STUDY OF TWO DIFFERENT DOSE FRACTIONATION SCHEDULES OF POST MASTECTOMY CHEST
WALL IRRADIATION IN CARCINOMA BREAST PATIENTS
Dr.Prashant Kumbhaj
Dr.Rameshwaram Sharma
Dr.Peeyush Saini
Dr. Prashant Patel
ABSTRACT
Background: Breast cancer is the most frequently diagnosed cancer and the
leading cause of cancer death in women.
Aims & Objective: To compare two different dose fractionation schedules in terms of overall
treatment, locoregional control, acute and late toxicities and patient compliance.
Material and Methods: Patients of postmastectomy non metastatic
breast cancer were randomized in two arms: Arm A (45) Arm B (46) according to dose
fractionation schedule of external radiation given to chest wall and draining lymphatics. Arm A was given 50
Gy in 25 fractions and Arm B was given 40 Gy in 17 fractions. After completion of radiation patients were kept
on follow up.
Results: Median follow up was 20 months. In arm A & B the median overall treatment time was
40 and 27 days with respective ranges of 36-47 days and 22-33 days .The patients in both the arms tolerated
radiation well, skin reactions were most common followed by nausea and vomiting .Grade II and III acute
reactions were comparable in both arms. There was non-significant increase in both late skin and subcutaneous
skin toxicities in arm B. Result of treatment of both arms are, chest wall failure 5% v/s 9% (p> 0.05),
nodal failure 8% v/s 7% (p> 0.05) and distant metastasis 25% v/s 28% (p> 0.05).
Conclusion: Both the studied dose fractionation schedules are equally efficacious in terms of
locoregional control, acute and late toxicities. The shorter schedules in Arm B gives an added
advantage of decreased overall treatment time giving better compliance and reduces work load of overburdened
department.
Key-Words: Breast Cancer; Radiation; Dose Fractionation
Schedules
Introduction-
Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in
women, accounting worldwide for 23% of total new cancer cases and 14% of total cancer deaths in 2008.[1] It is
the second most common leading site among women in India and incidence varies from 7 to 28 per 1 lakh women in
various parts of India and treated with multimodal approach like surgery, radiotherapy, chemotherapy,
hormonal therapy and immunotherapy.[2,3] Surgery is the treatment of choice which should be followed
by postoperative radiotherapy and adjuvant systemic treatment.[3] There is no general agreement in
literature regarding dose of radiation therapy which should be delivered to a patient after mastectomy.[4-6] The
doses, ranging from 32.5 Gy/3 weeks to 60 Gy/10 to 14 weeks have been given.[4-8] Adjuvant radiotherapy
has shown to improve local control and overall survival, with a 70% proportional reduction of the risk
of recurrence[9] and a 9%�12% proportional reduction of the risk of death[10-13]. Despite this established role
of radiotherapy, there are considerable disparities in the receipt of radiotherapy that are attributable to
various factors such as limited availability of treatment centers, geographical distance, long waiting times,
and costs.[14-16] Since developing countries are dependent on cobalt 60 teletherapy units for radiotherapy
and though our centre has linear accelerator but more no of patients coming from rural
background cannot afford treatment cost . The disparities can further be compounded by the long schedules
required with conventional radiotherapy, since the schedules that were evaluated in clinical
trials and were found to be associated with improved survival are based on conventional fractionation of
1.8-2.5Gy/fraction, delivering treatment over 5 to 7weeks.[10,13,17,18] Many researches are actively
investigating alternative approaches. Intraoperative
radiotherapy (IORT) or accelerated partial breast irradiation (APBI) provide the shortest
schedules.[19-21] However, IORT and APBI are limited to selected cases.[22] Whole breast
radiotherapy with a hypofractionated schedule delivering 42.5 Gy in 16 fractions over 22 days has
been shown by the Ontario randomized trial to be comparable with a conventional schedule of
50 Gy in 25 fractions over 35 days.[23] Therefore, we have conducted a study comparing two radiation dose
schedules in post mastectomy carcinoma of the breast.
