PO-0627 RESULTS WITH ACCELERATED HYPOFRACTIONATION BREAST IRRADIATION IN TERMS OF MOLECULAR CLASSIFICATION

S246

ESTRO 31

POSTER: CLINICAL TRACK: BREAST PO-0625 EXTERNAL BEAM PARTIAL BREAST IRRADIATION: DIFFERENCE IN PREAND POSTOPERATIVE TARGET VOLUME DELINEATION F. van der Leij1, P.H.M. Elkhuizen1, T.M. Janssen1, P. Poortmans2, M. van der Sangen3, A.N. Scholten4, C. van Vliet-Vroegindeweij1, L.J. Boersma5 1 The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Radiation Oncology, Amsterdam, The Netherlands 2 Dr. Bernard Verbeeten Institute, Radiation Oncology, Tilburg, The Netherlands 3 Catharina Hospital, Radiation Oncology, Eindhoven, The Netherlands 4 Leiden University Medical Centre, Radiation Oncology, Leiden, The Netherlands 5 MAASTRO Clinic University Medical Centre Maastricht, Radiation Oncology, Maastricht, The Netherlands Purpose/Objective: Partial breast irradiation (PBI) is increasingly performed using external beam radiotherapy. Delineation studies have shown a large inter-observer variability in defining the post-operative clinical target volume (CTV). The aim of this study was to compare the target volume delineation for preoperative external beam PBI with that for postoperative external beam PBI. We focussed on the inter-observer variation and the difference in size of the delineated volumes. Materials and Methods: Twenty-eight breast cancer patients underwent a CT scan prior to and after local tumour excision. Five observers delineated the gross tumour volume (GTV) on the preoperative scan, and expanded the volume with 15 mm (CTV-pre). On the postoperative scan the observers delineated the tumour bed, which was expanded with 15 mm minus the minimum histological free margin (CTV-post). Both targets were, if appropriate, adjusted at the chest wall and/or the skin. One observer delineated the whole breast on the pre- and postoperative scans of all patients. We tested the inter-observer variation by calculating the conformity index (CI = common volume divided by encompassing volume) and the distance between the centres of mass of the target (ComD) for each patient, for each observer pair and for both volumes. Also, we calculated the standard deviation (sd) of all target volume delineations with respect to the median delineation. Further, we compared the sizes of the CTV-pre and the CTV-post volumes, the sizes of the pre-and postoperative whole breast volumes and the CTVpre- versus the CTV-post/whole breast volume ratio. Statistical significance was determined using a Wilcoxon test. Results: The mean CI, the mean ComD and the mean sd all show significantly (all cases p<0.001) less inter-observer variation in the preoperative situation compared to the postoperative situation (table). See the figure for two examples of delineation. There was no significant difference between the size of the volumes of the CTV-pre and CTV-post (p=0.906). The whole breast volume was on average 31 cc larger on the postoperative scans (p=0.028). Also, for the CTV-preversus the CTV-post/whole breast volume ratio we found no significant difference (p=0.407). Table Mean CI Mean ComD (cm) Mean sd (cm) Mean volume breast (cc) Mean volume target (cc) Ratio target/mamma

