Johnny Ray Bernard, Jr., M.D.
October 19, 2012
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1852: Born in New York City Sept. 23
1870: Graduates from Phillips Academy Andover
1874: Graduates Yale University
◦ Enrolls in Columbia University College of
Physician and Surgeons in New York
1881: First emergency blood transfusion,
performed on sister
◦ Performs one of first operations for gallstones
in U.S., performed on mother
1882: Development of Halsted radical
mastectomy
1884: Begins cocaine research, developing the
nerve block and other local anesthesia
techniques.
1889: Invention of surgical gloves
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1889: Publishes inguinal hernia repair method at
the same time as Edoardo Bassini.
1890: Appointed first Chief of Surgery at Johns
Hopkins Hospital
1892: Performs first successful subclavian artery
ligation
1893: Started the first formal surgical residency
training program in the United States
1898: American Surgical Association establishes
Halsted's mastectomy and inguinal hernia repair as
gold standards
1922: Dies in Baltimore from post-op
complications of bile duct surgery September 7
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Developed and first
performed by William
Stewart Halsted in
1882.
En bloc removal of
the breast, muscles
of the chest wall, and
contents of the axilla
Osborne, MP. Lancet Oncol.
2007 Mar;8(3):256-65.
Bloodgood JC. Problems of cancer. J Kansas Med Soc 1930;31:311-6
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The “established and standardized
operation for cancer of the breast in all
stages, early or late”
From 1895 to the mid-1970s, about 90%
of the women being treated for breast
cancer in the US underwent the radical
mastectomy.
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Patient dissatisfaction with results, anecdotal
information regarding other procedures, some
surgeons advocating more extensive surgery, some
surgeons advocating more limited operations led to
controversy regarding the procedure by the mid
1960’s
Also new information about tumor spread
suggested that less radical surgery might be just as
effective as the more extensive operations that
were being performed.
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To help resolve the controversy, the NSABP
initiated the B-04 clinical trial in 1971
Aim: To determine whether patients with
either clinically negative or clinically positive
axillary nodes who received local or regional
treatments other than radical mastectomy
would have outcomes similar to those
achieved with radical mastectomy.
Fisher B, et al. N Engl J Med. 2002 Aug
22;347(8):567-75.
1765 women (1665 in this report) with operable breast cancer were randomized
between July 1971 and September 1974. No women received adjuvant
chemotherapy. 87% followed for at least 25 years or were known to have died
before that time.
Clinically Negative
Axilla, N=1079
Halsted Radical
Mastectomy,
N=362
Total Mastectomy,
no AD, +XRT
N=352
Total (simple)
Mastectomy Alone
N=365
Clinically Positive
Axilla, N=586
Halsted Radical
Mastectomy,
N=292
Total Mastectomy
+ XRT
N=294
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Supervoltage equipment
Tangential fields
Node negative: 50 Gy in 25 fractions,
2Gy/fraction
Node positive:
◦ An additional boost of 10 to 20 Gy
◦ 45 Gy in 25 fractions, 1.8 Gy/fraction, was
delivered to both the internal mammary nodes and
the supraclavicular nodes
Fisher B, et al. N Engl J Med. 2002 Aug
22;347(8):567-75.
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Local recurrence: recurrences in the chest wall, the
surgical scar, or both
Regional recurrence: recurrences in the
supraclavicular, subclavicular, or internal mammary
nodes or in the ipsilateral axilla of patients treated
with either radical mastectomy or total mastectomy
and regional irradiation
◦ Women with negative nodes who had total
mastectomy alone and who subsequently had
ipsilateral positive nodes that required axillary
dissection were not considered to have had a
recurrence unless the nodes could not be
removed
Fisher B, et al. N Engl J Med. 2002 Aug
22;347(8):567-75.
