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Year : 2020  |  Volume : 16  |  Issue : 6  |  Page : 1314-1322

Comparative retrospective analysis of locoregional recurrence in unselected breast cancer patients treated with conventional versus hypofractionated radiotherapy at a tertiary cancer center?

1 Department of Radiotherapy, SGPGIMS, Lucknow, Uttar Pradesh, India
2 Department of Biostatistics, SGPGIMS, Lucknow, Uttar Pradesh, India
3 Department of Endosurgery, SGPGIMS, Lucknow, Uttar Pradesh, India

Date of Submission13-Jun-2018
Date of Decision27-Jul-2018
Date of Acceptance06-Dec-2018
Date of Web Publication06-Feb-2020

Correspondence Address:
Shagun Misra
Department of Radiotherapy, SGPGIMS, Lucknow - 226 014, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_389_18

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 > Abstract 

Background: Role of hypofractionated radiotherapy (HFRT) in early breast cancer is established; comparatively, there are limited data for HFRT in locally advanced breast cancer (LABC). We report the impact of HFRT in unselected breast cancer patients in comparison with historically treated patients with conventional fractionated radiotherapy (CFRT).
Patients and Methods: Records of 463 breast cancer patients treated between January 09 and July 13 with CFRT (50 Gy/25 fr) or HFRT (42.4 Gy in 16 fractions or 40 Gy in 15 fractions) in two sequential periods were retrospectively reviewed. The analysis was done in August 2018. The primary endpoint was to compare the differences in locoregional recurrence rate.
Results: Of the 463 patients, 209 received CFRT and 254 received HFRT. The median age was 48 years (interquartile range: 40–56), premenopausal (CFRT: 23% vs. HFRT 39%, P = 0.005). The most common pathology was infiltrating ductal carcinoma (81%) with Grade III tumors (45%), estrogen receptor (+) was seen in 44%, triple-negative breast cancer in 34%, and Her2Neu (3+) were seen in 27%. Two hundred and fifty-four patients (54.5%) had undergone breast-conserving surgery (BCS) and 209 patients (45%) modified radical mastectomy (MRM). Nodal radiotherapy was delivered in 76% versus 64% in patients receiving CFRT versus HFRT, respectively (P = 0.005). With a median follow-up of 46 months in CFRT and 57 months in HFRT, 9/209 (4.3%) patients in CFRT and 7/254 (2.7%) in HFRT had locoregional relapse (LRR). The 4 years#39; actuarial local recurrence-free survival (LRFS) in CFRT versus HFRT was 95% versus 97% (P = 0.37). The mean estimated LRFS (local relapse-free survival) for CFRT is 113.4 months and for HFRT 94.2 months (P = 0.3).
Conclusions: The risk of local recurrence among patients of breast cancer treated with HFRT after BCS or MRM was not worse when compared to CFRT.

Keywords: Hypofractionated radiotherapy, local relapse-free survival, locally advanced breast cancer

How to cite this article:
Yadav R, Lal P, Agarwal S, Misra S, Verma M, Das K J, Senthil Kumar S K, Kumar A, Mishra S K, Agarwal A, Agarwal G, Mishra A, Chand G, Verma A K, Kumar S. Comparative retrospective analysis of locoregional recurrence in unselected breast cancer patients treated with conventional versus hypofractionated radiotherapy at a tertiary cancer center?. J Can Res Ther 2020;16:1314-22

How to cite this URL:
Yadav R, Lal P, Agarwal S, Misra S, Verma M, Das K J, Senthil Kumar S K, Kumar A, Mishra S K, Agarwal A, Agarwal G, Mishra A, Chand G, Verma A K, Kumar S. Comparative retrospective analysis of locoregional recurrence in unselected breast cancer patients treated with conventional versus hypofractionated radiotherapy at a tertiary cancer center?. J Can Res Ther [serial online] 2020 [cited 2021 Dec 4];16:1314-22. Available from: https://www.cancerjournal.net/text.asp?2020/16/6/1314/277814

