Major Trial: Partial Breast Radiation Good for Early Breast Cancer


Accelerated partial breast irradiation (PBI), although not 100% equivalent to whole-breast irradiation (WBI) for disease control in patients with early- stage breast cancer, yields outcomes so similar that it may be considered a viable treatment option for many patients, a long-term follow-up of the largest trial of its kind indicates.

“In an effort to improve quality of life for our patients, we studied whether or not we could reduce overall treatment times significantly down to a week or less by doing a technique known as partial breast irradiation, meaning limiting radiation only to the lumpectomy cavity region and accelerating treatment down to 5 days or less,” Frank Vicini, MD, MPH, Radiation Oncology Institute, Pontiac, Michigan, told a press briefing held here during the San Antonio Breast Cancer Symposium (SABCS) 2018.

“And while [we] cannot declare that WBI and PBI are equivalent in controlling local-in-breast tumor recurrence…the absolute difference in the 10-year cumulative incidence of IBTR [ipsilateral breast tumor recurrence] was only 0.7%…. So PBI may be an acceptable alternative to WBI for a proportion of women who undergo breast-conserving surgery,” he concluded.

The NRG (NSABP B-39/RTOG 0413) trial randomly assigned 4216 women who had recently undergone lumpectomy to receive either WBI or accelerated PBI. Women enrolled in the study had zero to three positive axillary nodes on study entry.

Twenty-five percent of the group had ductal carcinoma in situ (DCIS), 65% had stage I breast cancer, and 10% had stage II disease. The majority of women also had hormone receptor—positive tumors.

Women who were assigned to the WBI arm following adjuvant chemotherapy received daily treatment with 2.0 Gy/fraction of radiation totaling 50 Gy with a sequential boost to the surgical site.

Duration of WBI was 5 to 6 weeks, which was the standard of care at the time the trial was designed.

Those assigned to accelerated PBI prior to adjuvant chemotherapy received twice-daily treatment with 3.4 to 3.85 Gy given as either brachytherapy or 3D external-beam radiation.

Patients who underwent accelerated PBI received a total of 10 treatments over 5 to 10 days.

“The primary endpoint was to determine whether or not PBI results in IBTR — both DCIS and invasive breast cancer — was the same as it was for WBI,” Vicini noted.

At a median follow-up of 10.2 years, Vicini and colleagues documented a total of 161 IBTRs as first events — 90 among women treated with accelerated PBI, and 71 for those treated with WBI.

On the basis of the upper limit of the hazard ratio confidence interval, “PBI did not meet the criteria for equivalence to WBI in controlling IBTR,” Vicini reported.

On the other hand, the 10-year cumulative incidence of IBTR was very low in both groups, at 4.6% for patients in the accelerated PBI arm vs 3.9% for those in the WBI arm.

Furthermore, the difference in recurrence-free interval rates between the two arms — 91.8% in the accelerated PBI group vs 93.4% in the WBI group — was also negligible, at only 1.6%, Vicini added.

There were no differences in distant disease-free interval (DDFI), overall survival (OS), or disease-free survival (DSF).

For example, at 10 years, 96.7% of patients in the accelerated PBI arm were free of distant disease, as were 97.1% of patients in the WBI arm.

At the same follow-up point, 90.6% of patients in the accelerated PBI arm were still alive, as were 91.3% of those treated with WBI.

DSF rates were also very similar between the two treatment arms, Vicini noted.

Rates of grade 3 toxicity were similar between the two treatment groups, at 9.6% in the accelerated PBI group and 7.1% for those who received WBI. Rates of higher-grade toxicities were also very low and were similar between the two treatment groups.

Additional analyses are currently underway to evaluate secondary endpoints, including quality of life and cosmetic outcomes, Vicini noted.

“There have been many studies looking at quality of life [after radiotherapy], and you can imagine that quality of life is better with PBI — it’s pretty intuitive,” Vicini noted.

“And there is a pretty dramatic difference in the treatment interval from 5 to 7 weeks [with WBI] down to a week or less [with PBI], so as long as the control rates are the same, the trend in oncology now is ‘less is better,’ ” he added.

Furthermore, DDFI, OS, and DFS were not different between the two arms. Arguably, these endpoints are more important than recurrence, Vicini suggested, even though recurrence is an important event for patients.

