Cycles Of CT Research Articles

P-GEMOX with sequential or sandwiched radiotherapy for early-stage extranodal natural killer/T-cell lymphoma.

7075 Background: Combined modality therapy (CMT), namely chemotherapy combined with radiotherapy, has been recommended for patients with localized extranodal natural killer/T-cell lymphoma (ENKTL). However, the optimal CMT has not been fully clarified. As chemotherapy is more easily accessible than immediate radiotherapy in the routine clinical practice, the “chemotherapy-first” CMT including sequential or sandwiched radiotherapy deserves further exploration. In addition, the optimal non-anthracycline-based regimen needs to be confirmed. Methods: The P-GEMOX regimen was administrated as follows: pegaspargase 2000 IU/m2 intramuscular on day 1, gemcitabine 1000 mg/m2 intravenous on day 1 and 8, oxaliplatin 130 mg/m2 intravenous on day 1 and was repeated every 21 days. Patients who achieved at least stable disease (SD) subsequently underwent involved field radiotherapy (IFRT). The dose of IFRT ranged from 50 to 55 Gy. Performing sequential radiotherapy (4 cycles of CT+RT) or sandwich radiotherapy (2 cycles of CT+RT+2 cycles of CT) is determined by the clinician based on the patients' conditions. The primary endpoint was the overall response rate (ORR) after 2 cycles of chemotherapy, and secondary study endpoints were CR, PFS, and OS. Safety was also evaluated. Results: From August 2020 to April 2023, thirty-seven patients (23 men, 14 women; median age: 55, 26-76 years) with stage I/II ENKTL who had received P-GEMOX were collected. 14 patients were stage IE and 23 were IIE. ALL patients completed at least 2 cycles of P-GEMOX, which resulted in 94.6% (35/37) of ORR including 30 patients with CR and 5 patients with PR. Among the patients in remission, 15 patients received sequential radiotherapy, 15 received sandwich radiotherapy, 4 were waiting for or in the process of radiotherapy, and 1 patient progressed before radiotherapy. With a median follow-up of 14.8 months (range: 2.6-38.1 months), the 3-year PFS and OS were 87.2% (95%CI 69.3%-95%) and 90.6% (95%CI 72%-97.1%), respectively. Sandwich radiotherapy had an obvious trend for longer PFS than sequential radiotherapy (18moths-PFS 100% vs. 78%; P=0.073). During the treatment, 21.6% (8/37) of the patients experienced grade 3–4 treatment-emergent adverse events (TEAEs). The most grade 3–4 hematological TEAEs were neutropenia (7/37, 18.9%) and thrombocytopenia (4/37, 10.8%). As for grade 3–4 non-hematological TEAEs, elevated aminotransferase, hyperbilirubinemia and hypofibrinogenemia were 16.2%, 10.8% and 8.1%, respectively. The adverse events of this CMT were well-tolerated and manageable. No treatment-related death occurred. Conclusions: Our study demonstrated that CMT consisted of P-GEMOX showed favorable efficacy with acceptable toxicity, and sandwich radiotherapy (CT+RT+CT) seems give more favorable PFS than sequential radiotherapy. The CMT protocol could be an effective treatment option for early-stage ENKTL patients.

Abstract PO5-17-04: Tolerability of pertuzumab in older adults with HER2 positive breast cancer: A single institution experience

