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FINDINGS:
From our study we observed that
1. Our patients who defaulted from surgery
following
Neoadjuvant
chemoradiotherapy(CT-RT)
had a significantly poorer local control rates
and disease free survival.
2. Neoadjuvant therapy didnt seem to increase
the sphincter preservation rates in our study.
3. The acute toxicity of CT-RT was within
reasonable limits in our patients and there
were no life
threatening
consequences during treatment.
4. In the short follow up period, the local control
rate was very good. Achieving a negative
margin status at the time of surgery was found
to be of significant importance in local
control.
5. The patients who completed the treatment as
prescribed had a Disease Free Survival
comparable with those reported in the
literature.
6. Even though the number of patients receiving
Neoadjuvant Chemoradiotherapy and surgery
was small, their outcomes was comparable to
those
who
underwent
adjuvant
Chemoradiotherapy.
7. Disease Free survival was found to be
significantly poorer in patients with higher
stage disease and positive resection margin
status.
8. Interestingly, though not of statistical
significance, patients receiving adjuvant 5Fluorouracil(5FU) appeared to perform better
when
compared
to those receiving
capecitabine.
METHODS:
INTERPRETATION:
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I. INTRODUCTION
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IV. METHODOLOGY
Patients with rectal adenocarcinomas who received
neoadjuvant or adjuvant chemo radiotherapy, meeting the
inclusion/exclusion criteria were identified from the radiotherapy
and/or medical records. The details of the patients were collected
as per the proforma from the records. The last follow up of the
patient was noted, and an attempt was made to contact the patient
if last follow up was more than 3 months ago.
RADIOTHERAPY:
Radiotherapy was administered to all patients as per the
protocol followed by the Department. 3-D Conformal
radiotherapy(3D-CRT) was planned for all patients after
appropriate immobilization in supine position using a
thermoplastic mould. All patients were treated with megavoltage
beams on a multiple energy ELEKTA Linear Accelerator, with
conventional fractionation (1.8 Gy or 2 Gy per fraction, one
fraction per day, five days per week). As per the
recommendations, external-beam treatment fields for rectal
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during
Grade 0
Grade 1
Grade 2
Grade 3
Grade 4
Grade 5
Week 1
20
41
Week 2
13
45
Week 3
50
11
Week 4
44
17
Week 5
48
14
Grade 0
Grade 1
Grade 2
Grade 3
Grade 4
Grade 5
Week 1
65
Week 2
47
15
Week 3
50
14
Week 4
52
Week 5
35
24
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Grade 2 or lower thrombocytopenia was experienced by 31 (47%) of patients by the end of treatment. No patient had > Grade 2
thrombocytopenia.
Table 3: Thrombocytopenia during chemoradiotherapy
Thrombocytopenia during CT-RT
Grade 0
Grade 1
Grade 2
Grade 3
Grade 4
Grade 5
Week 1
59
Week 2
49
18
Week 3
41
25
Week 4
38
28
Week 5
35
30
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Gastrointestinal Toxicity:
The incidence and severity of diarrhea progressively
worsened during the course of treatment. The incidence of Grade
3 Diarrhea was 9 % (6 patients), 30 % (20 patients) and 54 % (36
patients) in weeks 3, 4 and 5, respectively. By the completion of
treatment, all patients had at least Grade 1 small bowel toxicity.
One patient discontinued treatment after the 2nd week, citing poor
tolerance. She had Grade 2 diarrhea at the time of
discontinuation. The incidence and severity of gastrointestinal
103
Grade 0
Grade 1
Grade 2
Grade 3
Grade 4
Grade 5
Week 1
42
25
Week 2
20
32
15
Week 3
12
21
27
Week 4
17
26
20
Week 5
12
18
36
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Patterns of Recurrence
With a median follow up duration of 11.1 months (Range: 1.9 to 55.8 months), a total of 24 patients (36%) had recurrences. Nine
patients (13%) had local recurrence, 12(18%) patients had systemic recurrence and 3 (4%) had a simultaneous local and systemic
recurrence.
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No Recurrence
Recurrence
Total
Surgery +RT-CT
RT-CT - No surgery
Total
49 (73%)
6 (9%)
55 (82%)
3 (4%)
9 (14%)
12 (18%)
52 (77%)
15 (23%)
67 (100%)
Local recurrence
Yes
2 (4%)
1 (2%)
3 (6%)
Total
No
47 (90%)
2 (4%)
49 (94%)
49 (94%)
3 (6%)
52 (100%)
Pathological T stage: Out of 44 patients who underwent surgery prior to adjuvant RT-CT, all 3 local recurrences were in patients
with pT4a disease.
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Local recurrence
No (%)
5 (11%)
13 (30%)
23 (52%)
41 (93%)
pT2
pT3
pT4a
Total
Total
Yes (%)
0 (0%)
0 (0%)
3 (7%)
3 (7%)
5 (11%)
13 (30%)
26 (59%)
44 (100%)
Pathological N stage: Out of 21 patients with pN0 status, one patient had local recurrence, whereas two of 15 with pN1 disease
suffered a local failure. None of the eight pN2 patients had a loco-regional failure.
Table No. 8 Effect of pN Stage on local control (p = 0.782)
Pathological N stage
Local recurrence
No (%)
20 (45%)
6 (14%)
7 (16%)
6 (14%)
2 (5%)
41 (94%)
pN0
PN1a
pN1b
pN2a
pN2b
Total
Total
Yes (%)
1 (2%)
1 (2%)
1 (2%)
0 (0%)
0 (0%)
3 (6%)
21 (47%)
7 (16%)
8 (18%)
6 (14%)
2 (5%)
44 (100%)
Stage of disease after upfront surgery: One patient had local recurrence out of 21 patients with stage II disease, whereas 2 out
of 23 patients with stage III disease had loco-regional recurrence on follow up.
