Radiation Oncology/Breast/Partial breast irradiation

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Front Page: Radiation Oncology | RTOG Trials

Breast: Main Page | Staging | Breast Overview | Prevention | Benign | DCIS | LCIS | Paget's | Phyllodes tumor | Early stage | Advanced stage | Post mastectomy | Inflammatory | Partial breast irradiation | Regional lymphatics | Hormonal therapy | Chemotherapy | RT technique | Recurrence | Toxicity of RT | Randomized | NSABP trials

Contents

[edit] Anatomical studies

  • Rationale for APBI is that majority of local recurrences occur in close proximity to tumor bed, and <20% appear "elsewhere" in the breast. Absolute number of "elsewhere" failures is quite low (<<1% per year) and is similar to rate of new contralateral tumors
  • Holland - Classic paper that justified the need for whole breast RT. Evaluated mastectomy specimens. 42% of extensive intraductal component (EIC) negative breasts had residual carcinoma; 74% of EIC+ had residual carcinoma. Most carcinoma was intraductal type. Most tumors were large and clinically detected.
    PMID 2153190 — "The presence of an extensive intraductal component following a limited excision correlates with prominent residual disease in the remainder of the breast." Holland et al., 1990.
  • Vaidya - A paper that paradoxically justified the rationale for partial breast irradiation. Multicentric foci were plotted in an abstract 3-D space and the conclusion was that although 63% (same result as Holland) of otherwise occult cancers were present in mastectomy specimens, over 79% of them were in other quadrants. This was in contrast with the results of breast conserving surgery trials in which early local recurrence occurred most commonly (>90%) of the time in the area around the primary tumour, thus justifying the approach of TARGeted Intraoperative radioTherapy [TARGIT]
    PMID 8795588 — "Multicentricity of breast cancer: whole-organ analysis and clinical implications." Vaidya JS, Vyas JJ, Chinoy RF, Merchant N, Sharma OP, Mittra I. 1996.
  • 3D studies of duct-lobular system
    • PMID 8630874 — "Intraductal extension of primary invasive breast carcinoma treated by breast-conservative surgery. Computer graphic three-dimensional reconstruction of the mammary duct-lobular systems." Ohtake et al. 1995.
      20 pts studied, all had quadrantectomy. Ductal anastamoses are present, and may be a risk for spread to other ductal-lobular systems. Maximum distance of spread, 11.9 mm.
    • PMID 11413514 — "Computer-assisted complete three-dimensional reconstruction of the mammary ductal/lobular systems: implications of ductal anastomoses for breast-conserving surgery." Ohtake et al. 2001.
      3D reconstruction of a single entire breast
  • PMID 11072782 Full Text — "Relationship between the morphological and biological characteristics of intraductal components accompanying invasive ductal breast carcinoma and patient age." Imamura et al. 2000.
    Median extension of intraductal component 9 mm. Related to patient age, with older patients having less extension.
  • PMID 15465188 (2004) — "Defining the clinical target volume for patients with early-stage breast cancer treated with lumpectomy and accelerated partial breast irradiation: a pathologic analysis." Vicini et al. Int J Radiat Oncol Biol Phys. 2004 Nov 1;60(3):722-30.
    Recommend 10 mm margin around tumor bed

[edit] APBI vs. Whole Breast RT

  • Ongoing trial NSABP B-39/RTOG 0413 is a randomized phase III trial looking at whole breast vs. APBI for stage 0, I and II patients (Ongoing)
    • For APBI using multi-catheter brachytherapy (34 Gy), Mammosite (34 Gy) or External Beam (38.5 Gy)
  • Hungary (1998-2004)
    • Randomized. 258 patients with T1N0-1mic, G1-2 nonlobular BCA, no EIC, SM-. Arm 1) WBI 50/25 vs. Arm 2) PBI 36.4/7 @ 5.2 Gy/fx multicatheter HDR or EB-APBI 50/25
    • 5-years; 2007 PMID 17531400 -- "Breast-conserving treatment with partial or whole breast irradiation for low-risk invasive breast carcinoma-5-year results of a randomized trial." (Polgar C, Int J Radiat Oncol Biol Phys. 2007 Nov 1;69(3):694-702.). Median F/U 5.5 years
      • Outcome: LR WBI 3.4% vs. PBI 4.7% (NS); no difference in DFS or OS
      • Toxicity: excellent/good cosmesis WBI 63% vs. PBI 78% (SS); HDR 81% and EB-APBI 70%
      • Conclusion: Similar outcomes, better cosmesis with HDR APBI
    • Fat necrosis; 2007 PMID 17524571 -- "Fat necrosis after partial-breast irradiation with brachytherapy or electron irradiation versus standard whole-breast radiotherapy-4-year results of a randomized trial." (Lovey K, Int J Radiat Oncol Biol Phys. 2007 Nov 1;69(3):724-31.)
      • 4-year fat necrosis: overall WBI 32% vs. HDR 36% vs. EB-APBI 18% (SS); symptomatic 8% vs. 11% vs. 7% (NS)
      • Conclusion: asymptomatic fat necrosis common; symptomatic fat necrosis comparable after conventional WBI and APBI

