|Ahead of print publication
Acute treatment-related toxicity in elderly patients with good performance status compared to young patients in locally advanced esophageal carcinoma treated by definitive chemoradiation: A retrospective comparative study
Shweta Mohata1, HS Kumar1, Neeti Sharma1, Shankar Lal Jhakhar1, Surendra Beniwal2, Kamlesh Kumar Harsh1
1 Department of Radiotherapy, Acharya Tulsi Regional Cancer Treatment and Research Institute, Bikaner, Rajasthan, India
2 Department of Medical Oncology, Acharya Tulsi Regional Cancer Treatment and Research Institute, Bikaner, Rajasthan, India
|Date of Submission||21-Dec-2018|
|Date of Decision||15-Apr-2019|
|Date of Acceptance||11-Sep-2019|
|Date of Web Publication||27-Feb-2020|
Department of Radiotherapy, Acharya Tulsi Regional Cancer Treatment and Research Institute, Bikaner, Rajasthan
Source of Support: None, Conflict of Interest: None
Introduction: The benefit of definitive chemoradiotherapy (CRT) in elderly patients with locally advanced esophageal cancer is not well established. We perform a single institutional retrospective study of CRT in terms of toxicity in elderly patients (age more than 60 years) as compared with young cohort (age <60 years) in locally advanced nonmetastatic esophageal cancer.
Patients and Methods: A total 145 of patients, 79 in young age (Group A) and 66 patients of elder age (Group B) with Stage II and III squamous cell carcinoma of the esophagus with ECOG PS of 0–1, who had undergone definitive CRT at our institute from January 2015 to November 2018 were selected for this analysis. Chemotherapy was cisplatin (40 mg/m2) given concurrently on weekly basis with radiotherapy (RT). Total prescribed dose of RT was 50.4 Gy at the rate of 1.8 Gy per fraction. Median age was 40 years (25–60 years) and 65 years (60–75 years) in young and elderly group, respectively. Follow-up is done at median of 28 months (1–48 months) after treatment.
Results: Acute Grade 2–3 esophagitis was seen in 48.10% in young cohort, while it was 60.6% in older group. Grade 2–3 nausea and vomiting was seen in 32.91% in young age patients, while it was 45.5% in elder patients. No statistically significant difference is seen in acute treatment-related toxicity in young and elderly group.
Conclusion: Our conclusion is that patients with adequate functional status should not be excluded from curative CRT based on age alone.
Keywords: Chemoradiotherapy, elderly patients, esophageal cancer, treatment-related toxicity
|How to cite this URL:|
Mohata S, Kumar H S, Sharma N, Jhakhar SL, Beniwal S, Harsh KK. Acute treatment-related toxicity in elderly patients with good performance status compared to young patients in locally advanced esophageal carcinoma treated by definitive chemoradiation: A retrospective comparative study. J Can Res Ther [Epub ahead of print] [cited 2020 Apr 1]. Available from: http://www.cancerjournal.net/preprintarticle.asp?id=279646
| > Introduction|| |
Esophageal cancer is the eighth most common cancer worldwide with an estimated 456,000 new cases diagnosed in 2012 with highest incidence and mortality in Asian and African countries. Fewer than 1 million cases occur per year in India. Esophageal cancer is the fourth common cause of cancer-related deaths in India. It is prevalent among both men and women. Squamous cell carcinoma (SCC) accounts for up to 80% of these cancers. Radiation oncologists increasingly face elderly patients of esophageal cancer, one of the reasons being prolongation of life expectancy. Approximately two-third of cancer-related death occur in elderly patients of age >60 years. Management of elderly patients with cancer is a therapeutic challenge because of associated comorbidities and poor functional reserve as compared to young patients, because of that they prefer less intensive treatment and wish to avoid surgery including surgery. Definitive chemoradiotherapy (CRT) could be the treatment of choice in this group of patients. RTOG 85-01 has established the superiority of chemoradiation to radiotherapy (RT) alone in terms of 5-year overall survival (26% vs. 0%) and median survival (12.5 vs. 9 months). However, only 23% of >70 years were taken in the study. A series of study shows definitive CRT will have more acute and chronic treatment-related toxic side effects. As not many studies are available for comparison in these groups of patients, the aim of our study is to assess the treatment-related major toxicity of squamous esophageal cancer in patients of age >60 years as compared to young population of age <60 years, undergoing definitive CRT.
| > Patients and Methods|| |
A total of 145 patients of nonmetastatic squamous cell esophageal cancer were treated with definitive CRT at ATRCTRI, Bikaner, Rajasthan, between January 2015 and November 2018. Patients inclusion criteria were (1) ECOG 0–1, (2) clinical Stage II and III based on AJCC-TNM classification in practice at the time of diagnosis, (3) histologically confirmed squamous cell esophageal carcinoma, (4) no prior therapy, (5) no history of concurrent or previous malignancy, (6) complete and retrievable records, (7) patients received prescribed curative RT dose, and (8) patients taken at least four cycles of concurrent chemotherapy. Patients were treated with weekly cisplatin chemotherapy concurrent with RT. All patients were strictly monitored for any treatment-related toxicity during the treatment.
