|Ahead of print
Chemo-radiation outcomes for esophageal cancer: A reflection from a tertiary cancer centre on selection of patients for more aggressive therapy
Janaki Gururajachar Manur1, MG John Sebastian2, Savitha Mary David3
1 Department of Radiation Oncology, M.S Ramaiah Medical College and Hospital, Bengaluru, Karnataka, India
2 Department of Radiation Oncology, St Johns Medical College, Bengaluru, Karnataka, India
3 Department of Radiation Oncology, Shankara Cancer Hospital, Bengaluru, Karnataka, India
Janaki Gururajachar Manur,
Department of Radiation Oncology, M.S Ramaiah Medical College and Hospital, Bengaluru, Karnataka
Source of Support: None, Conflict of Interest: None
INTRODUCTION: Most esophageal cancer patients present with poor nutritional status and may not tolerate radical treatment.
AIM: We aim to identify patients who are good candidates for chemo-radiation (CTRT).
MATERIALS AND METHODS: Fifty-four patients treated with CTRT were followed up for a mean period of 28 months and factors affecting the outcome were analyzed along with the recurrence pattern.
RESULTS: Forty-eight patients (88%) received CTRT and all completed treatment as scheduled. Eighteen (32%), 15 (27%) patients were alive with and without disease, respectively, at 28 months while 20 (37%) were dead. There was no statistically significant correlation between local failure and any of the factors like length, grade of the tumor, and chemotherapy received.
CONCLUSION: Esophageal cancer patients present at an advanced stage and hence careful selection of patients for radical CTRT is very important for providing relatively longer disease-free interval. Equally important is the close monitoring of patients during treatment which helps in completing the planned treatment which translates into a better long-term outcome.
Keywords: Chemo-radiation, esophageal cancer, outcome
|How to cite this URL:|
Manur JG, John Sebastian M G, David SM. Chemo-radiation outcomes for esophageal cancer: A reflection from a tertiary cancer centre on selection of patients for more aggressive therapy. Indian J Cancer [Epub ahead of print] [cited 2020 Jan 17]. Available from: http://www.indianjcancer.com/preprintarticle.asp?id=275396
| » Background|| |
Around 47,000 new esophageal cancer cases are reported each year and about 42,000 die every year in India. Almost 40% of patients of esophageal cancer patients present with metastatic disease and the 5-year survival rates with curative surgery and/or radiotherapy for non-metastatic disease has improved from 10% to 37% between 1970 and 2000. The outcome varies across globe and it reflects not only the incidence and expertise but also various patient and tumor-related factors. Out of 100 non-metastatic patients around half will be inoperable, 30 will be potentially resectable, and only 18 will undergo curative surgery. Trimodality treatment of neo-adjuvant chemo-radiation (CTRT) followed by surgery is the standard as of now for lesions which are 5 cm and beyond upper esophageal sphincter. It consists of CTRT followed by surgery for node negative patients resulting in a significant (P < 0.05) higher local control although there is no improvement in survival.
Surgery is the primary treatment but the associated pulmonary disease, compromised nutritional status with weight loss complicates postoperative recovery. Radiotherapy alone has dismal result as seen in RTOG 8501. Addition of chemotherapy to radiation and reserving surgery for non-responders has been tried in RTOG 0426. Over a period of three years based on tumor board decisions in our department, a group of patients not fit for trimodality treatment but otherwise suitable for radical treatment were treated with concurrent CTRT. This retrospective observational study is an effort to understand the pattern of presentation and to reflect upon the factors which affect the outcome.
Also, it is an attempt to propose different ways of overcoming the difficulties in the treatment of esophageal cancer in our country.
| » Materials and Methods|| |
Between January 2013 and December 2015, a total of 151 patients of squamous carcinoma of esophagus were registered in the department of Radiotherapy. Following tumor board decision, five patients were taken up for trimodality treatment and 61 patients were taken up for radical CTRT. Seven of these patients either discontinued treatment or requested reference to a hospital near their place. Hence a total of 54 patients were analyzed. After a thorough history taking and a detailed clinical examination, all patients underwent baseline hematological tests to assess the general condition and the status of associated co morbidity. All patients also underwent an endoscopy guided biopsy and contrast enhanced CT scan of the chest. Three patients had PEG placement outside our hospital for absolute dysphagia and prophylactic feeding procedure was not routinely performed.
