Study design and patients

All consecutive patients with LABC who received adjuvant breast/chest wall irradiation along with SCF and IMN using HT technique at our institute between November 2014 and May 2019 were identified. Electronic medical records of 65 patients were reviewed for clinico-pathological details, and treatment history including the radiotherapy treatment planning parameters and acute toxicities. The clinical, treatment and pathological details have been reported in Tables 1, 2, and 3, respectively. The diagnosis of IMN involvement was made on the cross-sectional imaging done for staging. No cytological or histological confirmation of the IMN involvement was attempted. None of the patient received prophylactic IMN irradiation. This study was approved by the institutional ethics committee, and waiver of consent was granted.

Table 1.

Clinical characteristics

^a One patient had occult primary.

* 2 patients had contralateral axillary nodal metastases, 2 patients had solitary liver metastases and 4 patients had sternal metastases.

cT: clinical tumour stage; cN: clinical nodal stage; cM: clinical metastatic stage; ER: estrogen receptor; PR: progesterone receptor; CT: computed tomography; PET: positron emission tomography.

Table 2.

Treatment characteristics

* One patient had occult primary hence did not undergo primary surgery.

BCS: breast conserving surgery; MRM: modified radical mastectomy; AI: aromatase inhibitor; TAM: Tamoxifen; OS: Ovarian suppression.

Table 3.

Pathological characteristics

IBC: invasive breast carcinoma; Tis: tumour insitu; pT: Pathological tumour stage; pN: pathological nodal stage.

The median age was 45 years (range 23–68). All patients treated with curative intent were included. Eight patients had oligometastatic disease: 4 had disease in the sternum out of which one patient also had ipsilateral 5^th rib metastases and one also had parasternal disease. Two patients had solitary nodule in liver which were treated with radiofrequency ablation (RFA). Two patients with contra-lateral axillary metastases underwent bilateral axillary dissection.

Sixty-one patients received neo-adjuvant chemotherapy (NACT), while 4 patients underwent upfront surgery followed by chemotherapy as they were operated outside. All patients received anthracyline and taxane-based chemotherapy. Thirty-four patients had partial response and 23 patients had complete response, 2 had stable disease whereas 2 had progression (response assessed clinic-radiologically). All 36 hormone-receptor-positive patients received appropriate hormonal therapy as per institutional protocol. Nineteen of the 22 patients who were HER 2neu positive received trastuzumab in neo-adjuvant or adjuvant setting of which only 12 patients received maintenance therapy due to affordability issues.

Immobilisation and volume delineation

All patients were immobilised in supine position in a customised vacuum bag with both arms abducted over head. Planning images without contrast with 3–5 mm slice thickness were acquired from the level of mandible to mid-abdomen on CT simulator (GE DISCOVERY IQ). Images were exported to the tomotherapy treatment planning system (Accuray Inc., Sunnyvale, CA, version 5.1.0). Clinical reference using wire placement on patient’s body during CT acquisition aided in the delineation of clinical target volume (CTV) for the breast and/or chest wall. The target volumes were contoured according to the ESTRO guidelines. ^{Reference Offersen, Boersma and Kirkove16} In all patients, primary (breast/chest wall) and regional nodes comprising of SCF and IMC were included in the radiotherapy targets, while sternum was included in four patients with sternal metastases. Axilla was not irradiated as full axillary clearance was performed in all patients as per institutional protocol.

A uniform 5 mm margin to the CTV was given for generating the planning target volume (PTV) for the primary as well as nodes and tumour bed (TB). The PTV primary was cropped from the skin by 5 mm. The CTV was restricted to the pectoral muscles posteriorly but included only in T4 disease especially post mastectomy. For IMN, one intercostal space below the involved space was included in the target volume. Additional targets like the sternum was treated in 4 patients, whereas 2 patients had bilateral IMN irradiation. Departmental guidelines for TB delineation were followed taking into account the seroma, base clips, post-operative changes and wired surgical scar. Thoracic OARs: individual lung, total lung, heart, left anterior descending artery (LAD), contra-lateral(C/L) breast, oesophagus, spinal cord and thyroid were contoured. Brachial plexus dosimetry was not included as none of the patients had axillary radiation and also dose prescribed was below the tolerance limit of brachial plexus.

Helical tomotherapy planning

A jaw width of 5·02 cm was used for planning with pitch of 0·287 and maximum modulation factor used was 3. The dose prescribed to the primary and nodal targets was 50 Gy in 25 fractions, and all cases of breast conserving surgery (BCS) received a SIB to the PTV_Boost. SIB was given in 16 patients out of which 12 received 61 Gy and 4 received 58 Gy and one received sequential boost. One patient with occult primary did not receive boost. The planning objectives were defined to achieve coverage of 95% of the target volume with 95% of the prescribed dose (it was difficult to achieve 98% dose coverage). However, in cases with unfavourable anatomy, a coverage up to 90% was considered acceptable (Figure 1). Target objectives were chosen according to priority – PTV IMN followed by PTV SCF then PTV CW/BR. For OARs, the planning objectives were set as V20 Gy < 35% for total lung, whereas V25 Gy < 10% for heart as per QUANTEC guidelines. ^{Reference Kong, Ritter and Quint17} OARs according to priority were set LAD > Heart high dose (high dose region defined as area within 2·5 margin from PTV; whereas low dose is area obtained after subtracting OAR from high dose region) > Lung HD > C/L Breast > Heart LD > Lung LD > C/L Lung > Oesophagus > Spine > Body.

Figure 1.

Coverage of <95% of target volume.

Standard criteria for target volumes (volumes receiving 95, 90 and 107%, mean dose) and OARs (mean, maximum, volume receiving 5 Gy (V5 Gy), V10 Gy, V20 Gy, V30 Gy, V40 Gy) were used for reporting the dose volume parameters (Tables 4 and 5).

Table 4.

Dosimetric parameters indicative of planning target volume (PTV) coverage

TB: tumour bed; SCF: supraclavicular fossa; IMN: internal mammary node.

Table 5.

Dose and volume parameters for organs at risk

* Dose maximum (not mean dose).

C/L: contralateral, LAD: left anterior descending artery.

Statistical analysis

The patient, treatment and pathological characteristics have been reported as numbers and percentage. The dosimetric characteristics have been reported as mean value with range. Actuarial survival curves were generated by Kaplan–Meier method and compared using log – rank test for univariate analysis. Disease-free survival (DFS) was measured as the time between initial treatment (date of surgery) and first evidence of disease progression. Overall survival (OS) was calculated from the date of initial treatment to date of death from any cause or last follow-up. Disease recurrence in the ipsilateral breast/chest wall was defined as local recurrences and those in ipsilateral axillary, supraclavicular, or IMN were defined as regional recurrences. Multivariate analysis was done by Cox proportional–hazards model and it included factors significant (p-value < 0·05) on univariate analysis. The analysis was done in Statistical Package for Social Sciences (SPSS) version 22.