- Email: [email protected]
Prone Positioning With Deep Inspiration Breath Hold for Left Breast Radiation Therapy: Initial Results of a Prospective Study
Volume 96 Number 2S Supplement 2016 up to one year after surgery. 28 patients were triple negative (TARGIT: 16; EBRT: 12) and 42 patients were HER2 positive (TARGIT: 24; EBRT: 18). Disease free survival and overall survival were compared. Results: Median follow-up was 49 months. The 5-year Kaplan-Meier estimate of overall survival showed no significant difference in HER2 positive tumors: TARGIT 0 events 100%, EBRT 1 event 91.7%, log-rank P Z 0.22. The same was seen for disease free survival: TARGIT 2 events 83.3%, EBRT 4 events 77.0%, log rank P Z 0.38. The results for triple negative cases were similar. Overall survival: TARGIT 2 events 87.5%, EBRT 3 events 74.1%, log rank P Z 0.488. Disease free survival: TARGIT 2 events 87.5%, EBRT 4 events 60%, log rank P Z 0.22. Conclusion: Although trends were favorable for TARGIT-IORT, no significant differences could be shown and the significantly positive result for overall survival in the whole cohort of 116 patients could not be reproduced in this substudy on triple negative and HER2 positive tumors. The reason for this may be the small number of events, but it may also indicate that the results for the whole cohort were mainly driven by ER and/or PR positive and HER2 negative patients. Author Disclosure: H. Kolberg: Honoraria; Carl Zeiss Meditec, TEVA, Theraclion, Amgen, Janssen, GSK. Consultant; LIV Pharma. Advisory Board; Novartis, Genomic Health. G. Loevey: Honoraria; Carl Zeiss Meditec. L. Akpolat-Basci: None. M. Stephanou: None. P.A. Fasching: Research Grant; Novartis. Honoraria; Roche, TEVA, Genomic Health, Pfizer, Novartis, Amgen. M. Untch: None. C. Liedtke: Honoraria; Celgene, TEVA, Pierre Fabre, Novartis, Amgen, Eisai, GSK. Advisory Board; Roche, Genomic Health. M. Bulsara: Research Grant; Carl Zeiss Meditec. Honoraria; Carl Zeiss Meditec. J.S. Vaidya: Honoraria; Carl Zeiss Meditec.
2016 Carbon Ion Radiation Therapy for Stage I Breast Cancer K. Karasawa,1 T. Omatsu,2 M. Wakatsuki,2 S. Shiba,2 S. Fukuda,2 T. Kamada,3 N. Yamamoto,4 T. Ishikawa,5 A. Arakawa,6 and M. Saito6; 1 Department of Radiation Oncology, Tokyo Women’s Medical University, Tokyo, Japan, 2National Institute of Radiological Sciences, Chiba, Japan, 3 Research Center Hospital for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan, 4Chiba Cancer Center, Chiba, Japan, 5Tokyo Medical University, Tokyo, Japan, 6Juntendo University, Tokyo, Japan Purpose/Objective(s): To evaluate 3-years treatment outcome of a clinical study of radical accelerated partial breast irradiation (APBI) for stage I breast cancer using carbon-ion radiation therapy (C-ion RT). Materials/Methods: Eligibility criteria of phase I study are (1) pathologically proven invasive ductal carcinoma, (2) tumor diameter 2 cm or less on MRI, UICC clinical stage I (T1N0M0), (3) Estrogen receptor (ER) positive, HER2 negative, No Lymphovascular space invasion, No extensive intraductal component, (4) Performance status 0w2, (5) Age 60 years old and above, (6) No other life-threatening illness, and (7) Tumor located more than 5 mm from the skin. A dose escalation study was designed as a phase I clinical trial with the dose level of 48.0 Gy (RBE), 52.8 Gy (RBE) and 60.0 Gy (RBE) in 4 fractions within one week, at fraction sizes of 12 Gy (RBE), 13.2 Gy (RBE) and 15 Gy (RBE), respectively. In phase I, patients were planned to undergo surgery for pathological evaluation 90 days after C-ion RT and then have been receiving endocrine therapy. In “general protocol,” eligibility criteria are patients with 1, 2, 4, 6, and 7. In “general protocol,” patients have been receiving endocrine therapy without surgery after C-ion RT. Three-field C-ion beams of 290 MeV/n energy are used by means of passive broad beam methods using respiratory gating. Primary end points are early normal tissue reaction and tumor control at recommended dose. Secondary end points are CR rate, late normal tissue reaction, cosmetic outcome, disease-free survival, and overall survival. Results: From April 2013 to November 2015, 21 cases were treated with C-ion RT. Patients’ age ranged from 44 to 81 years old, with a median of 66 years old. Tumor sizes were 4 to 20 mm, with a median of 12 mm. The follow-up period ranged from 3 to 31 months, with a median of 15 months. No adverse reactions in normal tissue were observed except for grade 1