 > Introduction Top

Long-term results of randomized trials have confirmed the safety and efficacy of hypofractionated radiotherapy (HFRT) using approximately 2.6 Gy per fraction to lower total doses of 40–42.6 Gy delivered over 3 weeks, for postoperative treatment of early breast cancer (EBC). HFRT is considered a standard of care in the United Kingdom[1],[2] and in some parts of Canada.[3] The NICE guideline recommends HFRT in all breast cancer patients.[4] The two hypofractionation schedules used were 40 Gy in 15 fractions over 3 weeks (based on START A and B trial)[1],[2] and 42.40 Gy in 16 fractions over 3 weeks (Canadian experience[3]). Radiobiologically (as per EQD2 calculation), they are equivalent to 46 Gy in 23 fractions and 48 Gy in 24 fractions, respectively, by conventional fractionation of 50 Gy in 25 fractions 5 weeks.

In “low-resource high-throughput” countries, logistics compel us to use such abbreviated schedules, wherever feasible. We and several centers in low-middle-income group countries adopted these schedules following the reports from the UK[1],[2] and Canada[3] (predominantly comprising of EBC, whereas we predominantly deal with advanced breast cancer population, which was not well represented in these trials). There is concern among clinicians regarding the potential increase in local recurrence rates with the use of hypofractionated schedule in this biologically aggressive patient population, as radiobiologically these schedules have a lower Biological Equivalent dose (BED) as compared to conventional fractionated radiotherapy (CFRT). Second, there is a fear of increased acute and late toxicity after hypofractionated regional nodal radiation to the axilla (lymphedema) and brachial plexus. Therefore, we report our single-center experience with hypofractionation schedule and compare the locoregional recurrence rates with the previously used conventional fractionation schedule in the unselected patient population, thereby testing any detriment in the efficacy across high-risk tumors. The median follow-up of these patients was short to permit long-term toxicity comparisons (brachial plexopathy) which will be reported later.

 > Patients and Methods Top

This is a single-center study of consecutively treated patients of carcinoma of the breast by two fractionation schema in different periods. A total of 463 breast cancer (all stages) who had undergone breast-conserving surgery (BCS)/modified radical mastectomy (MRM) and received radiotherapy (RT) between January 2009 and July 2013 were identified. RT was given by CFRT (50 Gy in 25 fractions) between 2009 and 2011, while HFRT (42.4 Gy in 16 fractions or 40 Gy/15) was adopted as a routine policy in October 2011. All the demographic, disease, treatment, and outcomes related data were extracted from patient case files and electronic hospital medical records. Those patients whose information on disease status was not available were contacted telephonically or using postal service.

All patients underwent a detailed clinical examination and staging workup which included histology/fine-needle aspiration proof, chest radiograph, and bilateral mammogram. Bone scan and ultrasonography of the abdomen and pelvis were done when indicated. All cases were staged based on the 7th AJCC-UICC staging system.[5] As is the existing treatment policy between the two departments (Department of RT and Department of Breast and Endocrine Surgery), neoadjuvant chemotherapy (NACT) was given to all locally advanced breast cancer (LABC) and majority of the large operable breast cancer patients.

We defined LABC as tumors more than 5 cm in size with regional lymphadenopathy (N1–3), tumors of any size with direct extension to the chest wall or skin, or both (including ulcer or satellite nodules), regardless of regional lymphadenopathy presence of regional lymphadenopathy (clinically fixed or matted axillary lymph nodes (LNs), or any of infraclavicular, supraclavicular, or internal mammary lymphadenopathy) regardless of tumor stage.

Anthracycline-based combination with or without taxanes was given in these cases. Six to eight such cycles were given (anthracycline-based or sequential taxanes). Patients were advised for surgery in the form of MRM or BCS either at presentation or following NACT depending on the stage of disease, the involvement of the skin, or patient choice. All EBC patients were consulted for BCS by the breast surgeons. Usually, the decision of BCS/MRM was joint, that is, family, patient, and surgeon keeping in mind the patient desire, age, and comorbidities.