[edit] APBI-EBRT

  • MRC IMPORT LOW Trial - ONGOING
    • Randomized. 40/15 to index quadrant vs. 40/15 index quadrant + 36/15 remaining quadrants vs. 40/15 to center of breast (whole breast control). No boost.
    • Eligibility: Low risk early stage BCA (>50 and BCS and T1 and invasive ductal and unifocal and GI-II/III and SM > 2mm and LVI- and LN- and DM-)


  • Rocky Mountain, 2007 (2004-2005) PMID 17234359 -- "Prospective trial of accelerated partial breast intensity-modulated radiotherapy." (Leonard C, Int J Radiat Oncol Biol Phys. 2007 Apr 1;67(5):1291-8.)
    • Prospective. 55 patients, Stage I BCA. IMRT 7 patients 34/10, then 48 patients 38.5/10. Median F/U 10 months
    • Outcome: no local or distant recurrences
    • Cosmesis: patient: excellent 73%, good 22%; physician: excellent 80%, good 18%. Pain: none 62%, mild 35%, moderate 4%. One telangiectasia. No significant edema
    • Dosimetry: compared to historical controls, reduced volume of breast within 100%, 75%, and 50% isodose
    • Conclusion: Feasible; deserves additional investigation
  • Manchester, 1996 (UK) PMID 8783398 -- "Prognostic factors for breast recurrence after conservative breast surgery and radiotherapy: results from a randomised trial." (Magee B, Radiother Oncol. 1996 Jun;39(3):223-7.)
    • Randomized. 708 patients. Tumor <4cm, SM-. No ALND. No systemic therapy. Randomized to tumor bed electron RT (Dose 40-42.5/8) or 4 field whole breast, no IMN (40/15)
    • 8-year LR: tumor bed 25% vs. 4F 13% (SS). Majority of recurrences within treated quadrant
    • Predictors for recurrence: technique, grade, LVI

[edit] MammoSite system

Usual dose: 34 Gy in 10 fractions (BID) over 5 consecutive days. Dose usually prescribed at 1 cm depth.


  • Multi-Institutional; 2008 (2000-2004) PMID 18037585 -- "Multi-Institutional Experience Using the MammoSite Radiation Therapy System in the Treatment of Early-Stage Breast Cancer: 2-Year Results." (Cuttino LW, Int J Radiat Oncol Biol Phys. 2008 May 1;71(1):107-14. Epub 2007 Nov 26.)
    • Retrospective. 483 patients from 9 institutions. 34/10 BID. Median F/U 2 years
    • Outcome: 1% in-breast failure, of these 2/3 were remote from lumpectomy site
    • Complications: infection 9%, but 5% if placement after lumpectomy. Predictors for acute toxicity: open cavity placement, skin spacing <6 mm, no prophylactic ABX, single dwell position
    • Conclusion: MammoSite acceptable toxicity and cosmetic outcome
  • Beaumont Hospital (2000-2001) PMID 17826055 -- "Five-year results: the initial clinical trial of MammoSite balloon brachytherapy for partial breast irradiation in early-stage breast cancer." (Benitez PR, Am J Surg 2007 Oct; 194(4):456-62)
    • Prospective study of Mammocyte therapy, enrolled 70 pts, implanted in 54 pts, 43 pts treated, 36 with long term f/u. Exluded 7% of treated pts due to death from metastatic disease.
    • Outcome: IBTR = 0%; Cosmesis improved with >= 7 mm from skin surface.
    • Complications: Infection 9%; Seroma 33%
    • 39 month results - ASTRO 2005 Abstract #10 — "Thirty-Nine Month Results with the MammoSite Brachytherapy Applicator: Details Regarding Cosmesis, Toxicity and Local Control in Partial Breast Irradiation." Keisch M et al. IJROBP Volume 63, Supplement 1, 1 October 2005, Page S6.
      • 85% with good/excellent cosmetic results. Good cosmesis associated with skin spacing of >= 7mm vs 5-6 mm, producing excellent/good in 91% vs 57%. Fat necrosis in 5% (radiographic findings but none symptomatic). Telangiectasias associated with skin spacing: 58% (>7 mm) vs 32% (5-7 mm). Breast tissue retraction in 25% vs 7%. No ipsilateral breast failures.
      • Good cosmesis associated with skin spacing.
  • U. Pittsburgh (2002-04) - ASTRO 2005 Abstract #11 — "Accelerated Partial Breast Irradiation: Single Institutional Experience of 100 Patients Using MammoSite Brachytherapy." Agarwal A et al.
    • 100 pts. All surgical margins >= 2mm. Median age 64 (45-89). Cosmetic outcome excellent good in 56%/37% (93%). Palpable seroma beyond 6 months in 27%.

