Elderly Esophageal Cancer Patients Research Articles

Multicenter analysis on the value of standard (chemo)radiotherapy in elderly patients with locally advanced adenocarcinoma of the esophagus or gastroesophageal junction

BackgroundTo assess the tolerability and oncological results of chemoradiation in elderly patients with locally advanced adenocarcinoma of the esophagus or gastroesophageal junction.MethodsThis multi-center retrospective analysis included 86 elderly patients (≥ 65 years) with esophageal or gastroesophageal junction adenocarcinoma (median age 73 years; range 65–92 years) treated with definitive or neoadjuvant (chemo)radiotherapy. The treatment was performed at 3 large comprehensive cancer centers in Germany from 2006 to 2020. Locoregional control (LRC), progression-free survival (PFS), distant metastasis-free survival (DMFS), overall survival (OS), and treatment-associated toxicities according to CTCAE criteria v5.0 were analyzed, and parameters potentially relevant to patient outcomes were evaluated.ResultsThirty-three patients (38%) were treated with neoadjuvant chemoradiation followed by surgery, while the remaining patients received definitive (chemo)radiation. The delivery of radiotherapy without dose reduction was possible in 80 patients (93%). In 66 patients (77%), concomitant chemotherapy was initially prescribed; however, during the course of therapy, 48% of patients (n = 32) required chemotherapy de-escalation due to treatment-related toxicities and comorbidities. Twenty-nine patients (34%) experienced higher-grade acute toxicities and 14 patients (16%) higher-grade late toxicities. The 2-year LRC, DMFS, PFS, and OS amounted to 72%, 49%, 46%, and 52%, respectively. In multivariate analysis, neoadjuvant chemoradiation followed by surgery was shown to be associated with significantly better PFS (p = 0.006), DMFS (p = 0.006), and OS (p = 0.004) compared with all non-surgical treatments (pooled definitive radiotherapy and chemoradiation). No such advantage was seen over definitive chemoradiation. The majority of patients with neoadjuvant therapy received standard chemoradiotherapy without dose reduction (n = 24/33, 73%). In contrast, concurrent chemotherapy was only possible in 62% of patients undergoing definitive radiotherapy (n = 33/53), and most of these patients required dose-reduction or modification of chemotherapy (n = 23/33, 70%).ConclusionsIn our analysis, omission of chemotherapy or adjustment of chemotherapy dose during definitive radiotherapy was necessary for the overwhelming majority of elderly esophageal cancer patients not eligible for surgery, and hence resulted in reduced PFS and OS. Therefore, optimization of non-surgical approaches and the identification of potential predictive factors for safe administration of concurrent chemotherapy in elderly patients with (gastro)esophageal adenocarcinoma is required.

Relationship Between Dynamic Compliance and Airway Resistance and Infection Indicators in Elderly Patients With Lung Infection After Radiotherapy for Esophageal Cancer

To investigate the performance of using lung dynamic compliance (Cdyn) and airway resistance (RAW) levels to predict lung infection in elderly esophageal cancer patients who have undergone radiotherapy. A total of 298 elderly esophageal cancer patients who received radiotherapy at Shanxi Fenyang Hospital between October 2017 and July 2022 were retrospectively enrolled and their clinical data were collected. The patients were divided into an infection group (124 cases) and a non-infection group (174 cases) according to their status of lung infection. Then, in the infection group, CURB-65 score was used to assess the severity of the patients' lung infection and the patients were further divided into subgroups accordingly, with 36 cases in the mild infection subgroup, 58 cases in the moderate infection subgroup, and 30 cases in the severe infection subgroup. The levels of Cdyn, RAW, and infection indicators, including serum procalcitonin (PCT), interleukin-6 (IL-6), and angiotensin Ⅱ (Ang Ⅱ), were measured in both groups of patients and the differences in the findings were compared between the infection and the non-infection groups and among patients with infection of varying degrees of severity. The correlation between Cdyn and RAW and the levels of PCT, IL-6, and Ang Ⅱ was analyzed. Receiver operating characteristic (ROC) curve was used to evaluate the performance of predicting infection with Cdyn and RAW. The Cdyn level of patients in the infection group was lower than that of patients in the non-infection group, while the RAW level of the infection group was higher than that of the non-infection group (P<0.05). Among the infection subgroup, the level of Cdyn of the mild infection subgroup was higher than those of the moderate and severe infection subgroups, while the levels of RAW, PCT, IL-6, and Ang Ⅱ of the mild infection subgroup were lower than those of the moderate severe subgroups. The level of Cdyn of the moderate infection subgroup was higher than that of the severe infection subgroup, while the RAW, PCT, IL-6, and Ang Ⅱ levels of the moderate infection subgroup were lower than those of the severe infection subgroup, with all difference being statistically significant (P<0.05). The Cdyn level of patients with lung infection was negatively correlated with PCT, IL-6, and Ang Ⅱ levels and the severity of infection (r=-0.501, -0.430, -0.367, and -0.484, respectively, P<0.05), while RAW was positively correlated with PCT, IL-6, and Ang Ⅱ levels and the severity of infection (r=0.483, 0.395, 0.374, and 0.423, respectively, P<0.05). The area under the curve (AUC) of Cdyn and RAW for predicting lung infection in elderly patients with esophageal cancer after radiotherapy were 0.898 (95% confidence interval [CI]: 0.857-0.930) and 0.823 (95% CI: 0.775-0.865), respectively, and the AUC of combined evaluation of Cdyn and RAW was 0.959 (95% CI: 0.930-0.979), which suggested that the predictive performance of combined evaluation was better than evaluation with Cdyn or RAW alone. When elderly esophageal cancer patients develop lung infection after radiotherapy, their Cdyn level is decreased, while the levels of RAW, PCT, IL-6, and Ang Ⅱ are increased. In addition, the levels of Cdyn and RAW are correlated with the PCT, IL-6, and Ang Ⅱ levels. The combined use of Cdyn and RAW shows good performance for predicting lung infection in patients.