“These findings suggest that the less burdensome radiation method of accelerated PBI may be an acceptable choice for many women,” Vicini said.

“So I think this is a very important study and it certainly is important to patients,” he concluded.

PBI Not Commonly Used

Asked by Medscape Medical News to comment on the findings, press briefing moderator Virginia Kaklamani, MD, University of Texas Health, San Antonio, noted that the majority of patients in the United States who are similar to those in the current study are still undergoing WBI. “PBI is not as common as it should be,” she noted.

“In the end, this is detrimental to patients, because if they have WBI, they have to come in for radiation therapy for at least 5 and sometimes 7 weeks, whereas otherwise [with PBI], they would be coming in for 5 to 10 days,” Kaklamani added.

She felt that findings from the current study “absolutely” should provide reassurance that radiation oncologists can offer accelerated PBI to patients who meet the same criteria as those included in the current study.

“We have many trials evaluating shorter radiation intervals,” Kaklamani noted.

“And the medical community needs to be implementing more PBI, and patients should also be asking for it,” she suggested.

Reshma Jagsi, MD, DPhil, professor and deputy chair, Department or Radiation Oncology, University of Michigan in Ann Arbor, felt that high-quality randomized trials such as this one in which shorter courses of accelerated PBI were compared to WBI are “critically important” to help inform treatment decisions that women who are diagnosed with breast cancer must make each year.

“These decisions depend on the patient’s own values and preferences,” Jagsi told Medscape Medical News in an email.

For example, some women might prefer to come in twice a day for a week rather than daily for many weeks to minimize disruption of their work schedule or because of problems involving transportation, whereas others might quite reasonably decide otherwise.

“The contribution of trials like these is to arm each woman with the precise risk information she needs to make the decision that is right for her,” Jagsi wrote.

“These trialists have made an enormous contribution through this work,” he concluded.

Major Trial: Partial Breast Radiation Good for Early Breast Cancer


SAN ANTONIO — Accelerated partial breast irradiation (PBI), although not 100% equivalent to whole-breast irradiation (WBI) for disease control in patients with early- stage breast cancer, yields outcomes so similar that it may be considered a viable treatment option for many patients, a long-term follow-up of the largest trial of its kind indicates.

“In an effort to improve quality of life for our patients, we studied whether or not we could reduce overall treatment times significantly down to a week or less by doing a technique known as partial breast irradiation, meaning limiting radiation only to the lumpectomy cavity region and accelerating treatment down to 5 days or less,” Frank Vicini, MD, MPH, Radiation Oncology Institute, Pontiac, Michigan, told a press briefing held here during the San Antonio Breast Cancer Symposium (SABCS) 2018.

“And while [we] cannot declare that WBI and PBI are equivalent in controlling local-in-breast tumor recurrence…the absolute difference in the 10-year cumulative incidence of IBTR [ipsilateral breast tumor recurrence] was only 0.7%…. So PBI may be an acceptable alternative to WBI for a proportion of women who undergo breast-conserving surgery,” he concluded.

The NRG (NSABP B-39/RTOG 0413) trial randomly assigned 4216 women who had recently undergone lumpectomy to receive either WBI or accelerated PBI. Women enrolled in the study had zero to three positive axillary nodes on study entry.

Twenty-five percent of the group had ductal carcinoma in situ (DCIS), 65% had stage I breast cancer, and 10% had stage II disease. The majority of women also had hormone receptor—positive tumors.

Women who were assigned to the WBI arm following adjuvant chemotherapy received daily treatment with 2.0 Gy/fraction of radiation totaling 50 Gy with a sequential boost to the surgical site.

Duration of WBI was 5 to 6 weeks, which was the standard of care at the time the trial was designed.

Those assigned to accelerated PBI prior to adjuvant chemotherapy received twice-daily treatment with 3.4 to 3.85 Gy given as either brachytherapy or 3D external-beam radiation.

Patients who underwent accelerated PBI received a total of 10 treatments over 5 to 10 days.

“The primary endpoint was to determine whether or not PBI results in IBTR — both DCIS and invasive breast cancer — was the same as it was for WBI,” Vicini noted.