Pre-CTV 0.765 0.44 0.30 891.7 37.5 0.0482

Post-CTV 0.361 1.12 0.61 922.8 41.9 0.0485

p-value <0.001 <0.001 <0.001 0.028 0.906 0.407

Conclusions: I. Preoperative external beam PBI leads to less inter-observer variation compared to postoperative external beam PBI. The results of this study can be an argument in PBI to treat patients preoperatively. II. Although the delineated postoperative tumour bed volume was larger than the preoperative GTV, in the postoperative situation the final CTV margin of 15 mm was subtracted with the minimum histological free margin, resulting in comparable sizes of the CTV-pre and CTV-post volumes. PO-0626 PREDICTION OF RELAPSE AND CONTRALATERAL TUMOR USING BREAST CANCER CLINICAL VARIABLES AND HISTOCHEMICAL SUBTYPES R. Pacelli1, M. Conson1, L. Cella2, R. Liuzzi2, R. Solla2, V. Iorio1, A. Farella1, M. Salvatore1 1 Università Federico II, Radiation Oncology, Napoli, Italy 2 CNR, Institute of Biostructure and Bioimages, Napoli, Ital Purpose/Objective: To evaluate the use of breast cancer clinical variables along with a surrogate approximation of genetic subtypes in building multivariable outcome predictive models. Materials and Methods: We retrospectively analyzed 599 consecutive female patients affected by localized breast cancer and treated between January 1999 and December 2006 . All patients underwent surgery plus radiotherapy. Median follow-up was 59 months (range 6132) from the diagnosis. Disease recurrences (DR), local and/or distant, and contralateral breast cancer (CBC) were registered and analyzed in relation to an approximation of genetic signature subtyping (luminal A, luminal B, HER-2, and basal), and classical prognostic factors (PFs), namely age, nodal status (N), tumor size (T), grading (G), estrogen and progesterone receptors (ER and PgR), and erb-B2 status. Automated logistic regression with bootstrap technique for variable selection and bootstrap resampling to test selection stability were used Results: Out of 599, 468 patients had a complete histopathological information available and were then analyzed. HER2 and Basal subtypes resulted more likely to recur than Luminal A and B cancers, while patients in the basal-like breast cancer group were more likely to have CBC compared with women with nonbasal tumors. Optimal multivariable predictive model for DR consisted of N, G and ER. A single variable model including basal subtype resulted as the optimal predictive model for CBC. Conclusions: A predictive multivariable model for disease recurrence based on N, G, and ER was identified. Contralateral breast cancers were demonstrated to be significantly and exclusively correlated with basal subtype. PO-0627 RESULTS WITH ACCELERATED HYPOFRACTIONATION BREAST IRRADIATION IN TERMS OF MOLECULAR CLASSIFICATION M. Cabezón Pons1, N. Rodríguez Ibarria1, L. García1, M. Lloret1, B. Pinar1, L.A. Henríquez-Hernández1, A. Valenciano1, P.C. Lara1 1 Hospital Universitario de Gran Canaria Dr. Negrín and Instituto Canario de Investigación del Cáncer (ICIC), Radiation Oncology, Las Palmas de Gran Canaria, Spain Purpose/Objective: Molecular classification is at present time a useful tool to predict clinical outcome in breast cancer patients. Triple negative and Her-2+ groups had worse survival and reduced local control after radiotherapy in patients treated by conventional fractionation, probably through increased repopulation during the radiotherapy course. The aim of the present study is study if accelerated hypofractionation breast irradiation can increase local control in those bad prognosis molecular classified tumours. Materials and Methods: From January 2008 to December 2010, 261 patients with unselected conservatively treated breast carcinomas were prospectively included in the present study. Mean age was 54,77+/-12,69, median 54 range 24-88, 64,7% menopausal. Most of the cases were DIC (89,7%), T1(76.5%), N0 (60.3%), stage 1(46.33%) and RE+ 81,9% & RP+ 72,8%. Her-2/neu was positive in 21,2% of the cases. Four patient groups were defined by receptor status: Group 1: Luminal A 71(27,2% ), Group 2: Luminal B 144(55,2%) Group 3: Her-2+ 14(5,4%) , and Group 4: Triple N 32(12,3%). All patients were treated by Accelerated Hypofractionation on the tumoral bed by a 2,35 Gy/frx scheme. Those with negative margins recieved 47 Gy in 20 frx, those at moderate risk 58,75 Gy in 25frx and most of those with higher risk(very close or affected margins) 63,75 Gy in 27 frx. Treatment acceleration allows for a planned total treatment time of 28, 35 or 37 days respectively.