Poster Viewing
E7
skin reaction of CTC-AE v4 in 12 cases. In phase I study, 7 cases (3 cases of 48 Gy (RBE), 3 cases of 52.8 Gy (RBE) and 1 case of 60 Gy (RBE)) were treated and recommended dose settled to 60 Gy (RBE). Two of 7 phase I patients reached pathological CR at 3 month period. The first 2 patients of this “general protocol” were treated by 52.8 Gy (RBE) and the other 12 by 60 Gy (RBE). Three of 14 at 3 month period, 3 of 9 at 6 month period, 4 of 6 at 12 month period and 2 of 2 at 24 month period after C-ion RT reached CR, respectively. One patient with basal type became PD at 6 month period after C-ion RT on MRI. The PD patient was successfully salvaged by surgery. Conclusion: C-ion RT for patients with stage I breast cancer seems useful without problematic adverse effects, and it might take longer period for breast cancer to reach CR on MRI. Author Disclosure: K. Karasawa: None. T. Omatsu: None. M. Wakatsuki: None. S. Shiba: None. S. Fukuda: None. T. Kamada: None. N. Yamamoto: None. T. Ishikawa: None. A. Arakawa: None. M. Saito: None.
2017 Is Postoperative Supraclavicular Fossa Radiation Therapy Necessary After Neoadjuvant Chemotherapy in Yp N Stage 0-1 Breast Cancer? R. White,1 T. Dinneen,2 and A. Makris1; 1Mt Vernon Cancer Centre, London, United Kingdom, 2University of Western Australia, Perth, Australia Purpose/Objective(s): To investigate the role of supraclavicular radiation therapy (SCRT) in addition to chest wall or breast radiation therapy in patients with combined clinical stage II-III breast cancer of pathological nodal status 0 or 1 following neoadjuvant chemotherapy (NAC) and surgery. Materials/Methods: From a prospectively collected breast cancer database of 713 females enrolled on NAC trials we retrospectively identified 233 with combined clinical stage II - III who received surgery inclusive of axillary node dissection, were staged post-operatively as ypN0-1, and received post-operative radiation therapy. Those who received SCRT (SCRT+) in addition to local radiation therapy were compared to those who did not (SCRT-). Freedom from regional recurrence (FFRR), disease free survival (DFS) and overall survival (OS) were compared. Further exploratory analysis of subgroups considered most likely to benefit from SCRT was performed. Multivariate analysis was performed to identify factors influencing FFRR, DFS, and OS. Results: Sixty-one patients received SCRT and 172 did not. At a median follow up of 63 months from diagnosis the 5 year actuarial estimates of FFRR, DFS and OS respectively were 88.2, 63.5 and 74.8% for the SCRT+ and 91.1, 69.7 and 79.6% for the SCRT- group. No differences were statistically significant. There were no specific subgroups identified that clearly benefited from the addition of SCRT to local radiation therapy. On multivariate analysis statistically significant predictive factors for FFRR were combined clinical stage II disease and hormonal therapy use. Prognostic factors were combined clinical stage II, clinical nodal stage 0, yp nodal stage 0, the use of hormonal therapy and the use of trastuzumab. SCRT was not predictive of FFRR or OS on univariate or multivariate analysis. Conclusion: The addition of SCRT did not clearly benefit this cohort of patients. Adjuvant local radiation therapy alone may be sufficient in many stage II-III patients with negative or minimal nodal involvement following NAC and surgery. Further confirmatory prospective studies are indicated. Author Disclosure: R. White: None. T. Dinneen: None. A. Makris: None.