Survival Impacts of Impaired Lung Functions and Comorbidities on Elderly Esophageal Cancer Patients.

Preoperative physiological assessments are crucial for optimizing clinical outcomes, especially those of elderly esophageal cancer (EC) patients who are generally frail and at the high risk of mortality. Patients who underwent surgery for EC between 2004 and 2018 were retrospectively reviewed. Patients were categorized into elderly (>70years) or non-elderly (≤70years) groups. Various physiological parameters including the Charlson Comorbidity Index (CCI), immunonutritional parameters and pulmonary functions were studied. Pulmonary functions included %vital capacity (VC) and forced expiratory volume in one second (FEV1.0) and FEV1.0%. The thresholds were set as the lowest quartile (100% for %VC and 2L for FEV1.0) in this cohort. Multivariate Cox hazards models were applied to determine independent predictors of non-EC-related deaths. In total, 824 patients were included (elderly; n = 306, non-elderly; n = 518). Elderly patients had a significantly lower 5-year OS rate than non-elderly patients (53.3% vs. 57.2%, P = 0.03), mainly due to increased risk of death from non-EC related causes. In the elderly group, multivariate Cox hazards analysis identified 3 independent predictors of non-EC-related deaths; high CCI (HR 1.98, P=0.006), low %VC (HR 2.01, P = 0.004) and low FEV1.0 (HR 1.6, P=0.048). Elderly patients without risk factors had a significantly better 5-year OS rate (63.5%) than those with 1 (50.0%) or 2-3 (36.3%) risk factors (P <0.01). Deaths due to pulmonary disease rose significantly as the number of risk factors increased (P=0.03). The severity of comorbidities and pulmonary function impairments are useful for predicting long-term outcomes, especially non-EC-related deaths, in elderly EC patients.

Impact of the G8 Score on Treatment Strategies and Outcome in Definitive Radiotherapy for the Elderly Esophageal Cancer Patients

Although chemoradiotherapy (CRT) is widely used as a curative treatment for esophageal cancer, it is often difficult to perform standard CRT for the elderly in the real world. This study aimed to investigate the impact of the Geriatric 8 (G8) score on treatment strategies and outcome in definitive radiotherapy (RT) for elderly esophageal cancer patients. We analyzed 81 esophageal cancer patients aged ≥65 years who received definitive RT between 2018 and 2021. The G8 score was acquired at the first visit to the radiation oncology department. The treatment strategy was decided by a multi-disciplinary conference, and the G8 score was not used to determine the treatment strategy. Standard treatment (standard CRT) was defined as RT with elective nodal irradiation and a total dose ≥50 Gy, and chemotherapy with two cycles of platinum (70 mg/m2) and 5FU (700 mg/m2 for 4 days) concurrently. The Kaplan-Meier method was used to generate actual survival curves. The Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 was used to assess toxicities. The Mann-Whitney U test was used to compare the two groups, and statistical significance was set at p<0.05. The Receiver Operating Characteristic (ROC) curve was used to calculate the cutoff value. The Median follow-up time was 30 months (range: 8-51) for survivors. The mean G8 scores by treatment strategy were 13.9 (range: 9-17) for standard CRT group (n = 26), 12.1 (range: 7-16) for reduced CRT group (n = 30), and 9.7 (range: 4.5-14) for RT alone group (n = 25). G8 score was significantly higher for standard CRT (p = 0.017) and significantly lower for RT alone (p<0.01). The cut-off value of the G8 score for standard treatment, calculated by the ROC curve, was 12.5 points. In the non-standard treatment group, the cut-off value of the G8 score for RT alone, calculated by the ROC curve, was 10.5 points. The 2-year overall survival (OS) rates for standard CRT, reduced CRT and RT alone were 74%, 71% and 35%, respectively, and significantly lower in RT alone (p<0.001). The 2-years OS rates for G8 score >10.5 points and ≤10.5 points were 69% and 48%, respectively (p = 0.039). Grade 3 or higher acute toxicities were observed in 33 patients (41%); 14 (54%) in standard CRT, 17 (57%) in reduced CRT and 2 (8%) in RT alone. Grade 5 acute toxicity was not observed. G8 scores tended to be higher in the patients with grade 3 or higher acute toxicities, but the difference was not statistically significant (p = 0.057). Grade 3 or higher late toxicities were observed in 7 patients. Our results suggest that there is an association between the G8 score and clinicians' treatment decisions. Although RT alone could be safely performed even in patients with low G8 scores, administration of chemotherapy strongly affected prognosis. These results suggest the importance of developing less toxic systemic therapy regimens for patients with low G8 scores.

