Top

Published in:

01-12-2021 | Breast Cancer | Research article

Intraoperative fluorescence imaging with aminolevulinic acid detects grossly occult breast cancer: a phase II randomized controlled trial

Authors: Kathryn Ottolino-Perry, Anam Shahid, Stephanie DeLuca, Viktor Son, Mayleen Sukhram, Fannong Meng, Zhihui ( Amy) Liu, Sara Rapic, Nayana Thalanki Anantha, Shirley C. Wang, Emilie Chamma, Christopher Gibson, Philip J. Medeiros, Safa Majeed, Ashley Chu, Olivia Wignall, Alessandra Pizzolato, Cheryl F. Rosen, Liis Lindvere Teene, Danielle Starr-Dunham, Iris Kulbatski, Tony Panzarella, Susan J. Done, Alexandra M. Easson, Wey L. Leong, Ralph S. DaCosta

Published in: Breast Cancer Research | Issue 1/2021

Abstract

Background

Re-excision due to positive margins following breast-conserving surgery (BCS) negatively affects patient outcomes and healthcare costs. The inability to visualize margin involvement is a significant challenge in BCS. 5-Aminolevulinic acid hydrochloride (5-ALA HCl), a non-fluorescent oral prodrug, causes intracellular accumulation of fluorescent porphyrins in cancer cells. This single-center Phase II randomized controlled trial evaluated the safety, feasibility, and diagnostic accuracy of a prototype handheld fluorescence imaging device plus 5-ALA for intraoperative visualization of invasive breast carcinomas during BCS.

Methods

Fifty-four patients were enrolled and randomized to receive no 5-ALA or oral 5-ALA HCl (15 or 30 mg/kg). Forty-five patients (n = 15/group) were included in the analysis. Fluorescence imaging of the excised surgical specimen was performed, and biopsies were collected from within and outside the clinically demarcated tumor border of the gross specimen for blinded histopathology.

Results

In the absence of 5-ALA, tissue autofluorescence imaging lacked tumor-specific fluorescent contrast. Both 5-ALA doses caused bright red tumor fluorescence, with improved visualization of tumor contrasted against normal tissue autofluorescence. In the 15 mg/kg 5-ALA group, the positive predictive value (PPV) for detecting breast cancer inside and outside the grossly demarcated tumor border was 100.0% and 55.6%, respectively. In the 30 mg/kg 5-ALA group, the PPV was 100.0% and 50.0% inside and outside the demarcated tumor border, respectively. No adverse events were observed, and clinical feasibility of this imaging device-5-ALA combination approach was confirmed.

Conclusions

This is the first known clinical report of visualization of 5-ALA-induced fluorescence in invasive breast carcinoma using a real-time handheld intraoperative fluorescence imaging device.

Trial registration

Clinicaltrials.gov identifier NCT01837225. Registered 23 April 2013.

Available only for authorised users

Chen K, Li S, Li Q, Zhu L, Liu Y, Song E, et al. Breast-conserving surgery rates in breast cancer patients with different molecular subtypes: an observational study based on Surveillance, Epidemiology, and End Results (SEER) database. Medicine (Baltimore). 2016;95:e2593.CrossRef

Porter G, Wagar B, Bryant H, Hewitt M, Wai E, Dabbs K, et al. Rates of breast cancer surgery in Canada from 2007/08 to 2009/10: retrospective cohort study. CMAJ open. 2014;2(2):E102–8. https://doi.org/10.9778/cmajo.20130025.CrossRefPubMedPubMedCentral

Menes TS, Tartter PI, Bleiweiss I, Godbold JH, Estabrook A, Smith SR. The consequence of multiple re-excisions to obtain clear lumpectomy margins in breast cancer patients. Ann Surg Oncol. 2005;12(11):881–5. https://doi.org/10.1245/ASO.2005.03.021.CrossRefPubMed

Hennigs A, Fuchs V, Sinn HP, Riedel F, Rauch G, Smetanay K, et al. Do patients after reexcision due to involved or close margins have the same risk of local recurrence as those after one-step breast-conserving surgery? Ann Surg Oncol. 2016;23(6):1831–7. https://doi.org/10.1245/s10434-015-5067-1.CrossRefPubMed

Ali AN, Vapiwala N, Guo M, Hwang WT, Harris EE, Solin LJ. The impact of re-excision and residual disease on local recurrence after breast conservation treatment for patients with early stage breast cancer. Clin Breast Cancer. 2011;11(6):400–5. https://doi.org/10.1016/j.clbc.2011.08.003.CrossRefPubMed

Moran MS, Schnitt SJ, Giuliano AE, Harris JR, Khan SA, Horton J, et al. Society of Surgical Oncology-American Society for Radiation Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in stages I and II invasive breast cancer. Int J Radiat Oncol Biol Phys. 2014;88(3):553–64. https://doi.org/10.1016/j.ijrobp.2013.11.012.CrossRefPubMedPubMedCentral