A detailed counselling and informed consent was taken and radiation was planned. After aquaplast immobilization, patients underwent CT simulation with oral contrast from mandible till 2nd lumbar vertebra. Radiological detected gross primary and nodes were included as GTVP, three cm cephalocaudal and one cm circumferential expansion was given for CTV excluding pleura and pericardium. A PTV of seven mm was created and one cm expansion GTV was given for boost. All patients were treated to a dose of 4500 cGy in 25 fractions to gross disease with margins while the gross tumor received additional 540 cGy in three fractions as boost. Concurrent chemotherapy was given to patients who had a KPS of minimum 70. Chemotherapy used was either single agent cisplatin and carboplatin paclitaxel combination given once a week during the course of radiation. Patients who were elderly, frail, and had uncontrolled co morbidities were decided in the multidisciplinary joint clinic for single agent chemotherapy. Patient's weight was checked before the beginning of treatment and at the end and percentage of weight loss was calculated.
Patients were monitored weekly once for acute reactions during treatment and at two weeks after completion of treatment. Subsequently they were followed up once a month for six months, once every two months for a year and once in three months later. Follow up included clinical examination; weight recording and investigations were done only if clinical examination was suspicious for recurrence.
Study end points and statistical methods
Overall survival, disease free survival and recurrence patterns at a median follow up of 28 months were looked into. Descriptive statistical tabulation was carried out using Microsoft excel and the statistical software SPSS IBM version 18 2009 was used for analysis of the data. Fisher exact test was used as the sample size was less to analyze impact of various factors on the outcome and P value of <0.05 was considered significant.
| » Results|| |
A total of 54 patients were the subjects of this analysis. Patient characteristics are as shown in [Table 1]. The length of the lesion was less than five cm in 30 patients while 21 patients had the tumor between six and nine cm. Since only three patients had tumors of more than 10 cm, they were not included while testing for correlation between length and the failure. Single agent Cisplatin was used in all 10 patients who were above 70 years and six patients who were frail and no chemo was used for six patients.
Radiotherapy alone was used in 6 (11.11%) patients. All patients completed radiotherapy as scheduled. Most commonly used chemotherapy was weekly cisplatin and patients received a minimum of three and a maximum of five cycles. A combination of paclitaxel, carboplatin, and cisplatin, 5-fluorouracil was used for nine and seven patients, respectively. Weight loss during treatment of less than 10% and more than 10% was seen in 38 and 16 patients, respectively. All patients were seen once a week for assessment of nutrition and advised Ryles tube placement when required. Our observation was that most patients are reluctant in spite of counseling.
Outcome and correlation
At a median follow up of 28 months 20 (37.03%) were dead and 33 (61.11%) were alive and one patient was lost to follow up [Table 2]. Nine patients had local failure and nine patients had distant metastasis. One patient who failed systemically also had local failure. Out of the 20 patients who were dead, 12 patients died due to various other factors. Eighteen patients were alive with disease. We tried correlating various factors such as length of the lesion, administration of chemotherapy, grade of the tumor, weight loss during treatment, and association of distant metastasis with occurrence of local failure. None of these factors had any significant correlation with local failure [Table 3].
|Table 2: Showing survival/Recurrence pattern at 28 months of median follow up|
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| » Discussion|| |
This study is a retrospective analysis of esophageal squamous cancer patients treated with radical radiation with or without concurrent chemotherapy. The purpose was to see if our patients are different in terms of presentation, tolerance to chemoradiation, and to compare the outcome at a decent period of follow up with the available literature.
Although we had seen 151 patients during the study period, 85 (56.9%) patients had an advanced disease either with metastasis, uncontrolled systemic diseases or poor nutritional reserve, and hence were taken up for best supportive care or palliation. In the Dutch study by Van Hagen et al., it was seen that only 44% of the patients were fit for radical treatment of either CTRT followed by surgery or upfront surgery. This reflects that world over the patient characteristics are probably similar and 63% of our patients were from poor socioeconomic status. It is interesting to note that all these patients had a maximum tumor length of 6 cm and a minimum KPS of 90, which goes to say that stringent selection of patients is the most important aspect of treatment decision. All our patients were jointly assessed in the tumor board. Since most patients were from lower socio-economic status and did not have any insurance, affordability was also considered apart from all other factors in making treatment decision.