366. SARCOPENIA DECIDED FROM LOWER PSOAS MUSCLE INDEX IS STRONGLY POOR PROGNOSTIC FACTOR FOR ELDERLY ESOPHAGEAL CANCER PATIENTS

Abstract Background Elderly esophageal cancer patients undergoing esophagectomy are increasing. Although esophageal cancer patients suffering sarcopenia are already well known to have poor prognosis, the impact of sarcopenia for each age group may differ, since older patients have a higher frequency of primary sarcopenia than younger patients. Methods To clarify the relationship between sarcopenia and surgical outcomes in elderly esophageal cancer patients, we measured the psoas muscle index (PMI) in 103 elderly esophageal cancer patients aged 75 years or older who underwent radical esophagectomy from 2007 to 2021. The patients were then classified into two groups, sarcopenia group and non-sarcopenia group, using the 25th percentile of PMI as a cut-off value, and the relationship with outcomes of surgery and neoadjuvant chemotherapy (NAC) was examined. Results The 103 patients included 83 males and 20 females. The sarcopenia group had significantly lower BMI, but there was no correlation with oncological factors such as tumor depth or lymph node metastasis. NAC (FP) was performed in 39 patients and there was no clear correlation between completion, efficacy, or adverse events and sarcopenia. Thoracoscopic esophagectomy was performed in 93 patients, and there was no clear correlation between short-term surgical outcomes and sarcopenia. However, the 5-year overall survival and 5-year disease free survival were significantly lower in the sarcopenia group, resulted sarcopenia was an independent poor prognostic factor. Conclusion In elderly esophageal cancer patients over 75-year-old who underwent radical esophagectomy, sarcopenia does not significantly affect short-term surgical outcomes, and NAC is possibly able to administer as in the non-sarcopenia group. However, the indication of surgery to sarcopenic patients should be carefully decided because they have worse long-term prognosis than non-sarcopenic patients.

Prognostic analysis and treatment utilization of different treatment strategies in elderly esophageal cancer patients with distant metastases: a SEER database analysis.

The purpose of this study was to explore which therapeutic strategy is more beneficial for elderly esophageal cancer (EC) patients with distant metastasis, the treatment utilization status and the screening of factors related to prognosis, so as to better guide the treatment of these patients. Patients in the Surveillance Epidemiology and End Results (SEER) database were divided into chemoradiotherapy (Group A), chemotherapy (Group B), radiotherapy (Group C), and no treatment (Group D) according to different treatment methods. Propensity score matching (PSM) was performed to adjust for baseline differences between the two groups. Overall survival (OS) and esophageal cancer-specific survival (ECSS) was calculated using the Kaplan-Meier method and compared using the log-rank test. A total of 7027 patients were included in this study, 5739 males (81.7%) and 1288 females (18.3%) with the median age was 70 (60-98). In the original cohort, the number of patients in the four groups was 2260 (Group A), 2087 (Group B), 945 (Group C) and 1735 (Group D), respectively. After PSM, there was no significant difference in mean OS (A vs B, 13.5months VS 13.4months, P = 0.511) and mean ECSS (A vs B, 15.6 vs 15.5months, P = 0.374), while both OS (B vs C, 7 vs 3months, P < 0.001) and ECSS (B vs C, 8 vs 3months, P < 0.001) of chemotherapy alone were significantly better than those of radiotherapy alone. Subgroup analysis of patients older than 80years showed that the median OS (A vs B, 7 vs 6months) and median ECSS (A vs B, 8 vs 7months) of Group A were significantly better than those of Group B (P < 0.05). In addition, all patients were randomly divided into a training set and a validation set with a ratio of 7:3. Based on the independent risk factors for OS, a nomogram model was constructed and validated. For elderly EC patients with distant metastasis, aggressive treatment was still necessary after a comprehensive assessment of the patient's physical condition, especially for patients over 80years old, and chemoradiotherapy maybe still the first choice. In addition, a nomogram model was constructed to intuitively and accurately evaluate the prognosis of this population.