[edit] Interstitial brachytherapy

HDR Ir-192:

  • Tufts/Brown U. (1995- ) - ASTRO 2005 Abstract #12 — "Accelerated Partial Breast Irradiation (APBI): An Analysis of Variables Associated with Late Toxicity after HDR Interstitial Brachytherapy." Kaufman S et al. IJROBP Volume 63, Supplement 1, 1 October 2005, Page S7.
    • 75 pts. T1-2 N0-1 (0-3 nodes positive). Used HDR implant 34 Gy in 10 fractions BID over 5 consecutive days.
    • Median f/u 73 mo. Excellent/good cosmesis in 67%/24% (91%). Poor cosmesis associated with higher V150 and V200 and poor dose homogeneity index.
  • U. Wisconsin (2000-05) - ASTRO 2005 Abstract #13 — "Multi-catheter Breast Brachytherapy Following Lumpectomy in Select Early Stage Breast Cancer Patients: The University of Wisconsin Experience." Patel RR et al. IJROBP Volume 63, Supplement 1, 1 October 2005, Pages S7-S8.
    • 268 pts (240 treated with interstitial, the rest with MammoSite).
    • Median f/u 30 mos. IBTR in 1.4%. Symptomatic fat necrosis in 8.9%.
  • RTOG 95-17 (1997-2000)
    • Phase I-II. 99 pts. Brachytherapy with LDR (45 Gy in 3.5 - 5 days) or HDR (34 Gy in 10 fractions BID). Stage T1-2 (<3 cm), pN0-1
    • Toxicity: PMID 16503383, 2006 — "Phase II trial of brachytherapy alone after lumpectomy for select breast cancer: Toxicity analysis of RTOG 95-17." Kuske RR et al. Int J Radiat Oncol Biol Phys. 2006 May 1;65(1):45-51.
    • Median f/u 2.7 yrs. Grade 3-4 acute toxicity in 3% (HDR) or 9% (LDR). Grade 3 late toxicity in 18% (LDR) and 4% (HDR).
  • Ochsner Clinic, 2000 (1992-1993) PMID 11113440 -- "Long-term results of wide-field brachytherapy as the sole method of radiation therapy after segmental mastectomy for T(is,1,2) breast cancer." (King TA, Am J Surg. 2000 Oct;180(4):299-304.)
    • Original Phase I-II. 50 patients, Tis-T2, <=4cm, N0-1, SM-. Retrospective comparison to EBRT during same time. Median F/U 6.25 years
    • RT: Wide-field brachy (target volume 2cm peripheral and 1cm superficial/deep). Either LDR (45 Gy over 4 days) or HDR (32/8 in 4 Gy/fx BID) in blocks of 10 patients.
    • Outcomes: No difference in toxicity, local/regional recurrence, or cosmesis
    • Toxicity: 6% Grade 3 complications (3.8% LDR vs 7.7% HDR) - 2 severe fat necrosis on HDR requiring surgery (resulting in dosimetry adjustment) and 1 abscess from infected seroma. 56% Grade 2 complications (24% symptomatic fat necrosis, 12% telangiectasia, breast shrinkage, infection, pain, fibrosis). Fat necrosis worse if chemo (50% vs. 12%, SS), and if bad dosimetry gradient >30% (40% vs. 17%)
    • Conclusion: Brachytherapy attractive alternative to EBRT
    • Comment: Original fractionation scheme based on soft-tissue sarcomas, as per PMID 8407399


Review

  • Ochsner, 1999 PMID 10432428 -- "Breast brachytherapy." (Kuske RR Jr, Hematol Oncol Clin North Am. 1999 Jun;13(3):543-58, vi-vii.)