Locoregional recurrence (LRR) was defined as any relapse in the ipsilateral breast or chest wall or nodal recurrence in ipsilateral supraclavicular or ipsilateral axillary region. Any patient who had not presented for follow-up for more than 6 months or who could not be contacted for survival analysis were taken as lost to follow-up. The Kaplan–Meier survival curves were plotted to obtain relapse rates. All local failures rates were calculated at the time of the median follow-up. Logrank tests were used for univariate analysis.

Woman having experienced 12 consecutive months without menstruation was categorized as postmenopausal.

All radiation data were obtained by primary chart abstraction. For each case, we abstracted the following information: the radiation scheme used (total dose and number of fractions), beam energy (MV), and whether additional radiation treatment was delivered to the tumor cavity (“boost” radiation). The radiation therapy regimen administered was in accordance with institutional treatment policies. Decision to deliver RT to the chest wall was based on the presence of high-risk features (tumor size >5.0 cm >3 axillary nodes). The practice has been variable for 1–3 positive LNs in terms of giving or withholding RT. All patients of breast conservation surgery were planned for RT to whole breast and tumor bed boost. Supraclavicular field was added in four or more axillary LN-positive disease. Supraclavicular fossa (SCF) field was extended to cover the axilla in incompletely dissected axilla (<10 LN dissected) and usually in heavy nodal burden (>10 LN positive). The practice was inconsistent in extranodal spread. Oncologist felt inclined toward giving RT (any of the portal) if the competence of an outside surgeon/setup was not known to them. It is not a practice to give internal mammary chain LN at our center.

All patients underwent simulation on computed tomography simulator. They were asked to lie supine on wing board/breast board with arms raised above the head; wires to demarcate medial border of the contralateral breast with wires as medial and lateral borders for tangential fields along with scar were placed. Plain CT scan with 5-mm axial slice thickness was taken from the upper neck to upper abdomen. CT image data set was transferred to eclipse treatment planning system using DICOMRT software (Varian). Delineation of both breasts (and contralateral breast in case of mastectomy of diseased site), both lungs, and heart (especially in left-sided lesions) was the usual practice. Tumor bed cavity was identified (in BCS cases) with the help of clips (if placed), seroma/fibrotic area along with the information obtained from the baseline mammogram (if available). For the whole-breast irradiation, bitangential portals were placed with or without wedges using 6 or occasional 15 MV photons. Chest wall RT was delivered either as a direct single anterior field with 0°–10° gantry tilt, usually 9–12 MeV electron beams were considered adequate, and the choice was made based on chest wall thickness as ascertained on the CT scan. This was the usual practice till mid-2012. Due to challenges with electron dosimetry and challenges with photon-electron beam abutment, the practice was gradually abandoned and was replaced by monoisocentric bitangential cheat wall ± supraclavicular fossa fields using 6 MV photons with advantage of asymmetric jaws and multileaf collimators.

Supraclavicular (±axillary) field was essentially a 6 MV photon field. SCF alone was a single direct field, while axillary field may have to be supplement by post axillary boost if the dose at mid-axillary depth was insufficient. Tumor bed boost was planned by either photon portals using three-dimensional conformal radiotherapy (CRT) technique or a single direct electron portal. Tumor bed boost was given between 10 Gy/4 Fr to 12.5 Gy/5 Fr to 16 gy/8 Fr. Dose prescription was done at 95% isodose based on the The International Commission on Radiation Units and Measurements (ICRU) report 62 (95% +7%). The slice of ipsilateral lung coming within the tangential portal was attempted to be kept between 2 and 2.5 cm Central Lung Distance (CLD), if possible. There was no consistent policy regarding the heart; however, usually, we attempted to keep the maximum heart distance to within 1 cm in left-sided breast cancer patients. As the awareness grew, individualized Multileaf collimator (MLCs) were placed to save the heart (without compromising the target area). Since 2010, it has been a department policy to check the 1st-day portal image for field verification.

