Initial Efficacy Results of RTOG 0319: Three Dimensional Conformal Radiation Therapy (3D-CRT) Confined to the Region of the Lumpectomy Cavity for Stage I/II Breast Carcinoma

Reviewer: Christine Hill, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: September 22, 2008

Presenter: F.A. Vicini
Presenter's Affiliation: William Beaumont Hospital, Royal Oak, MI
Type of Session: Scientific


  • Breast conservation treatment, consisting of lumpectomy followed by radiotherapy, has been demonstrated in large trials to be equivalent to mastectomy for treatment of early-stage breast cancer (Fisher B, NEJM, 2002).
  • Breast radiotherapy in these trials has consisted of radiation delivered to the whole breast, followed by a boost to the tumor bed.
  • Recently, the concept of partial breast radiotherapy following lumpectomy has gained interest. Delivering radiotherapy only to the tumor bed, rather than the whole breast, may allow full dose radiation to be given in a hypofractionated manner. Benefits of accelerated partial breast irradiation (APBI) may include shorter treatment time (1 week total treatment rather than 6-7 total weeks), reduced dose to neighboring organs at risk including the heart, ipsilateral lung, and chest wall, and reduced contralateral breast dose..
  • Although APBI is being employed in many centers, a relative paucity of long-term data exists regarding outcome after this type of treatment.
  • The Radiation Therapy Oncology Group (RTOG) published the results of a phase I/II trial, RTOG 0319, designed to evaluate APBI using three-dimensional conformal radiotherapy (3D-CRT) confined to the tumor bed in 2005 (Vicini F, IJROBP, 2005).
    • This trial was designed to measure reproducibility, with a primary goal of demonstrating feasibility of applying a 3D CRT technique in a multicenter setting.
    • Patients enrolled on RTOG 0319 received 38.5 Gy in 10 fractions, delivered on a twice-daily schedule (5 days total). 
    • The clinical target volume (CTV) included the lumpectomy cavity plus a 10 – 15 mm margin bounded by a 5 mm limit from the skin surface and/ or lung-chest wall interface.
    • The planning target volume (PTV) included the CTV plus a 10 mm margin.
    • A total of 42 patients were enrolled, and the authors concluded that the technique described was technically feasible and reproducible.
    • A phase III trial, NSABP B39/ RTOG 0413 was designed in response to these findings, and that trial is currently accruing patients.
  • Efficacy was a secondary endpoint of the RTOG 0319 trial, and the authors report the efficacy of the treatment used in this Phase I/II trial here.

Materials and Methods

  • Eligibility requirements for enrollment on the RTOG 0391 trial included AJCC stage I or II breast cancer, tumor size no more than 3 cm, negative surgical margins, and 3 or fewer positive axillary lymph nodes.
  • Additionally, patients were required to have unifocal breast cancer, and surgical clips present to designate the lumpectomy cavity.
  • Most recent chemotherapy was required to have been given no less than 2 weeks prior to beginning radiotherapy.
  • The cumulative incidence method was used to evaluate recurrences, including distant failures as well as those within the ipsilateral breast, ipsilateral axilla, and contralateral breast.
  • The Kaplan-Meier method was used to estimate mastectomy-free, disease-free, and overall survival.