2018 Prone Positioning With Deep Inspiration Breath Hold for Left Breast Radiation Therapy: Initial Results of a Prospective Study U. Goyal and V.J. Gonzalez; University of Arizona, Tucson, AZ Purpose/Objective(s): Left breast radiation therapy for breast cancer has been shown to deliver clinically significant radiation dose to the heart. Prone positioning on a breast board and supine positioning with deep
E8
International Journal of Radiation Oncology Biology Physics
inspiratory breath hold (DIBH) have independently demonstrated significant reduction in cardiac exposure during left breast radiation therapy. We investigated the combination of prone position and DIBH to decrease cardiac doses for left-sided breast radiation therapy. Materials/Methods: Twelve patients with left-sided breast cancer were enrolled on an IRB-approved prospective study. Each patient underwent two prone positioned CT-simulation scans utilizing free breathing (FB) and DIBH. Breathing motion was controlled using a RPM system paired with visual feedback via LCD monitor. Separate treatment plans for each CTsimulation scan were created, and the heart and left lung mean doses were compared between FB and DIBH treatment plans. The technique with lower mean dose for the heart was used during treatment. All patients were treated with a hypofractionated regimen of 40-42 Gy in 15-16 fractions followed by a lumpectomy cavity boost of 10 Gy in 5 fractions when indicated. Two-tailed paired t-tests were performed for dosimetric endpoints. Results: One patient was not able to tolerate prone positioning at simulation leaving 11 patients with evaluable scans. Average mean heart dose with FB was 0.80 Gy (range 0.53-1.07 Gy) and 0.69 Gy (0.52-0.85 Gy) with DIBH (P Z 0.03). The average max heart dose with FB was 8.9 Gy vs 3.8 Gy with DIBH (P Z 0.1). The average heart V5 Gy was 5.1cc with FB and 0.5cc with DIBH (P Z 0.06). Average mean left lung dose with FB was 0.51 Gy (range 0.18-0.76 Gy) and 1.19 Gy (0.26-1.24 Gy) with DIBH (P Z 0.008). Two patients at study initiation were treated prone FB while technique was optimized to accommodate RPM in prone position. One patient was treated prone FB due to minimal reduction in cardiac dose from DIBH, and one patient was treated supine with DIBH. Seven remaining patients were treated using prone DIBH. Conclusion: Our preliminary results indicate that DIBH using the RPM system can provide additional cardiac dose reduction in patients receiving prone left-breast radiation therapy with a small increase in mean left lung dose. Tolerance of prone treatment did not appear to be affected by the addition of DIBH. Further studies are required to estimate clinical advantages from further cardiac dose reduction and to better evaluate which patients may benefit the most from the combination of DIBH and prone positioning. Author Disclosure: U. Goyal: None. V.J. Gonzalez: None.
correlated with grade (Spearman Rho Z 0.446, P<0.001) and negatively correlated with age (Spearman Rho Z -0.246, P<0.001). Introducing the Ki-67 into sub-typing shifted significant number of patients with good prognosis into the poor prognosis group. The median Ki-67 LI for grades 1, 2, and 3 were 7.5%, 25%, and 45% respectively.
2019 Immunophenotyping to Approximate Molecular Subtyping Using Ki67 Labeling Index N. Rao,1 A. Ram,2 and B.S. Ajaikumar1; 1Healthcare Global Enterprises Ltd., Bangalore, India, 2HCG Cancer Hospitals, Bangalore, India Purpose/Objective(s): Gene-expression profiling studies have emphasized the prognostic value of assessing the proliferation index Ki-67. The aims of the present study were to assess the relationship of Ki-67 labeling index (LI) to histological grade and to examine if the addition of Ki-67 LI had any impact on routine immunophenotyping with the triple markers panel (ER, PR, and HER2). Materials/Methods: We examined the reports of 124 consecutive breast cancer patients seen at our institution between September 2011 and February 2013, who had an invasive ductal carcinoma, were ER/PR positive and undergone examination with a panel of four markers (ER, PR, HER2 and Ki-67) by immunohistochemistry (IHC). We studied the data for correlation between Ki-67 LI and age, grade and HER2 status. Tumors were first classified into good / poor prognostic groups based on the triple marker IHC profiles of ER, PR, and HER2. The same patients were then reclassified on a four markers panel that included ER, PR, Her2, and Ki-67 and these proportions compared using the Chi square test for goodness of fit. The median of KI-67 was chosen as the cut-off to divide between good and bad prognostic groups. Results: When phenotyping was based on three markers there were 102 (82.25%) ER/PR+ve, HER2-ve (good prognostic /Luminal A group) and 22 (17.75%) ER/PR+ve, HER2+ve (poor prognostic / Luminal B group). The KI-67 percentage had a median score of 25%, which was used as the cut-off score to determine the prognostic groups; Ki-67 LI positively
Abstract 2019; Table 1.