While on treatment, these patients were followed up on a weekly basis to document acute reactions which were graded according to the acute Radiation Therapy Oncology Group (RTOG) criteria. Following completion of treatment, the patients were followed at 6-monthly intervals wherein a clinical examination was done, and the mammogram was advised once a year. In case of local/regional/distant failure, the patient treatment was tailored as per the type of recurrence and patient condition.

Statistical analysis

Descriptive statistics were used to report the distribution of various characteristics among our cohort of women. Differences in proportions for categorical variables were tested using the Chi-square test, and differences in the means for continuous variables were tested using t-tests. Probabilities of local recurrence-free survival (LRFS), distant disease-free survival, and overall survival were calculated using the Kaplan–Meier approach. The differences between the Kaplan–Meier curves between various groups were tested using the log-rank test.

 > Results Top

Analysis of 463 patients of carcinoma breast (EBC and LABC), registered from January 2009 to July 2013 were included in the study. Data were analyzed in June 2018. Of the patients included in this study, 209 received CFRT and 254 received HFRT.

The median age of the women was 48 years in both groups. The fractionation groups were well balanced for most of the baseline factors. Exceptions were premenopausal women were more in HFRT (CFRT: 23% vs. HFRT 38.7%, χ2 = 0.005). Similarly, higher proportion of LABC at clinical presentation was seen in HFRT (CFRT36.4% vs. HFRT 51.6%, χ2 P = 0.01). EBC cases were 113 (54.1%) CFRT in conventional versus 109 (42.9%) in HFRT.

Demographic and patient-related characteristics of the patients included in the study are summarized in [Table 1].
Table 1: Overall and group-wise distribution of demographic characteristics, disease characteristics, and interventions

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A total of 176 (37.8%) patients were treated with 42.4 Gy/16#, 71 (15.2%) were treated with 40 Gy/15#, and 7 (1.5%) with 40 Gy/15# (with simultaneous boost to lumpectomy cavity).

With a mean follow-up of 46 months in CFRT and 57 months in HFRT, 9/209 (4.3%) patients in CFRT and 7/254 (2.7%) in HFRT had locoregional relapse (LRR). The 4-year actuarial local replace free survival (LRFS) in CFRT versus HFRT was 95% versus 97% (P = 0.37).

In CFRT arm, 94 (45%) were alive, 52 (25.9%) were dead, 45 (21.5%) were lost to follow-up (LFU) without disease, and 18 (8.6%) were LFU with disease. In HFRT arm, 159 (62.6%) were alive, 33 (13%) were dead, 52 (20.5%) were LFU without disease, and 10 (3.9%) were LFU with disease.

The overall local recurrence was seen in a total of 16 patients wherein 9/209 (4.3%) patients in CFRT and 7/254 (2.7%) in HFRT had local relapse. In 10 (2.1%) patients, recurrence was seen in breast/chest wall; in 4 (0.9%) patients, it was seen in SCF; and in 2 (0.4%), it was seen in the axilla. The overall incidence and pattern of local recurrence were not different between the two cohorts [Table 2]. The 4-year actuarial LRFS in CFRT versus HFRT was 95% versus 97% (P = 0.37), respectively [Figure 1]. The mean estimated LRFS (Local Relapse-Free Survival) for CFRT is 113.4 months and for HFRT 94.2 months (P = 0.3) [Figure 2].
Table 2: Local and regional recurrence patterns in two groups

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Figure 1: Kaplan–Meier plot showing overall survival in years in the two groups

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Figure 2: Kaplan–Meier plot showing the LRFS in years in two subgroups

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The absolute number of local recurrences was higher in age <50 years, LABC, Grade III tumors, triple-negative breast cancer (TNBC), patients, and MRM but were not significantly different between the two cohorts [Table 3]. On univariate analysis, none of the factors affected LRFS at 2 years [Table 4]. The trend toward significance seen in univariate analysis in 2 years LRFS electrons (95.9%) versus photons (88.8%) (P = 0.08). [Table 4] does not appear significant on multivariate analysis. Imbalance of baseline prognostic factors did not permit multivariate analysis.
Table 3: Influence of demography, disease-related factors, and interventions on local recurrence patterns in each group

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Table 4: Univariate analysis for local recurrence in two groups

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Overall estimated local relapse-free survival was 114 months, 113 months for the conventional arm and 94 for hypofractionated arm, this difference was not significant statistically (P = 0.3).