Materials and Methods
The study has been conducted on 91 histopathologically proved breast cancer patients
in a tertiary care center for radiotherapy after modified radical mastectomy. Patients
of
postmastectomy non metastatic breast cancer were randomized in two arms: arm A (45) Arm B
(46) according to dose fractionation schedule of external radiation given to chest wall and draining
lymphatics. Arm A was given 50 Gy in 25fractions in 5 weeks and Arm B was given 40Gy in 17
fractions in 3.2 weeks. The postoperative radiation therapy was given to chest flap and
drainage areas in all patients. Radiation therapy was given on a Co 60 teletherapy machine using
tangent pair technique for chest wall irradiation. After completion of radiation patients were
kept
on regular follow up. The patients included in the study were; all patients surgically treated
with
modified radical mastectomy, radiotherapy and chemotherapy naive patients, having karnofsky
performance status (KPS) >70. Patients with distant metastasis, inoperable cases, peaud
orange, fixed inoperable nodes, any surgery other than modified radical mastectomy and Karnofsky
performance status (KPS) <70 were excluded. All relevant investigations were done. Adjuvant
chemotherapy schedule was similar in both the groups. All node positive patients were given CAF
regimen (24). All post-menopausal patients received hormonal treatment in form of
Tamoxifen 10 mg BD. Radiation reactions were carefully noted during treatment. The patients
were advised regular follow up. At every follow up, patients were assessed for radiation reactions
and status of disease. The radiation reactions and response were graded as per WHO criteria.
Results
Median follow up was 20 months. In arm A &B the median overall treatment time was 40 and 27
days with respective ranges of 36-47 days and 22- 33 days. The median age at presentation was 46
years (range 31-70 years). 56% patients in Group A and 60 in Group B were postmenopausal. All
the patients in both groups presented with painless lump in breast and axillary mass present in
44%
of patients in Group A and 50% of patients in Group B. Infiltrating duct carcinoma was the most
common histopathology in both groups (84% in Group A and 87% in Group B). The other less
common histopathological types were; colloid carcinoma, medullary carcinoma, lobular
carcinoma etc. The most common stage at presentation was stage III (58% in Group A and
57.4% in Group B).
Table-1: Carcinoma of the Breast: Stages at Presentation
| Stage |
Group A -N (%) |
Group B -N (%) |
| Stage I |
2 (4%) |
3 (5.5%) |
| Stage II |
17 (38%) |
17 (37%) |
| Stage III |
26 (58%) |
26 (57.4%) |
| TOTAL no patients |
45 (100) |
46 (100) |
Table-2: Post Mastectomy Radiation Therapy: Radiation Reactions
Table-3: Post Mastectomy Radiation Therapy: Status at Last Follow Up
The results of treatment of 91 patients (45 of Group A and 46 of group B) were: The patients in
both the groups tolerated radiation well.
Skin reactions were most common radiation reactions followed by difficulty in swallowing and
nausea/vomiting.
Results of treatment in Group A versus Group B were as follows; chest wall failure 5% v/s 9 % (p> 0.05), axillar
lymph node failure 8% v/s7% (p> 0.05), distant metastasis 25% v/s 28% (p> 0.05). Most of the patients in both
the groups had no evidence of disease at last follow-up i.e. 28/45 (62%) in Group A and 26/46 (56%) in Group B.
There was no statistically significant difference in local control and efficacy of these two radiation schedules in
post mastectomy carcinoma of the breast.
Discussion
Surgery and radiotherapy are important for
locoregional control in carcinoma breast.[3,26] Surgical
treatment is mandatory for cure of breast carcinoma.[27] Three types of surgery practised are; conservative surgery
(
lumpectomy, quadrantectomy, tylectomy, partial mastectomy or segmental mastectomy etc.), moderate
surgery (modified radical matsectomy, simple mastectomy with axillary clearance etc.) and
radical surgery
(Halsted mastectomy, Extended radical mastectomy and supraradical mastectomy etc.).[27] Modified radical
mastectomy is the most common form of mastectomy performed now a days.[3] This was the operation done in all our
patients included in the present study. Modified radical mastectomy includes removal of breast with axillary nodal
dissection but with preservation of pectoralis major muscle.[27] Radiation after surgery decreases loco-regional
recurrence.[28] There are several reasons or end points that might justify the use of
postmastectomy
radiotherapy (PMRT) for patients with
invasive breast cancer. These include a reduction in
the risk of local-regional failure (LRF), with its potential physical and psychological morbidity, as well as a
reduction in the risks of distant relapse and death. In the
cancer research campaign trial of 2248
evaluable patients with clinical stage I and breast cancers, the patients were randomly assigned to treatment with
simple mastectomy alone or simple mastectomy combined with irradiation.[3] A threefold greater incidence of local
recurrence was noted in control group (30% with simple mastectomy alone and 10% with simple mastectomy and
irradiation.