Landercasper J, Attai D, Atisha D, Beitsch P, Bosserman L, Boughey J, et al. Toolbox to reduce lumpectomy reoperations and improve cosmetic outcome in breast cancer patients: The American Society of Breast Surgeons Consensus Conference. Ann Surg Oncol. 2015;22(10):3174–83. https://doi.org/10.1245/s10434-015-4759-x.CrossRefPubMedPubMedCentral

Vandergrift JL, Niland JC, Theriault RL, Edge SB, Wong YN, Loftus LS, et al. Time to adjuvant chemotherapy for breast cancer in National Comprehensive Cancer Network institutions. J Natl Cancer Inst. 2013;105(2):104–12. https://doi.org/10.1093/jnci/djs506.CrossRefPubMedPubMedCentral

Pataky RE, Baliski CR. Reoperation costs in attempted breast-conserving surgery: a decision analysis. Curr Oncol. 2016;23(5):314–21. https://doi.org/10.3747/co.23.2989.CrossRefPubMedPubMedCentral

10.

Baliski CR, Pataky RE. Influence of the SSO/ASTRO margin reexcision guidelines on costs associated with breast-conserving surgery. Ann Surg Oncol. 2017;24(3):632–7. https://doi.org/10.1245/s10434-016-5678-1.CrossRefPubMed

11.

Orosco RK, Tapia VJ, Califano JA, Clary B, Cohen EEW, Kane C, et al. Positive surgical margins in the 10 most common solid cancers. Sci Rep. 2018;8(1):5686. https://doi.org/10.1038/s41598-018-23403-5.CrossRefPubMedPubMedCentral

12.

Zhan QH, Fu JQ, Fu FM, Zhang J, Wang C. Survival and time to initiation of adjuvant chemotherapy among breast cancer patients: a systematic review and meta-analysis. Oncotarget. 2018;9(2):2739–51. https://doi.org/10.18632/oncotarget.23086.CrossRefPubMed

13.

Findlay-Shirras LJ, Outbih O, Muzyka CN, Galloway K, Hebbard PC, Nashed M. Predictors of residual disease after breast conservation surgery. Ann Surg Oncol. 2018;25(7):1936–42. https://doi.org/10.1245/s10434-018-6454-1.CrossRefPubMed

14.

Fisher S, Yasui Y, Dabbs K, Winget M. Re-excision and survival following breast conserving surgery in early stage breast cancer patients: a population-based study. BMC Health Serv Res. 2018;18(1):94. https://doi.org/10.1186/s12913-018-2882-7.CrossRefPubMedPubMedCentral

15.

Hughes L, Hamm J, McGahan C, Baliski C. Surgeon volume, patient age, and tumor-related factors influence the need for re-excision after breast-conserving surgery. Ann Surg Oncol. 2016;23(S5):656–64. https://doi.org/10.1245/s10434-016-5602-8.CrossRefPubMed

16.

Wilke LG, Czechura T, Wang C, Lapin B, Liederbach E, Winchester DP, et al. Repeat surgery after breast conservation for the treatment of stage 0 to II breast carcinoma: a report from the National Cancer Data Base, 2004-2010. JAMA Surg. 2014;149(12):1296–305. https://doi.org/10.1001/jamasurg.2014.926.CrossRefPubMed

17.

Jeevan R, Cromwell DA, Trivella M, Lawrence G, Kearins O, Pereira J, et al. Reoperation rates after breast conserving surgery for breast cancer among women in England: retrospective study of hospital episode statistics. BMJ. 2012;345(jul12 2):e4505. https://doi.org/10.1136/bmj.e4505.CrossRefPubMedPubMedCentral

18.

Langhans L, Jensen MB, Talman MM, Vejborg I, Kroman N, Tvedskov TF. Reoperation rates in ductal carcinoma in situ vs invasive breast cancer after wire-guided breast-conserving surgery. JAMA Surg. 2017;152(4):378–84. https://doi.org/10.1001/jamasurg.2016.4751.CrossRefPubMedPubMedCentral

19.

Lovrics PJ, Gordon M, Cornacchi SD, Farrokhyar F, Ramsaroop A, Hodgson N, et al. Practice patterns and perceptions of margin status for breast conserving surgery for breast carcinoma: National Survey of Canadian General Surgeons. Breast. 2012;21(6):730–4. https://doi.org/10.1016/j.breast.2012.07.017.CrossRefPubMed

20.

Parvez E, Hodgson N, Cornacchi SD, Ramsaroop A, Gordon M, Farrokhyar F, et al. Survey of American and Canadian general surgeons' perceptions of margin status and practice patterns for breast conserving surgery. Breast J. 2014;20(5):481–8. https://doi.org/10.1111/tbj.12299.CrossRefPubMed

21.