[edit] Protons

[edit] Clinical

  • MGH; 2006 (2004-2005) PMID 17011445 -- "Accelerated partial-breast irradiation using proton beams: initial clinical experience." (Kozak KR, Int J Radiat Oncol Biol Phys. 2006 Nov 1;66(3):691-8.)
    • Phase I/II. 20 patients, Stage I BCA. Proton 3D-CPBI 32 CGE/8 fractions BID over 4 days. PTV=lumpectomy + 1.5-2cm, but <5 mm from skin. 1-3 beams, inhomogeneity <15%. Median F/U 1 year
    • Cosmesis: good/excellent 100% at 1 year; bt significant acute skin toxicity, moderate/severe skin color changes in 79% at 3-4 weeks, moderate/severe moist desquammation 22% at 6-8 weeks
    • Conclusion: Significant acute skin toxicity, but good/excellent cosmetic outcome at 1 year


[edit] Dosimetric

  • Loma Linda
    • 2007 PMID 17476139 -- "A technique of partial breast irradiation utilizing proton beam radiotherapy: comparison with conformal x-ray therapy." (Bush DA, Cancer J. 2007 Mar-Apr;13(2):114-8.)
      • Prospective. 20 patients. Technique described. 2-4 proton beams. 40/10 CGE. Comparison with conformal XRT
      • Plan comparison: Protons significantly less to ipsilateral breast, skin; eliminating dose to heart and lung
      • Acute toxicity: occasional radiation dermatitis Grade 1-2
      • Conclusion: Well tolerated, reproducible, with substantial normal tissue sparing
      • Editorial (PMID 17476135)
  • Paul Scherrer Institute
    • 2006 PMID 16857055 -- "Radiation therapy planning with photons and protons for early and advanced breast cancer: an overview." (Weber DC, Radiat Oncol. 2006 Jul 20;1:22.)
    • 2003 PMID 12573766 -- "Potential role of intensity-modulated photons and protons in the treatment of the breast and regional nodes." (Lomax AJ, Int J Radiat Oncol Biol Phys. 2003 Mar 1;55(3):785-92.)
      • Treatment plan comparison: standard photon/electron, IMRT, and forward planned protons. Target involved breast, axilla, SCV, and IM nodes.
      • Conclusion: IMRT can greatly improve target homogeneity, but proton plan had potential to also minimize dose delivered to organs at risk
  • MGH (2004-2005)
    • 2006 PMID 16863934 -- "Dosimetric comparison of proton and photon three-dimensional, conformal, external beam accelerated partial breast irradiation techniques." (Kozak KR, Int J Radiat Oncol Biol Phys. 2006 Aug 1;65(5):1572-8.)
      • 24 patients, Stage I, treated with proton 3D-CPBI. Treatment plans also generated using photon-electron 3D-CPBI. PTV and prescribed dose held constant.
      • Outcome: PTV coverage: 95% received >90% of prescribed dose in all cases. Only one case >10% inhomogeneity. Significantly better volume of nontarget breast, lung, and heart for proton plans
      • Conclusion: Proton 3D-CPBI significantly reduces volume of irradiaated nontarget breast tissue
    • 2006 PMID 16730137 -- "Accelerated partial breast irradiation using proton beams: Initial dosimetric experience." (Taghian AG, Int J Radiat Oncol Biol Phys. 2006 Aug 1;65(5):1404-10. Epub 2006 May 26.)
      • Retrospective. 25 patients. Tumor <=2 cm, N0. Proton 3D-CPBI 32 CGE/8 fractions BID over 4 days. 1-3 beams.
      • Dosimetry: Median PTV receiving >95% prescribed dose 100%. Dose inhomogeneity >10% in 1 patient (4%). Median volume of nontarget breast tissue receiving 50% of prescribed dose 23%. Median lung receiving 20 CGE 0%, 10 CGE 1%, 5 CGE 2%
      • Cost-analysis: modestly more expensive (25%) than whole breast RT
      • Conclusion: Technically feasible, excellent PTV coverage and normal tissue sparing
  • Southern Switzerland; 2002 PMID 11937240 -- "Critical appraisal of treatment techniques based on conventional photon beams, intensity modulated photon beams and proton beams for therapy of intact breast." (Fogliata A, Radiother Oncol. 2002 Feb;62(2):137-45.)
    • Treatment planning. 5 patients, highly concave breast tissue. 2 field conventional vs 2 field IMRT vs 3 field conventional vs 3 field IMRT and single field protons
    • Outcome: PTV comparable for photon techniques, improved with single field protons. Lung volume and cardiac volume better with protons
    • Conclusion: Geometrically difficult breast cancer patients benefited from proton therapy
  • Uppsala; 2002 PMID 12443804 -- "Node-positive left-sided breast cancer patients after breast-conserving surgery: potential outcomes of radiotherapy modalities and techniques." (Johansson J, Radiother Oncol. 2002 Nov;65(2):89-98.)
    • Treatment planning. 11 patients with left-sided node-positive breast cancer. Conventional plan vs. IMRT vs. protons
    • Conclusion: Proton plans significantly better for lung and heart dose
  • Indiana University; 1997 PMID 9240659 -- "Phantom assessment of lung dose from proton arc therapy." (Sandison GA, Int J Radiat Oncol Biol Phys. 1997 Jul 1;38(4):891-7.)
    • Chest wall irradiation of Rando phantom. 200 MeV beam, modulated to 4cm, 20x4 field size, rotated at 1 rpm. Comparison to 12 MeV electron arc therapy
    • Outcome: Reduced lung dose at all levels, 50% integral lung dose
    • Conclusion: Potential role for proton arc therapy in chest wall RT