All patients were undertaken for initial workup which included complete history; physical examination; routine blood investigations such as complete blood count, liver function test, and renal function test; barium swallow; upper gastrointestinal endoscopy (UGIE) with biopsy; contrast-enhanced computed tomography (CECT) scan thorax and abdomen; and ultrasound abdomen and pelvis as per need. All patients were checked for viral markers (HIV, HBsAg, and HCV) routinely. Tumor baseline characteristics were collected as much as possible (Location, length, diameter, histology, nodal involvement, involvement of surrounding structures, any metastasic lesion). TNM staging was done according to AJCC guidelines in practice at the time of diagnosis.
Cisplatin (40mg/m2) was given concurrently with radiotherapy to all patients on weekly basis with standard premedication and adequate hydration. Application of CRT was performed after careful evaluation of organ function, performance status, after sensitivity testing, and severity of comorbidities. Dose modification of chemotherapy was considered if any Grade 3 hematological or gastrointestinal (GI) toxicity occur. Treatment was stopped at Grade 4 toxicities. Radiation therapy was delivered by telecobalt machine (Bhabhatron II (Panacea medical technologist, India), Theratron, 780C and 780 E, Team Best, Canada). Radiation was given at 1.8 Gy per fraction 5 days in a week. Target volume was 3–5 cm superior and inferior and 2.5–3 cm radially to tumor bulk as seen on endoscopy or imaging. Total prescribed dose was 50.4 Gy to target volume in at 1.8 Gy per fraction.
Evaluation of response and toxicities
During the whole treatment, all patients were under strict vigilance for any treatment-related local or systemic toxicities. All patients were seen on weekly basis during the treatment. National cancer institute, common terminology criteria for adverse events (CTCAE, version 4.0) was used to score treatment toxicities.
Patients were divided into two groups according to age; Group A – Young patients of age <60 years and Group B – Elderly patients with good performance status of age more than 60 years. Chi-square test was done on all confounding factors, with a two-sided significance value of 0.05.
| > Results|| |
Patient and tumor characteristics
Median age was 65 years (range 60-75 years) in elderly group and 40 years in younger group (range 25-60 years). There were 85 male and 60 female patients. All patients had a good performance status ECOG 0–1. All 145 patients had histologically proven SCC, Out of which 16 were well-differentiate (A=10, B=06), 89 were moderately differentiated (A=46, B=43), 19 were poorly differentiated (A = 10, B = 9), and 21 patients had unknown differentiation (A=13, B=8). All patients were of clinically Stage II/III by barium swallow, UGIE, or CECT scan. Baseline characteristics are listed in [Table 1].
A total of 86.21% (total n = 125; A = 62/B = 63) patients were having dysphagia grade >2. Weight loss was noted in 81.38% (total n = 118; A = 56/B = 62) of patients of mean weight loss of >10% from baseline (range of 5–25 kg). A total of 43 (A = 20/B = 23) patients received Ryles tube feeding and 2 (A = 1/B = 1) patients require feeding jejunostomy before treatment for nutritional support [Table 2].
Additional 38.62% (total 56; A = 26/B = 30) patients require Ryles tube feeding during treatment [Table 3]. Routine blood investigations done before each cycle of chemotherapy and were analyzed for assessment of hematological toxicity. Highest hematological and GI toxicity of Grade 2–3 were noted in 68.2% (total n = 99; A = 44/B = 55) patients and require hospitalization with symptomatic therapy during treatment. Distribution of acute treatment related toxicity grade 2/3 in both groups is shown in [Table 4]. Treatments have to be delayed for more than 1 week in these patients, but finally, they completed the treatment [Table 3]. No treatment-related deaths were seen during treatment.
| > Discussion|| |
Esophagus presenting at mean age group is approximately 67.3 years (Dale et al., 2003,) and they present with late Stage of III or IV. Based on several clinical trials, CRT has been the standard treatment for locally advanced esophageal carcinoma (LAEC), and it is superior to RT alone.,,,,,, Despite the increasing incidence of late age group presentation of esophageal cancer, very few studies have been done on this particular subject. Because of associated co-morbid conditions tolerance of aggressive CRT therapy may be restricted in geriatric group of patients.
