Radiotherapy In Metastatic Breast Cancer Research Articles

Concurrent Use of Abemaciclib and Radiotherapy in Metastatic Breast Cancer Patients: A Single-Center Experience.

There is little evidence regarding the safety and efficacy of the combination of abemaciclib plus radiotherapy (RT). The majority of studies investigated the combination of RT with palbociclib or ribociclib reporting that hematological toxicity is common. Given the unique toxicity profile of abemaciclib with greater gastrointestinal toxicity compared to hematological toxicity, we wanted to evaluate the toxicity of the combination with RT in metastatic breast cancer (BC) patients. Patients with histologically proven metastatic or locally advanced BC treated with RT and concurrent abemaciclib were selected. Toxicity was assessed according to the NCI-CTCAE V4.0. Thirty-two metastatic sites were treated in 19 patients and analyzed. All patients received abemaciclib during the RT course. A total of 68% of patients received a full dose of abemaciclib during RT. Also, 71.9% of patients received a palliative intent (median dose = 30 Gy, range = 8-30 Gy), and 26.3% were treated for 9 oligo-metastatic or oligo-progressive sites of disease with stereotactic body RT (median dose = 30 Gy, range 21-30 Gy, given in 3-5 fractions). Overall, the rate of G3 toxicity was 15.7%. The rate of G3 hematological toxicity was 10.6% (2/19 patients, one G3 neutropenia and one G3 anemia). No patient presented diarrhea, including those treated for RT sites close to the bowel. One patient developed G3 skin toxicity. Pain significantly improved after RT (mean value NRS pre-RT = 3.9, SD = 3.07; mean value NRS after RT = 0.9, SD = 0.46; p < 0.0001). Abemaciclib and concomitant RT seem well tolerated showing acceptable toxicity.

440P Palliative radiotherapy in metastatic breast cancer: Does molecular subtype predict patient response to radiotherapy?

440P Palliative radiotherapy in metastatic breast cancer: Does molecular subtype predict patient response to radiotherapy?

Outcomes of extra-cranial stereotactic body radiotherapy for metastatic breast cancer: Treatment indication matters

Background and purposeTo summarize the clinical outcomes of stereotactic body radiotherapy (SBRT) for metastatic breast cancer (mBC) from a large institution. Materials and methodsPatients with mBC who received extra-cranial SBRT to metastatic lesions from 2011 to 2017 were identified. Treatment indications were: oligometastases, oligoprogression, and local control of dominant tumor (CDT). Endpoints included overall survival (OS), progression-free survival (PFS), local control (LC) and cumulative incidence of starting/changing chemo or hormonal therapy (SCT). Univariate and multivariate analyses were used to identify predictive factors. ResultsWe analyzed 120 patients (193 treated metastatic lesions) with a median follow up of 15.25 months. 1-and 2-year LC rates were 89% and 86.6%, respectively. 1-and 2-year OS rates were 83.5% and 70%, respectively, with treatment indication and molecular subtype being the predictive factors on MVA. 1-year OS was 91.0%, 78.5% and 63.9% for oligometastases, oligoprogression and CDT, respectively (p = 0.003). The worst OS was seen in basal subtype with 1-and 2-year OS rates of 59.2% and 39.5% (p = 0.01). Treatment indication was found to be predictive for PFS and lower rates of SCT on MVA. 1-and 2-year PFS rates were 45% and 32%, respectively. The 1-year PFS for oligometastases, oligoprogression, and CDT was 66%, 19.6%, and 14.3%, respectively (p < 0.001). The cumulative incidence of SCT at 1-year was 12% for oligometastases, 39.7% for oligoprogression and 53.3% for CDT (p < 0.001). ConclusionPatients treated for oligometastases have better OS and PFS than those treated for oligoprogression or CDT. SBRT may delay SCT in mBC patients, particularly those with oligometastases. SBRT provided an excellent LC in mBC patients.

EP-1270 Outcomes and toxicity of stereotactic radiotherapy for metastatic breast cancer -a retrospective study

EP-1270 Outcomes and toxicity of stereotactic radiotherapy for metastatic breast cancer -a retrospective study

Ribociclib plus letrozole and concomitant palliative radiotherapy for metastatic breast cancer

Ribociclib is a CDK4-6 inhibitor recently approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) as first-line treatment for metastatic breast cancer (MBC). The pivotal trial showed a significant improvement in progression-free survival when compared to endocrine therapy alone. However, having a challenging toxicity profile in comparison with exclusive endocrine therapy, safety may be a concern when combined to radiotherapy (RT) with palliative approach.There are no available published data regarding the combination of ribociclib and palliative RT. We reported our preliminary experience on the first five patients treated at the Radiation Oncology Unit of the Florence University (Florence, Italy) giving palliative RT concomitant to ribociclib plus letrozole as first-line treatment for MBC.