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Calculated from the date of mastectomy
Disease-free survival: The first local, regional, or
distant recurrence of tumor; contralateral breast
cancer or a second primary tumor other than a
tumor in the breast; and death of a woman who
had no evidence of cancer
Relapse-free survival: The first local, regional, or
distant recurrence or an event in the contralateral
breast that was judged to be a recurrence
Distant-disease-free survival: Distant recurrences
that occurred either as the first recurrence or after
a local or regional recurrence, contralateral breast
cancers, and other second primary cancers
Overall Survival: All deaths
Fisher B, et al. N Engl J Med. 2002 Aug
22;347(8):567-75.
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Node Negative: No significant difference (P=0.65)
◦ 19% percent vs. 13%, RM vs. TM+XRT (P=0.49)
◦ 19% with TM alone (P=0.39, compared to RM)
◦ TM+XRT vs. TM alone (P=0.78)
Node Positive: No significant difference
◦ 11% vs. 10%, RM vs. TM+XRT (P=0.20)
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Node Negative: No significant difference (P=0.46)
◦ 53% percent vs. 52%, RM vs. TM+XRT (P=0.74)
◦ 50% with TM alone (P=0.27, compared to RM)
◦ TM+XRT vs. TM alone (P=0.15)
Node Positive: No significant difference
◦ 36% vs. 33%, RM vs. TM+XRT (P=0.40)
Regardless of nodal status, most first events were
related to distant recurrences of tumor and to deaths
that were unrelated to breast cancer.
Fisher B, et al. N Engl J Med. 2002 Aug
22;347(8):567-75.
Clinically Negative
Axilla, N=1079
Halsted Radical
Mastectomy,
no XRT, N=362
Total Mastectomy,
no AD, +XRT
N=352
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Total (simple)
Mastectomy Alone
N=365
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68/365 women with negative
nodes who underwent total
mastectomy without
radiation therapy (18.6%)
subsequently had
pathological confirmation of
positive ipsilateral nodes.
◦ Identified within 2 years
after surgery in 51/68
(75%) women
◦ Between 2-5 years in
10/68 (15%) women
◦ Between 5-10 years in
6/68 (9%) women
◦ Between 10-25 years in
1/68 (1%) woman
Median time from
mastectomy to the
identification of positive
axillary nodes was 14.8
months (range, 3.0 to
134.5).
Node negative: 68.3% of breast-cancer–related events occurred within the first 5 years of f/u
-65.1% of these were distant recurrences, 10.3% contralateral breast cancer
Node positive: 81.7% of breast-cancer–related events occurred within the first 5 years of f/u
-68.1% of these were distant recurrences
Also, no difference in distant-disease-free survival
or overall survival
Fisher B, et al. N Engl J Med. 2002 Aug
22;347(8):567-75.
The cumulative incidence of death after a
recurrence or a diagnosis of contralateral breast
cancer was 40% in women with negative nodes and
67% in women with positive nodes.
Fisher B, et al. N Engl J Med. 2002 Aug
22;347(8):567-75.
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Similar outcomes for patients with either clinically negative or
clinically positive axillary nodes who received local or regional
treatments other than the gold standard Halsted radical
mastectomy.
Thus, less extensive surgery can be safely performed.
No benefit for radiation in clinically node negative patients in
terms of DFS, RFS, DDFS, OS vs. those with axillary node
dissection
◦ Benefit in local control vs. those without axillary treatment.
Without any axillary treatment, ~20% risk of axillary disease,
less with treatment, but still no change in DDFS or OS.
Most events occurred within 5 years but long term follow-up
of patients is still needed as events still occurred after 5
years.
Treatment to improve distant recurrence needed.
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Numerous surgical series of mastectomy
specimens showed that breast cancer was
multifocal and multicentric in nature.
Holland, et. al. noted that of 282 mastectomy
specimens with invasive cancer, 177 (63%)
specimens exhibited additional cancer aside from
the index tumor, with 121 (43%) specimens having
tumor more than 2cm away from the index tumor.