Abstract Background: Tumor HER2 over-expression occurs in 10 to 15% of older adults with breast cancer (BC). Combination HER2-directed therapy (pertuzumab and trastuzumab) with chemotherapy (CT) is the standard treatment for early and advanced HER2-positive bc. However, a study of more than 1,300 Medicare beneficiaries showed that about half of patients (pts) aged 65 or older with stage I to III HER2 positive bc did not receive trastuzumab-based therapy. This is likely due to concern for tolerability as older women remain underrepresented in clinical trials of breast cancer making it difficult to extrapolate tolerability of these agents in these patients. In the Neosphere and TRYPHAENA studies, the mean age of pts were 49.8 and 50.6 years, respectively. We examined the real-world tolerability of pertuzumab in combination with trastuzumab and systemic ct in women over the age of 65 with HER2 positive bc. Methods: An IRB approved retrospective review of medical records was conducted evaluating pts over the age of 65 with early or advanced HER2 positive bc treated at The Ohio State University Comprehensive Cancer center from January 1, 2015 to May,1 2020. Descriptive statistics (means, standard deviations, medians and ranges for continuous variables and frequencies and percents for categorical variables) were used to summarize disease and patient characteristics for pts enrolled in this study and treated with pertuzumab. The total number of planned and completed cycles of treatment as well as the number of treatment delays and dose reductions were also summarized using frequencies and percentages. The same descriptive statistics were used to summarize the number of grade II or IV toxicities and pathologic complete response (pCR) in the neoadjuvant setting. Results: A total of 71 pts met inclusion criteria. Mean age was 76 years (SD 4.1). Of these pts, 62 had stage I-III disease and 9 had metastatic disease. Additionally, 68% (48/71) had estrogen positive (ER) disease whereas 32% (23/71) had ER negative disease. Neoadjuvant systemic therapy was provided to 81% (50/62) of non-metastatic pts and 19% (12/62) received adjuvant therapy. The median number of completed neoadjuvant cycles (ct plus trastuzumab and pertuzumab) was 5.4 (SD 1.5). Among those who received pertuzumab with systemic ct in the neoadjuvant setting, 46% (23/50) of pts achieved a pCR (56% for ER negative disease and 41% for ER positive disease) The median number of completed adjuvant cycles (ct plus trastuzumab and pertuzumab) was 4.9 (SD 2.0). Pts with stage I to III disease completed a mean of 8.6 (SD 5.0) targeted therapy cycles (pertuzumab/trastuzumab). Pts with metastatic disease had a median of 5.7 (SD 1.0) cycles of ct plus trastuzumab and pertuzumab and received a mean of 34.4 (SD 36.0) cycles of maintenance pertuzumab. Treatment delay by 7 or more days occurred in 11% (8/71) of pts whereas 25% (18/71) of pts discontinued pertuzumab early. Pertuzumab termination occurred due to toxicity in 44% (8/18), metastasis in 11% (2/18), and other causes in 44% (8/18) of cases. For toxicities, 2% (1/51) of patients reported grade 3 pain, 25% (2/8) reported grade 3 fatigue, and 12% reported grade 4 diarrhea (1/8) (Table 1). Conclusions: Our study showed that pertuzumab was well tolerated in older pts with bc in the real-world setting. However, 25 % of pts still discontinued pertuzumab early which illustrates the importance of identifying pts who are at higher risk for toxicities prior to starting treatment. Table 1 Reported adverse events in patients age 65 and older receiving pertuzumab Citation Format: Nicole Williams, Austin Warmbier, Dureti Doto, Marilly Palettas, Julie Stephens, Dionisia Quiroga, Kai Johnson, Ashley Pariser, Mathew Cherian, Sagar Sardesai, Daniel Stover, Margaret Gatti-Mays, Robert Wesolowski, Bhuvana Ramaswamy. Tolerability of pertuzumab in older adults with HER2 positive breast cancer: A single institution experience [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-17-04.

Intracranial non-germinomatous germ cell tumors in children and adolescents: how can the experience from an uppermiddle-income country contribute to the worldwide effort to improve outcomes?

Non-germinomatous germ cell tumors (NGGCT) accounts for one third of intracranial GCT. While the germinoma group have an excellent overall survival, the standard of practice for children with NGGCT is still under evaluation. Describe the results of the of the Brazilian consortium protocol. Since 2013, 15 patients with a diagnosis of NGGCT by histopathology and/or serum/cerebrospinal fluid (CSF) tumor markers, βHCG >200mlU/ml and/or positive alpha-fetoprotein were treated with neoadjuvant chemotherapy with carboplatin, cyclophosphamide and etoposide followed by ventricular radiotherapy (RTV) of 18Gy with boost (32Gy) to the primary site. Metastatic patients underwent craniospinal irradiation (CSI) and "slow responders" to the four initial cycles of CT, to autologous stem cell transplantation (ASCT) followed by CSI. Mean age, 13.1 years. Thirteen males. Primary sites: pineal (n=12), suprasellar (n=2) and bifocal (n=1). Four patients were metastatic at diagnosis. Eight patients had CSF and/or serum alpha-fetoprotein levels > 1,000ng/ml. Tumor responses after chemotherapy demonstrated complete in six cases and partial in seven, with "second-look" surgery being performed in five cases, and two patients presenting viable lesions being referred to ASCT. The main toxicity observed was hematological grades 3/4. Two patients with metastatic disease, one with Down Syndrome and AFP > 1,000ng/ml and the other with choriocarcinoma and pulmonary metastases, developed progressive disease resulting in death, as well as two other patients without evidence of disease, due to endocrinological disorders. Event-free and overall survival at 2 and 5 years were 80% and 72.7%, respectively, with a mean follow-up of 48 months (range, 7-107). Despite the small number of patients, in our series, treatment with six cycles of chemotherapy and RTV with focal boost for localized disease (n=11) and ACST for identified slow responders (n=2) seem to be effective strategies contributing to the overall effort to improve outcomes of this group of patients.

