Concurrent chemo-radiotherapy with paclitaxel in locally advanced breast cancer: prospective observational data collection

Introduction

Locally advanced breast cancers (LABC) account for 30-50% of all breast cancer diagnosed in India . LABC have been defined as tumors larger than 5 cm, those associated with bulky/fixed axillary lymph nodes or tumors with skin involvement. (TNM stage III, T3-4 or N2-3).  Treatment of LABC includes a multimodality approach comprising of chemotherapy, surgery and radiation therapy. Majority of the patients with LABC have inoperable disease at diagnosis due to a large tumor mass or axillary nodal fixity and are therefore treated with neoadjuvant chemotherapy (NACT) or concurrent chemoradiotherapy (CTRT) to downsize the tumor to make it operable.  The current standard of care for treating LABC is NACT followed by surgery and sequential radiotherapy. However, few centres in the World including Cancer Institute use neoadjuvant CTRT in addition to NACT for downsizing LABC. Pathological complete response (CR) to neoadjuvant treatment is an important surrogate marker for Overall Survival (OS) in breast cancer especially in triple negative and Her2 positive subset.  Pathological CR rates have over the years increased in LABC with the incorporation of taxanes and anti-Her2 therapy in Her2 positive breast cancer . Studies have shown that neoadjuvant CTRT in LABC improves pathological CR. However, majority of these studies are retrospective in nature and have small number of patients. Literature has also shown that CTRT in LABC is safe and tolerable in majority of the patients. The rationale of using chemotherapy combined with radiation is that chemotherapy will act as a radiosensitizer, thereby, enhancing the effect of radiation and tackling distant micro-metastasis. The common toxicities of CTRT are skin morbidity and neutropenia.  Cancer Institute has been practicing CTRT in LABC for last 5 decades. Over the years the choice of chemotherapy regimens and radiation planning at Cancer Institute has changed. The present study aims to collect data prospectively regarding the use of concurrent CTRT with paclitaxel in LABC at our centre and assess it safety, efficacy and effect on long-term survival outcome.

Rationale of Study

It is important to collect prospective data on CTRT with paclitaxel in breast cancer at Cancer Institute to assess its efficacy and safety and understand the benefit of the practice to our patients. There is lesser chance of missing important data in prospective study when compared to retrospective study. The data will help in planning future randomized trials with CTRT in breast cancer at Cancer Institute. Publication of CTRT data in the future will require ethical clearance.

Aim of Study

·       To evaluate the safety, tolerability and efficacy of concurrent chemo-radiotherapy (CTRT) with paclitaxel in locally advanced breast cancer (LABC)

Primary Objective

·       To assess the pathological response rate with CTRT in LABC

Secondary Objective

·     To assess toxicity of CTRT in LABC

·     To assess event free survival (EFS) with use of CTRT in LABC.

Materials and Methods

Study type/design:  prospective, observational, data collection

Study site:  Cancer Institute (WIA), Chennai

Study enrolment period:4 years

Follow-up duration: 5 years from date of last enrollment

Expected enrollment:  50 patients/year (Total 200 patients)

Cancer Institute Practice

For the past 60 years, Cancer Institute has been practicing concurrent chemoradiation in breast cancers. The Institute has been a pioneer in introducing CTRT in LABC. LABC in developed countries is much smaller and usually operable in contrast to LABC in India where the majority of the patients present with bulky tumors that are not amenable to upfront surgery and therefore, Cancer Institute started the practice of adding chemotherapy to enhance the effect of radiation, especially in inoperable breast cancers to make it operable during an era where limited chemotherapy agents were available. With the advent of newer chemotherapy agents, the use of concurrent CTRT has come down, but even today we see patients with bulky LABC tumors that do not respond to NACT alone but have responded to treatment with concurrent CTRT with good tolerability. Also, in tumors with skin involvement, CTRT helps to sterilize the skin and ensures negative margins which in turn leads to good pathological response rates, this may translate to better survival and lesser local recurrence rates.

A retrospective review conducted at cancer institute of 100 patients who received neoadjuvant CTRT with taxol in LABC (Stage III) during 2015-2016 has been published in the Indian Journal of Cancer(     Neoadjuvantconcurrent chemoradiation in male breast cancer: Experience from a tertiarycancer center. Indian J Cancer. 2019;56(1):37-40.)

. In this study, pCR was observed in 12/22 (54.5%) patients with the triple-negative disease, 10/34 (29.4%) patients with hormone receptor-positive disease and 12/35 (34.2%) patients with Her2 positive disease. The 2-year event-free survival (EFS) and OS for the entire cohort was 88 % and 73.1 % respectively.

We were the first to report the use of neoadjuvant concurrent CTRT in male breast cancer. The study included 31 male patients with LABC. None of the patients showed a pCR in contrast to what has been seen in female patients with LABC.

Hence we propose to do a prospective observational study inorder to capture data accurately and for better reporting of safety and efficacy.