Development and validation of a prognostic nomogram for predicting cancer-specific survival in lymph node-negative elderly esophageal cancer patients: A SEER-based study.

In this study, we explored the prognostic risk factors of elderly patients (≥65 years old) with lymph node-negative esophageal cancer (EC) and established a nomogram to evaluate the cancer-specific survival of patients. The surveillance, epidemiology, and end results database was used to collect data on patients diagnosed with EC. Univariate and multivariate Cox analyses were used to determine independent prognostic factors, and the nomogram for predicting cancer-specific survival of EC patients was constructed based on the independent prognostic factors obtained from the multivariate Cox analysis. To evaluate the predictive ability of the nomogram, calibration curves, concordance index (C-index), receiver operating characteristic curves, and decision curve analysis were conducted. Kaplan-Meier method was used to analyze the long-term outcomes of EC patients with different risk stratifications. A total of 3050 cases with lymph node-negative EC were randomized into the training cohort (1525) and the validation cohort (1525). Cancer-specific mortality at 1, 3, and 5 years in the entire cohort was 30.7%, 41.8%, and 59.2%, respectively. In multivariate Cox analysis, age (P < .001), marital status (P < .001), tumor size (P < .001), Tumor-node-metastasis stage (P < .001), chemotherapy (P = .011), radiotherapy (P < .001), and surgery (P < .001) were independent prognostic factors. The C-index for the training cohort was 0.740 (95% confidence interval [CI]: 0.722-0.758), and the C-index for the validation cohort was 0.738 (95% CI: 0.722-0.754). The calibration curve demonstrated the great calibration ability of the nomogram. Based on the area under the receiver operating characteristic curve, the nomogram demonstrated a higher sensitivity than the tumor-node-metastasis stage. Decision curve analysis showed the good clinical utility of the nomogram. The risk stratification system was established using the Kaplan-Meier curve and verified by the log-rank test (P < .001). The nomogram and risk stratification system can improve the accuracy of prediction to help clinicians identify high-risk patients and make treatment decisions.

Assessment of photodynamic therapy as a salvage treatment for local failure after chemoradiotherapy or radiotherapy for esophageal cancer in patients aged 80 years or older.

ObjectivesChemoradiotherapy (CRT) or radiotherapy (RT) alone is often the treatment of choice for elderly patients with esophageal cancer with the expectation of organ preservation. However, salvage treatment remains a problem when endoscopic resection is not indicated for local failure after CRT/RT. Photodynamic therapy (PDT) is indicated for local failure after CRT/RT, but there are few reports on its efficacy and safety in elderly patients. This study aimed to assess the outcome of PDT for local failure after CRT/RT for esophageal cancer in elderly patients.MethodsThis retrospective single‐center study included 42 patients who first underwent PDT between April 2013 and June 2021. Patients aged ≥80 and <80 years were classified into the elderly and nonelderly groups, respectively. Local complete response rate, overall survival, progression‐free survival, and incidence of adverse events related to PDT were compared retrospectively between the groups.ResultsThe local complete response rate was 93.3% in the elderly group and 85.7 in the non‐elderly group. The 2‐year overall survival rate was 68.6% and 72.5%, and the 2‐year progression‐free survival rate was 49.5% and 70.0% in the elderly and nonelderly groups, respectively. There was no significant difference in any of these outcomes between the groups. In terms of adverse events, pneumonia and delirium tended to occur more frequently in the elderly group, but there were no serious adverse events in either group.ConclusionThe outcome of salvage PDT in the local control was comparable between the elderly and nonelderly patients for local failure after CRT/RT for esophageal cancer.

407. A STUDY OF OUTCOMES OF ESOPHAGEAL CANCER SURGERY FOR ELDERLY PATIENTS OVER 80 YEARS OF AGE

Abstract According to the 2020 edition of the situation in Japan, the population aged 65 and over reached 35.89 million, accounting for 28.4% of the total population. Esophageal cancer is a common disease among the elderly, and it is expected that the number of encounters with elderly esophageal cancer patients will increase further in the future. We examined the outcomes of esophageal cancer surgery for elderly patients at our hospital. Of 769 thoracic esophageal cancer resections performed at our hospital from 2015–2019, 53 (6.8%) patients aged 80 years or older were included. The mean age was 82 (80–94) years, the male/female ratio was 45/8, tumor localization was Ut/Mt/Lt 5/23/25, and cStage (UICC 7th edition) was I/II/III/IV 12/8/30/3. The surgical technique was 1-stage resection/2-stage segmental resection/mediastinoscopy in 9/32/12 cases. Surgical complications were suture failure, recurrent nerve palsy, and pulmonary complications in 2/12/11 patients. The 3-year survival rate was 66.7%, and the 3-year recurrence-free survival rate was 62.1%. The 3-year survival rate was 66.7% and the 3-year recurrence-free survival rate was 62.1%. Esophageal cancer surgery may be a treatment option for elderly patients who are able to tolerate surgery, even if they are over 80 years of age. Our hospital provides a multidisciplinary team intervention for patients over 70 years of age 3–4 weeks prior to surgery, during the perioperative period, and after discharge, which may be useful in reducing postoperative complications.