Abstract P1-17-06: Outcomes of central nervous system radiotherapy for metastatic breast cancer: The Royal Marsden experience 2000 - 2016

Abstract Background: Breast cancer (BC) is one of the most common malignancies affecting women. Brain metastatses (BM) are frequently seen in BC, and can have devastating consequences with significant associated morbidity and mortality. Whole brain radiotherapy (WBRT) is commonly used to treat BM, with variable use of stereotactic radiotherapy (SRT). This study reports on the outcomes of BC patients with BM who received central nervous system (CNS) radiotherapy over a 17-year period at the Royal Marsden Hospital (RMH). Methods: We included all BC patients who had WBRT with or without SRT for intra-parenchymal BM secondary to BC at RMH between 2000 and 2016 inclusive. Instances of meningeal involvement were excluded from analysis. Data collected included age, histological subtype, tumor grade, stage at original BC presentation, receptor status, date of BM diagnosis, number of metastases, size of largest BM, Eastern Cooperative Oncology Group (ECOG) score, presence of extra-cranial metastases (ECM), neurosurgery (NS) and stereotactic radiotherapy (SRT) details, and date of last follow up or death. Univariate and multivariate analyses were performed to analyze the effect of each variable on overall survival (OS) from date of BM. Results: A total of 426 patients were included with a median age of 54 years at BM diagnosis and a median time to BM from BC diagnosis of 43 months. At diagnosis, 94% had invasive ductal carcinoma (IDC) and 70% had Grade 3 disease. Stage IV disease at original BC presentation was seen in 18% of patients. Estrogen receptor (ER+) was positive in 57% (n = 236), progesterone receptor (PR+) in 44% (n = 147), and HER2 (HER2+) in 44% (n = 166). Twenty-two percent (n = 89) were triple negative (TN). Median number of BM was 4 (range 1 – 205) and 20% (n = 72) of patients had only 1 BM. Average size of the largest lesion was 26 mm (range 1 – 75). The ECOG score was 0 – 1 in 61% of patients. Ten percent of patients (n = 44) underwent SRT and 10% (n = 43) underwent NS. Three hundred and eighty patients had died at the time of analysis. Median OS from date of BM was 6.4 months. On univariate analysis, age &amp;lt; 60 years at BC diagnosis (8.1 vs. 4.0 months, p = 0.0007) and BM diagnosis (8.0 vs. 5.6 months, p = 0.03), ECOG status 0-1 (9.6 vs. 4.0 months, p = &amp;lt;0.0001), ER+ (8.0 vs. 6.0 months, p = 0.0007), PR+ (7.6 vs. 6.9 months, p = 0.04), HER2+ (10.5 vs. 5.6 months, p &amp;lt; 0 .0001), SRT (20.3 vs. 5.9 months, p &amp;lt; 0.0001) and NS (20.3 vs. 6.2 months, p &amp;lt; 0.0001) significantly predicted for improved OS. Triple negative status predicted for worse survival (5.6 months vs. 8.1 months, p &amp;lt; 0.0001). On multivariate analysis, ECOG status, ER+, HER2+, treatment with SRT and NS were independent predictors for OS. Conclusions: This study confirms substantial heterogeneity of prognosis in patients with BM from BC, with significantly improved survival in patients selected for SRT or surgery. Further studies are required to optimize the role of CNS radiotherapy techniques such as SRT and hippocampal sparing WBRT in patients with a favorable prognosis. Citation Format: Kothari G, De Ieso PB, Mohammed K, Ross GM. Outcomes of central nervous system radiotherapy for metastatic breast cancer: The Royal Marsden experience 2000 - 2016 [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-17-06.

Radiotherapy for Metastatic Breast Cancer in Mexico: Results from the 2015 National Survey.