Lisocabtagene Maraleucel (liso-cel) Versus Standard of Care (SOC) with Salvage Chemotherapy Followed By Autologous Stem Cell Transplantation (ASCT) As Second-Line (2L) Treatment in Patients with Relapsed or Refractory Large B-Cell Lymphoma (LBCL): Primary Analysis of the Randomized, Phase 3 Transform Study

Background: Liso-cel is an autologous, CD19-directed, CAR T cell product administered at equal target doses of CD8+ and CD4+ CAR+ T cells. Results of a prespecified interim analysis of the TRANSFORM study (NCT03575351) demonstrated superior efficacy of liso-cel compared with the SOC of salvage immunochemotherapy (CT) followed by high-dose chemotherapy and ASCT in responders, as 2L treatment for patients (pts) with LBCL primary refractory to or relapsed within 12 months of first-line (1L) therapy (Kamdar et al. Lancet 2022). At the interim analysis, the primary endpoint of EFS and key secondary endpoints of CR rate and PFS met statistical significance in favor of liso-cel and OS data were immature. Here we report results from the primary analysis with a median follow-up of 17.5 months. Methods: TRANSFORM is a global, randomized, multicenter, phase 3 study comparing efficacy and safety of liso-cel versus SOC (R-DHAP, R-ICE, or R-GDP followed by BEAM + ASCT) in adults (aged ≤ 75 years) with LBCL primary refractory to or relapsed ≤ 12 months after 1L therapy who were eligible for ASCT. Key inclusion criteria were ECOG PS ≤ 1 and adequate organ function. Pts in the liso-cel arm underwent lymphodepletion with fludarabine/cyclophosphamide followed by liso-cel at a target dose of 100 × 106 CAR+ T cells. Bridging therapy with R-DHAP, R-ICE or R-GDP was allowed at investigator discretion. Pts in the SOC arm received 3 cycles of CT. Responding pts (CR or PR) proceeded to high-dose chemotherapy + ASCT. Crossover to receive liso-cel was allowed for pts in the SOC arm not achieving CR or PR after 3 cycles of CT, not in CR after ASCT, or demonstrating PD at any time. The primary endpoint was event-free survival (EFS) based on independent review committee (IRC). Key secondary endpoints included IRC-assessed CR rate, PFS, and OS. The primary endpoint of EFS was met at the interim analysis and is updated here; thus, only the key secondary endpoints were retested at the primary analysis, as prespecified by the statistical analysis plan. The significance threshold to reject the null hypothesis for the key secondary endpoints was ≤ 0.021 (adjusted for the actual number of events available for analysis and the alpha spent at previous interim analyses). Median follow-up for the primary analysis was 17.5 months (range, 0.9‒37.0). Results: A total of 184 pts were randomized, with 92 pts in each arm. Baseline characteristics were as previously reported, 33% of pts were aged ≥ 65 y, 64% had DLBCL (55% not otherwise specified, 8% transformed from indolent lymphomas), 12.5% had double-hit lymphoma, and 73% were refractory (PD, stable disease, PR, or CR with relapse within 3 months) to 1L therapy. Median (95% CI) EFS was not reached (NR; 9.5-NR) for liso-cel versus 2.4 months (2.2-4.9) for SOC (Figure). CR rate and PFS met statistical significance; CR rate was 74% for liso-cel versus 43% for SOC (P < 0.0001) and median PFS (95% CI) was NR (12.6-NR) for liso-cel versus 6.2 months (4.3-8.6) for SOC (HR, 0.400; P < 0.0001) (Table). Of 26 pts with a PR at the interim analysis, the response deepened to CR for 9 pts at the primary analysis (6/18 in the liso-cel arm; 3/8 in the SOC arm). Of 91 pts treated in the SOC arm, 61 (67%) crossed over to receive liso-cel. At the primary analysis, 66 pts had died (28 in the liso-cel arm and 38 in the SOC arm, including 29 after crossover); the most frequent cause of death was disease progression. Median OS favored liso-cel versus SOC, although it did not meet statistical significance (NR versus 29.9 mo, respectively; HR, 0.724; P = 0.0987). Safety results were consistent with those reported in the interim analysis. Conclusions: This primary analysis, with a median follow-up of 17.5 months, confirmed the clinical benefit of liso-cel over SOC. In TRANSFORM, liso-cel resulted in statistically significant and clinically meaningful improvements in EFS, CR rate, and PFS. These data reinforce liso-cel as a 2L treatment in pts with primary refractory or early relapsed LBCL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Improved Quality of Life (QOL) with Lisocabtagene Maraleucel (liso-cel), a CD19-Directed Chimeric Antigen Receptor (CAR) T Cell Therapy, Compared with Standard of Care (SOC) As Second-Line (2L) Treatment in Patients (Pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL): Results from the Phase 3 Transform Study