Distant relapse was documented in 87 (18.7%) patients, of these 50 (24%) were seen in conventional RT arm and 41 (17%) in HFRT (P = 0.15). The most common site of distant relapse was brain seen in 20 (23%) patients, bone 15 (17.2%), followed by liver 14 (16.1%).

Acute toxicity was documented by acute RTOG criteria on weekly follow-up. Grade III or more skin reactions were seen in 40% of patients with CFRT and 29% of patients with HFRT. The incidence of Grade ¾ toxicity was higher for MRM patients treated with electrons than photons irrespective of fractionation. For BCS patients, 25% had Grade III in CFRT and 18.4% in HFRT toxicity details are shown in [Table 5] and [Table 6]. Due to a short follow-up, the authors could not delve into late toxicities (i.e., brachial plexus and cardiac toxicities).
Table 5: Acute Radiation Therapy Oncology Group skin reaction grading in conventional fractionated radiotherapy versus hypofractionated radiotherapy group

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Table 6: Radiation Therapy Oncology Group acute skin reaction grading in modified radical mastectomy versus breast-conserving surgery group

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 > Discussion Top

Haviland et al. reported 10-year outcomes of (START)-A and START-B trials. These trials examined whether hypofractionation radiation schedule was as safe and effective as the standard 5 weeks' fractionation schedule. They concluded that the shorter treatment was associated with equivalent outcomes. Long-term results from a similar randomized trial led by the Ontario Clinical Oncology Group, these findings provide robust evidence that most patients with breast cancer can receive a hypofractionated schedule that remains beneficial while decreasing the duration of treatment.

It was confirmed by START-A and START-B independently that a course of RT with fewer daily treatments can be safe and effective. START-B trial is more clinically relevant because this study reduced the overall treatment time from 5 to 3 weeks, which provides clear logistic benefits for both patients and healthcare system in low-middle income countries. These outcomes were the similar irrespective of age, tumor grade, stage, chemotherapy use, or use of tumor bed boost.

These studies, however, predominantly dealt with the early disease. We aimed to compare the effectiveness of hypofractionated radiation therapy (compared with conventional treatment) in consecutively treated patients of carcinoma breast. We reviewed all radiation therapy records to validate the dose/fractionation regimen administered, especially in terms of local recurrence. This study shows no evidence that HFRT with doses between 42.5 and 40 Gy in 15–16 fractions is inferior in terms of local control compared to conventionally fractionated treatment (50 Gy in 25 fractions) in unselected patient population, majority being locally advanced. Overall 3.4% (16) local recurrences were documented. Out of total 16 locoregional recurrences, seven were in HFRT arm while nine in CFRT arm. The hypofractionated arm did not have a worse local recurrence rate at 4 years.

We looked into the patient groups possessing different aggressive features such as node positivity, receptor negativity, Her2neu 3+ and TNBCs, and their impact on local recurrence. The time to local recurrence was shorter in patients of TNBC (2 months) versus hormone receptor (HR) +ve patients (9 months). About 80% of the recurrences that occurred in TNBC were within the 1st year whereas 80% of the recurrences occurred within 2 years for HR+, and 100% recurrences occurred within 2 years for Her2+ tumors. The time to local recurrence is an important prognostic factor as reported in various series.[6]