Thill M, Baumann K, Barinoff J. Intraoperative assessment of margins in breast conservative surgery-still in use? J Surg Oncol. 2014;110(1):15–20. https://doi.org/10.1002/jso.23634.CrossRefPubMed

22.

Biganzoli L, Marotti L, Hart CD, Cataliotti L, Cutuli B, Kuhn T, et al. Quality indicators in breast cancer care: an update from the EUSOMA working group. Eur J Cancer. 2017;86:59–81. https://doi.org/10.1016/j.ejca.2017.08.017.CrossRefPubMed

23.

Butler-Henderson K, Lee AH, Price RI, Waring K. Intraoperative assessment of margins in breast conserving therapy: a systematic review. Breast. 2014;23(2):112–9. https://doi.org/10.1016/j.breast.2014.01.002.CrossRefPubMed

24.

Singh M, Singh G, Hogan KT, Atkins KA, Schroen AT. The effect of intraoperative specimen inking on lumpectomy re-excision rates. World J Surg Oncol. 2010;8(1):4. https://doi.org/10.1186/1477-7819-8-4.CrossRefPubMedPubMedCentral

25.

Maloney BW, McClatchy DM, Pogue BW, Paulsen KD, Wells WA, Barth RJ. Review of methods for intraoperative margin detection for breast conserving surgery. J Biomed Opt. 2018;23(10):1–19. https://doi.org/10.1117/1.JBO.23.10.100901.CrossRefPubMed

26.

Gray RJ, Pockaj BA, Garvey E, Blair S. Intraoperative margin management in breast-conserving surgery: a systematic review of the literature. Ann Surg Oncol. 2018;25(1):18–27. https://doi.org/10.1245/s10434-016-5756-4.CrossRefPubMed

27.

Whitley MJ, Cardona DM, Lazarides AL, Spasojevic I, Ferrer JM, Cahill J, et al. A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer. Sci Transl Med. 2016;8:320ra324.CrossRef

28.

Miampamba M, Liu J, Harootunian A, Gale AJ, Baird S, Chen SL, et al. Sensitive in vivo visualization of breast cancer using ratiometric protease-activatable fluorescent imaging agent, AVB-620. Theranostics. 2017;7(13):3369–86. https://doi.org/10.7150/thno.20678.CrossRefPubMedPubMedCentral

29.

Zhang RR, Schroeder AB, Grudzinski JJ, Rosenthal EL, Warram JM, Pinchuk AN, et al. Beyond the margins: real-time detection of cancer using targeted fluorophores. Nat Rev Clin Oncol. 2017;14(6):347–64. https://doi.org/10.1038/nrclinonc.2016.212.CrossRefPubMedPubMedCentral

30.

Nagaya T, Nakamura YA, Choyke PL, Kobayashi H. Fluorescence-guided surgery. Front Oncol. 2017;7:314. https://doi.org/10.3389/fonc.2017.00314.CrossRefPubMedPubMedCentral

31.

DaCosta RS, Kulbatski I, Lindvere-Teene L, Starr D, Blackmore K, Silver JI, et al. Point-of-care autofluorescence imaging for real-time sampling and treatment guidance of bioburden in chronic wounds: first-in-human results. Plos one. 2015;10(3):e0116623. https://doi.org/10.1371/journal.pone.0116623.CrossRefPubMedPubMedCentral

32.

Wu YC, Smith M, Chu A, Lindvere-Teene L, Starr D, Tapang K, et al. Handheld fluorescence imaging device detects subclinical wound infection in an asymptomatic patient with chronic diabetic foot ulcer: a case report. Int Wound J. 2015;13:449–53.CrossRef

33.

Wu YC, Kulbatski I, Medeiros PJ, Maeda A, Bu J, Xu L, et al. Autofluorescence imaging device for real-time detection and tracking of pathogenic bacteria in a mouse skin wound model: preclinical feasibility studies. J Biomed Opt. 2014;19(8):085002. https://doi.org/10.1117/1.JBO.19.8.085002.CrossRefPubMed

34.

Loh CS, MacRobert AJ, Bedwell J, Regula J, Krasner N, Bown SG. Oral versus intravenous administration of 5-aminolaevulinic acid for photodynamic therapy. Br J Cancer. 1993;68(1):41–51. https://doi.org/10.1038/bjc.1993.284.CrossRefPubMedPubMedCentral

35.

Ohgari Y, Nakayasu Y, Kitajima S, Sawamoto M, Mori H, Shimokawa O, et al. Mechanisms involved in delta-aminolevulinic acid (ALA)-induced photosensitivity of tumor cells: relation of ferrochelatase and uptake of ALA to the accumulation of protoporphyrin. Biochem Pharmacol. 2005;71(1-2):42–9. https://doi.org/10.1016/j.bcp.2005.10.019.CrossRefPubMed

36.

