiotherapy, intensity-modulated; Vascular endothelial growth factors

Perfusion computed tomography in predicting treatment response of advanced esophageal squamous cell carcinomas.

The purpose of this study was to prospectively evaluate the predictive value of perfusion computed tomography (CT) for response of local advanced esophageal carcinoma to radiotherapy and chemotherapy. Before any treatment, forty-three local advanced esophageal squamous cell carcinomas were prospectively evaluated by perfusion scan with 16-row CT from June 2009 to January 2012. Perfusion parameters, including perfusion (BF), peak enhanced density (PED), blood volume (BV), and time to peak (TTP) were measured using Philips perfusion software. Seventeen cases received definitive radiotherapy and 26 received concurrent chemo-radiotherapy. The response was evaluated by CT scan and esophagography. Differences in perfusion parameters between responders and non-responders were analyzed, and ROCs were used to assess predictive value of the baseline parameters for treatment response. There were 25 responders (R) and 18 non-responders (NR). Responders showed significantly higher BF (R:34.1 ml/100 g/min vs NR: 25.0 ml/100 g/min, p=0.001), BV (23.2 ml/100g vs 18.3 ml/100g, p=0.009) and PED (32.5 HU vs 28.32 HU, P=0.003) than non-responders. But the baseline TTP (R: 38.2 s vs NR: 44.10 s, p=0.172) had no difference in the two groups. For baseline BF, a threshold of 36.1 ml/100 g/min achieved a sensitivity of 56%, and a specificity of 94.4% for detection of clinical responders from non-responders. The results suggest that the perfusion CT can provide some helpful information for identifying tumors that may respond to radio-chemotherapy.

Long-term cardiopulmonary mortality after radiation for locally advanced esophageal cancer.

99 Background: Radiation (RT) is considered an integral component of trimodality therapy for locally-advanced esophageal carcinoma to improve locoregional control and potentially survival. However, the long-term risk of cardiopulmonary mortality (CPM) is not well-understood in this population. Methods: Patients age 20-85 with esophageal carcinoma with T3, T4 or node positive (N+) disease who underwent esophagectomy were identified within 17 Surveillance, Epidemiology, and End Results registries from 1988-2006. Patients with metastatic disease or &lt;6 mo follow up were excluded. CPM was calculated for patients receiving vs not receiving RT and compared by the Kaplan-Meier method. The log-rank test was used for univariate associations and Cox proportional hazards model was used for multivariate analysis (MVA). Results: A total of 4,079 patients met the defined selection criteria of whom 2,408 were treated with RT, and 1,671 were not. Median age was 62.2 yrs (22-84) and follow-up was 22 mos (6-248). There was no significant difference in CPM in patients who received RT versus those who did not (p=0.8). At 10 yr, the majority of deaths were from esophageal cancer (73 with vs 78% without RT) compared to CPM (13.7 with vs 11.6% without RT). On univariate analysis ( table ), age &lt;60, diagnosis era, and histology were significant independent predictors of CPM. On MVA, age &lt;60 (HR 0.36) and diagnosis era (0.63 for 1994-2000 and 0.55 for 2000-2006) remained statistically significant for CPM. Conclusions: RT for esophageal cancer is not associated with an increased long-term risk of CPM in the overall population. Older age and earlier diagnosis era predict for CPM. Although survival in esophageal cancer is dominated by cancer deaths, advances in RT are still needed to prevent excess treatment-related mortality. [Table: see text]

A Retrospective Study of Local Control and Survival for Esophageal Squamous Cell Carcinoma Treated with Three-Dimensional Conformal Radiotherapy (3DCRT)

Locally advanced esophageal carcinoma (LAEC) is associated with poor survival and more effective treatments are needed. The aim of this study was to investigate the long-term outcomes and explore particular imaging prognostic factors of LAEC treated with 3DCRT.

Neo-adjuvant Chemotherapy versus Neo-adjuvant Chemoradiation Therapy followed by Esophagectomy versus Definitive Chemoradiation Therapy in Management of Locally-advanced Esophageal Carcinoma: A Single Institution Experience

Neo-adjuvant Chemotherapy versus Neo-adjuvant Chemoradiation Therapy followed by Esophagectomy versus Definitive Chemoradiation Therapy in Management of Locally-advanced Esophageal Carcinoma: A Single Institution Experience

6567 Preoperative radiochemotherapy with cisplatin plus infusional high-dose 5-fluorouracil/leucovorin (LV5FU2) in locally-advanced esophageal carcinoma of UICC stages II and III – ongoing study

6567 Preoperative radiochemotherapy with cisplatin plus infusional high-dose 5-fluorouracil/leucovorin (LV5FU2) in locally-advanced esophageal carcinoma of UICC stages II and III – ongoing study

A single institution experience with neoadjuvant chemoradiation (CRT) with irinotecan (I) and cisplatin (C) in locally advanced esophageal carcinoma (LAEC)

e15619 Background: Multimodal therapy is considered standard for LAEC with cisplatin and 5FU-based CRT being commonly used, though with significant toxicity. Novel agents are needed to improve pathologic response (pCR) which predicts for better prognosis. We analyzed our experience with CRT using I + C in LAEC. Methods: LAEC patients (PTS) who underwent surgery preceded by CRT with I + C were identified from the Roswell Park tumor registry. Treatment consisted of Day 1,8 of C 30mg/m2 and I 65mg/m2in a 21 day cycle. PTS concurrently received 45–50.4 Gy radiation in1.8Gy fractions. Data retrieved included toxicity, pCR rate and survival. Results: 44 eligible PTS, median age 61 yr, 43 males and 1 female. Histology included adenocarcinoma (n=38), squamous cell (n=4), mixed (n=2); 12 PTS had signet-ring cell features. 29 PTS had poorly differentiated tumors. Clinical stage was II (n=5), III (n=24), IVa(n=6), IVb(n=1), not available (n=8). ECOG PS was 0 (n=34) and 1 (n=10). Most common toxicities observed were fatigue (n=24), diarrhea (n=19), vomiting (n=15), hematologic (n=11), constipation (n=11) and neurologic (n=7). Dose delay or reduction was required in 10 PTS, usually from hematologic toxicity. Of these,1 week delay in 45% and 2 weeks in 36%; 1 PT discontinued treatment due to toxicity. There was no CRT-related mortality. 2 PTS died post-operatively (anastamotic leak and sepsis). Dyphagia improved in 33/35 (94%) PTS following CRT. All PTS underwent R0 resection and pCR rate was 25% (11/44). 15 PTS have experienced recurrence. The median disease-free and overall survival is 24 months and 34 months, respectively; 3-yr overall survival is 46%. Available pre- and post-CRT FDG uptake on PET imaging in 28 PTS did not correlate with pCR status (p=0.77). Conclusions: Neo-adjuvant CRT with I + C has modest efficacy in the treatment of LAEC and can be given safely in the out-patient setting. PTS should be monitored closely for toxicity, specifically diarrhea that requires prompt intervention. Efficacy results appear better than those reported in ECOG 1201. This regimen is being evaluated in CALGB 80302 and results are awaited. No significant financial relationships to disclose.