We presented our experience with the use of IORT among patients with BC in our region using our own specific institutional criteria. We found that during a median follow-up of 2 years 2.4% of our patients developed recurrence, furthermore no mortality was documented among patients.
The ELIOT clinical trial study (5) compared standard EBRT and IORT. They used the following criteria of: age 48–75 years, tumor size ≤ 2.5 cm for selection of patients for IORT. In their study they did not consider hormone receptor status and pathology sub-type as criteria for patient selection. Authors reported a five year loco-regional recurrence of 5.4% vs. 0.8% (p < 0.0001) and a 5.1% vs. 4.8% (p = 0.94) rate of distant metastasis for patients who received IORT compared to those who received external radiotherapy. Moreover, they recorded a death rate of 3.2% among patients in the IORT arm. Majority of their patients in the IORT arm were between 50–70 years old (84%), had a tumor size of less than 1.5 cm (69%), had zero positive lymph nodes (74%), had grade 2 tumors (48%), were oestrogen (90%) and progesterone (76%) receptor positive. Most of their patients also received endocrine therapy alone (75%) compared to chemotherapy and combined endocrine and chemotherapy.
One of the largest studies on the comparison of WBR and IORT is the TARGIT-A study which was conducted in 11 countries (4). In this large study they only included women older than 45 years old with unifocal ductal carcinomas and low energy photon was used. They recorded a 3.3% rate of local recurrence and a 3.9% mortality rate among patients who received IORT. In their study most of their cancers were grade 1 and 2 (85%), smaller than 2 cm (87%), ER positive (93%) and PR positive (82%). The overall, median follow-up of their patients was 2 years and five months.
Following the two large clinical trial studies on IORT other centers have further reported their institutional experiences with IORT in early stage BC (12–14). Among which chowdhry et al. (15) from the Massachusetts General Hospital reported on 109 patient who received IORT. They had a median follow-up of 29.9 months, during which 2 of their patients (1.8%) experienced local recurrence and one patient (0.9%) had regional recurrence. In this study they included only patients with T1N0 with smaller than 3 cm tumors that were estrogen positive. All their patients also had a negative margin. Their median tumor size was 9.3 mm and majority of their patients had invasive ductal carcinoma (69.7%) followed by ductal carcinoma in-situ (27.5%). Their three year diseases free survival and overall survival was 97.2% (95%CI 88.9–99.3) and 96.0% (95%CI 84.9–99.0), respectively.
Patient selection for IORT is of vital importance and requires a multidisciplinary approach. Accordingly we set-up our criteria based on a consensus of a joint committee of surgical oncologists, pathologists and radiation oncologists. We have further compared our criteria with that of the two largest clinical trial studies on IORT (the ELIOT and the TARGIT-A) in Table 3. We selected patients for IORT who were older than 45 years old for IORT, which was younger than the criteria of the American Society for radiation oncology (10). This was mainly due to the fact that Iranians tend to show BC at a lower age compared to norms of other regions in the world (16, 17). When comparing our outcomes with that of other centers in the world, we had similar, if not better, outcomes. This shows that our modified criteria for patient selection rendered good clinical outcomes. During our median follow-up of 24 months we had no mortality among our patients who received IORT. Our 97.7% 5-year disease free survival is similar to reports from other regions and centers of the world (12).
Table 3
Comparison of inclusion criteria for IORT between our study and the ELIOT and TARGIT-A studies.
Criteria
|
Our study
|
ELIOT
|
TARGIT-A
|
Age - yrs
|
≥ 45
|
48 ≤ age < 75
|
≥ 45
|
Histology sub-type
|
Invasive ductal carcinoma
|
Invasive carcinoma (unifocal)
|
Invasive carcinoma
|
|
Lobular carcinoma (with MRI and radio-concologist confirmation)
|
Lobular carcinoma (with MRI confirmation)
|
No lobular
|
|
DCIS (low and intermiediat grade, tumor size ≤ 2.5sm and margin of 2–3 mm)
|
-
|
-
|
Tumor size
|
45-50yrs old then 0-2cm
|
≤ 2.5 cm
|
< 2 cm or < 3.5 (with N0-1 and M0 with cytology or histology confirmation)
|
|
50-55yrs old then 2-2.5 cm
|
-
|
-
|
|
> 55yrs old then 2.5-3cm
|
-
|
-
|
Marginal status
|
Invasive tumor = negative margin
|
-
|
-
|
|
DCIS = > 3 mm
|
-
|
-
|
Nodal status
|
Negative
|
-
|
-
|
|
Or micro-metastasis
|
-
|
|
Hormone receptor status
|
ER+
|
-
|
-
|
Others
|
-
|
-
|
Previously diagnosed and treated contralateral breast cancer
|
IORT: intraoperative radiation therapy; DCIS: ductal carcinoma in-situ; ER: estrogen receptor
|
None of our 11 patients with DCIS experienced any recurrence during a medial follow-up of 22 months in our study. This shows that with careful patient selection those with DCIS will safely benefit from IORT.
Another interesting point was that almost one third of our patients had a family history of BC, this may be the result of the screening program of family members of individuals with BC, which is applied in our center.
We had a low local recurrence rate (1.2%) during a median (IQR) follow-up of 24 months, which may be attributed to multiple factors. First was the follow-up duration as longer follow-ups may result in higher rates of recurrence. Second relates to our criteria for patient selection which resulted in appropriate selection of candidates for IORT.
For the first time, we categorized patients according to age and tumor size and those older with larger tumor sizes were considered appropriate candidates for IORT. This specific classification was done as younger individuals usually demonstrate more aggressive tumor behavior (18–20). Our experience showed that based on our classification this form of patients selection resulted in good clinical outcomes. This approach could further be implemented in the selection criteria for IORT in other centers in the world.
This study was not without limitation and warrant further discussion. Although this was one of the largest single-center reports in literature and the largest in the Middle East, due to the low number of patients who had recurrence conducting a separate analysis to determine the predictors of recurrence in this population was not feasible. As this is among main referral centers in Iran and among few centers that have facilities for IORT, patients referred from different regions of Iran to receive IORT, accordingly this study can be representative of the Iranian population. As IORT is relatively new in the Middle East and guidelines on the use IORT are constantly being modified, certain modification to selection criteria of patients to receive IORT are expected according to characteristics of BC within each specific population. Facilities for IORT are still not widely available in Iran and in other centers in the Middle East, and our results may not be applicable in most centers due to lack of infrastructure. Although our experience showed good outcomes at 24 months (median) follow-up, long term follow-ups are still lacking due to the novelty of the procedure in our region and institution. In this study we merely reported on clinical outcomes and epidemiology of patients who received IORT in our institution, it would be interesting to cross compare these patients with those who had similar BC conditions and received WBR to evaluate percentage of local recurrence as some studies have shown that these individuals will experience higher rates of local recurrence (11).