After modified
radical mastectomy external radiotherapy is delivered to chest flap and drainage areas
which include
ipsilateral supraclavicular fossa, axilla and internal mammary nodes.[3]
External
radiotherapy is delivered by tangent pair technique which spares lungs. This has been followed in our
institute. There is no general agreement in literature regarding dose of radiation therapy which should be delivered
to a patient after mastectomy.[4-6] The doses, ranging from 32.5 Gy/3 weeks to 60 Gy/10 to 14 weeks have been
given.[4-8] Post mastectomy breast irradiation in our study showed that there is no significant difference between
50 Gy in 25 fractions and 40 Gy in 17 fractions, so 40 Gy in 17 fraction regimen are more convenient for the
patients by limiting the number of treatment attendances. Moreover, the reduced resource use in terms of personnel
and machine time is advantageous for radiotherapy departments and translates into lower treatment costs. In order to
formally validate this therapeutic approach from a societal perspective, however, cost-effectiveness evaluations
weighing long-term outcome against the societal costs incurred until many years after treatment are needed.[29,30]
Treatment of women with breast cancer, confirm the safety and efficacy of schedules using fraction
sizes of >2 Gy, provided the correct downward adjustments to total dose are made.[31]
Hypofractionated
radiation therapy offers the advantage of a more efficient and productive use of radiotherapy
departments resources; whether machine time, staffing of treatment units, lower expenses in addition to far better
patients convenience.[32] As our hospital is largest hospital in our state and patients from all our state as well
as from nearby states come to our department and
breast cancer is common cancer among females and most
females presenting in our department are cases of
breast carcinoma ,and due to longer treatment time
in conventional fractionation many patients cannot get radiotherapy timely due to overburdened department, so this
hypofractionated regimen is very advantageous for overburdened departments like our department. On the other
hand,hypofractionation, with larger radiation dose per fraction increases the possibility of late normal tissue
damage.[33,34] However, the linear-quadratic model predicts that the normal
tissue toxicity is not increased
when the fraction dose is modestly increased and the total dose is reduced.[31] This is confirmed by results of many
trials where
hypofractionated radiotherapy protocols are as effective as the conventional radiation of
50 Gy in 25 fractions, regardless of disease stage or type of breast surgery.[35-37]
Our results of chest wall recurrence, axillary failure and distant metastasis as 5/50 (10%), 3/50 (6%) and ;16/50
(32%) in group A versus 3/54 (5.6%), 4/54 (7%) and 15/54 (28%) in Group B. Main side effects noted were reversible
cutaneous reactions, difficulty in swallowing and nausea/ vomiting.
Conclusion
Our study justifies the routine use of HF for adjuvant
radiotherapy in women with breast cancer.
Hypofractionated radiation therapy resulted in OAS rate comparable to that of conventional
fractionation (50 Gy/ 25 fractions/ 5 weeks) without evidence of
inferior local tumour control or
higher adverse effects. This therapy can be recommended as safe and effective alternatives to
Conventional
fractionation for postmastectomy chest wall radiotherapy: Both the studied dose fractionation schedules
of 50 Gy /25 fractions/ 5 weeks, and 40 Gy/17 fractions /3.2 weeks are equally efficacious in terms of locoregional
control, acute and late toxicities. The shorter schedules in Arm B gives an added advantage of decreased overall
treatment time, which in turn can result in better patient compliance and decrease the work load of overburdened
department.
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