Radiation therapy is a keystone to improve survival and quality of life in breast cancer patients. In Mexico, however, scarce information is available on the obstacles faced by radio-oncologists to provide appropriate treatment. To determine the most frequent issues faced by physicians to provide radiation therapy for metastatic breast cancer in Mexico. A survey of 16 multiple-choice questions to be answered electronically by 167 radio-oncologists currently working in Mexico was designed and thereafter analyzed for differences between private and public practices, based on the responses from the surveyed participants. 98.5% of surveyed responders attended patients with breast cancer. We observed a significant difference between private vs. public practice for the main difficulties in providing radiation therapy, with an increased frequency (85.8%) of "treatment cost by itself" in private practice vs. 50.7% in public practice (p < 0.05). Significant differences were observed in the "Time to initiate treatment" question, with "Less than one week" as the response in 86% of those physicians in private practice vs. 50% for those in public practice (p < 0.001). Using a survey targeted at radio-oncologists, we analyzed the most important obstacles for accessing radiation therapy for metastatic breast cancer in Mexico. This information may be useful for healthcare decisions related to radiation therapy in women with breast cancer in Mexico.

Safety of eribulin mesylate and concomitant radiotherapy for metastatic breast cancer: a single-center experience.

This study evaluates, for the first time, the safety of eribulin in metastatic breast cancer patients concomitantly treated with palliative radiotherapy (RT). Patients & materials: A total of 17 patients were pretreated for metastatic breast cancer. Patients received eribulin mesylate and bone RT. The most frequent grade 3 hematologic adverse events were neutropenia (56%) and anemia (20%). Mean pain score decreased from 2 (baseline) to 0.7 (end of observation). Analgesic score remained stable (1.8 vs 1.6). Bone pain scores dropped within a few weeks and remained below baseline values throughout the analysis. The overall response rate was 29%, and the clinical benefit rate was 59%. Eribulin is characterized by a manageable safety profile also when combined with palliative RT.

Fractionation of palliative radiotherapy in metastatic breast cancer: Selection and survival.

201 Background: Various schedules of palliative radiotherapy (pRT) are prescribed for metastatic breast cancer (MBC) patients. Length of treatment can vary from a single day to three weeks. Single fraction pRT provides similar pain relief vs. multi-fraction pRT for bone metastases, but retreatment rates are higher. In the era of targeted and hormonal therapy, patients with MBC can survive many years after their initial diagnosis. We investigated whether patients with MBC who were prescribed single fraction pRT had poorer prognoses and experienced shorter survival than patients who were prescribed multi-fraction pRT. Methods: Patients at a single institution with MBC underwent pRT, with fractionation schedules including 8 Gy in 1 fraction (fx), 20 Gy in 5 fx, 30 Gy in 10 fx, 37.5 Gy in 15 fx between 2001-2015. 392 treatments were prescribed (109/241/29/13 in each regimen as above). Date of death was obtained from medical records, Social Security Death Index, or published obituaries. Patients who were alive or whose date of death could not be determined were censored at the date of their last encounter. Survival was calculated from the start of treatment to the date of death or censorship. Results: Patients treated with 37.5 Gy in 15 fx (MS 20 months, p = 0.002) or 30 Gy in 10 fx (MS 22 months, p = 0.03) experienced longer survival than patients treated with 8 Gy in 1 fx (MS 8 months). There was no significant survival difference between patients treated with 20 Gy in 5 fx (MS 18 months, p = 0.49) and patients treated with 8 Gy in 1 fx. There was no significant survival difference between patients treated by the three multi-fractionation schedules. Conclusions: MBC patients who were prescribed 37.5 Gy and 30 Gy lived longer than patients who were prescribed 8 Gy of pRT. No statistically significant difference was found between patients who were prescribed 20 Gy compared to 8 Gy, possibly due to the lower number of patients who received these regimens. Single fraction pRT was more likely to be prescribed to patients who would ultimately have shorter survival. More research is needed, ideally across multiple institutions, to explore the correlation between physician estimation of patient survival and selection of pRT regimen for patients with MBC.