Good Prognosis Poor Prognosis
Triple Marker Panel
Triple Marker Panel + KI-67
102 (82.25%) 22 (17.75%)
67 (54.03%) 57 (45.97%)
Conclusion: A strong correlation was detected between Ki-67 labeling index and grade and age and this holds prognostic relevance. Inclusion of Ki-67 Labeling Index into phenotyping did suggest that a significant number of patients with good prognosis (per the 3 marker panel) might have a poorer prognosis. The high Ki-67 LI in this group might also explain the comparatively inferior outcomes observed in this good prognostic group in India. While multi-gene expression arrays might be able to better prognosticate and allow make confident treatment decisions, they are expensive and not easily accessible in India. Our results indicate that inclusion of a single marker like KI-67 labeling index might predict prognosis better and serve as a reasonable surrogate. Author Disclosure: N. Rao: None. A. Ram: None. B.S. Ajaikumar: None.
2020 First Outcome Analysis of the TARGIT E(lderly) TrialdProspective Phase 2 Study of Intraoperative Radiation Therapy (IORT) in Elderly Patients With Small Breast Cancer F. Wenz; Department of Radiation Oncology, Universita¨tsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany Purpose/Objective(s): The purpose is to further investigate the efficacy of a single intraoperative radiation therapy treatment within elderly low risk patients with breast cancer ( 70 years, 3.5cm, cN0, cM0, invasiveductal histology) which is followed by whole breast radiation therapy (WBRT) only when risk factors are present. This prospective, multicentric single arm phase II study (NCT01299987) is based on the experimental arm of the randomized protocol of the international TARGIT A study. Here we present the first outcome analysis. Materials/Methods: Five hundred thirty-eight patients from 28 international centers were recruited between February 2011 and September 2014. The current analysis is based on 447 patients (median age 74yrs) excluding patients with screening failure, drop-out or loss to follow-up. During breast conserving surgery a single dose of 20 Gy of intraoperative radiation therapy was given using the targeted intraoperative radiation therapy system (Carl Zeiss Meditec, Germany). Additional postoperative WBRT (46e50 Gy) was prescribed only in patients with risk factors (larger size, other histology, small free margin, lymph vessel invasion, positive nodes, multifocality/multicentricity, extensive intraductal component (EIC)). Systemic therapy was given according to international standards. The primary outcome was local relapse. Overall survival was a secondary outcome. Discontinuation of the trial is scheduled if rates of local relapse rates rise to 3/4/6% after 2.5/5/7.5 years. Results: After a median follow-up of 14.0 months in 447 patients, one ipsilateral in-breast recurrence (20 mon after IORT) and three deaths (11, 14, 23 mon) were observed resulting in an actuarial local relapse free survival of 99.4% and actuarial overall survival of 98.6% after 2.5 years. Conclusion: The results of the prospective TARGIT E trial consolidate earlier reports from the randomized TARGIT A trial supporting the use of accelerated partial breast radiation therapy (APBI) in selected patients. The observed local relapse rate after 2.5 years is well below the prospectively defined stopping rules (Neumaier et al. BMC Cancer 2012). Further follow-up will be performed.
