Hypofractionated radiotherapy for breast cancer Preliminary results from CMC Vellore Sham Sundar Christian Medical College Vellore Radiotherapy unit 1

Balukrishna S, Sunitha Susan Varghese, Selvamani B

Background Breast cancer is the most frequent cancer among women according to the Globocan 2012 update In India, it is the most common cancer contributing to 27% of all new cancers in women Radiation therapy is an integral part of multi-modality management

Radiotherapy in breast cancer The local cancer control and overall survival benefits of adjuvant RT for women with early breast cancer have been established by a systematic review of 17 RCT’s involving more than 10000 patients by EBCTCG In most studies 50Gy in 25 fractions was delivered in 5 weeks . This standard regimen is based on a historical assumption that breast cancer is less sensitive to changes in the dose per fraction than dose-limiting healthy normal tissues.

Rationale for hypofractionation Radiobiologic models suggested that a larger daily dose (hypofractionation) given over a shorter time (accelerated therapy) might be just as effective Such regimen may also be more convenient for patients and less resource- intensive than the standard schedule breast cancer might be much more sensitive to changes in radiotherapy dose per fraction than most other cancers. Fowler JF. The linear-quadratic for- mula and progress in fractionated radio- therapy. Br J Radiol 1989;62:679-94. Cohen L. Radiotherapy in breast cancer I. The dose–time relationship theoretical considerations. Br J Radiol 1952; 25: 636–42. Douglas BG. Superfractionation: its rationale and anticipated benefits. Int J Radiat Oncol Biol Phys 1982; 8: 1143–53.

START trials START A - 2 regimens (39 Gy and 42·9 Gy) of a 13 fraction regimen delivered over 5 weeks START B - 40 Gy in 15 fractions over 3 weeks 5 year and 10 year results - safe and effective Consistent with the hypothesis that breast cancer tissue and the dose- limiting normal tissues are similarly sensitive to fraction size

Purpose To review the acute toxicity and feasibility of hypofractionated regimen radiotherapy in post mastectomy and post BCS in our patient population We here report initial results for 51 patients treated at our center with the START-B type of fractionation.

Methods and Materials From January 2013 till July 2014 Reviewed patients who had hypo fractionated radiotherapy This included patients with all stages of breast cancer (If metastatic, had oligo bone metastases) Undergone BCS or mastectomy. Had received to chest wall or whole breast, supraclavicular fossa and axilla (where indicated) followed by tumour bed boost in BCS patients.

Methods and Materials Conventional or conformal technique. All these patients had weekly assessement by a radiation oncologist during radiotherapy and at 3 months after completion of radiotherapy. The oncologist grades skin changes according to RTOG Acute Radiation Morbidity Scoring Criteria other complaints of patients were also noted and addressed.

Methods and Materials Nearly 83% of patients had 3 months of follow up Skin changes at follow up were also noted The results were analysed using SPSS version 20

Results We had 51 female breast cancer patients

Age Median age 47

Patient characteristics Laterality Right Left 21 30 Surgery Mastectomy BCS 37 14 Technique Conventional Conformal Neoadjuvant chemotherapy Yes No 33 18

Co-morbidities Diabetes - 7 patients Hypertension - 9 patients Others - 4 patients Will have a chart or graph here

End of RT assessment Pie chart Two patients(4%) developed grade 3 dermatitis. Six patients(12%) had grade 2 and 25(50%) had grade 1 acute radiation dermatitis

Assessment at 3 months post RT 43 patients(83%) had 3 months follow up. Eight(15.68%) had persistent hyper pigmentation at the end of three months post RT. 11% had developed early onset of lymphedema Will represent these as graphs

Chemotherapy before RT Correlations Chemotherapy before RT End of RT reactions 3 months post RT changes and taxanes -0.15 -0.32 P - value 0.294 0.04 In these patients have a significant gap between start of adjuvant radiotherapy and surgery.

Correlations Technique End of RT reactions 3 months post RT changes Conformal 0.14 -0.314 P - value 0.325 0.045 Use of conformal technique had decreased incidence of 3 months post RT skin changes

End of RT reactions - likelihood ratio Correlations The patients were classified as 6 groups WB WB + SCF WB + SCF+ Axilla CW CW + SCF CW + SCF + Axilla analysis End of RT reactions - likelihood ratio p-value Whole breast 8.553 0.006 axilla 4.659 0.05

Lymphedema likelihood ratio Correlations Early onset of lymphedema was seen with use of axillary irradiation, though the association was significant it was confounded by other variables. analysis Lymphedema likelihood ratio p-value Axillary RT 14.5 0.001

Grade III reactions Will see skin dose, hot spot and if significant will add them here.

Conclusion The safety and efficacy of hypo fractionated regimen in conserved breast has been proven by many trials The acute skin toxicity with hypo fractionated regimen in our patient population is acceptable. In chest wall irradiation, the acute skin toxicity is significantly lower, when compared to whole breast irradiation.

Correlations Hypofractionated RT is feasible and very relevant in Indian population in terms of acute skin toxicity. Hypofractionated regimen should be encouraged to increase throughput and for cost minimization