1. A Study to predict stenosis in Esophageal Cancer patients after definitive radiation therapy
Venkata Krishna Reddy P* Simon Pavamani*,Selvamani B*, A.J Josepha, Reuben Thomas Kuriena Leena R.V^, Antonisamy B+
*Department of Radiation Oncology, a Department of Gastroenterology, ^ Department of Radiology, + Department of Biostatistics, Christian Medical College and Hospital, Vellore.

2. Background Esophageal cancer has a poor prognosis
As survival rates are low, Quality of life is one of the aims of treatment.
Multimodality approach – treatment of choice
For patients who are inoperable or refusing surgery – Definitive chemoirradiation
Dysphagia – distressing complication of radiation therapy

3. Dysphagia decreases quality of life
Various tumour and treatment factors have been responsible for esophageal stenosis following definitive radiation therapy.
There are limited studies for evaluation of frequency and severity of esophageal stenosis following radiation therapy

4. Aim
To identify the incidence of esophageal stenosis and risk factors causing stenosis following definitive radiation therapy
To formulize an equation for prediction of esophageal stenosis based on the risk factors
To assess the dysphagia scores before and after RT in the patients who were prospectively analyzed

5. Methodology Retrospective and Prospective Observational study
Retrospective data – January 2008 to February 2013.
Prospective data – February 2013 to August 2013
Includes data from esophageal cancer patients seen in Department of Radiation Oncology Unit I.

6. Inclusion criteria
All patients who underwent definitive radiation therapy for esophageal cancer
(External beam RT +/- Intraluminal RT with or without chemotherapy)

7. Variables used for prediction of esophageal stenosis
Tumour stage – CT imaging (<T4 vs T4)
Wall Thickness – CT imaging (<20 mm vs >20mm)
Tumour length - CT imaging; (<8 cm vs > 8 cm)
Circumference of the esophageal wall involved – CT imaging ( involvement of full circumference vs partial involvement)
Scope negotiability prior to radiation therapy (Yes vs No)

8. Assessment of the outcome – Esophageal stenosis
Stenosis of the esophagus was assessed objectively whether the endoscope could be passed through the esophagus
Endoscope diameter was 9 mm
15 mm is the esophageal luminal diameter required for swallowing without dysphagia

9. Statistical analysis
Sample size was calculated on the principle of one variable in multivariate analysis for every 10 patients with the outcome of interest
Expected rate of stenosis was 50 %
100 patients were recruited both prospectively and retrospectively

10. In univariate analysis – chi-square test was performed
In Multivariate analysis – logistic regression analysis was performed
Bootstrapping method was done for the validation of the results
Prediction formula was derived based on the β co-efficients obtained from the odds ratios

11. Results Could not be analysed
(Dept of Radiation Oncology, Unit I, From January 2008 to August 2013 )
Received Definitive Radiation Therapy
100 esophageal cancer patients
75 patients had follow up
Assessed for the development of esophageal stricture and its risk factors
72 patients
Had no pre-treament imaging or follow up Scopy
3 patients
25 patients - Lost to follow up
Could not be analysed

12. Median follow up period of the patients was 6 months (Range: 3 to 56 months)
Of the 72 patients, 31 patients (43%) had esophageal stenosis following definitive RT

13. Tumour Characteristics-Univariate Analysis
Tumour Charactersitics
No of Patients
p value
Without Stenosis
With Stenosis
Not F/u
Tumour Stage
<T4 T4 23 18 6 25 14
0.002
Tumour length
<8 cm
>8 cm 35 21 10 24 4
0.075
Wall Thickness
<20 mm
>20 mm 30 11 13 15
0.616
Circumference
Invovled
Full
Partial 31 1 5
0.013
Scope Neg
Yes No 32 9 16
0.009

14. Tumour Charactersitics Variables Used in the study
Cont ..
Tumour Charactersitics
Variables Used in the study
p value
Periesophageal
Extension
Present or Absent
0.139
Type of RT
Co-60, Linac Radical, 3DCRT, IMRT
0.721
Total Duration of RT
< 50 days or > 50 days
0.208
Interval Between EBRT and ILRT
< 7 days , 7 days or more
0.954
Concurrent Chemotherapy
Yes or No
0.326

15. Multivariate analysis
Tumour Charactersitics OR
95 % C.I
p value
p value – Univariate Analysis
Tumour Stage
<T4 (ref) T4
1.88
0.03
0.002
Tumour length
<8 cm(ref)
>8 cm
0.62
0.09
0.075
Wall Thickness
<20 mm (ref)
>20 mm
1.70
0.45
0.616
Circumference
Invovled
Full
Partial (ref)
0.88
0.013
Scope Neg
Yes
No (ref)
1.65
0.15
0.009