Outcomes of treatment
We have tried to compare our results with those from the French group, Japanese group and from our own country. Initial efforts to improve the results were seen by Cooper et al. where Cisplatin and 5-fluorouracil were used along with radiation in a randomized prospective trial and the results were impressive with a 5-year survival of up to 26%. Associated acute side effects were severe in the chemo arm probably because patients with a KPS as less as 50 were also included and the study was conducted between 1985 and 1990. Subsequently the same combination was used in JCOG 9906 between 2000 and 2002. A median survival at 3 years of 44.7% with a DFS of 32.9% was seen as opposed to 60% and 27.7% in our patients at 28 months. It is to be noted that radiation used was split course with a 2 weeks rest to a total dose of 60 Gy. The acute grade 3/4 toxicities were as high as 17%, probable reason being the use of cisplatin and 5 FU as opposed to cisplatin alone in our study and all our patients completed the radiation schedule on time.
Bendenne et al. in a phase III randomized observed that definitive chemo-RT was superior to trimodality in terms of median survival (19.3 vs 17.7 months, 2 years survival (40% vs 34%) with a 3-month treatment related morality (0.8% vs 9%, P = 0.002). They concluded that addition of surgery does not improve the results but actually increases the complications.
The Cochrane database analysis comparing addition of surgery to CTRT showed little or no difference (HR0.99, P = 0.92) in overall survival but improved freedom from locoregional relapse (HR 0.55, P = 0.0004), however there was increased the risk of treatment-related mortality (RR 5.11, P = 0.003). The authors concluded that addition of surgery did not have overall benefit.
Looking at the data from India, Bhandari et al. in a prospective study of 31 inoperable patients had used CTRT with weekly cisplatin of 30 mg/m2 and radiation to a dose of 60 Gy/30 Fr and observed a 35.5% survival at 2 years. Their patient characteristics, the toxicity profile, and recurrence rates were similar to that of ours.
Correlation with outcome
The best results are observed in selected group of patients with a short segment of involvement, good performance status, less weight loss. Compared to western data, our patients had longer tumor, greater weight loss at presentation and were from lower socio-economic status. We did not observe any significant correlation between local failure and any of the factors that we studied such as the length of the lesion, grade of the tumor, distant metastasis, and chemotherapy received, probable reason being small number of patients.
Jae et al. tried to see predictive factors for local recurrence among 61 patients who had pathological complete response to preoperative CTRT followed by surgery. Lymph node involvement and pre-treatment weight loss of more than 2 kg predicted lesser control by 13%. Almost all our patients could not provide us the pre-treatment weight loss which reflects the socioeconomic status; however, we looked into the weight loss during treatment indicating tolerance to treatment. Despite many patients being from poor socioeconomic status (63%), only on third had a weight loss of more than 10% during therapy which implies that even though their reserves were compromised the care during treatment becomes very important to see that they tolerate the treatment well. Affordability takes a back seat in selection of patients for a costlier treatment as at present most patient's treatment cost is covered under various schemes.
| » Strength and Limitations|| |
This study helps us to define the factors based on which selected patients can be chosen for radical treatment. Limitations are, first, it's a retrospective study and, second, the patient number is small. Presently, the multidisciplinary tumor board is in place and helps us to choose the right patient for trimodality treatment and unless there is a randomized study, the results cannot be compared.
It's important to note that over three years only 8% of our patients were suitable for trimodality treatment and at this time of writing this article more patients are being treated with the same at our place.
Since most of our patients are form lower socio-economic background, the follow up included clinical assessment only and imaging was done as and when required. Hence, it was not possible to objectively assess the response. Despite these limitations our work does throw light on the fact that our patients do tolerate concurrent CTRT and the results are similar to other authors. It is prudent to use concurrent CTRT as a definitive treatment and surgery should be reserved for highly selected patient and non-respondersto CTRT. This will ensure optimal control with acceptable sequelae especially when nutrition is compromised and hence better therapeutic ratio. Possibly, the approach can be improved once the results of the pre-SANO trial comes out which addresses selection of particular group of patients who are likely to fail after CTRT in whom surgery can be added.
| » Conclusion|| |
With our experience and the available data, we understand that esophageal cancer patients have poor reserve and carry dismal outcome and hence stringent selection of patients for trimodality should be done, otherwise radical CTRT also provides relatively longer disease-free interval. Equally important is the close monitoring of patients during treatment which helps in completing the planned treatment which translates into a better long-term outcome.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]