484. UPFRONT SURGERY VERSUS PREOPERATIVE TREATMENT FOR PATIENTS AGED 80 YEARS OLDER WITH ESOPHAGEAL CANCER

Abstract In recent years, with the aging of the population, there have been more opportunities to operate on very elderly esophageal cancer patients over the age of 80. The safety of neoadjuvant chemotherapy has become the standard, but for very elderly patients is not clear. In our hospital, it is selected if general condition is acceptable. This time, we examined cases of very elderly esophageal cancer patients aged over 80 years performed esophagectomy at our hospital. The subjects were 28 patients aged 80 years or older who underwent esophagectomy at our hospital for advanced esophageal cancer from January 2017 to December 2020. A retrospective study was performed by dividing into the upfront surgery group (S) and the preoperative treatment group (Neo: neoadjuvant chemotherapy group, preoperative chemoradiation group, salvage surgery group). The primary endpoints were recurrence rate and recurrence-free survival (month), and the secondary endpoints were preoperative adverse event incidence, R0 achievement rate, and perioperative complication rate in the preoperative treatment group. Median age is 82 years (range: 80-89 years). S/Neo= 21/7 cases. Chemotherapy were DCF: 1 case, FOLFOX: 2 cases, FP: 2 cases, CDDP + VP: 1 case. Preoperative adverse event incidence of Grade 3 or higher was 14.2%. The R0 achievement rate was 90%/100% (S/Neo, p= 0.442; t-test). Perioperative complications rate of Clavien-Dindo IIIa or higher was 33.3%/71.4% (S/Neo, p= 0.083; t test). The recurrence rate was 57.1%/14.2% (S/Neo), which were significantly lower in the Neo than in the S(p= 0.049; Logistic regression model). The median recurrence-free survival was 13 months in the S and 10 months in the Neo. It is necessary to select a treatment method that balances curative and postoperative QOL for the elderly based on organ function, tumor factors, social background, etc. Since it is difficult to use CDDP for very elderly patients, FOLFOX is the first choice at our hospital. Operation techniques such as less invasive mediastinoscopic and two-staged surgery are selected. From the results of this study, preoperative treatment may reduce the recurrence rate.

300. RETROSPECTIVE STUDY FOR EVALUATING IMPACT OF NEOADJUVANT THERAPY USING CDDP +5-FU TOWARD ELDERLY ESOPHAGEAL CANCER PATIENTS

Abstract A number of elderly esophageal cancer patients who have eligibility for radical esophagectomy are increasing. However, we have no clearly evidence of treating strategy for these population because mostly high evidential clinical studies doesn’t include over 75-year-old patients. In this study, we retrospectively assessed efficacy of neoadjuvant chemotherapy using CDDP +5-FU in over 75-year-old patient in our hospital. We extracted total 105 over 75-year-old esophageal cancer patients who underwent radical esophagectomy from 2007 to 2020 in our hospital. We classified them Group A (surgery alone) and Group B (neo-FP(±RT) + surgery) and analyzed perioperative surgical risk, surgical outcomes, and adverse events or effectiveness for neoadjuvant therapy. Furthermore, long-term survival was assessed by using matched cohort from propensity score matching. Preoperative risk score calculated by E-pass scoring system was significantly higher in group A while surgical score was similar between two groups. Among group B, 86% of patients were underwent neoadjuvant chemotherapy (NAC) and its completion rate was 78.9%. Number of the patients occurred adverse events during NAC were 8/7/12/3 in the G1/2/3/4 respectively. Postoperative complications decided by Clavien-Dindo classification weren’t seen significant difference between two groups. Postoperative in hospital days were significantly shorter in group A. Survival analysis showed significantly worse overall survival and disease-free survival in group A in both all cohort and matched cohort. The level of preoperative risk score was different between two different treatment strategies. Although this study has several limitations including low number population, difference of preoperative risk, and short follow up period, neoadjuvant therapy using FP may safety and effective treatment for elderly esophageal cancer patients.

Essential risk factors for operative mortality in elderly esophageal cancer patients registered in the National Clinical Database of Japan.