16. The ‘Goodness of Fit’ for multivariate analysis was 0.70
It suggests that the results are valid

17. Bootstrapping method
Novel technique which resamples the parent cohort multiple times and tests the valediction of the results from the multivariate analysis

18. Bootstrapping Statistics (n=1000)
Tumour Charactersitics OR
95 % C.I
Std. Err.
Tumour Stage
<T4 (ref) T4
1.90
0.364
Tumour length
<8 cm(ref)
>8 cm
1.70
1.443
Wall Thickness
<20 mm (ref)
>20 mm
0.90
1.369
Circumference
Invovled
Full
Partial (ref)
5.18
0.777
Scope Neg
Yes
No (ref)
0.62
0.354

19. Prediction formula for esophageal stenosis
Variable
Odds Ratio (OR)
β coefficients
Staging
1.8881
0.6356
Scope Negotiation
0.6266
Tumour Length
1.0705
0.5340
Wall thickness
0.9079
Circumference involved
5.1840
1.6455
Constant

20. Prediction equation:
= *staging *scopnego *length *wallthick *circumference
For staging :0– T1 to T3 stage
2 – T4 stage
For Scopenegotiability :2 – Scope negotiable prior to starting treatment
0 – Scope not negotiable prior to treatment
For Length :1 – If tumour less than or equal to 8 cm length
2 – If tumour more than 8 cm length
For Wallthickness :1 – If wall thickness less than or equal to 20 mm
2 – if wall thickness greater than 20 mm
For Circumference :1 – 1 to 3 quadrants involved
2 – 4 quadrants are involved

21. After substituting the variables in the equation, the resultant value will be between 0 and 1.
If the value is < less likelihood of formation of stenosis
If the value is between 0.5 and 1 – higher chance of stenosis

22. Dysphagia Scores before and after RT
S. No
Tumour Stage
Scope
Negotiability
Tumour length
Wall thickness
Circumference
Dysphagia Score** before RT
Dysphagia Score after RT
Stenosis after RT
Predicted
Value 1 T4 No
>8 cm
< 20 mm 4 3
3 (Remained Same)
Stenosis
0.80 2
Yes
>20 mm
2 (Improved)
0.59
<T4
<8 cm
3 (Improved)
No Stenosis
0.37
5 (Worsened)
0.78 5
<20mm
No stenosis
0.04 6
>20mm
3 (Worsened) 7
Scopy not done
0.40 8
0.48 9
4 (Remained Same)
Sopy not done
0.68
** Dysphagia Score based on Modified O’Rourke swallowing-status staging system

23. Operability Vs Stenotic rates
Total
OPERABLE
INOPERABLE
OUTCOME
NO STENOSIS
Count 11 30 41
STENOSIS 10 21 31
NOT FOLLOW UP 6 22 28 27 73
100

24. Of these 27 patients, who were operable and refused surgery, 10 patients had developed stricture after RT
4 out of 10 patients had complete response

25. Tumour response at follow up

26. Limitations of the study
Most of the patients recruited in the study were retrospectively analyzed
Scope negotiability was taken as indirect parameter to assess the dysphagia in the retrospective group

27. Conclusions
The incidence of stenosis in patients who came for follow up was 43 % (31 patients out of 72 patients).
The risk factors for the formation of esophageal stenosis following definitive radiation therapy are T4 stage tumours, scope not negotiable before initiation of treatment and tumour involving full circumference of esophageal wall
Tumour length greater than 8 cm showed a trend towards increased risk of stenosis

28. A formula to predict esophageal stenosis was derived which needs to be validated on a larger data set
Predicting the esophageal stenosis prior to radiation therapy may aid in selecting the best modality of treatment without compromising patient’s quality of life.
A prospective study with larger number of patients in whom dysphagia is assessed both patient reported dysphagia scores as well as endoscopy and imaging would be an ideal study to predict esophageal stenosis.

29. References
Atsumi K, Shioyama Y, Nakamura K, Nomoto S, Ohga S, Yoshitake T, et al. Predictive factors of esophageal stenosis associated with tumor regression in radiation therapy for locally advanced esophageal cancer. J. Radiat. Res. 2010;51(1):9–14.
Khurana R, Dimri K, Lal P, Rastogi N, Joseph K, Das M, et al. Factors influencing the development of ulcers and strictures in carcinoma of the esophagus treated with radiotherapy with or without concurrent chemotherapy. J Cancer Res Ther Mar;3(1):2–7.
Atsumi K, Shioyama Y, Arimura H, Terashima K, Matsuki T, Ohga S, et al. Esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer: frequency and prediction. Int. J. Radiat. Oncol. Biol. Phys Apr 1;82(5):1973–80.

30. Thank you