[edit] Economics

  • Sweden; 2005 PMID 15885828 -- "Economic evaluation of proton radiation therapy in the treatment of breast cancer." (Lundkvist J, Radiother Oncol. 2005 May;75(2):179-85.)
    • Markov model simulation, 55 year old patient with left-sided BCA
    • Outcome: Euro 67,000 cost per QALY gained; better if high risk cardiac patients treated
    • Conclusion: Proton therapy for BCA can be cost-effective if appropriate risk groups are chosen

[edit] Consensus Statements

  • ASTRO Consensus Statement (2009) PMID 19545784 -- "Accelerated partial breast irradiation consensus statement from the American Society for Radiation Oncology (ASTRO)." (Smith BD, Int J Radiat Oncol Biol Phys. 2009 Jul 15;74(4):987-1001.)
    • Suitable group: APBI outside of a clinical trial is acceptable
      • Age >= 60, node negative pN0(i-/i+),invasive ductal (or favorable histology), no pure DCIS allowed, no invasive lobular, tumor <=2 cm, T1, margins negative (>= 2mm), ER+, no LVSI, unicentric, clinically unifocal + total size <= 2cm (may be microscopic multifocality as long as unifocal by ultrasound + mammogram), no extensive intraductal component, associated LCIS allowed, neoadjuvant therapy not allowed, BRCA1/2 mutation negative, any grade
    • Cautionary group: caution and concern should be used when considering APBI outside of a clinical trial
      • Any of the following: Age 50-59, tumor 2.1-3.0 cm, T2 or T0, close margins (<2 mm), limited or focal LVSI, ER-, invasive lobular, pure DCIS <= 3cm, EIC <= 3 cm; microscopic multifocality allowed (if total size 2.1-3.0 cm)
    • Unsuitable group: APBI outside of a clinical trial is not generally warranted
      • Any of the following: Age <50, BRCA1/2 mutation, tumor >3 cm, T3 or T4, positive margins, extensive LVSI, multicentric tumor, multifocal tumor >3cm in total size or clincally multifocal, DCIS > 3cm, EIC > 3cm, pN1-N3 or pNx (no nodal surgery performed), neoadjuvant therapy

[edit] Review

  • Royal Marsden; 2009 PMID 19178972 -- "Accelerated partial breast irradiation trials: Diversity in rationale and design." (Mannino M, Radiother Oncol. 2009 Apr;91(1):16-22. Epub 2009 Jan 27.)
  • Aarhus, Denmark; 2009 PMID 18783840 -- "Accelerated partial breast irradiation as part of breast conserving therapy of early breast carcinoma: A systematic review." (Offerssen BV, Radiother Oncol. 2009 Jan;90(1):1-13. Epub 2008 Sep 8.)
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