Kobayashi H, Choyke PL. Target-cancer-cell-specific activatable fluorescence imaging probes: rational design and in vivo applications. Acc Chem Res. 2011;44(2):83–90. https://doi.org/10.1021/ar1000633.CrossRefPubMed

37.

Krieg RC, Messmann H, Rauch J, Seeger S, Knuechel R. Metabolic characterization of tumor cell-specific protoporphyrin IX accumulation after exposure to 5-aminolevulinic acid in human colonic cells. Photochem Photobiol. 2002;76(5):518–25. https://doi.org/10.1562/0031-8655(2002)076<0518:MCOTCS>2.0.CO;2.CrossRefPubMed

38.

Valdes PA, Leblond F, Kim A, Harris BT, Wilson BC, Fan X, et al. Quantitative fluorescence in intracranial tumor: implications for ALA-induced PpIX as an intraoperative biomarker. J Neurosurg. 2011;115(1):11–7. https://doi.org/10.3171/2011.2.JNS101451.CrossRefPubMedPubMedCentral

39.

Valdes PA, Kim A, Brantsch M, Niu C, Moses ZB, Tosteson TD, et al. delta-aminolevulinic acid-induced protoporphyrin IX concentration correlates with histopathologic markers of malignancy in human gliomas: the need for quantitative fluorescence-guided resection to identify regions of increasing malignancy. Neuro Oncol. 2011;13:846–56.CrossRef

40.

Valdes PA, Bekelis K, Harris BT, Wilson BC, Leblond F, Kim A, et al. 5-Aminolevulinic acid-induced protoporphyrin IX fluorescence in meningioma: qualitative and quantitative measurements in vivo. Neurosurgery. 2014;10(Suppl 1):74–82.PubMed

41.

Millon SR, Ostrander JH, Yazdanfar S, Brown JQ, Bender JE, Rajeha A, et al. Preferential accumulation of 5-aminolevulinic acid-induced protoporphyrin IX in breast cancer: a comprehensive study on six breast cell lines with varying phenotypes. J Biomed Opt. 2010;15(1):018002. https://doi.org/10.1117/1.3302811.CrossRefPubMedPubMedCentral

42.

Palasuberniam P, Yang X, Kraus D, Jones P, Myers KA, Chen B. ABCG2 transporter inhibitor restores the sensitivity of triple negative breast cancer cells to aminolevulinic acid-mediated photodynamic therapy. Sci Rep. 2015;18:13298.CrossRef

43.

Lakomkin N, Hadjipanayis CG. Fluorescence-guided surgery for high-grade gliomas. J Surg Oncol. 2018;118(2):356–61. https://doi.org/10.1002/jso.25154.CrossRefPubMed

44.

Nakai Y, Inoue K, Tsuzuki T, Shimamoto T, Shuin T, Nagao K, et al. Oral 5-aminolevulinic acid-mediated photodynamic diagnosis using fluorescence cystoscopy for non-muscle-invasive bladder cancer: A multicenter phase III study. Int J Urol. 2018;25(8):723–9. https://doi.org/10.1111/iju.13718.CrossRefPubMed

45.

Inoue K, Anai S, Fujimoto K, Hirao Y, Furuse H, Kai F, et al. Oral 5-aminolevulinic acid mediated photodynamic diagnosis using fluorescence cystoscopy for non-muscle-invasive bladder cancer: a randomized, double-blind, multicentre phase II/III study. Photodiagnosis Photodyn Ther. 2015;12(2):193–200. https://doi.org/10.1016/j.pdpdt.2015.03.008.CrossRefPubMed

46.

Tsuruki ES, Saito Y, Abe S, Takamaru H, Yamada M, Sakamoto T, et al. Evaluating the efficacy and safety of a novel endoscopic fluorescence imaging modality using oral 5-aminolevulinic acid for colorectal tumors. Endosc Int Open. 2016;4(1):E30–5. https://doi.org/10.1055/s-0041-110432.CrossRefPubMedPubMedCentral

47.

Kitada M, Ohsaki Y, Yasuda S, Abe M, Takahashi N, Okazaki S, et al. Photodynamic diagnosis of visceral pleural invasion of lung cancer with a combination of 5-aminolevulinic acid and autofluorescence observation systems. Photodiagnosis Photodyn Ther. 2017;20:10–5. https://doi.org/10.1016/j.pdpdt.2017.08.013.CrossRefPubMed

48.

Ladner DP, Steiner RA, Allemann J, Haller U, Walt H. Photodynamic diagnosis of breast tumours after oral application of aminolevulinic acid. Br J Cancer. 2001;84(1):33–7. https://doi.org/10.1054/bjoc.2000.1532.CrossRefPubMedPubMedCentral

49.

