How to sequence systemic therapies and radiotherapy in early breast cancer?

Transcription

1 S. Arcangeli, MD How to sequence systemic therapies and radiotherapy in early breast cancer? H. Wildiers, MD, PhD 1,2, T. Pecceu, MD 1, C. Weltens, MD, PhD 2,3, P. Neven, MD, PhD 2, S. Peeters, MD, PhD 2,3 (Belg J Med Oncol 2014;8(3):72-80)

2

3 ER + ER + ER - ER -

4 CLINICAL INVESTIGATION Breast Cancer CHANGES IN PUL MONARY FUNCTION UP TO 10 YEARS AFTER LOCOREGI ONAL BREAST IRRADIATION KATRIEN ERVEN,M.D.,* CAROLINE WELTENS, M.D.,PH.D.,* KRISTIAAN NACKAERTS,M.D.,PH.D., y STEFFEN FIEUWS,PH.D., z MARC DECRAMER,M.D.,PH.D., y AND YOLANDE LIEVENS,M.D.,PH.D.* Int. J. Radiation Oncology Biol. Phys., Vol. 82, No. 2, pp , 2012 Copyright Ó 2012 Elsevier Inc.

5 in-vitro studies support the notion of antagonistic effects of concurrent tamoxifen and radiotherapy on tumour cells in-vivo research suggests a synergistic effect that could be attributable to micro-environmental changes in tumour responsiveness to ionising radiation and hormone therapy

6 Seminar article Why does androgen deprivation enhance the results of radiation therapy? Jennifer Y. Wo, M.D. a, *, Anthony L. Zietman, M.D. b a Harvard Radiation Oncology Program, Boston, MA 02114, USA b Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA Technical advantages: Volume Reduction Urologic Oncology: Seminars and Original Investigations 26 (2008)

7 Seminar article Why does androgen deprivation enhance the results of radiation therapy? Jennifer Y. Wo, M.D. a, *, Anthony L. Zietman, M.D. b a Harvard Radiation Oncology Program, Boston, MA 02114, USA b Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA Biological advantages: prior ADT increase the probability of eradicating tumor by irradiation Urologic Oncology: Seminars and Original Investigations 26 (2008) Treatment failure and poor prognosis of PCa could be due to the anomalous and inefficient pattern of vascularization, leading to intermittent/chronic hypoxia

8 Phoenix ASTRO

9 Proc. Natl. Acad. Sci. USA 95 (1998) Hormone withdrawal inhibits VEGF expression and angiogenesis in hormone-dependent PCa, thereby mimicking anti-vegf therapy

10 po2 increased from 6.4 to 15 mmhg

11 Importance of monitoring changes in tumor hypoxia during ADT Hypoxia biomarker such HIF1a could be helpful for planning RT initiation and potential use of hypoxia-targeted therapy. ANTICANCER RESEARCH 35: (2015) Protective Effect of L euprorelin on Radiation-induced Intestinal Toxicity MONICA MANGONI 1, MARIANGELA SOTTILI 1, CHIARA GERINI 1, ROSSELLA FUCCI 1, ALESSANDRO PINI 2, LAURA CALOSI 2, PIERLUIGI BONOMO 1, BEATRICE DETTI 1, DANIELA GRETO 1, ICRO MEATTINI 1, GABRIELE SIMONTACCHI 1, MAURO LOI 1, DANIELE SCARTONI 1, ILARIA FURFARO 1, STEFANIA PALLOTTA 3 and LORENZO LIVI 1

12 Synthesis of Trials Data Overall Survival Benefit - EORTC yrs vs. 0 (18.3% at 10 yrs) - TROG months vs. 0 (13.3% at 3 yrs) - DFCI months vs. 0 (13% at 8 yrs) - RTOG months vs. 0 (8.8% at 10 yrs) - RTOG months vs. 0 (5% at 10 yrs) - RTOG months vs. 4 months (1% at 10 yrs) - EORTC yrs vs. 6 months (3.8% at 5 yrs)

13 Are these results transferable in daily clinical practice? Population: inhomogeneity of intermediate risk group Intervention: use of ineffective RT total dose Outcomes: improvement in OS and DFS likely overestimated Int J Rad Oncol Biol Phys 2008

14 RT <72 Gy RT 72 Gy High dose RT reduced PCSM from 14 to 4% in high risk pts CLINICAL INVESTIGATION Prostate LACK OF BENEFIT FOR THE ADDITION OFANDROGEN DEPRIVATION THERAPY TO DOSE-ESCALATED RADIOTHERAPY IN THE TREATMENT OF INTERMEDIATE- AND HIGH-RISK PROSTATE CANCER 75% ADT 31.6% 25% ADT 66%

15 Int J Rad Oncol Biol Phys 2012 RT + long vs. long ADT PCS IV. #NCT GyRT + 18 monthsht vs. 36 monthsht -no OS neitherpscm benefit atmedianfollowup of 6.4 yrs -T3-T4; PSA >20; GS >7; N0 Very HR PCa EORTC vs. PCS IV Study N. pts Median f-up (years) 5-year Survival (%) Duration of ADT 6 months 18 months 36 months EORTC PCS IV Bolla M et al. N Engl J Med Nabid A, et al. JCO 2013;31(S6):3 (abs)

16 95% 86% P=0.009 High dose RT ± ADT Ongoing Trials RTOG GyRT ±6 monthsht in IR-HR PCa The only trial stratified by Adult Comorbidity Evaluation-27 comorbidity score EORTC Gy/74 Gy/78 GyRT ±6 monthsht in IR PCa -819 ptsfrom 14 EuropeanCountries

17 ADT ± RT SPCG-7 NCI MRC 55% 49% 24% 12% 10 yrs ADT+RT ADT p bf 26% 75% < CSS 88% 76% < OS 70% 61% yrs ADT+RT ADT p TTP 63% 27% < CSS 68% 46% < OS 55% 49% ADT ± RT

18 The synergy between RT and ADT is independent of the sequencing of both more in Critical Reviews in Oncology/Hematology xxx (2014) xxx xxx Combination of androgen deprivation therapy and radiotherapy for localized prostate cancer in the contemporary era Rolando M. D Angelillo a,, Pierfrancesco Franco b, Berardino De Bari c, Alba Fiorentino d, Stefano Arcangeli e, Filippo Alongi d a Radiation Oncology Campus Bio-Medico University, Rome Italy b Department of Oncology, Radiation Oncology, University of Turi n School of Medicine, Turi n, Italy c Radiation Oncology Department, Centre Hospitalier Universitaire Vaudois CHUV, Lausanne Swi tzerl and d Radiation Oncology Department, Sacro Cuore-Don Calabria Hospital, Negrar-Verona, Italy e Radiation Oncology, Azienda Ospedalier a S. Camillo-Forlanini, Rome, Italy Received 14 February 2014; received in revised form 18 August 2014; accepted 1 October 2014