The median number of positive nodes in N+ patients, the present study was four (interquartile range [IQR] 2–8) in patients undergoing upfront surgery, while as well as in patients undergoing NACT, the median node positivity was 1 (IQR 0–5). The median number of nodes dissected was 15 (range 2–44) in conventional and 13 (range 0–43) in HFRT group. The scarcity of population with positive nodes in the randomized trials provides insufficient data to permit firm evidence-based endorsement of HRRT in this setting.[7] Only 7%–14% of patients in the START trials received supraclavicular RT, and none of the patients received axillary RT.[8],[9] In the present study, 76.5% of patients in CFRT and 63% of patients in HFRT received nodal radiation (supraclavicular ± axilla). The most common reason for giving axillary RT and posterior axillary boost (PAB) was heavy nodal burden followed by inadequate dissection and physician preference. The median number of nodes positive in patients receiving PAB was 7 (IQR 4–14), and the median number of dissected nodes was 14 (IQR 11–22). Inadequate dissection was documented in 20% of patients. However, the use of PAB declined in the hypofractionated cohort (CFRT 1.9% vs. HFRT 1.2%) despite heavy nodal burden and inadequate dissection in some cases. The reasons were fear of added morbidity with the use of hypofractionated axillary RT as seen from previous studies using inappropriate dose reductions.[10] Second, low incidences of axillary failures are seen in the present era with the improvisation of surgical treatment and effective systemic therapies available. The most common site of local recurrence was the chest wall, both in HFRT and CFRT (1.6% vs. 2.9%). Despite heavy nodal burden in a significant proportion of patients, in this unselected population, the risk of nodal failures was <1.5% further reinforcing the fact that chest wall; breast has the highest risk of recurrence. The local recurrence rate is similar to what is mentioned in the literature.[1],[2]

Since the UK and Canadian trials dealt with early tumors, chemotherapy was not warranted in majority of their patient population. Only a fraction of patients received anthracycline and taxane-based chemotherapy in the Candian trial,[3] while in the START B trial,[2] 13% received anthracycline and 0.4% taxanes. Unlike these trials, majority of the patients received anthracyclines (86.7%) in the present study. The use of any systemic therapy was similar in both groups (80.4% vs. 85.9%). Similarly, we had an overall 178 (38%) of cases of NACT, while the randomized trials did not include such patients. Out of 178, 79 (38%) in CRT arm, while 99 (39%) in HFRT arm. The Canadian trial[3] had 40% estrogen receptor (ER)(+) and the UK trial[1],[2] had 85%. In the present analysis, HR+ was was seen in 28% and 27% in CFRT and HFRT, respectively. The patients with high-grade tumors comprised 20% in Canadian trial[3] and 25%–30% in START A/B trial.[1],[2] In the present study, high-grade patients are 171 (44%), out of which 73 (34.9%) in CRT while 98 (39%) in HFRT arm. With 12-year median follow-up, the Canadian trial found a statistically significant interaction of the grade with randomization arm.[11] Specifically, for patients with high-grade tumors, the 10 years' risk for Ipsilateral breast tumor recurrence (IBTR) was 15% (in whole breast RT) with HFRT compared to 5% inpatient managed with CFRT. However, no such interaction of grade, hormone receptor status, and use of NACT were seen on local recurrence rates between the two cohorts in the present study. There is uncertainty on the issue of compounded effect of HFRT with the type of chemotherapy used. The Canadian study did not show any significant difference adverse effects regardless of treatment arms; anthracyclines and trastuzumab were rarely used in that period. The use of HFRT with anthracyclines and trastuzumab may have cumulative adverse effect on the heart[12] (especially in left-sided lesions). Available data today regarding the long-term cardiac effects of the use of HFRT with anthracyclines and trastuzumab are not satisfactory,[7] this needs to be further studied in the future.