Matoba Y, Banno K, Kisu I, Aoki D. Clinical application of photodynamic diagnosis and photodynamic therapy for gynecologic malignant diseases: a review. Photodiagnosis Photodyn Ther. 2018;24:52–7. https://doi.org/10.1016/j.pdpdt.2018.08.014.

50.

Messmann H. 5-Aminolevulinic acid-induced protoporphyrin IX for the detection of gastrointestinal dysplasia. Gastrointest Endosc Clin N Am. 2000;10(3):497–512. https://doi.org/10.1016/S1052-5157(18)30119-3.CrossRefPubMed

51.

Leunig A, Betz CS, Mehlmann M, Stepp H, Arbogast S, Grevers G, et al. Detection of squamous cell carcinoma of the oral cavity by imaging 5-aminolevulinic acid-induced protoporphyrin IX fluorescence. Laryngoscope. 2000;110(1):78–83. https://doi.org/10.1097/00005537-200001000-00015.CrossRefPubMed

52.

Wang I, Clemente LP, Pratas RM, Cardoso E, Clemente MP, Montan S, et al. Fluorescence diagnostics and kinetic studies in the head and neck region utilizing low-dose delta-aminolevulinic acid sensitization. Cancer Lett. 1999;135(1):11–9. https://doi.org/10.1016/s0304-3835(98)00271-7.CrossRefPubMed

53.

Vanseviciute R, Venius J, Zukovskaja O, Kanopiene D, Letautiene S, Rotomskis R. 5-aminolevulinic-acid-based fluorescence spectroscopy and conventional colposcopy for in vivo detection of cervical pre-malignancy. BMC Womens Health. 2015;15(1):35. https://doi.org/10.1186/s12905-015-0191-4.CrossRefPubMedPubMedCentral

54.

Malik E, Berg C, Meyhofer-Malik A, Buchweitz O, Moubayed P, Diedrich K. Fluorescence diagnosis of endometriosis using 5-aminolevulinic acid. Surg Endosc. 2000;14(5):452–5. https://doi.org/10.1007/s004640000160.CrossRefPubMed

55.

Kitada M, Ohsaki Y, Matsuda Y, Hayashi S, Ishibashi K. Photodynamic diagnosis of pleural malignant lesions with a combination of 5-aminolevulinic acid and intrinsic fluorescence observation systems. BMC Cancer. 2015;15(1):174. https://doi.org/10.1186/s12885-015-1194-0.CrossRefPubMedPubMedCentral

56.

Kanick SC, Davis SC, Zhao Y, Hasan T, Maytin EV, Pogue BW, et al. Dual-channel red/blue fluorescence dosimetry with broadband reflectance spectroscopic correction measures protoporphyrin IX production during photodynamic therapy of actinic keratosis. J Biomed Opt. 2014;19(7):75002. https://doi.org/10.1117/1.JBO.19.7.075002.CrossRefPubMed

57.

Ozog DM, Rkein AM, Fabi SG, Gold MH, Goldman MP, Lowe NJ, et al. Photodynamic therapy: a clinical consensus guide. Dermatol Surg. 2016;42(7):804–27. https://doi.org/10.1097/DSS.0000000000000800.CrossRefPubMed

58.

A. Nabavi, H. Thurm, B. Zountsas, T. Pietsch, H. Lanfermann, U. Pichlmeier, M. Mehdorn, A. L. A. R. G. S. Group, Five-aminolevulinic acid for fluorescence-guided resection of recurrent malignant gliomas: a phase ii study. Neurosurgery. 2009;65:1070-1076. discussion 1076-1077

59.

Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol. 2006;7(5):392–401. https://doi.org/10.1016/S1470-2045(06)70665-9.CrossRefPubMed

60.

Stummer W, Stepp H, Wiestler OD, Pichlmeier U. Randomized, prospective double-blinded study comparing 3 different doses of 5-aminolevulinic acid for fluorescence-guided resections of malignant gliomas. Neurosurgery. 2017;81(2):230–9. https://doi.org/10.1093/neuros/nyx074.CrossRefPubMedPubMedCentral

61.

Stummer W, Tonn JC, Mehdorn HM, Nestler U, Franz K, Goetz C, et al. Counterbalancing risks and gains from extended resections in malignant glioma surgery: a supplemental analysis from the randomized 5-aminolevulinic acid glioma resection study. Clinical article. J Neurosurg. 2011;114(3):613–23. https://doi.org/10.3171/2010.3.JNS097.CrossRefPubMed

62.

NX Development Corp. (2019). Gleolan (aminolevulinic acid hydrochloride): Highlights of prescribing information. Author.

63.