ESTRO 31

S247

Results: After a mean follow-up of 26,51+/-10.47 median 27 months range 6-52, the 3-year ipsilateral breast tumor control rates was 99,8% in Luminal A/B cases and 97,1% in Her2+/Triple Negative cases (p=0.438). The 3-year distant disease relapse-free survival rates for Groups 1 and 2 were 94,7%, 87,4% (p = 0.01).The 3-year relapse free survival was 98,8% vs 84% (p=0.005) for Luminal vs H2r2+/Triple Negative. Conclusions: Accelerated hypofractionated radiotherapy seems to be useful for bad prognosis molecular subtypes as local control was excellent and comparable with low molecular risk cases. Triple negative/ Her-2+ tumors had a significantly worse distant metastatsis disease free survival and disease free survival. Longer follow-up will be needed to confirm the encouraging result of accelerated treatment in molecular high risk breasy cancer patients. PO-0628 TOXICITY PREDICTORS FOR HYPOFRACTIONATED FIMRT IN BREAST CANCER A. Fodor1, P. Mangili2, C.I. Fodor3, G. Rinaldin2, E. Villa1, M. Pasetti1, C. Fiorino2, I. Dell'Oca1, A. Bolognesi1, N.G. Di Muzio1 1 San Raffaele Scientific Institute, Radiotherapy, Milano, Italy 2 San Raffaele Scientific Institute, Medical Physics, Milano, Italy 3 European Institute of Oncology, Radiotherapy, Milano, Italy Purpose/Objective: The evaluation of the breast volume effect on early and late toxicity and chemotherapy(CT) effect on late toxicity for our Hypofractionated whole-breast irradiation(HWBI) protocol with Forward-Planned IMRT(FIMRT). Materials and Methods: From 02/2009 early breast cancer pts were treated with HWBI, 40Gy/15fr, delivered in 3 weeks. The first 150 pts, with more than 18 mts of f-up, were analysed. The median patient age: 62.2 yrs (28-81.7yrs). A median number of 4 segments was used (2-12) within a tangential two field irradiation technique. 72% of the pts needed ≥4 segments to obtain a homogeneous dose, with hot spots ≤ 108% on PTV, and with 3% of the heart ≤ 40 Gy, and ≤20% of ipsilateral lung ≤ 17 Gy. For 28% of pts <4 fields were sufficient to reach the constraints. To report the acute toxicity the RTOG/EORTC scale was used, while for late toxicity the SOMA LENT scale was used. Results: One patient was lost to follow up after the end of the treatment and the 6 month and 2 year toxicity are thus missing for her. One patient died of distant metastasis after 7.7 months of follow up and the toxicity result at 2 years is missing for him. One patient underwent concomitant bilateral HWBI, and both breasts were considered in the analysis. The median follow-up of this group of pts was 21.1 mts (7.7-26.6 months). The median target volume (breast PTV eff) was of 603.4 cc (172.4-2649 cc) which was thus chosen as the cut-off value. Two groups of pts were considered in the analysis: those with target volume ≤600 cc, and those with target >600 cc. The toxicity results for 73 breast cancers ≤600 cc versus 77 breast cancers > 600 cc were: Toxicity grade

End of RT

At 6 months

At 18 -24 months

G0

37 vs 25

66 vs 62

64 vs 66

G1

32 vs 38

6 vs 15

7 vs 11

G2

4 vs 11

0 vs 0

0 vs 0

G3

0 vs 3

0 vs 0

0 vs 0

The impact of the volume on acute toxicity is significant (p=0.025), as well as on G1 toxicity at 6 months (p=0.05). The pts who underwent sequential or concomitant CT showed a higher rate of G1 late toxicity(p=0.027). Thirty five pts underwent CT and 114 had no CT; the late toxicity was as follows: G0:27 (77.1%) vs102(89.51%), G1: 8(22.9%)vs10(8.8%), no toxicity≥G2 was registered. Missing data in 2 patients (1.7%) without chemo-therapy. Also the 108 pts needing >4 segments to obtain good dose distribution presented higher late toxicity than the 42 pts needing <4 segments, but not statistically significant (p=0.56): G0:93(86.1%)vs37(88.1%),G1:14(13%)vs4(9.5%), no toxicity ≥G2 was registered; the data were missing in 1(0,9%)vs1(2,4%) pts. Skin toxicity was intended as skin discoloration, subcutaneous fibrosis or breast oedema. No lung or heart toxicity were recorded Conclusions: The FIMRT approach adopted allowed us to obtain a good result of acute and late skin toxicity. Breast volume, use of