With the aging of society and increasingly longer of life expectancy, elderly patients with esophageal cancer are more commonly encountered. This study aimed to identify the risk factors for operative mortality after esophagectomy in elderly patients. We used data from the National Clinical Database of Japan. After cleaning the data, 10,633 records obtained from 861 hospitals were analyzed. A risk model for operative mortality was developed using risk factors from the entire study population. Then, odds ratios (OR) were compared between age categories using this risk model. In this study, 1959 (18.4%) patients were ≥ 75years (defined as "elderly" in this study). Eighteen variables, including T4b, N2-N3, and M1 in the TNM classification, were included in the risk model for operative mortality. The ORs increased in age categories < 65, 65-74, and ≥ 75years for N2-N3 (1.172, 1.200, and 1.588, respectively), and M1 (2.189, 3.164, and 4.430, respectively). Based on these results, we also focused on residual tumors, which are caused by extensive tumor development. The operative mortality in the elderly group with residual tumors increased to more than twice than that in the non-elderly groups (15.9 vs. 5.5 or 6.5%) and was much higher than that in elderly patients without residual tumors (15.9 vs. 4.6%). We should carefully select the treatment for elderly patients with highly advanced tumors, which result in N2-N3 and M1, to avoid unfavorable short-term outcomes. In addition, R0 resection is important in preventing operative mortality among elderly patients.

Comparison of involved-field intensity-modulated radiotherapy combined with S-1 vs radiotherapy alone for elderly patients with esophageal cancer.

BACKGROUNDIt is estimated that about 30% of esophageal cancer (EC) patients are over 70 years old. Therefore, there is less evidence on the diagnosis and management of elderly EC patients. It is important to explore how elderly EC patients benefit from radical radiochemotherapy regimens, including the target area of radiotherapy (RT), radiation dose and fraction, and choice of chemotherapy drugs.AIMTo compare the efficacy of involved-field intensity-modulated RT (IF-IMRT) combined with S-1 vs RT alone in the treatment of elderly EC patients in terms of safety, short-term response, and survival.METHODSThirty-four EC patients aged > 70 years were prospectively enrolled between December 2017 and December 2019. Based on the random number table, they were divided into an IF-IMRT + S-1 group and an IF-IMRT alone group, with 17 patients in each group. All patients were treated with IF-IMRT at a dose of 50.4-56 Gy in 28-30 fractions (1.8-2 Gy/fraction, 5 fractions/wk). Oral S-1 was administered concomitantly in the IF-IMRT + S-1 group for 14 consecutive days, and a second cycle was started 7 d after drug withdrawal. After RT, 4 cycles of S-1 treatment were offered as the consolidation chemotherapy. The safety, short-term response, and survival were observed after the treatment.RESULTSAs of April 2022, these 34 patients had been followed up for 15.2-32.5 mo, with a median follow-up period of 24.5 mo. Complete efficacy indicators were obtained from all the patients. The objective response rate was 88.2% vs 76.5%, respectively, in the IF-IMRT + S-1 group and the RT alone group, where as the disease control rate was 100% vs 82.4%, respectively. The incidence of adverse events including grade 1-2 fatigue, granulocytopenia, thrombocytopenia, anemia, radiation esophagitis, radiation-induced skin injury, and radiation-induced lung injury was not significantly different between these two groups, so was the incidence of the grade 3 radiation esophagitis (0% vs 5.7%). The rate of progressive disease (PD) was 52.9% (n = 9) in the IF-IMRT + S-1 group and 64.7% (n = 11) in the RT alone group. The median progression-free survival (PFS) was 23.4 mo vs 16.3 mo, and the 2-year PFS rate was 42% vs 41.2%. The median overall survival (OS) was 27.0 mo vs 23.0 mo, and the 2-year OS rate was 58.8% vs 47.1%. Multivariate analysis showed that age was a significant prognostic factor (P = 0.0019); patients aged < 75 years had a significant survival advantage over patients aged ≥ 75 years. The locations of EC also affected the prognosis. In the IF-IMRT + S-1 group, the number of chemotherapy cycles was a significant prognostic factor (P = 0.0125), and the risk of PD was significantly lower in EC patients who had received 6 cycles of chemotherapy than those who had received 2-5 cycles of chemotherapy.CONCLUSIONCompared with IF-IMRT alone, IF-IMRT + S-1 shows the benefits of preventing PD and prolonging survival without increasing adverse reactions. Therefore, this concurrent radiochemotherapy deserves clinical application.

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.

Clinical Outcomes of Radiotherapy in Elderly and Younger Patients With T4 Esophageal Cancer: A Retrospective Single-center Analysis.