2016 Carbon Ion Radiation Therapy for Stage I Breast Cancer K. Karasawa,1 T. Omatsu,2 M. Wakatsuki,2 S. Shiba,2 S. Fukuda,2 T. Kamada,3 N. Yamamoto,4 T. Ishikawa,5 A. Arakawa,6 and M. Saito6; 1 Department of Radiation Oncology, Tokyo Women’s Medical University, Tokyo, Japan, 2National Institute of Radiological Sciences, Chiba, Japan, 3 Research Center Hospital for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan, 4Chiba Cancer Center, Chiba, Japan, 5Tokyo Medical University, Tokyo, Japan, 6Juntendo University, Tokyo, Japan Purpose/Objective(s): To evaluate 3-years treatment outcome of a clinical study of radical accelerated partial breast irradiation (APBI) for stage I breast cancer using carbon-ion radiation therapy (C-ion RT). Materials/Methods: Eligibility criteria of phase I study are (1) pathologically proven invasive ductal carcinoma, (2) tumor diameter 2 cm or less on MRI, UICC clinical stage I (T1N0M0), (3) Estrogen receptor (ER) positive, HER2 negative, No Lymphovascular space invasion, No extensive intraductal component, (4) Performance status 0w2, (5) Age 60 years old and above, (6) No other life-threatening illness, and (7) Tumor located more than 5 mm from the skin. A dose escalation study was designed as a phase I clinical trial with the dose level of 48.0 Gy (RBE), 52.8 Gy (RBE) and 60.0 Gy (RBE) in 4 fractions within one week, at fraction sizes of 12 Gy (RBE), 13.2 Gy (RBE) and 15 Gy (RBE), respectively. In phase I, patients were planned to undergo surgery for pathological evaluation 90 days after C-ion RT and then have been receiving endocrine therapy. In “general protocol,” eligibility criteria are patients with 1, 2, 4, 6, and 7. In “general protocol,” patients have been receiving endocrine therapy without surgery after C-ion RT. Three-field C-ion beams of 290 MeV/n energy are used by means of passive broad beam methods using respiratory gating. Primary end points are early normal tissue reaction and tumor control at recommended dose. Secondary end points are CR rate, late normal tissue reaction, cosmetic outcome, disease-free survival, and overall survival. Results: From April 2013 to November 2015, 21 cases were treated with C-ion RT. Patients’ age ranged from 44 to 81 years old, with a median of 66 years old. Tumor sizes were 4 to 20 mm, with a median of 12 mm. The follow-up period ranged from 3 to 31 months, with a median of 15 months. No adverse reactions in normal tissue were observed except for grade 1
Poster Viewing
E7
skin reaction of CTC-AE v4 in 12 cases. In phase I study, 7 cases (3 cases of 48 Gy (RBE), 3 cases of 52.8 Gy (RBE) and 1 case of 60 Gy (RBE)) were treated and recommended dose settled to 60 Gy (RBE). Two of 7 phase I patients reached pathological CR at 3 month period. The first 2 patients of this “general protocol” were treated by 52.8 Gy (RBE) and the other 12 by 60 Gy (RBE). Three of 14 at 3 month period, 3 of 9 at 6 month period, 4 of 6 at 12 month period and 2 of 2 at 24 month period after C-ion RT reached CR, respectively. One patient with basal type became PD at 6 month period after C-ion RT on MRI. The PD patient was successfully salvaged by surgery. Conclusion: C-ion RT for patients with stage I breast cancer seems useful without problematic adverse effects, and it might take longer period for breast cancer to reach CR on MRI. Author Disclosure: K. Karasawa: None. T. Omatsu: None. M. Wakatsuki: None. S. Shiba: None. S. Fukuda: None. T. Kamada: None. N. Yamamoto: None. T. Ishikawa: None. A. Arakawa: None. M. Saito: None.
2017 Is Postoperative Supraclavicular Fossa Radiation Therapy Necessary After Neoadjuvant Chemotherapy in Yp N Stage 0-1 Breast Cancer? R. White,1 T. Dinneen,2 and A. Makris1; 1Mt Vernon Cancer Centre, London, United Kingdom, 2University of Western Australia, Perth, Australia Purpose/Objective(s): To investigate the role of supraclavicular radiation therapy (SCRT) in addition to chest wall or breast radiation therapy in patients with combined clinical stage II-III breast cancer of pathological nodal status 0 or 1 following neoadjuvant chemotherapy (NAC) and surgery. Materials/Methods: From a prospectively collected breast cancer database of 713 females enrolled on NAC trials we retrospectively identified 233 with combined clinical stage II - III who received surgery inclusive of axillary node dissection, were staged post-operatively as ypN0-1, and received post-operative radiation therapy. Those who received SCRT (SCRT+) in addition to local radiation therapy were compared to those who did not (SCRT-). Freedom from regional recurrence (FFRR), disease free survival (DFS) and overall survival (OS) were compared. Further exploratory analysis of subgroups considered most likely to benefit from SCRT was performed. Multivariate analysis was performed to identify factors influencing FFRR, DFS, and OS. Results: Sixty-one patients received SCRT and 172 did not. At a median follow up of 63 months from diagnosis the 5 year actuarial estimates of FFRR, DFS and OS respectively were 88.2, 63.5 and 74.8% for the SCRT+ and 91.1, 69.7 and 79.6% for the SCRT- group. No differences were statistically significant. There were no specific subgroups identified that clearly benefited from the addition of SCRT to local radiation therapy. On multivariate analysis statistically significant predictive factors for FFRR were combined clinical stage II disease and hormonal therapy use. Prognostic factors were combined clinical stage II, clinical nodal stage 0, yp nodal stage 0, the use of hormonal therapy and the use of trastuzumab. SCRT was not predictive of FFRR or OS on univariate or multivariate analysis. Conclusion: The addition of SCRT did not clearly benefit this cohort of patients. Adjuvant local radiation therapy alone may be sufficient in many stage II-III patients with negative or minimal nodal involvement following NAC and surgery. Further confirmatory prospective studies are indicated. Author Disclosure: R. White: None. T. Dinneen: None. A. Makris: None.
