Omitting Radiation Therapy in Ductal Carcinoma In Situ

• A survey (Jagsi, 2010):
  • Demonstrated that 95% of women with breast cancer and strong indications for post-lumpectomy radiation:
    • Went on to receive it:
      • But rates of post-lumpectomy radiation therapy use have been shown to vary:
        • Depending on the region of the country that the patient lives in
        • The age of the patient
        • The disease being treated (DCIS vs Invasive Disease)
• Among patients who undergo BCT for DCIS:
  • Only 50% are estimated to receive adjuvant radiation
• Many patients choose mastectomy over breast-conserving surgery for DCIS:
  • Because they are not able or willing to complete 6 weeks of daily radiation therapy:
    • Secondary to social or health considerations
• Other patients who are candidates for breast-conserving surgery:
  • Choose to undergo a mastectomy:
    • Because of concerns about postradiation complications
• Breast-conserving surgery alone (i.e., without radiation therapy):
  • May be sufficient in a select subgroup of patients with DCIS
• Initial data that supported the use of breast-conserving surgery alone in the treatment of DCIS came from a study by Lagios et al. (1989):
  • In which 79 patients with mammographically detected DCIS underwent margin-negative excision alone
  • After a follow-up time of 124 months:
    • The local recurrence rate was 16% overall, specifically:
      • 33% for the subgroup of patients with high-grade lesions and comedo necrosis versus only 2% for the patients with low- or intermediate-grade lesions
• The USC / VNPI score can be a helpful tool in clinical decision making:
  • But even though margin width is an independent prognostic factor for recurrence using the USC / VNPI score:
    • It is unlikely that margin width alone can identify the patients with DCIS treated with breast conservation for whom radiation therapy can be safely omitted
• In a retrospective analysis of 469 patients with DCIS who underwent breast conservation with margins that were at least 10 mm, Silverstein et al. (1999):
  • Did not detect a lower recurrence rate:
    • When postoperative radiation therapy was employed
• In contrast, even on reanalysis of the NSABP B-17 data:
  • All patient cohorts benefited from radiation therapy:
    • Regardless of the clinical or mammographic tumor characteristics
• Furthermore, Wong et al. (2003, 2014):
  • Reported the early termination of a prospective single-arm trial conducted at the Dana-Farber / Harvard Cancer Center:
    • In which radiation therapy was omitted in patients with grade 1 to 2 DCIS that was no more than 25 mm and excised with 10 mm or greater margins:
      • At a median follow-up of 3.3 years:
        • The number of local recurrences observed was 2.5% per patient-year:
          • Corresponding to a 5-year rate of 12.5%
• In 2010, Rudloff and colleagues at Memorial Sloan Kettering Cancer Center:
  • Published a multivariable nomogram:
    • To estimate risk for local recurrence in women with DCIS treated with breast-conserving surgery
  • The nomogram incorporates commonly available factors that have previously been shown to affect risk of ipsilateral breast tumor recurrence, these include:
    • Age at diagnosis
    • Family history
    • Type of patient presentation:
      • Radiologic or clinical
    • Nuclear grade
    • Necrosis, margins
    • Number of excisions
    • Receipt of radiation and / or adjuvant endocrine therapy
  • The nomogram calculates an actual, individualized estimate of absolute risk of ipsilateral breast tumor recurrence at 5 or 10 years:
    • Which can be weighed against the use of available adjuvant treatment options
• There are two large, prospective, observational studies:
  • Designed to investigate the role of observation versus radiation therapy after breast-conserving therapy in patients with DCIS
  • As mentioned earlier, Wong and colleagues at Harvard:
    • Conducted a single-arm, phase III observational study examining long-term outcomes in women with small (≤ 2.5 cm), low- and intermediate-grade DCIS who were treated with lumpectomy and margins ≥ 1 cm and did not receive adjuvant tamoxifen or radiation:
    • With a median follow-up of 11 years:
      • 13% (19 of 143) of patients experienced local recurrence:
        • Approximately two-third of which were DCIS
  • In the Eastern Cooperative Oncology Group–American College of Radiology Imaging Network (ECOG-ACRIN; formerly known as the Eastern Cooperative Oncology Group) Cancer Research Group E5194 study:
    • Patients with low- or intermediate-grade DCIS smaller than 25 mm (cohort 1), or high-grade DCIS smaller than 10 mm (cohort 2), with excisional margins of at least 3 mm, underwent breast-conserving surgery without radiation therapy:
      • 30% of patients received tamoxifen
    • At 12 years:
      • 14.4% of the participants in cohort 1 experienced an in-breast even while 24.6% of those in cohort 2 experienced an in-breast event (p = 0.0003), and this difference was driven by a statistically significant difference (p = 0.02) in noninvasive recurrence
      • In addition, membership in cohort 2 and larger tumor size were both found to be associated with increased likelihood of recurrence (Solin, 2015)
• Finally, in patients over 70:
  • There is increasing evidence that radiation therapy:
    • Depending on the aggressiveness of the DCIS and the expected life expectancy of the patient:
      • Can be omitted on a case-by-case basis

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