At a median follow-up of 10.2 years, Vicini and colleagues documented a total of 161 IBTRs as first events — 90 among women treated with accelerated PBI, and 71 for those treated with WBI.

On the basis of the upper limit of the hazard ratio confidence interval, “PBI did not meet the criteria for equivalence to WBI in controlling IBTR,” Vicini reported.

On the other hand, the 10-year cumulative incidence of IBTR was very low in both groups, at 4.6% for patients in the accelerated PBI arm vs 3.9% for those in the WBI arm.

Furthermore, the difference in recurrence-free interval rates between the two arms — 91.8% in the accelerated PBI group vs 93.4% in the WBI group — was also negligible, at only 1.6%, Vicini added.

There were no differences in distant disease-free interval (DDFI), overall survival (OS), or disease-free survival (DSF).

For example, at 10 years, 96.7% of patients in the accelerated PBI arm were free of distant disease, as were 97.1% of patients in the WBI arm.

At the same follow-up point, 90.6% of patients in the accelerated PBI arm were still alive, as were 91.3% of those treated with WBI.

DSF rates were also very similar between the two treatment arms, Vicini noted.

Rates of grade 3 toxicity were similar between the two treatment groups, at 9.6% in the accelerated PBI group and 7.1% for those who received WBI. Rates of higher-grade toxicities were also very low and were similar between the two treatment groups.

Additional analyses are currently underway to evaluate secondary endpoints, including quality of life and cosmetic outcomes, Vicini noted.

“There have been many studies looking at quality of life [after radiotherapy], and you can imagine that quality of life is better with PBI — it’s pretty intuitive,” Vicini noted.

“And there is a pretty dramatic difference in the treatment interval from 5 to 7 weeks [with WBI] down to a week or less [with PBI], so as long as the control rates are the same, the trend in oncology now is ‘less is better,’ ” he added.

Furthermore, DDFI, OS, and DFS were not different between the two arms. Arguably, these endpoints are more important than recurrence, Vicini suggested, even though recurrence is an important event for patients.

“These findings suggest that the less burdensome radiation method of accelerated PBI may be an acceptable choice for many women,” Vicini said.

“So I think this is a very important study and it certainly is important to patients,” he concluded.

PBI Not Commonly Used

Asked by Medscape Medical News to comment on the findings, press briefing moderator Virginia Kaklamani, MD, University of Texas Health, San Antonio, noted that the majority of patients in the United States who are similar to those in the current study are still undergoing WBI. “PBI is not as common as it should be,” she noted.

“In the end, this is detrimental to patients, because if they have WBI, they have to come in for radiation therapy for at least 5 and sometimes 7 weeks, whereas otherwise [with PBI], they would be coming in for 5 to 10 days,” Kaklamani added.

She felt that findings from the current study “absolutely” should provide reassurance that radiation oncologists can offer accelerated PBI to patients who meet the same criteria as those included in the current study.

“We have many trials evaluating shorter radiation intervals,” Kaklamani noted.

“And the medical community needs to be implementing more PBI, and patients should also be asking for it,” she suggested.

Reshma Jagsi, MD, DPhil, professor and deputy chair, Department or Radiation Oncology, University of Michigan in Ann Arbor, felt that high-quality randomized trials such as this one in which shorter courses of accelerated PBI were compared to WBI are “critically important” to help inform treatment decisions that women who are diagnosed with breast cancer must make each year.

“These decisions depend on the patient’s own values and preferences,” Jagsi told Medscape Medical News in an email.

For example, some women might prefer to come in twice a day for a week rather than daily for many weeks to minimize disruption of their work schedule or because of problems involving transportation, whereas others might quite reasonably decide otherwise.

“The contribution of trials like these is to arm each woman with the precise risk information she needs to make the decision that is right for her,” Jagsi wrote.

“These trialists have made an enormous contribution through this work,” he concluded.

Liquid biopsy-based clinical research in early breast cancer


Highlights

This study evaluates the concept of targeting minimal residual disease (presence of circulating tumour cells).

Liquid-based biopsy clinical research is feasible.

This is the first study of its kind in adjuvant therapy of breast cancer.