Improved Quality of Life (QOL) with Lisocabtagene Maraleucel (liso-cel), a CD19-Directed Chimeric Antigen Receptor (CAR) T Cell Therapy, Compared with Standard of Care (SOC) As Second-Line (2L) Treatment in Patients (Pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL): Results from the Phase 3 Transform Study

First-line treatment with chemotherapy plus cetuximab in Chinese patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck: Efficacy and safety results of the randomised, phase III CHANGE-2 trial

BackgroundThe EXTREME regimen (chemotherapy [CT; cisplatin/carboplatin and 5-fluorouracil]) plus cetuximab is a standard-of-care first-line (1L) treatment for patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN), as supported by international guidelines. The phase III CHANGE-2 trial assessed the efficacy and safety of a modified CT regimen (with a reduced dose of both components) and cetuximab versus CT for the 1L treatment of Chinese patients with R/M SCCHN. MethodsPatients were randomised to receive up to six cycles of CT plus cetuximab followed by cetuximab maintenance until progressive disease or CT alone. The primary end-point was the progression-free survival (PFS) time assessed by the independent review committee (IRC). ResultsOverall, 243 patients were randomised (164 to CT plus cetuximab; 79 to CT). The hazard ratios for PFS by IRC and overall survival (OS) were 0.57 (95% CI: 0.40–0.80; median: 5.5 versus 4.2 months) and 0.69 (95% CI: 0.50–0.93; median: 11.1 versus 8.9 months), respectively, in favour of CT plus cetuximab. The objective response rates (ORR) by IRC were 50.0% and 26.6% with CT plus cetuximab and CT treatment, respectively. Treatment-emergent adverse events of maximum grade 3 or 4 occurred in 61.3% (CT plus cetuximab) and 48.7% (CT) of patients. ConclusionsCHANGE-2 showed an improved median PFS, median OS and ORR with the addition of cetuximab to a modified platinum/5-fluorouracil regimen, with no new or unexpected safety findings, thereby confirming CT plus cetuximab as an effective and safe 1L treatment for Chinese patients with R/M SCCHN. Clinical trial registration numberNCT02383966.

Reduction of febrile neutropenia by using long-acting granulocyte colony-stimulating factors in patients with solid tumors receiving every-2-week chemotherapy

Neutropenia is a common hematological complication of chemotherapy (СT). The number of studies showed that the underperformance of the treatment program due to the development of this type of hematological toxicity could lead to the decrease in therapy efficacy and to the increase in cancer mortality. Infections that occur as a result of prolonged neutropenia are extremely dangerous. The most severe manifestation of grade 4 neutropenia is febrile neutropenia (FN), which can lead to death from severe infections. Such patients should be immediately hospitalized and should receive empirical therapy with broad-spectrum antibiotics. The costs, associated with the hospitalization, due to FN increase total cost of cancer patients treatment. The application of recombinant forms of the natural protein granulocyte colony-stimulating factor (G-CSF) in clinical practice has solved the number of important problems on that front. The clinical studies and common use show that primary and secondary prevention using recombinant G-CSF reduces the risk of FN development and improves the results of the treatment of malignancies. The review provides actual data concerning pharmacological properties, clinical efficacy and reasonable use of G-CSF with prolonged action to prevent FN in patients with solid tumors during 2-week CT cycles. Special attention is paid to CH regimens with the inclusion of 5-fluorouracil, oxaliplatin, irinotecan in the treatment of colorectal cancer (CRC). The use of neoadjuvant treatment in such patients allows to achieve resectability of the tumor and to perform radical surgery. The maintenance of drugs dose intensity throughout the cycle of CT plays an important role in achieving the treatment success. Therefore, the prevention of CT-induced severe neutropenia and FN is especially important in patients who are the candidates for surgical treatment. The results of some studies confirm the necessity of using G-CSF with prolonged action during 2-week CT cycles in patients with CRC.