This suggested that women undergoing breast
conservation would have a significant rate of local
recurrence by removing only the primary tumor.
Holland R, et al. Cancer.
1985 Sep 1;56(5):979-90.
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To help resolve the controversy, the NSABP
initiated the B-06 clinical trial in 1976.
Aim: To determine whether women with stage
I or II breast tumors that were 4 cm or less in
diameter who received breast-conserving
surgery would have outcomes similar to those
achieved with total (new standard)
mastectomy.
Fisher B, et al. N Engl J Med.
2002 Oct 17;347(16):1233-41.
2163 women (1851 in this report) with invasive breast
tumors that were <4 cm and with either negative or positive
axillary lymph nodes (stage I or II breast cancer) were
randomized between August 1976 and January 1984.
Axillary nodes were removed regardless of the treatment
assignment.
Stage I/II Breast
Cancer <4cm
N=1851
Total Mastectomy
N=589
Lumpectomy
(Segmental
Mastectomy)+XRT
N=628
Lumpectomy
Alone
N=634
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Lumpectomy: Removal of sufficient normal breast tissue to
ensure both negative margins (no tumor at inked margin) and
a satisfactory cosmetic result
◦ Only the lower two levels of the axillary nodes were
removed
◦ +margins underwent total mastectomy but continued to be
followed for subsequent events
Total Mastectomy:
◦ The axillary nodes were removed en bloc with the tumor
Radiation:
◦ 2Gy/fraction to 50 Gy to the breast, but not the axilla
Chemo: Any positive axillary nodes received adjuvant
systemic therapy with melphalan and fluorouracil
Fisher B, et al. N Engl J Med.
2002 Oct 17;347(16):1233-41.
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Local recurrence: A first recurrence of a tumor in
the chest wall or in the operative scar, but not in
the ipsilateral breast, was classified as a local
recurrence.
◦ Ipsilateral breast recurrence after lumpectomy was
considered to be a cosmetic failure since women who
underwent total mastectomy were not at risk for such
an event.
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Regional recurrence: Recurrences in the internal
mammary, supraclavicular, or ipsilateral axillary
nodes were classified as regional occurrences.
Fisher B, et al. N Engl J Med.
2002 Oct 17;347(16):1233-41.
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Calculated from the date of surgery
Disease-free survival: The first recurrence of
disease at a local, regional, or distant site; the
diagnosis of a second cancer; and death without
evidence of cancer
Distant-disease–free survival: Distant metastases
as first recurrences, distant metastases after a local
or regional recurrence, and all second cancers,
including tumors in the contralateral breast
Overall survival: All deaths
Fisher B, et al. N Engl J Med.
2002 Oct 17;347(16):1233-41.
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14.3 % L+XRT vs. 39.2% L
alone (P<0.001)
Benefit of XRT independent
of nodal status
◦ Node Neg: 17% vs. 32%
(P<0.001)
◦ Node Pos: 44% vs. 9%
(P<0.001)
L+XRT Time to Recurrence
◦ <5yrs: 40%
◦ 5-10yrs: 29%
◦ >10yrs: 31%
L alone Time to Recurrence
◦ <5yrs: 73%
◦ 5-10yrs: 18%
◦ >10yrs: 9%
Fisher B, et al. N Engl J Med.
2002 Oct 17;347(16):1233-41.
As in B-04, the most frequent first events were distant recurrences
Fisher B, et al. N Engl J Med.
2002 Oct 17;347(16):1233-41.
No significant difference (P=0.26)
36% vs. 35% vs. 35%, TM vs. L+XRT vs. L alone
DDFS: No significant difference (P=0.34)
49% vs. 46% vs. 45%, TM vs. L+XRT vs. L alone
OS: No significant difference (P=0.57)
47% vs. 46% vs. 46%, TM vs. L+XRT vs. L alone
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69% of first
recurrences
were
detected
<5yrs of
surgery, 20%
between 510yrs, and
11% after 10
years
9% of local
recurrences,
7% of
regional
recurrences,
and 13% of
distant
recurrences
were
detected after
10 years
Contralateral
breast: 38%
detected
<5yrs of
surgery, 30%
5-10yrs, and
32% after 10
years.