Webber J, Kessel D, Fromm D. Plasma levels of protoporphyrin IX in humans after oral administration of 5-aminolevulinic acid. J Photochem Photobiol B. 1997;37(1-2):151–3. https://doi.org/10.1016/S1011-1344(96)07348-4.CrossRefPubMed

64.

Cozzens JW, Lokaitis BC, Moore BE, Amin DV, Espinosa JA, MacGregor M, et al. A Phase 1 dose-escalation study of oral 5-aminolevulinic acid in adult patients undergoing resection of a newly diagnosed or recurrent high-grade glioma. Neurosurgery. 2017;81(1):46–55. https://doi.org/10.1093/neuros/nyw182.CrossRefPubMed

65.

Webber J, Kessel D, Fromm D. Side effects and photosensitization of human tissues after aminolevulinic acid. J Surg Res. 1997;68(1):31–7. https://doi.org/10.1006/jsre.1997.5004.CrossRefPubMed

66.

Olivotto I, Levine M. Clinical practice guidelines for the care and treatment of breast cancer: the management of ductal carcinoma in situ (summary of the 2001 update). CMAJ. 2001;165(7):912–3.PubMedPubMedCentral

67.

Hagiya AS, Etman A, Siddiqi IN, Cen S, Matcuk GR Jr, Brynes RK, et al. Digital image analysis agrees with visual estimates of adult bone marrow trephine biopsy cellularity. Int J Lab Hematol. 2018;40(2):209–14. https://doi.org/10.1111/ijlh.12768.CrossRefPubMed

68.

Monici M. Cell and tissue autofluorescence research and diagnostic applications. Biotechnol Annu Rev. 2005;11:227–56. https://doi.org/10.1016/S1387-2656(05)11007-2.CrossRefPubMed

69.

Priye A, Ball CS, Meagher RJ. Colorimetric-luminance readout for quantitative analysis of fluorescence signals with a smartphone CMOS sensor. Anal Chem. 2018;90(21):12385–9. https://doi.org/10.1021/acs.analchem.8b03521.CrossRefPubMedPubMedCentral

70.

Morrow M, Van Zee KJ, Solin LJ, Houssami N, Chavez-MacGregor M, Harris JR, et al. Society of Surgical Oncology-American Society for Radiation Oncology-American Society of Clinical Oncology Consensus Guideline on margins for breast-conserving surgery with whole-breast irradiation in ductal carcinoma in situ. Ann Surg Oncol. 2016;23(12):3801–10. https://doi.org/10.1245/s10434-016-5449-z.CrossRefPubMedPubMedCentral

71.

M. Morrow, P. Abrahamse, T. P. Hofer, K. C. Ward, A. S. Hamilton, A. W. Kurian, S. J. Katz, R. Jagsi, Trends in reoperation after initial lumpectomy for breast cancer: addressing overtreatment in surgical management. JAMA Oncol. 2017;3(10):1352-7. https://doi.org/10.1001/jamaoncol.2017.0774.

72.

DeSnyder SM, Hunt KK, Smith BD, Moran MS, Klimberg S, Lucci A. Assessment of practice patterns following publication of the SSO-ASTRO consensus guideline on margins for breast-conserving therapy in stage I and II invasive breast cancer. Ann Surg Oncol. 2015;22(10):3250–6. https://doi.org/10.1245/s10434-015-4666-1.CrossRefPubMedPubMedCentral

73.

K. J. L. Blair, M., Re-excision rates following breast conserving therapy: a single institutions experience over ten years. Marshal J Med. 2017;3:68-74

74.

Merrill AL, Coopey SB, Tang R, McEvoy MP, Specht MC, Hughes KS, et al. Implications of new lumpectomy margin guidelines for breast-conserving surgery: changes in reexcision rates and predicted rates of residual tumor. Ann Surg Oncol. 2016;23(3):729–34. https://doi.org/10.1245/s10434-015-4916-2.CrossRefPubMed

75.

Chung A, Gangi A, Amersi F, Bose S, Zhang X, Giuliano A. Impact of Consensus Guidelines by the Society of Surgical Oncology and the American Society for Radiation Oncology on Margins for Breast-Conserving Surgery in Stages 1 and 2 Invasive Breast Cancer. Ann Surg Oncol. 2015;22(Suppl 3):S422–7.CrossRef

76.

Rosenberger LH, Mamtani A, Fuzesi S, Stempel M, Eaton A, Morrow M, et al. Early adoption of the SSO-ASTRO Consensus Guidelines on margins for breast-conserving surgery with whole-breast irradiation in stage i and ii invasive breast cancer: initial experience from Memorial Sloan Kettering Cancer Center. Ann Surg Oncol. 2016;23(10):3239–46. https://doi.org/10.1245/s10434-016-5397-7.CrossRefPubMedPubMedCentral

77.