2018 Prone Positioning With Deep Inspiration Breath Hold for Left Breast Radiation Therapy: Initial Results of a Prospective Study U. Goyal and V.J. Gonzalez; University of Arizona, Tucson, AZ Purpose/Objective(s): Left breast radiation therapy for breast cancer has been shown to deliver clinically significant radiation dose to the heart. Prone positioning on a breast board and supine positioning with deep
E8
International Journal of Radiation Oncology Biology Physics
inspiratory breath hold (DIBH) have independently demonstrated significant reduction in cardiac exposure during left breast radiation therapy. We investigated the combination of prone position and DIBH to decrease cardiac doses for left-sided breast radiation therapy. Materials/Methods: Twelve patients with left-sided breast cancer were enrolled on an IRB-approved prospective study. Each patient underwent two prone positioned CT-simulation scans utilizing free breathing (FB) and DIBH. Breathing motion was controlled using a RPM system paired with visual feedback via LCD monitor. Separate treatment plans for each CTsimulation scan were created, and the heart and left lung mean doses were compared between FB and DIBH treatment plans. The technique with lower mean dose for the heart was used during treatment. All patients were treated with a hypofractionated regimen of 40-42 Gy in 15-16 fractions followed by a lumpectomy cavity boost of 10 Gy in 5 fractions when indicated. Two-tailed paired t-tests were performed for dosimetric endpoints. Results: One patient was not able to tolerate prone positioning at simulation leaving 11 patients with evaluable scans. Average mean heart dose with FB was 0.80 Gy (range 0.53-1.07 Gy) and 0.69 Gy (0.52-0.85 Gy) with DIBH (P Z 0.03). The average max heart dose with FB was 8.9 Gy vs 3.8 Gy with DIBH (P Z 0.1). The average heart V5 Gy was 5.1cc with FB and 0.5cc with DIBH (P Z 0.06). Average mean left lung dose with FB was 0.51 Gy (range 0.18-0.76 Gy) and 1.19 Gy (0.26-1.24 Gy) with DIBH (P Z 0.008). Two patients at study initiation were treated prone FB while technique was optimized to accommodate RPM in prone position. One patient was treated prone FB due to minimal reduction in cardiac dose from DIBH, and one patient was treated supine with DIBH. Seven remaining patients were treated using prone DIBH. Conclusion: Our preliminary results indicate that DIBH using the RPM system can provide additional cardiac dose reduction in patients receiving prone left-breast radiation therapy with a small increase in mean left lung dose. Tolerance of prone treatment did not appear to be affected by the addition of DIBH. Further studies are required to estimate clinical advantages from further cardiac dose reduction and to better evaluate which patients may benefit the most from the combination of DIBH and prone positioning. Author Disclosure: U. Goyal: None. V.J. Gonzalez: None.
correlated with grade (Spearman Rho Z 0.446, P<0.001) and negatively correlated with age (Spearman Rho Z -0.246, P<0.001). Introducing the Ki-67 into sub-typing shifted significant number of patients with good prognosis into the poor prognosis group. The median Ki-67 LI for grades 1, 2, and 3 were 7.5%, 25%, and 45% respectively.