Fisher B, et al. N Engl J Med.
2002 Oct 17;347(16):1233-41.
The cumulative incidence of death after a
recurrence or a diagnosis of contralateral breast
cancer was 40% in women with negative nodes and
67% in women with positive nodes.
Fisher B, et al. N Engl J Med.
2002 Oct 17;347(16):1233-41.
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Women with early stage breast cancer who have
breast conserving surgery have outcomes similar to
those achieved with total mastectomy.
Radiation therapy is a critical component of breast
conservation.
Breast conservation should be offered to women
with early stage breast cancer.
Most events occurred within 5 years but long term
follow-up of patients is still needed as events still
occurred after 5 years
Treatment to improve distant recurrence needed.
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110 local breast recurrences were observed in
1108 pathologically evaluable patients
All 110 recurrences were noted to be in or close
to the quadrant of the initial or index cancer.
The most common presentation of breast
recurrence appeared to be a localized mass
within or close to the quadrant of the index
cancer (86%).
In 14% the recurrence not only involved the
same quadrant, but was more diffuse within the
breast.
Fisher ER, et al. Cancer.
1986 May 1;57(9):1717-24.
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Other pathologic studies confirming findings
Patients not desiring weeks of radiation
treatment
Phase I/II studies of accelerated WBI in 4-5
days using multi-catheter interstitial brachy
Radiation to just the tumor bed
◦ Multi-catheter interstitial brachytherapy
◦ Balloon catheters and 3DCRT
◦ Strut based catheter (SAVI)
Interstitial
Balloon
Strut Applicator
Multi-catheter
Single catheter
Multi-catheter
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Balloon applicators
 Symptomatic: 3%-46%
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Potential causes
 Contiguous V200
 Tissue compression
 Both?
Greater flexibility
Treats the widest array of cavity & breast sizes
Enhanced performance
Eliminates skin spacing restrictions
Better outcomes
Lowers toxicity & risk of persistent seroma
Exceptional precision
Sculpt dose with selective radiation
Added convenience
Simple, secure placement and removal
APBI Data Review
# of Cases
Median F/U (months)
Local Recurrence (%)
Cosmesis Good/Excellent
(%)
ASBS MammoSite Registry
1440
60.5
1.8
90
Virginia Commonwealth University
483
24
1.2
91
127 APBI
131 WBI
66
William Beaumont Hospital
199
71
1.6
92
Ochsner Clinic
164
65
3
75
RTOG 95-17
99
51
4
Not Reported
Mass General Hospital
48
84
2
68
National Institute of Oncology, Hungary
Phase I/II Trial
45
80
6.7
84
MammoSite FDA Trial
43
66
0
83
Tufts/Brown
33
84
6.1
88
2681
65
Institution
National Institute of Oncology, Hungary
Phase III Trial*
Total
4.7 APBI
3.4 WBI
3.1 APBI
2.8 WBI
81 APBI
62 WBI
84
* Conclusion - Partial breast irradiation using interstitial HDR implants or EB to deliver radiation
to the tumor bed alone for a selected group of early-stage breast cancer patients produces 5year results similar to those achieved with conventional WBI. Significantly better cosmetic
outcome can be achieved with carefully designed HDR multi-catheter implants compared with
the outcome after WBI.
There have been no differences in survival with APBI compared to WBI.
Strut Based Applicator Data Review
Strut Based Applicator Data Review
Strut Based Applicator Data Review
Strut Based Applicator Data Review
Johnny Ray Bernard, Jr., M.D., DABR
Southern Ohio Medical Center
Senior Medical Director
Radiation Oncology
(O) 740-356-7490
bernardj@somc.org