Schulman AM, Mirrielees JA, Leverson G, Landercasper J, Greenberg C, Wilke LG. Reexcision surgery for breast cancer: an analysis of the American Society of Breast Surgeons (ASBrS) MasterySM database following the SSO-ASTRO “No Ink on Tumor” Guidelines. Ann Surg Oncol. 2017;24(1):52–8. https://doi.org/10.1245/s10434-016-5516-5.CrossRefPubMed

78.

Heelan Gladden AA, Sams S, Gleisner A, Finlayson C, Kounalakis N, Hosokawa P, et al. Re-excision rates after breast conserving surgery following the 2014 SSO-ASTRO guidelines. Am J Surg. 2017;214(6):1104–9. https://doi.org/10.1016/j.amjsurg.2017.08.023.CrossRefPubMed

79.

Tang SS, Kaptanis S, Haddow JB, Mondani G, Elsberger B, Tasoulis MK, et al. Current margin practice and effect on re-excision rates following the publication of the SSO-ASTRO consensus and ABS consensus guidelines: a national prospective study of 2858 women undergoing breast-conserving therapy in the UK and Ireland. Eur J Cancer. 2017;84:315–24.CrossRef

80.

Chagpar AB, Horowitz NR, Killelea BK, Tsangaris T, Longley P, Grizzle S, et al. Economic impact of routine cavity margins versus standard partial mastectomy in breast cancer patients: results of a randomized controlled trial. Ann Surg. 2017;265(1):39–44. https://doi.org/10.1097/SLA.0000000000001799.CrossRefPubMed

81.

Chagpar AB, Killelea BK, Tsangaris TN, Butler M, Stavris K, Li F, et al. A randomized, controlled trial of cavity shave margins in breast cancer. N Engl J Med. 2015;373(6):503–10. https://doi.org/10.1056/NEJMoa1504473.CrossRefPubMedPubMedCentral

82.

Molinaro AM. Diagnostic tests: how to estimate the positive predictive value. Neurooncol Pract. 2015;2(4):162–6. https://doi.org/10.1093/nop/npv030.CrossRefPubMedPubMedCentral

83.

Lalkhen AG, McCluskey A. Clinical tests: sensitivity and specificity. BJA Educattion. 2008;8:221–3.

84.

Coble J, Reid V. Achieving clear margins. Directed shaving using MarginProbe, as compared to a full cavity shave approach. Am J Surg. 2017;213:627–30.CrossRef

85.

Pappo I, Spector R, Schindel A, Morgenstern S, Sandbank J, Leider LT, et al. Diagnostic performance of a novel device for real-time margin assessment in lumpectomy specimens. J Surg Res. 2010;160(2):277–81. https://doi.org/10.1016/j.jss.2009.02.025.CrossRefPubMed

86.

Schnabel F, Boolbol SK, Gittleman M, Karni T, Tafra L, Feldman S, et al. A randomized prospective study of lumpectomy margin assessment with use of MarginProbe in patients with nonpalpable breast malignancies. Ann Surg Oncol. 2014;21(5):1589–95. https://doi.org/10.1245/s10434-014-3602-0.CrossRefPubMedPubMedCentral

87.

Omoto K, Matsuda R, Nakagawa I, Motoyama Y, Nakase H. False-positive inflammatory change mimicking glioblastoma multiforme under 5-aminolevulinic acid-guided surgery: A case report. Surg Neurol Int. 2018;9:49.CrossRef

88.

Utsuki S, Oka H, Sato S, Shimizu S, Suzuki S, Tanizaki Y, et al. Histological examination of false positive tissue resection using 5-aminolevulinic acid-induced fluorescence guidance. Neurol Med Chir (Tokyo). 2007;47:210–3; discussion 213-214.CrossRef

89.

Wilbers E, Hargus G, Wolfer J, Stummer W. Usefulness of 5-ALA (Gliolan(R))-derived PPX fluorescence for demonstrating the extent of infiltration in atypical meningiomas. Acta Neurochir (Wien). 2014;156(10):1853–4. https://doi.org/10.1007/s00701-014-2148-z.CrossRef

90.

Nakhlis F. How do we approach benign proliferative lesions? Curr Oncol Rep. 2018;20(4):34. https://doi.org/10.1007/s11912-018-0682-1.CrossRefPubMed

91.

DaCosta RS, Andersson H, Wilson BC. Molecular fluorescence excitation-emission matrices relevant to tissue spectroscopy. Photochem Photobiol. 2003;78(4):384–92. https://doi.org/10.1562/0031-8655(2003)0780384:MFEMRT2.0.CO;2.CrossRefPubMed

92.

Vera-Badillo FE, Napoleone M, Ocana A, Templeton AJ, Seruga B, Al-Mubarak M, et al. Effect of multifocality and multicentricity on outcome in early stage breast cancer: a systematic review and meta-analysis. Breast Cancer Res Treat. 2014;146(2):235–44. https://doi.org/10.1007/s10549-014-3018-3.CrossRefPubMed

93.