Cabazitaxel in Platinum Pre-treated Patients with Locally Advanced or Metastatic Transitional Cell Carcinoma Who Developed Disease Progression after Platinum based Chemotherapy: Results of the Phase II CAB-B1 Trial

There is a paucity of chemotherapy options for patients with urothelial cancers who have relapsed following platinum based chemotherapy (CT). CAB-B1 was a single centre phase II randomised controlled trial of Cabazitaxel (CAB; 25mg/m2 q3 week for 6 cycles) versus best supportive care (BSC) in patients with histologically proven transitional cell carcinoma (TCC), locally advanced or metastatic, who had recurred after receiving platinum based treatment. Primary outcome was overall response rate (ORR) using RESIST. Secondary outcomes included Progression Free Survival (PFS) and Overall Survival (OS). Between January 2013 and October 2016, 20 patients were randomised (10 on each arm). BSC included paclitaxel CT for 9 patients and radiotherapy for 1 patient. 8 patients completed 6 cycles of CT (3 on CAB; 5 on BSC). 2 patients had an ORR on CAB and 1 patient on BSC. Median OS was 5.8 months (95% confidence interval (CI) 0.7-14.6) for CAB patients and 7.5 months (95% CI 1.0-10.8) for BSC patients. Median PFS was 4.8 months (95% CI 0.7-8.3) for CAB patients and 3.7 months (95% CI 1.0-7.0) for BSC patients. CAB-B1 successfully reached the efficacy target for 1st stage, showing that there could be a role for CAB in these patients.

Comparison of Concurrent Cisplatin Chemoradiotherapy Plus Adjuvant Chemotherapy Versus Concurrent Chemoradiotherapy Alone in Locally Advanced Cervical Cancer

According to NCCN guidelines, concurrent chemoradiation (CCRT) is the standard care for locally advanced cervical cancer (LACC) patients , but the benefit of adjuvant chemotherapy (ACT) after CCRT for LACC patients is still controversial. This study is designed to answer the question by comparing the efficacy and toxicities of concurrent chemoradiation (CCRT) with adjuvant chemotherapy (ACT) (CCRT+ACT) versus concurrent chemoradiation (CCRT) alone in LACC. Patients with stage IB2,IIA2,IIB-IVA (2009 FIGO staging) cervical cancer were recruited from June 2013 to June 2018 at 4 cancer centers in China. The patients were randomly assigned to two arms: CCRT +ACT and CCRT alone. All patients were treated with IMRT (external-beam radiotherapy up to 50.4 Gy) with concurrent cisplatin, followed by intra-cavitary brachytherapy. The chemotherapy consisted of concurrent cisplatin(40 mg/m2 weekly) during IMRT, and 3 cycles of adjuvant CT with TP (docetaxel 75 mg/m2, day 1, and cisplatin 25 mg/m2, day 1-3 or carboplatin AUC 4-5 ,day 1)every 3 weeks. The primary endpoint was progression free survival(PFS), and the secondary endpoints included overall survival (OS), locoregional recurrence rate, distance metastasis rate , and toxicities. Survivals were calculated with Kaplan-Meier method. The differences between survivals were calculated with Log-rank test. Toxic effects were analyzed using the χ2 test. All statistical tests were two-sided. A total of 176 patients were recruited in the study and 161 were eligible for intent-for-treat analysis. 82patients were assigned to the CCRT+ACT arm and 79 in the CCRT alone arm. With a median follow-up of 60.1 months, the 5-year PFS and OS of all the patients were 68.32% and72.05%, respectively. The 5-year PFS was 75.61% in the CCRT+ACR arm, and was 60.76% in the CCRT arm. There was significant difference in PFS between the two arms （P=0.043). The 5-year OS was 76.83% in the CCRT+ACT arm and was, and was 67.09% in the CCRTarm. There was no significant difference in OS between the two arms （P=0.169). There was significant difference between the CCRT+ACT and CCRT arms in distant alone recurrence (p=0.048),but not in locoregional recurrence rate (p=0.752).There were significantly higher acute systemic side effects in the CCRT+ACT arm, especially the incidence of grade 3-4 hematologic and gastrointestinal reactions (P =0.000). Most of locoregional recurrence and distant metastases occurred with staging IIIB-IVA patients in the CCRT alone arm. Adjuvant chemotherapy after concurrent cisplatin chemoradiation for LACC patients improves PFS but not improves OS. It reduces distance metastasis but is correlated with poorer response to locoregional recurrence.There were more significant toxicities during adjuvant chemotherapy but it was well tolerated by patients. Further research and longer follow up is needed, especially for the staging IIIB-IVA LACC patients.