2019 Immunophenotyping to Approximate Molecular Subtyping Using Ki67 Labeling Index N. Rao,1 A. Ram,2 and B.S. Ajaikumar1; 1Healthcare Global Enterprises Ltd., Bangalore, India, 2HCG Cancer Hospitals, Bangalore, India Purpose/Objective(s): Gene-expression profiling studies have emphasized the prognostic value of assessing the proliferation index Ki-67. The aims of the present study were to assess the relationship of Ki-67 labeling index (LI) to histological grade and to examine if the addition of Ki-67 LI had any impact on routine immunophenotyping with the triple markers panel (ER, PR, and HER2). Materials/Methods: We examined the reports of 124 consecutive breast cancer patients seen at our institution between September 2011 and February 2013, who had an invasive ductal carcinoma, were ER/PR positive and undergone examination with a panel of four markers (ER, PR, HER2 and Ki-67) by immunohistochemistry (IHC). We studied the data for correlation between Ki-67 LI and age, grade and HER2 status. Tumors were first classified into good / poor prognostic groups based on the triple marker IHC profiles of ER, PR, and HER2. The same patients were then reclassified on a four markers panel that included ER, PR, Her2, and Ki-67 and these proportions compared using the Chi square test for goodness of fit. The median of KI-67 was chosen as the cut-off to divide between good and bad prognostic groups. Results: When phenotyping was based on three markers there were 102 (82.25%) ER/PR+ve, HER2-ve (good prognostic /Luminal A group) and 22 (17.75%) ER/PR+ve, HER2+ve (poor prognostic / Luminal B group). The KI-67 percentage had a median score of 25%, which was used as the cut-off score to determine the prognostic groups; Ki-67 LI positively
Abstract 2019; Table 1.
Good Prognosis Poor Prognosis
Triple Marker Panel
Triple Marker Panel + KI-67
102 (82.25%) 22 (17.75%)
67 (54.03%) 57 (45.97%)
Conclusion: A strong correlation was detected between Ki-67 labeling index and grade and age and this holds prognostic relevance. Inclusion of Ki-67 Labeling Index into phenotyping did suggest that a significant number of patients with good prognosis (per the 3 marker panel) might have a poorer prognosis. The high Ki-67 LI in this group might also explain the comparatively inferior outcomes observed in this good prognostic group in India. While multi-gene expression arrays might be able to better prognosticate and allow make confident treatment decisions, they are expensive and not easily accessible in India. Our results indicate that inclusion of a single marker like KI-67 labeling index might predict prognosis better and serve as a reasonable surrogate. Author Disclosure: N. Rao: None. A. Ram: None. B.S. Ajaikumar: None.
2020 First Outcome Analysis of the TARGIT E(lderly) TrialdProspective Phase 2 Study of Intraoperative Radiation Therapy (IORT) in Elderly Patients With Small Breast Cancer F. Wenz; Department of Radiation Oncology, Universita¨tsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany Purpose/Objective(s): The purpose is to further investigate the efficacy of a single intraoperative radiation therapy treatment within elderly low risk patients with breast cancer ( 70 years, 3.5cm, cN0, cM0, invasiveductal histology) which is followed by whole breast radiation therapy (WBRT) only when risk factors are present. This prospective, multicentric single arm phase II study (NCT01299987) is based on the experimental arm of the randomized protocol of the international TARGIT A study. Here we present the first outcome analysis. Materials/Methods: Five hundred thirty-eight patients from 28 international centers were recruited between February 2011 and September 2014. The current analysis is based on 447 patients (median age 74yrs) excluding patients with screening failure, drop-out or loss to follow-up. During breast conserving surgery a single dose of 20 Gy of intraoperative radiation therapy was given using the targeted intraoperative radiation therapy system (Carl Zeiss Meditec, Germany). Additional postoperative WBRT (46e50 Gy) was prescribed only in patients with risk factors (larger size, other histology, small free margin, lymph vessel invasion, positive nodes, multifocality/multicentricity, extensive intraductal component (EIC)). Systemic therapy was given according to international standards. The primary outcome was local relapse. Overall survival was a secondary outcome. Discontinuation of the trial is scheduled if rates of local relapse rates rise to 3/4/6% after 2.5/5/7.5 years. Results: After a median follow-up of 14.0 months in 447 patients, one ipsilateral in-breast recurrence (20 mon after IORT) and three deaths (11, 14, 23 mon) were observed resulting in an actuarial local relapse free survival of 99.4% and actuarial overall survival of 98.6% after 2.5 years. Conclusion: The results of the prospective TARGIT E trial consolidate earlier reports from the randomized TARGIT A trial supporting the use of accelerated partial breast radiation therapy (APBI) in selected patients. The observed local relapse rate after 2.5 years is well below the prospectively defined stopping rules (Neumaier et al. BMC Cancer 2012). Further follow-up will be performed.