Cox TR, Erler JT. Molecular pathways: connecting fibrosis and solid tumor metastasis. Clin Cancer Res. 2014;20(14):3637–43. https://doi.org/10.1158/1078-0432.CCR-13-1059.CrossRefPubMed

94.

Macmillan RD, McCulley SJ. Oncoplastic breast surgery: what, when and for whom? Curr Breast Cancer Rep. 2016;8(2):112–7. https://doi.org/10.1007/s12609-016-0212-9.CrossRefPubMedPubMedCentral

95.

Dickson-Witmer D, Bleznak AD, Kennedy JS, Stewart AK, Palis BE, Bailey L, et al. Breast cancer care in the community: challenges, opportunities, and outcomes. Surg Oncol Clin N Am. 2011;20:555–580, ix.CrossRef

96.

Rick K, Sroka R, Stepp H, Kriegmair M, Huber RM, Jacob K, et al. Pharmacokinetics of 5-aminolevulinic acid-induced protoporphyrin IX in skin and blood. J Photochem Photobiol B. 1997;40(3):313–9. https://doi.org/10.1016/S1011-1344(97)00076-6.CrossRefPubMed

97.

Korb ML, Hartman YE, Kovar J, Zinn KR, Bland KI, Rosenthal EL. Use of monoclonal antibody-IRDye800CW bioconjugates in the resection of breast cancer. J Surg Res. 2014;188(1):119–28. https://doi.org/10.1016/j.jss.2013.11.1089.CrossRefPubMed

98.

Lamberts LE, Koch M, de Jong JS, Adams A, Glatz J, Tranendonk MEG, Terwisscha van Scheltinga AGT, Jansen L, de Vries J, Lub-de Hooge MN, Schroder CP, Jorritsma-Smit A, Linssen MD, de Boer E, van der Vegt B, Nagengast WB, Elias SG, Oliveira S, Witkamp A, Mali WPTM, van der Wall E, Van Diest PJ, de Vries EG, Ntziachristos V, van Dam GM. Tumor-specific uptake of fluorescent bevacizumab-IRDye800CW microdosing in patients with primary breast cancer: a phase I feasibility study. Clin Cancer Res. 2016;23(11):2730–41. https://doi.org/10.1158/1078-0432.CCR-16-0437.

99.

Tummers WS, Warram JM, Tipirneni KE, Fengler J, Jacobs P, Shankar L, et al. Regulatory aspects of optical methods and exogenous targets for cancer detection. Cancer Res. 2017;77(9):2197–206. https://doi.org/10.1158/0008-5472.CAN-16-3217.CrossRefPubMedPubMedCentral

Title: Intraoperative fluorescence imaging with aminolevulinic acid detects grossly occult breast cancer: a phase II randomized controlled trial
Authors: Kathryn Ottolino-Perry
Anam Shahid
Stephanie DeLuca
Viktor Son
Mayleen Sukhram
Fannong Meng
Zhihui ( Amy) Liu
Sara Rapic
Nayana Thalanki Anantha
Shirley C. Wang
Emilie Chamma
Christopher Gibson
Philip J. Medeiros
Safa Majeed
Ashley Chu
Olivia Wignall
Alessandra Pizzolato
Cheryl F. Rosen
Liis Lindvere Teene
Danielle Starr-Dunham
Iris Kulbatski
Tony Panzarella
Susan J. Done
Alexandra M. Easson
Wey L. Leong
Ralph S. DaCosta
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Breast Cancer
Breast Cancer
Published in: Breast Cancer Research / Issue 1/2021
Electronic ISSN: 1465-542X
DOI: https://doi.org/10.1186/s13058-021-01442-7

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Trial registration

Please log in to get access to this content

Other articles of this Issue 1/2021

The role of stromal immune microenvironment in the progression of ductal carcinoma in situ (DCIS) to invasive breast cancer

Sensitivity to targeted therapy differs between HER2-amplified breast cancer cells harboring kinase and helical domain mutations in PIK3CA

Evaluation of FGFR targeting in breast cancer through interrogation of patient-derived models

Leronlimab, a humanized monoclonal antibody to CCR5, blocks breast cancer cellular metastasis and enhances cell death induced by DNA damaging chemotherapy

Comparative validation of the BOADICEA and Tyrer-Cuzick breast cancer risk models incorporating classical risk factors and polygenic risk in a population-based prospective cohort of women of European ancestry

18F-fluorodeoxyglucose (FDG) PET or 18F-fluorothymidine (FLT) PET to assess early response to aromatase inhibitors (AI) in women with ER+ operable breast cancer in a window-of-opportunity study

Keynote webinar | Spotlight on antibody–drug conjugates in cancer