National cancer data base review, 2017, shows that elderly patients should not be deprived of treatment that may improve their survival, but they are less likely to receive aggressive therapy.,
Tougeron et al., 2008, evaluated tolerance and outcome of 109 elderly patients older than 70 years treated with cisplatin-based CRT for nonmetastatic esophageal cancer. Toxicity of grade >3 was seen in 23.8%. They also suggest that CRT can be given in elderly patient without major toxicity.,
Zhang et al., 2014, suggest that elderly patients with esophageal SCC could benefit from CRT without much toxicities, but their study has no survival benefit in age >72 years with CRT as compare to RT alone.
Our study suggests that in LAEC cisplatin-based CRT regimen is as tolerable in old age group patients as in young population of <60 years of age. The mean age is 25–75 years. We found that this regimen could be an alternative for esophageal cancer patients who cannot tolerate standard CRT regimen of cisplatin, 5-FU especially, elderly patients who cannot tolerate surgical morbidity and have associated comorbid conditions. This regimen has low and manageable hematologic, GI toxicity.
| > Conclusion|| |
Geriatric group should have proper treatment and have not to modify treatment just because of their perception of increased toxicity. We are showing the comparable result outcome in elderly patients as to younger population. As our study is retrospective, minor nonhematologic toxicities were not recorded and hence not reported. Limitation of our study is small sample as well as retrospective in nature.,
Financial support and sponsorship
Conflicts for interest
There are no conflicts for interest.
| > References|| |
International Agency for Research on Cancer. Globocan 2012:Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. International Agency for Research on Cancer (WHO); Dec 2013.
Herskovic A, Martz K, al-Sarraf M, Leichman L, Brindle J, Vaitkevicius V, et al.
Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med 1992;326:1593-8.
Dale DC. Poor prognosis in elderly patients with cancer: The role of bias and undertreatment. J Support Oncol 2003;1(4 Suppl 2):11-7.
Bedenne L, Michel P, Bouché O, Milan C, Mariette C, Conroy T, et al.
Chemoradiation followed by surgery compared with chemoradiation alone in squamous cancer of the esophagus: FFCD 9102. J Clin Oncol 2007;25:1160-8.
Di Fiore F, Lecleire S, Galais MP, Rigal O, Vié B, David I, et al.
Impact of radiation schedule and chemotherapy duration in definitive chemoradiotherapy regimen for esophageal cancer. Gastroenterol Clin Biol 2006;30:845-51.
Anderson SE, Minsky BD, Bains M, Hummer A, Kelsen D, Ilson DH, et al.
Combined modality chemoradiation in elderly oesophageal cancer patients. Br J Cancer 2007;96:1823-7.
Coia LR, Minsky BD, Berkey BA, John MJ, Haller D, Landry J, et al.
Outcome of patients receiving radiation for cancer of the esophagus: Results of the 1992-1994 patterns of care study. J Clin Oncol 2000;18:455-62.
Minsky BD, Neuberg D, Kelsen DP, Pisansky TM, Ginsberg RJ, Pajak T, et al.
Final report of intergroup trial 0122 (ECOG PE-289, RTOG 90-12): Phase II trial of neoadjuvant chemotherapy plus concurrent chemotherapy and high-dose radiation for squamous cell carcinoma of the esophagus. Int J Radiat Oncol Biol Phys 1999;43:517-23.
Seitz JF, Milan C, Giovannini M, Dumas F, Cauvin JM, Conroy T, et al.
Concurrent concentrated radio-chemotherapy of epidermoid cancer of the esophagus. Long-term results of a phase II national multicenter trial in 122 non-operable patients (FFCD 8803). Gastroenterol Clin Biol 2000;24:201-10.
Stahl M, Stuschke M, Lehmann N, Meyer HJ, Walz MK, Seeber S, et al.
Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus. J Clin Oncol 2005;23:2310-7.
Tougeron D, Di Fiore F, Thureau S, Berbera N, Iwanicki-Caron I, Hamidou H, et al.
Safety and outcome of definitive chemoradiotherapy in elderly patients with oesophageal cancer. Br J Cancer 2008;99:1586-92.
Tougeron D, Hamidou H, Scotté M, Di Fiore F, Antonietti M, Paillot B, et al.
Esophageal cancer in the elderly: An analysis of the factors associated with treatment decisions and outcomes. BMC Cancer 2010;10:510.
Zhang P, Xi M, Zhao L, et al
. Is there a benefit in receiving concurrent chemoradiotherapy for elderly patients with inoperable thoracic esophageal squamous cell carcinoma?. PLoS One 2014;9:e105270. doi:10.1371/journal.pone.0105270.
[Table 1], [Table 2], [Table 3], [Table 4]