Acute toxicity (Grade III/IV) was seen in 40% patients with CFRT as opposed to 30% patients with HFRT. Patients with MRM and treated with CFRT electrons had 50% Grade III/IV reactions as compared to 32.2% with HFRT. The corresponding rates (Grade III/IV) for photons were 14.7% with CFRT photons and 7% with HFRT photons. Similarly, inpatients treated with BCS Grade III/IV reactions were seen in 25% patients with CFRT as opposed to 18.8% patients with HFRT Irrespective of the modality of radiation (electron/photon) and the surgical strategy (BCS/MRM) used HFRT had lower incidence of Grade III/IV reactions.

HFRT decreases the overall treatment time by 2 weeks, enabling centers with constrained resources to increase the turnover of patients without compromising on results. This is an issue of immense importance in a country like India where the resources and infrastructure are overburdened, long waiting periods are a norm, and many patients fail to get treatment for this reason.[13] Adoption of the hypofractionated schedule was supported by evidence from several randomized trials.[1],[2],[3] Apparently, these trials have shown, backed up by sound theoretical radiobiological basis, that neither recurrence rate nor cosmesis is worsened in any of these studies;[1],[2],[3] however, they had included a highly select and screened patients population of T1 and T2, N0 tumors, where 85% had undergone BCS, followed by breast alone RT in 99% of cases.[1],[2],[3] In contrast, we present the outcomes of an unselected patient population, predominantly LABC, with heavy nodal burden following (anthracycline/taxane) chemotherapy, mastectomy, and higher proportion of TNBC. Routine use of HFRT was based on long-term data from another tertiary care hospital in Northern India[14],[15],[16] and Manchester experience[5] who have treated their patients with HFRT over the decades, apart from above-mentioned recent randomized trials.[1],[2],[3]

Apart from the regular limitations of documentation, selection, etc., of any retrospective audit of two different time zones, it is also plagued by a high LFU rate (although the worst case was scenario considered for the analysis). There is nearly 20% LFU without disease in both arms (20.5 vs. 21.5%) and nearly 6% LFU with disease (4% vs. 9%). Therefore, at best, this audit report may be considered as a hypothesis generation exercise for the future, and possibly to initiate a multicentric randomized trial. One major limitation of this study is that treatment assignment was nonrandomized and at different times. There are, therefore, imbalances in potentially significant prognostic factors between the two groups which were noted in regard to age and locally advanced presentation; however, both these factors were unfavorably balanced for HFRT. With respect to other factors deterministic of the biological aggressiveness (grade, ER−, HER+, TNBC), the two cohorts were similar. We also admit that this comparison in two different periods may not be entirely fair as the treatment modalities such as technique (use of electron) and use of superior or “more effective” adjuvant treatment in the form of taxanes, trastuzumab changed to some extent during this period. Therefore, although LRR is a function of several factors, including total dose and dose schedule, we failed to see the difference in LRR in a group where HFRT was used as per current practice. These drugs, that is, taxanes, trastuzumab, and aromatase inhibitors were more commonly used in the present audit as compared to the PGI, Chandigarh, India/Manchester, and the UK data.[6],[17] Therefore, one cannot rule out their impact on the LRR rate. Despite the fact that Our study had a higher percentage of advanced disease the outcomes in terms of local and regional relapses were similar to the studies which had a predominantly early stage population [Table 7].
Table 7: Comparison of outcomes of hypofractionated breast radiotherapy studies

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The strength of the study lies in it being a large series of HFRT with decent follow-up.

A 4-year follow-up may be sufficient to witness significant locoregional recurrences in an aggressive/unselected patient population treated by dose schedule that has been tested primarily in EBCs. Our analysis did not include information regarding cosmesis. This cannot be obtained retrospectively because baseline cosmesis was not included in our database. The incidence of lymphedema was neither documented at baseline nor was a formal grading system used on follow-up visits; hence, it could not be extracted retrospectively. This follow-up may not be sufficient for the cardiac or brachial toxicity; however, these issues were not the points considered for this study. These patients are being followed up, and with longer follow-up, we may in future be able to present the toxicity data of the two groups as well.