Abstract P4-08-13: Prognostic significance of CD8+ tumor-infiltrating lymphocytes (TILs) in patients with early breast cancer (EBC) treated with dose-dense sequential adjuvant chemotherapy (dds-CT). An observational study (ACTRN12616001043426)

Abstract Background - aim: Information on the prognostic role of cytotoxic CD8+ T cells in the era of modern adjuvant CT is limited. The primary objective of the present report is to assess the prognostic impact of CD8+ cells in patients with intermediate or high-risk EBC (T1-3N1-2M0) treated with dds-CT. Secondary endpoints are safety, disease-free survival (DFS) and overall survival (OS). Patients and Methods: Patients (N=1,000) were treated with 4 cycles of Epirubicin, 75mg/m2, and Cyclophophamide, 600mg/m2 every 2 weeks followed by 4 cycles of Docetaxel (D), 100mg/m2 every 3 weeks with G-CSF support in all cycles. Trastuzumab was initiated concurrently with D and continued for a total of 1 year. Hormonal and radiation therapy were given post CT, as indicated. Formalin-fixed paraffin-embedded tumors were available for 642 patients (64.2%) and were centrally assessed for immunohistochemical subtypes (IHC4; N=526), stromal TILs density by morphology (N=636), as well as stromal and intratumoral cytotoxic CD8+ T cell numbers (N=554). TILs and CD8+ were assessed as continuous variables for associations and as 10% increments for outcome. Results: In total, 901/1,000 pts (90.1%) completed 8 cycles of CT. Severe (gradeIII-IV) toxicitiesincludedneutropenia (5.6%), leucopenia (3.6%), lymphopenia (2.1%), hand-footsyndrome (2.1%), and hepatotoxicity (1.8%). Febrileneutropenia occurred in 1.6% of the patients. The 5-year DFS and OS rates were 89.5% and 93.1%, respectively. Luminal A tumors were classified in 26.2%, Luminal B in 35.2%, luminal HER2 in 9.5%; HER2-enriched in 7.2%; and, triple-negative (TNBC) in 21.9% of informative patients. Among subtypes, stromal TILs density was higher in HER2-enriched and TNBC (p&amp;lt;0.001); intratumoral CD8+ values were higher in TNBC (p&amp;lt;0.001); and, stromal CD8+ were higher in HER2-enriched (p=0.034). In all patients, TILs density and intratumoral CD8+ cell numbers were not associated with DFS and OS, while increased stromal CD8+ were marginally associated with prolonged DFS (HR=0.98, 95%CI 0.96-1.00, p=0.066).Adjusted for histological grade, menopausal, ER/PgR and nodal status, higher stromal CD8+ were associated with prolonged DFS (HR=0.98, 95% CI 0.96-1.00, p=0.043). In TNBC, higher stromal TILs density conferred prolonged DFS (HR=0.97, 95%CI 0.94-0.99, p=0.029), which retained its prognostic significance in multivariate analysis (HR=0.97, 95% CI 0.94-1.00, p=0.049). Conclusions: In this study, dds-CT was well tolerated and active in patients with EBC. We confirm the presence of morphologically assessed higher TILs density, and of higher cytotoxic CD8+ T cell numbers in hormone receptor negative EBC, as well as the favorable prognostic impact of higher stromal TILs density in TNBC. In comparison to stromal TILs density, higher stromal CD8+ may confer favorable prognosis irrespectively of EBC subtype. Stromal CD8+ seems to be a marker worth further standardizing for reporting on immune cell infiltrates in EBC. Citation Format: Kourea HP, Koletsa T, Kotoula V, Koliou G-A, Batistatou A, Pentheroudakis G, Arapantoni-Dadioti P, Zagouri F, Bobos M, Sotiropoulou M, Papoudou-Bai A, Chrisafi S, Efstratiou I, Aravantinos G, Nicolaou I, Gogas H, Visvikis A, Christodoulou C, Petraki C, Koutras A, Psyrri A, Pectasides D, Fountzilas G. Prognostic significance of CD8+ tumor-infiltrating lymphocytes (TILs) in patients with early breast cancer (EBC) treated with dose-dense sequential adjuvant chemotherapy (dds-CT). An observational study (ACTRN12616001043426) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-08-13.