Abstract P1-15-21: Safety of eribulin mesylate and concomitant palliative radiotherapy for metastatic breast cancer: A single-center experience

Abstract Background. Eribulin mesylate is a recently approved new therapeutic option for patients with metastatic breast cancer (BC). It is a structurally simplified synthetic analogue of halichondrin B that inhibits the growth phase of microtubule dynamics and sequesters tubulin into non-productive aggregates, inhibiting microtubule polymerization, and inducing irreversible mitotic block at G2-M phases and apoptosis. Three phase II trials of eribulin in chemotherapy pretreated advanced BC patients were completed. In all these studies, eribulin showed a manageable tolerability profile, with most of the common drug-related adverse events being neutropenia, fatigue, alopecia, nausea, and anemia, according to the phase I trials findings. Eribulin was also associated with an overall low incidence of peripheral neuropathy. When new chemotherapy options become available, one of the most important questions regarding the sequence of treatments is to address the safety of concomitant radiation treatments. Recently has been reported a clinical case treated with eribulin mesylate and whole-brain radiotherapy (RT) in a heavily pretreated patient with multiple visceral and bone metastases from triple negative breast cancer. In our knowledge this is the first analysis focusing on the safety of eribulin in patients concomitantly treated with palliative RT. Methods. All patients where heavily pretreated for metastatic breast cancer (≥4 previous chemotherapy lines), including anthracyclines and taxanes-based regimens. Patients received eribulin mesylate (1.4 mg/m2 i. v., on days 1 and 8, of a 21-day cycle). Tumor response was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST), every 8 weeks, or sooner if disease progression was suspected. Safety was assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Measures of bone-pain scores and analgesic consumption were evaluated at each visit, using a patient-rated scoring system. Results. Concerning 25 consecutive treated patients, median performance status at baseline was 2 (range 1-3). A median of 4 cycles of eribulin (range 2-10) were administered. All patients received palliative bone RT during eribulin treatment. No suspension or delay in chemotherapy administration was necessary. 20/25 cases underwent spinal bone irradiation; 8 Gy in single fraction was given in 13/25 patients, 12 cases received 20 Gy in 5 fractions. The overall response rate was 24% and the clinical benefit rate was 40%. Toxicity was manageable and in line with main published series; the most frequent grade 3 hematologic adverse events were neutropenia (56%), and anemia (20%). Bone pain scores fell within a few weeks and remained below baseline value throughout the analysis. The mean pain score was 2 at baseline and 0.7 at the end of observation period. The mean analgesic score was 1.8 at baseline and 1.6 at the end of follow-up. Conclusions. Our clinical practice experience supports the evidence that eribulin has clinical activity and is characterized by a manageable safety profile, also when combined to palliative RT. Concomitant treatment is feasible also in patients heavily pretreated, and with poor performance status. Citation Format: Icro Meattini, Vieri Scotti, Carla De Luca Cardillo, Beatrice Detti, Vanessa Di Cataldo, Lorenzo Livi. Safety of eribulin mesylate and concomitant palliative radiotherapy for metastatic breast cancer: A single-center experience [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-15-21.

139IN - Combining Systemic Treatment with Radiation Therapy: Quantifying the Therapeutic Gain

ABSTRACT Optimal systemic therapy still is the most important modality in metastatic breast cancer. However, improved imaging and diagnostic tools combined with biological targeted systemic therapies and possibilities to 3D conformal and stereotactic radiotherapy make new possibilities in multidisciplinary approaches of metastatic/oligometastic breast cancer. The presentation will review data (as well as paucity of data) regarding effects of extensive locoregional radiotherapy in metastatic breast cancer, concurrent radiochemo approaches in advanced breast cancer and data on combination of radiotherapy and systemic therapy in the treatment of metastatic disease in different sites. The selection bias of the published retrospective series will be addressed as well as what we may learn in the future from analyzing treatments and patient related factors in long-term survivors among patients with metastatic breast cancer. Disclosure: The author has declared no conflicts of interest.

Is there still a role for radiotherapy in metastatic breast cancer?

The question in the title could be considered rhetorical if the questioner assumes that all the undoubted therapeutic advances – bisphosphonates, cytotoxics, targeted and hormonal therapies – have cured advanced breast cancer (ABC) and no longer fail. That women still die with and from ABC and, in so doing, require palliation is evidence that radiotherapy (RT) still has a role. The most obvious role is in the palliation of bone metastases. These are not restored to normal integrity permanently by any current systemic therapies; fractures threaten or occur; pain is common; and spinal metastases can and do cause cord compression. RT still has a beneficial and proven role in all of these situations. Intracranial secondaries have also been shown to respond to either whole brain RT or stereotactic RT (SRT) or a combination of both and SRT may obviate the need for invasive surgical excision. Soft tissue disease – as seen in skin, compressive lymphadenopathy and the orbit – will also respond to RT. Where RT has always had much less of a role is in the treatment of solid visceral metastases such as in lung or liver. Proponents of the newer RT technologies such as Intensity Modulated RT (IMRT) or extracranial SRT for oligometastatic disease need to be aware that in breast cancer, unlike some other malignancies such as colonic or renal carcinomata or the sarcomata, the disease is seldom oligometastatic even in one organ. Evidence is required of efficacy before such sophisticated and expensive therapies are applied. When RT is prescribed for palliation in ABC, it should be delivered according to best available evidence, of which there is much, in terms of numbers of fractions, dose and technique. This will maximise the palliative effect and minimise not just the toxicity but also the potential socio-economic and psychological stress, impact and inconvenience of a treatment that, while absolutely essential to reduce symptoms, is unlikely to prolong life. Quality of life is unlikely to improve with prolonged therapeutic interventions. And, in delivering a high quality palliative RT service, radiation oncologists must work closely with their other colleagues in the broader palliative multidisciplinary team that includes not only surgical and medical oncologists but also support staff and palliative medicine physicians.