If we shift the focus from the science and statistics to the grim reality of conditions in low-middle-income group countries, it may partly explain why public health hospital found adopting such a schedule in all patients of breast cancer, as the only way out. These hospitals are constrained by the excess patient numbers, limited infrastructures, and overburdened existing “old” machines. In addition, these patients are usually underprivileged, less educated, and financially dependent women. They depend on their male counterparts to fund for their treatment and travel and accompany her long distance to get her radiation treatment completed. This often implies abstinence from work and loss of wages for the male counterpart. Although health economics consideration was beyond the scope of this audit, Gill Thomas in her editorial very succinctly described how women cancers take a beating in a country like ours where women occupy a secondary position in the society.[18]

We intend to prospectively maintain a database of patients being treated with hypofractionated schedules, to improvise data capture, permitting long-term comparisons of efficacy and morbidity, and design further studies on novel “hypo” fractionation schema.

 > Conclusions Top

The risk of local recurrence among patients of breast cancer treated with HFRT after BCS or MRM was not worse when compared to conventional radiation therapy even in the face of LABC.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

 > References Top

START Trialists' Group, Bentzen SM, Agrawal RK, Aird EG, Barrett JM, Barrett-Lee PJ, et al. The UK standardisation of breast radiotherapy (START) trial A of radiotherapy hypofractionation for treatment of early breast cancer: A randomised trial. Lancet Oncol 2008;9:331-41.  Back to cited text no. 1
START Trialists' Group, Bentzen SM, Agrawal RK, Aird EG, Barrett JM, Barrett-Lee PJ, et al. The UK standardisation of breast radiotherapy (START) trial B of radiotherapy hypofractionation for treatment of early breast cancer: A randomised trial. Lancet 2008;371:1098-107.  Back to cited text no. 2
Whelan T, MacKenzie R, Julian J, Levine M, Shelley W, Grimard L, et al. Randomized trial of breast irradiation schedules after lumpectomy for women with lymph node-negative breast cancer. J Natl Cancer Inst 2002;94:1143-50.  Back to cited text no. 3
The Guidelines Manual. London, U.K.: National Institute for Health and Clinical Excellence; 2006. Available from: http://www.nice.org.uk/aboutnice/howwework/developingniceclinicalguidelines/clinicalguideline/developmentmethods/theguidelinesmanual2006/theguidelines manual2006.jsp. [Last cited on 2009 Jan 07].  Back to cited text no. 4
Edge S, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. AJCC Cancer Staging Manual. 7th ed. New York: Springer; 2010.  Back to cited text no. 5
McBain CA, Young EA, Swindell R, Magee B, Stewart AL. Local recurrence of breast cancer following surgery and radiotherapy: Incidence and outcome. Clin Oncol (R Coll Radiol) 2003;15:25-31.  Back to cited text no. 6
Smith BD, Bentzen SM, Correa CR, Hahn CA, Hardenbergh PH, Ibbott GS, et al. Fractionation for whole breast irradiation: An American Society for Radiation Oncology (ASTRO) evidence-based guideline. Int J Radiat Oncol Biol Phys 2011;81:59-68.  Back to cited text no. 7
Hopwood P, Haviland JS, Sumo G, Mills J, Bliss JM, Yarnold JR, et al. Comparison of patient-reported breast, arm, and shoulder symptoms and body image after radiotherapy for early breast cancer: 5-year follow-up in the randomised standardisation of breast radiotherapy (START) trials. Lancet Oncol 2010;11:231-40.  Back to cited text no. 8
Haviland JS, Owen JR, Dewar JA, Agrawal RK, Barrett J, Barrett-Lee PJ, et al. The UK standardisation of breast radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up results of two randomised controlled trials. Lancet Oncol 2013;14:1086-94.  Back to cited text no. 9
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Whelan TJ, Pignol JP, Levine MN, Julian JA, MacKenzie R, Parpia S, et al. Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med 2010;362:513-20.  Back to cited text no. 11
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  [Figure 1], [Figure 2]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]


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