Table No. 9 Effect of Stage of disease on local control (p = 0.605)
Pathological
stage group
II
III
Total
AJCC
Local recurrence
No (%)
20 (45%)
21 (48%)
41 (94%)
Total
Yes (%)
1 (2%)
2 (5%)
3 (6%)
21 (47%)
23 (53%)
44 (100%)
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Histopathological grade: The estimated mean disease free survival was 48.7 months (CI: 39.3-58.1) for well differentiated
tumors, compared to 30.7 months (CI:23.1-38.2) and 31.2 months (CI: 9.3-53) for grade II and grade III tumors, respectively. The
difference was not statistically significant (p=0.49)
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Figure No. 25: Disease free survival based on grade of primary (Grade I: blue, Grade II: green, Grade III: brown)
Resection margin status: Negative resection margins significantly impacted on disease free survival; the patients with R0
resection had a mean survival of 41.1 months (CI: 33.8-48.5) compared to 11.5 months (CI: 8.4-14.7) for patients who had a R1
resection (p<0.0001).
Figure No. 26: Disease free survival based on margin status (Negative margins: blue, positive: green)
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Type of chemotherapy: The estimated mean disease free survival was 41.5 months (CI: 32.7-50.2) for 5FU-LV regimen,
compared to 24.1 months (CI:17.6-30.6) for capecitabine. The difference was not statistically significant (p=0.235). Nevertheless, of
the 8 patients treated with Neoadjuvant CT-RT prior to surgery, all the patients achieving pCR or yp Stage I received capecitabine.
Both the patients who received Neoadjuvant 5-FU chemotherapy had yp Stage III disease.
Figure No. 27: Disease free survival based on chemotherapy regimen (5FU-LV: blue, capecitabine: green)
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Stage of disease: As patients with Neoadjuvant therapy were few in numbers, analyses of the impact of stage of disease on
disease free survival data was limited to patients who underwent adjuvant therapy.
pT stage: The estimated Disease free survival at 2 years was 50% for pT2, 100% for pT3 and 52% for pT4a. The median
survival couldnt be calculated because of the censored data; however, the difference in survival was statistically significant
(p=0.036).
Figure No. 28: Disease free survival based on pT stage (pT2: blue, pT3: green, pT4a:brown)
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pN stage: The estimated mean disease free survival was 48.8 months (CI: 40.6-56.9) for pN0 tumors, compared to 24.1 months
(CI:17.8-30.4) and 16.6 months (CI: 10.3-22.9) for pN1 and pN2 tumors, respectively. The difference was statistically significant
(p=0.003).
Figure No. 29: Disease free survival based on pN stage (pN0: blue, pN1: green,pN2:brown)
pAJCC stage: The estimated median disease free survival was 54.6 months (CI: 6.4-102.8) for p stage II tumors, compared to
23.0 months (CI:3.4-42.6) for p stage III. The difference was statistically significant (p=0.002)
Figure No. 30: Disease free survival based on pAJCC stage (stage II: blue, stage III: green)
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VI. DISCUSSION
This observational study was conducted to identify the
outcomes of patients with rectal cancers undergoing chemoradiotherapy as a part of definitive treatment at our centre. A
total of 67 patients were found to be eligible during the study
period, between 2009 and 2013. Though a major cancer
worldwide, at our centre where head and neck, cervical and
breast cancers predominate, it constitutes a relatively small
proportion.
Of the 67 patients, 25 patients were females and 42 were
males. F:M ratio was 1:1.68. this difference is likely the result of
higher incidence of the disease in males. Age standardized
Female:Male incidence ratio of 1:1.35 has been reported for
colo-rectal cancers in the United States .(1)
In our study the median age of all the analyzable 67 patients
was 50 years (Range: 26-72 years). Median age of the female
cohort was 51 years (Range: 32-72 years). Median age of the
male cohort was 50 years (Range: 26-72 years). Age groups of
40-60 years constituted more than 50% of the patients in the
study. Age is a major risk factor for sporadic CRC. The
incidence begins to increase significantly between the ages of 40
and 50, and age-specific incidence rates increase in each
succeeding decade thereafter. (5) However, nearly 15% of our
patients were younger than 40 years.
By predominant location of primary, nearly 85% of our
patients had primary in the middle third or lower third rectum.
Location of primary impacts on the choice of treatment, and
potentially also on outcomes. Middle and lower third rectal
cancers are more likely to be considered for upfront chemoradiotherapy with an intent on organ preservation.
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VII. CONCLUSION
REFERENCES
[1]
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AUTHORS
First Author First Author Dr.Prahalad Elamarthi, Senior
resident, Sri Venkateswara Institute of medical
sciences(SVIMS), Tirupathi, Andhra Pradesh, India. E-mail:
prahalad_doc@yahoo.co.in
Second Author Dr. Donald J Fernandes, Prof and Head of
Department, Dept of Radiation oncology, Kasturba medical
college, Manipal. E-mail: donaldjf@gmail.com
Third Author Dr. Krishna Sharan, Associate professor, Dept.
of Radiation Oncology, Kasturba medical college, Manipal.
India. E-mail: tk.sharan@gmail.com
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Contributors:
1) Dr.Prahalad Elamarthi
2) Dr. Donald J Fernandes
3) Dr.Krishna Sharan
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