The standard of treatment for esophageal cancer with adjacent organ invasion (T4) has not been established. We retrospectively analyzed the clinical outcomes of radiotherapy (RT) in elderly and younger patients with T4 esophageal cancer. Sixty-nine patients with T4 esophageal cancer who underwent RT at the Kanagawa Cancer Center between January 2014 and November 2020 were included in this study. Patients aged ≥70 years were defined as the elderly group and those aged <70 years were defined as the younger group. The total dose of RT was set at 60 Gy in 30 fractions. Chemotherapy combined with 5-fluorouracil and cisplatin was administered concurrently with RT in general. The overall survival (OS) rate was estimated using the Kaplan-Meier method. Adverse events were assessed using CTCAE v4.0. The median survival time (MST) of the elderly group (n=35) was 21.5 months, and the OS rates at 1, 3, and 5 years were 63.7%, 31.3%, and 15.6%, respectively. The MST of the younger group (n=34) was 12.5 months, and the OS rates at 1, 3, and 5 years were 52.2%, 29.4%, and 29.4%, respectively. No significant difference in OS was observed between the two groups (p=0.767). Toxicities were not significantly different between the two groups except for thrombocytopenia and esophageal fistula (p=0.012 and p=0.022, respectively). The clinical outcomes of RT for T4 esophageal cancer in elderly patients were generally similar to those in the younger group.

Impact of chemotherapy and radiotherapy on the survival of elderly esophageal cancer patients undergoing surgery: a SEER database analysis

BackgroundEsophageal cancer (EC) is a common and lethal carcinoma; however, the effectiveness and feasibility of the chemo- and radio-therapy (CRT) for the elderly patients (≥ 70 years) with surgery have not been fully discussed. The purpose of this study was to investigate the potential effect of CRT on the prognosis.MethodsA total of 1085 patients (534 CRT patients vs. 551 non-CRT patients) from 1998 to 2016 were collected from the Surveillance, Epidemiology, and End Results database according to the inclusion and exclusion criteria. Using the competing risk regression and survival analysis, an overall estimation of the effectiveness of CRT was performed on a well-balanced cohort via performing propensity score matching. Then, the specific impact of CRT on high- (n = 557) and low-risk (n = 528) cohorts derived from the nomogram’s risk quantification for every patient were further evaluated respectively. Additionally, the advantages of the nomogram model and the conventional tumor, node, metastasis (TNM, 6th revision) staging system were compared.ResultsA better survival outcome was observed among patients receiving both surgery and CRT than those who underwent surgery alone (HR: 0.55, 95% CI 0.45–0.68, P < 0.001), especially for those with tumors characterized by poor differentiation, large tumor size, advanced T staging, lymphatic metastasis, and distant metastasis (HR: 0.48, 95% CI 0.39–0.59, P < 0.001), while no benefit was observed among the low-risk patients. Furthermore, the newly established nomogram model might be better than the TNM (6th revision) staging system but more data needed.ConclusionAggressive treatments, such as surgery, chemotherapy, and radiotherapy, were considered effective for selected elderly patients with EC according to the newly established nomogram model.

Chemoradiotherapy Is Superior to Radiotherapy Alone in Esophageal Cancer Patients Older Than 65 Years: A Propensity Score-Matched Analysis of the SEER Database.

IntroductionRadiotherapy (RT) is the main treatment for unoperated esophageal cancer (EC) patients. It is controversial whether adding chemotherapy (CT) to RT is beneficial for elderly EC patients. The purpose of our study was to compare the efficacy of chemoradiotherapy (CRT) with RT alone for non-surgical elderly esophageal cancer patients.MethodsA total of 7,101 eligible EC patients older than 65 years diagnosed between 2000 and 2018 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. All the samples were divided into the radiotherapy group and the chemoradiotherapy group. After being matched by propensity score matching (PSM) at a 1:1 ratio, 3,020 patients were included in our analysis. The Kaplan–Meier method and log-rank test were applied to compare overall survival (OS) and cancer-specific survival (CSS).ResultsAfter PSM, the clinical characteristics of patients between the RT and CRT groups were comparable. For EC patients older than 65 years, the 3-year OS and CSS in the CRT group were 21.8% and 27.4%, and the 5-year OS and CSS in the CRT group were 12.7% and 19.8%, respectively. The 3-year OS and CSS in the RT group were 6.4% and 10.4%, and the 5-year OS and CSS in the RT group were 3.5% and 7.2%, respectively. Next, these patients were divided into five subgroups based on the age stratification (ages 65–69; 70–74; 75–79; 80–84; ≥85). In each subgroup analysis, the 3- and 5-year OS and CSS showed significant benefits in the CRT group rather than in the RT group (all p < 0.05). We were unable to assess toxicities between the two groups due to a lack of correlated information.ConclusionsCRT could improve OS and CSS for non-surgical EC patients older than 65 years. Adding chemotherapy to radiation showed a significant prognostic advantage for elderly esophageal cancer patients.

Feasibility of esophagectomy for esophageal cancer in elderly patients: a case-control study.