Radiotherapy in patients with metastatic breast cancer

Radiotherapy in metastatic breast cancer is aimed at palliation of symptoms and prevention or improvement of functional deficits. The majority of randomised controlled trials focus on the effect of different fractionation regimens and total radiation doses in the treatment of bone and brain metastasis, and spinal cord compression. Breast cancer patients were well represented in these trials and showed usually considerably better outcome than most other investigated cancers, indicating that metastatic breast cancer is a radiosensitive disease. Typically, about 80−90% of patients with metastatic breast experience significant clinical response to local radiotherapy [1,2]. None of these trials had a control arm without radiotherapy. Overall survival was either not investigated or a secondary end-point with the exception of trials on brain metastasis. Randomised trials on the potential impact of local radiotherapy of primary tumours with or without surgery or asymptomatic distant metastasis on survival have not been conducted. Keeping in mind these limitations, the possible impact on survival of local radiotherapy to the primary site and distant metastasis will be briefly reviewed in the following.

Effects of magnetic induction hyperthermia and radiotherapy alone or combined on a murine 4T1 metastatic breast cancer model

Purpose: The purpose of this study was to explore the effects of MIH and radiotherapy alone or combined on metastatic breast cancer and the underlying mechanisms.Materials and methods: A murine 4T1 metastatic breast cancer model was established and randomly assigned into four treatment groups: C (control), R (radiotherapy), MIH, and MIH + R. Tumour volume, lung metastasis, the expression of Bax and MMP-9, T cell subsets, serum cytokine levels, and mouse survival were evaluated.Results: Group MIH + R showed significantly reduced tumour volume, lung metastasis, improved survival and increased Bax expression compared to group R or MIH (P < 0.05). MMP-9 expression in the primary tumour tissue was significantly increased in group R compared to the other groups (P < 0.05), which could be brought down by combined MIH treatment. Group MIH + R showed significantly higher CD4+ T cell percentage as well as CD4+/CD8+ cell ratio than group R (P < 0.05). Group MIH + R showed significantly higher serum levels of TNF-α, IFN-γ and IL-2 than group R (P < 0.05).Conclusions: MIH not only promotes the tumour-cell killing effect of radiotherapy through Bax-mediated cell death, but also improves cellular immunity in mice under radiotherapy and decreases the potential of radiotherapy to enhance MMP-9 expression, which leads to significant improvement in lung metastasis and overall survival of mice under combined treatment of MIH and R. This study is the first to have explored the effect of combined hyperthermia and radiotherapy on tumour metastasis and the underlying mechanisms. It provides insights into the application of MIH as an adjuvant to radiotherapy for metastatic breast cancer.

Bisphosphonate treatment and radiotherapy in metastatic breast cancer

Patients with advanced breast cancer frequently develop metastasis to bone. Bone metastasis results in intractable pain and high risk of pathologic fractures due to osteolysis. The treatment of breast cancer patients with bone metastases requires a multidisciplinary approach. Radiotherapy is an established treatment for metastatic bone pain. It may be delivered either as a localized low dose treatment for localized bone pain or systemically for more widespread symptoms. Bisphosphonates have been shown to reduce morbidity and bone pain from bone metastases when given to patients with metastatic bone disease. In vivo studies indicate that early bisphosphonates administration in combination with radiotherapy improves remineralization and restabilization of osteolytic bone metastases in animal tumor models. This review focused on a brief discussion about biology of bone metastases, the effects of radiotherapy and bisphosphonate therapy, and possible mechanisms of combination therapy in metastatic breast cancer patients.