Abstract

There is increasing evidence that breast cancer evolves over time under the selection pressure of systemic treatment. Today, treatment decisions in early breast cancer are based on primary tumour characteristics without considering the disease evolution. Chemoresistant micrometastatic disease is poorly characterised and thus it is not used in current clinical practice as a tool to personalise treatment approaches. The detection of chemoresistant circulating tumour cells (CTCs) has been shown to be associated with worse prognosis in early breast cancer. The ongoing Treat CTC trial is the first international, liquid biopsy-based trial evaluating the concept of targeting chemoresistant minimal residual disease: detection of CTCs following adjuvant chemotherapy (adjuvant cohort) or neoadjuvant chemotherapy in patients who did not achieve pathological complete response (neoadjuvant cohort). This article presents the rational and design of this trial and the results of the pilot phase after 350 patients have been screened and provides insights that might provide information for future trials using the liquid biopsy approach as a tool towards precision medicine

Follow-up strategies for women treated for early breast cancer.


BACKGROUND: Follow-up examinations are commonly performed after primary treatment for women with breast cancer. They are used to detect recurrences at an early (asymptomatic) stage. This is an update of a Cochrane review first published in 2000.

OBJECTIVES: To assess the effectiveness of different policies of follow-up for distant metastases on mortality, morbidity and quality of life in women treated for stage I, II or III breast cancer.

SEARCH METHODS: For this 2014 review update, we searched the Cochrane Breast Cancer Group’s Specialised Register (4 July 2014), MEDLINE (4 July 2014), Embase (4 July 2014), CENTRAL (2014, Issue 3), the World Health Organization (WHO) International Clinical Trials Registry Platform (4 July 2014) and ClinicalTrials.gov (4 July 2014). References from retrieved articles were also checked.

SELECTION CRITERIA: All randomised controlled trials (RCTs) assessing the effectiveness of different policies of follow-up after primary treatment were reviewed for inclusion.

DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for eligibility for inclusion in the review and risk of bias. Data were pooled in an individual patient data meta-analysis for the two RCTs testing the effectiveness of different follow-up schemes. Subgroup analyses were conducted by age, tumour size and lymph node status.

MAIN RESULTS: Since 2000, one new trial has been published; the updated review now includes five RCTs involving 4023 women with breast cancer (clinical stage I, II or III).Two trials involving 2563 women compared follow-up based on clinical visits and mammography with a more intensive scheme including radiological and laboratory tests. After pooling the data, no significant differences in overall survival (hazard ratio (HR) 0.98, 95% confidence interval (CI) 0.84 to 1.15, two studies, 2563 participants, high-quality evidence), or disease-free survival (HR 0.84, 95% CI 0.71 to 1.00, two studies, 2563 participants, low-quality evidence) emerged. No differences in overall survival and disease-free survival emerged in subgroup analyses according to patient age, tumour size and lymph node status before primary treatment. In 1999, 10-year follow-up data became available for one trial of these trials, and no significant differences in overall survival were found. No difference was noted in quality of life measures (one study, 639 participants, high-quality evidence).The new included trial, together with a previously included trial involving 1264 women compared follow-up performed by a hospital-based specialist versus follow-up performed by general practitioners. No significant differences were noted in overall survival (HR 1.07, 95% CI 0.64 to 1.78, one study, 968 participants, moderate-quality evidence), time to detection of recurrence (HR 1.06, 95% CI 0.76 to 1.47, two studies, 1264 participants, moderate-quality evidence), and quality of life (one study, 356 participants, high-quality evidence). Patient satisfaction was greater among patients treated by general practitioners. One RCT involving 196 women compared regularly scheduled follow-up visits versus less frequent visits restricted to the time of mammography. No significant differences emerged in interim use of telephone and frequency of general practitioners’s consultations.

AUTHORS’ CONCLUSIONS: This updated review of RCTs conducted almost 20 years ago suggests that follow-up programs based on regular physical examinations and yearly mammography alone are as effective as more intensive approaches based on regular performance of laboratory and instrumental tests in terms of timeliness of recurrence detection, overall survival and quality of life.In two RCTs, follow-up care performed by trained and not trained general practitioners working in an organised practice setting had comparable effectiveness to that delivered by hospital-based specialists in terms of overall survival, recurrence detection, and quality of life.