Surgery in elderly patients with esophageal cancer is challenging due to high mortality and limited survival. This study aimed to evaluate the safety and effectiveness of curative esophagectomy in elderly patients with esophageal cancer. This study included 77 and 112 patients with esophageal cancer aged ≥ 70 and 40-64years, respectively, who underwent R0 esophagectomy between January 1998 and December 2016. Patient characteristics, intraoperative outcomes, postoperative complications, and long-term survival were compared. The proportions of comorbid diseases (85.7% vs. 57.1%; P < 0.001), the American Society of Anesthesiologists score (1/2/3; 2.6%/94.8%/2.6% vs. 42.9%/57.1%/0%; P < 0.001), the preoperative systemic inflammation score (SIS) (0/1/2; 20.8%/48.1%/31.2% vs. 38.4%/38.4%/23.2%; P = 0.036), and postoperative complications (Clavien-Dindo grade ≥ III) (33.8% vs. 20.5%; P = 0.041) were significantly higher in the elderly group than those in the non-elderly group. However, long-term overall survival (OS) and relapse-free survival were not significantly different between the groups. On multivariate analysis, SIS (hazard ratio, 3.06; P = 0.037) and severe postoperative complications (hazard ratio, 2.01; P = 0.039) were significantly correlated with OS in the elderly group. As SIS and severe postoperative complications lead to poor prognosis after R0 esophagectomy in elderly patients, selecting appropriate patients for esophagectomy and preventing severe postoperative complications is essential.

Esophageal Cancer in Elderly Patients, Current Treatment Options and Outcomes; A Systematic Review and Pooled Analysis.

Simple SummaryAny given treatment may provide improve survival for elderly patients with oesophageal cancer compared to best supportive care. Although surgery may be related to a higher rate of complications in these patients, it also offers the best chance for survival, especially when combined with perioperative chemo-or chemoradiation. Definitive chemoradiation remains also a valid and widely used curative approach in this population. Quality of life after oesophageal cancer treatment does not seem to be particularly compromised in elderly patients, although the risk of loss of autonomy after the disease is higher. Based on the available data, excluding a priori elderly patients from curative treatment based on age alone cannot be supported. A thorough general health status and geriatric assessment is necessary to offer the optimal treatment, tailored to the individual patient.Esophageal cancer, despite its tendency to increase among younger patients, remains a disease of the elderly, with the peak incidence between 70–79 years. In spite of that, elderly patients are still excluded from major clinical trials and they are frequently offered suboptimal treatment even for curable stages of the disease. In this review, a clear survival benefit is demonstrated for elderly patients treated with neoadjuvant treatment, surgery, and even definitive chemoradiation compared to palliative or no treatment. Surgery in elderly patients is often associated with higher morbidity and mortality compared to younger patients and may put older frail patients at increased risk of autonomy loss. Definitive chemoradiation is the predominant modality offered to elderly patients, with very promising results especially for squamous cell cancer, although higher rates of acute toxicity might be encountered. Based on the all the above, and although the best available evidence comes from retrospective studies, it is not justified to refrain from curative treatment for elderly patients based on their age alone. Thorough assessment and an adapted treatment plan as well as inclusion of elderly patients in ongoing clinical trials will allow better understanding and management of esophageal cancer in this heterogeneous and often frail population.

Prognostic Significance of the L3 Skeletal Muscle Index and Advanced Lung Cancer Inflammation Index in Elderly Patients with Esophageal Cancer.

ObjectiveTo evaluate the correlation between the advanced lung cancer inflammation index (ALI) and the L3 skeletal muscle index (L3SMI) and their prognostic value in elderly patients with esophageal cancer (EC).Materials and MethodsThe clinical data of 158 elderly patients with EC were collected retrospectively. The L3SMI measures the area of skeletal muscle at the level of the third lumbar (L3) vertebra using computed tomography (CT). A high L3SMI and low L3SMI group were created using sex-based quartiles. The ALI, prognostic nutrition index (PNI), and geriatric nutrition risk index (GNRI) were calculated according to standard laboratory protocols.ResultsThe CT diagnostic criteria for senile sarcopenia in South China are height ≤32.96 cm2/m2 for females and height ≤35.4 cm2/m2 for males. The logistic regression analysis showed that a low L3SMI was significantly associated with a low ALI. Survival analysis revealed EC patients with a low L3SMI and a low ALI had poorer overall survival (OS) than patients with a high L3SMI and a high ALI. Univariate and multivariate Cox analyses showed that the L3SMI and ALI were independent predictors of EC prognosis in elderly individuals.ConclusionThere was a significant correlation between the PNI, GNRI, ALI, and L3SMI. Overall, our findings show the L3SMI and ALI are clinical indicators that can potentially be used to independently predict the prognosis of elderly EC patients and display good predictive value.