  • Between August, 2003 and April, 2004, 58 patients were enrolled on this study. Fifty-three of these were both eligible for the trial and evaluable for efficacy.
  • Median patient age was 61 years, and 87% of patients enrolled on this study were post-menopausal.
  • Median tumor size was 1 cm. All tumors had invasive histology, and 85% were invasive ductal carcinoma.
  • Cancers evaluated in this study were stage I (T1 N0) in 92% of cases.
  • All patients enrolled had surgical margins negative for cancer; of these, 94% had initially negative margins, and 6% required re-excision to achieve negative margins.
  • Most patients in this study received no systemic treatment: Chemotherapy was given to 15%, and hormonal treatments to 33%.
  • Median follow-up was 4.3 years (range 1.6 – 4.6 years).
  • Three-year recurrence rates were as follows:
    • Ipsilateral breast: 6% (n = 3), 4% (n = 2) of which were within the radiation field.
    • Ipsilateral lymph nodes: 2% (n = 1).
    • Contralateral breast: 0%.
  • Distant failures occurred in 6% of patients.
  • Mastectomy-free, disease-free, and overall survival were 92%, 88%, and 96%, respectively.
  • In addition to the presentation of these results, preliminary results of the NSABP B39/ RTOG 0413 trial currently underway were also presented:
    • This trial was opened for enrollment in March, 2005. Since that time, 3225 patients have enrolled, with an accrual goal of 4300 patients.
    • Interim analysis is planned after 44 local failures have been observed.
    • As of July 31, 2008, 3188 patients had been enrolled.
      • No reportable toxicities have been reported.
      • Most observed toxicities have been dermatologic in nature, and have been grade 1/2.
      • Results appear to be similar among patients receiving chemotherapy and those receiving no chemotherapy.

Author's Conclusions

  • The authors conclude that the initial efficacy results using 3D-CRT to deliver APBI appear to be similar to experiences at other institutions. 
  • They acknowledge that follow-up in this and other studies remains limited, and that larger trials, longer follow-up, and mature Phase III data will be needed to establish the role of APBI in treatment of patients with early-stage breast cancer.
  • They request that clinicians support enrollment on the current Phase III trial being supervised in part by the RTOG in efforts to answer the many questions surrounding APBI.

Clinical/Scientific Implications

  • This trial represents an interesting contribution to other small trials evaluating APBI for early-stage breast cancer.
  • Although the results of this trial are interesting and appear to be equivalent to those found with use of breast conservation treatment utilizing whole breast radiotherapy, the limited follow-up time and small number of patients enrolled prevent meaningful comparison. The authors acknowledge this, and have initiated a Phase III trial that is currently underway. As they describe, Phase III evidence from this trial will contribute significantly to the body of literature regarding APBI that currently exists.
  • Even when these data are available, however, the question of the equivalence of oncologic outcomes with APBI compared to conventional whole breast radiotherapy will likely remain unanswered for quite some time. Patients undergoing radiotherapy for early-stage breast cancer have been demonstrated to be at risk for in-breast recurrence and local-regional failure for at least 15 years after completion of treatment (Santiago RJ, IJROBP, 2004), and this risk is expected to exist for patients receiving APBI as well. For this reason, until mature data are available with 10-20 years of follow-up, assessment of the true risks and benefits of ABPI will not be possible.
  • In this study, the authors do not comment on cosmetic outcomes for patients receiving ABPI. Risk of late-tissue scarring and fibrosis has been demonstrated to be increased with use of hypofractionated radiotherapy. In the case of breast cosmesis, this detriment may contribute significantly to cosmetic outcomes. Comment on cosmesis from the available data would be interesting. Late-tissue effects many develop many years after completion of radiotherapy, so cosmetic outcomes may not be fully evaluable for quite some time.
  • The information provided by the authors is also limited with regard to the lymph node status and axillary evaluation for patients treated as part of this trial. The authors state that 92% of patients had stage I disease, and thus negative axillary lymph nodes, presumably by surgical assessment. Certainly, in the case of axillary lymph nodes positive for cancer, local/ regional recurrence rates would be expected to be increased for patients receiving APBI, which does not address the axilla, compared to standard radiotherapy. More information regarding this would be helpful in light of the fact that patients with up to three positive lymph nodes were eligible for participation.
  • Despite these limitations, the authors of this study should be commended for having undertaken the important task of designing a Phase III trial to fully evaluate APBI versus conventional breast conserving therapy with whole breast radiotherapy. While the results of that study are awaited by the oncology community, the results presented here and by other groups with smaller populations are certainly of interest.