chemotherapy and the number of segments needed to obtain a good dose distribution could be predictive of acute and late toxicity. PO-0629 IMRTAND REGIONAL NODAL IRRADIATION IN LEFT SIDED BREAST CANCER PATIENTS CAN SPARE MORE NORMAL TISSUES K. Thabet1, M. Abd El- Moez1, M. EL-Haddad1, M. Sayed1, N. ElSherbiny1, A. El-Kashef1, S. El-Mesidy1 1 Cairo University, Clinical Oncology, Cairo, Egypt Purpose/Objective: Radiotherapy plays an important role in the management of breast cancer. In the last early breast cancer collaborative study group meta-analysis post-operative radiotherapy added to the survival for node positive patients. Recently regional nodal irradiation in patients with one to three lymph nodes again added to patient’s survival. The aim of this study is to compare 3DCRT plans with intensity modulated radiation therapy in regional nodal irradiation and evaluate its value in reducing tissue complications. Materials and Methods: Thirty patients with left sided post mastectomy node positive breast cancer patients were selected. For each patient one 3DCRT and another IMRT plan was generated. Supraclavicular and internal mamary nodal regions were included. Dose coverage, dose homogeneity, and normal tissue complication probabilities (NTCPs) for the organs at risk (ORs) were calculated. Results: PTV dose coverage was better in IMRT than 3D-CRT with D90% of 48.8Gy Vs 47.8Gy and D95% was 48.2Vs 46.3Gy. Dose homogeneity was better in 3D-CRT than IMRT 0.1570 Vs 0.1857. TCP was also better in 3D-CRT than IMRT 68.34±4.74% Vs 66.24±4.89%. Internal mammary chain coverage, was better in IMRT than 3D-CRT with D90% 47.3Gy Vs 46.7Gy and D95% 47 Gy Vs 45.6 Gy. Dose to left lung was significantly lower in IMRT than 3D-CRT with V20Gy of 17% Vs 26.7%. V30Gy of 10% Vs 22.6%, and NTCP 0.928±0.396% Vs 3.69±2.98%. Max. dose to the heart was significantly lower in IMRT plans 34Gy Vs. 47.3Gy. V40Gy 0.381±0.795% VS 8.791±4.546%, and NTCP 0.7563±0.287% VS 2.436±1.051%. Right breast dose was significantly higher in IMRT than 3D-CRT mean of 4.1Gy VS 1.6Gy, V5Gy 20.1±12.3% VS 4.3±4.6%, and the estimated excess relative risk of right breast cancer incidence was 2.29±0.62% VS 0.93±0.43%. Conclusions: IMRT can spare more critical structures than 3DCRT while giving adequate dose coverage to the PTV and Internal mammary nodes. PO-0630 PBI WITH INTERSTITIAL HIGH DOSE RATE BRACHYTHERAPY: RESULTS OF A PHASE II PROSPECTIVE STUDY I. Palumbo1, A. Farneti1, G. Capezzali1, L. Falcinelli2, M. Margaritelli1, V. Lancellotta1, C. Zucchetti3, M. Marcantonini3, C. Raymondi3, C. Aristei1 1 Radioterapia, Dipartimento di Scienze Chirurgiche radiologiche e Odontostomatologiche, Perugia, Italy 2 Radioterapia, Azienda Ospedaliera di Perugia, Perugia, Italy 3 Fisica Sanitaria, Azienda Ospedaliera di Perugia, Perugia, Italy Purpose/Objective: To investigate long-term results of PBI with 192Ir interstitial HDR brachytherapy in patients with early breast cancer Materials and Methods: From August 2003 to December 2008 100 patients aged 49-84 years (median 66) were treated. There were 86 with infiltrating tumors and 14 CDIS (median tumor size 9 mm, range 2-28) ER and PgR were positive in 85 and 63 cases respectively, axillary nodes were negative in 98 patients, sentinel node was positive in 2 (1 with micrometastasis). Eight patients received adjuvant chemotherapy, 78 hormonal therapy. Treatment schedule was 4 Gy twice a day for 4 days, up to a total dose of 32 Gy with an interval between fractions of at least 6 hours. Skin and subcutaneous toxicity, teleangectasia and pain were graded using CTCAE v3.0, fat necrosis with the scoring system described by Lövey et al. Mann-Whitney non-parametric test, Cosmetic results were evaluated, using the Harvard criteria, by radiation oncologists and patients, Cohen’s k-test of inter-rater agreement (k-value ranging from 0 to 1) estimated concordance between patients and physicians. Results: Median follow-up was 60 months (range 5-92). Late toxicity (shown in Table 1) occurred at a median of 12 months (range 3- 49). A 75% size reduction was observed in the 2 fat necrosis (1 symptomatic) after 44 months, 1 of the 2 G2 subcutaneous toxicity doubled in 53 months, 3 teleangiectasias increased from G1 to G2 after 13, 22 and 27 months. In 1 patient seroma size was reduced of 50% in 37 months and in another it almost disappeared in 36 months.