The Predictive Impact of Tumor Volume Assessment Using Magnetic Resonance Imaging Before and During Chemorradiation in Patients With Locally Advanced Cervical Cancer

The aim of this study was to evaluate the predictive impact of tumor volume (TV) measured on baseline and mid-treatment magnetic resonance imaging (MRI) on long-term outcomes in cervical cancer patients treated with chemorradiation (CRT). We analyzed 51 women with cervical cancer enrolled on an IRB-approved single-institution prospective observational trial of multiparametric MRI performed at baseline (MRI1) and after external beam radiation therapy (EBRT) prior to brachytherapy (MRI2). The initial- (GTV-Tinit) and residual-gross tumor volume after EBRT (GTV-Tres) were estimated by the product of the tumor measurements (superior-inferior; left-right; anterior-posterior) x π/6. The receiver operating characteristic (ROC) curves were built to choose the most accurate cutoff value for predicting locorregional control (LRC), progression free survival (PFS) and overall survival (OS). Uni- and Multi-variate Cox modeling were used to test associations of clinical and radiological parameters with clinical endpoints. Patients were treated with 45 Gy EBRT concomitant to platinum-based chemotherapy followed by 2D-brachytherapy (BT - most received 7Gy times 4). Mean age was 47.3 ± 1.8 years. Most had squamous cell carcinoma (86.3%) and were classified as FIGO stage I-II (58.8%). After a median follow-up time of 20.9 months six women died and ten had disease progression (1 locorregional, 3 distant, 6 combined). The median volumes were GTV-Tinit = 84.4cm3 (36.4-133.4) and GTV-Tres = 12.8cm3 (8.7-26.3). The area under ROC curve for GTV-Tinit/GTV-Tres was 0.87/0.76 for locorregional progression, 0.72/0.65 for progression and 0.70/0.77 for death, respectively. On univariate analysis the LRC was associated with GTV-Tinit (p<0.001), GTV-Tres (p=0.002), FIGO stage (p=0.04), ≥4 cycles of CT (p=0.01), adjacent structures invasion on MRI1 (p=0.018) and MRI2 (p= 0.005) and vaginal invasion at MRI2 (p=0.01); PFS was correlated with GTV-Tinit (p=0.005), GTV-Tres (p=0.01), ≥4 cycles of CT (p=0.012), endometrial invasion on MRI2 (p<0.001) and adjacent structures invasion on MRI2 (p=0.02); and OS was associated with GTV-Tinit (p=0.02), GTV-Tres (p=0.02), ≥4 cycles of CT (p=0.006) and adjacent structures invasion on MRI2 (p=0.03). On multivariate analysis LRC was related to GTV-Tinit (p=0.045), GTV-Tres (p=0.005) and FIGO staging (p=0.038); PFS was associated with GTV-Tinit (p=0.04), GTV-Tres (p=0.02) and endometrial invasion on MRI2 (p=0.003); and OS was associated with ≥4 cycles of CT (p=0.01) and invasion of adjacent structures on MRI2 (p=0.04). TV assessed on MRI was an important predictive parameter for LRC and PFS in patients with cervical cancer treated with definitive CRT. Longer follow up may be necessary to demonstrate a possible correlation with OS.

Three-year survival after combined treatment with induction chemoimmunotherapy in patients (pts) with non-small cell lung cancer (NSCLC).

e20064 Background: Induction chemotherapy (iCT) for NSCLC has potential advantages over adjuvant CT, high therapeutic compliance, the ability to influence the primary tumor and metastatic disease. Standard approaches to iCT improving are largely exhausted. However, the development of iCIT techniques using recombinant cytokines and assessment of the effectiveness of its clinical application remains poorly understood. Methods: Clinical trial included 65 pts. with stage IIB, IIIA (N2), IIIB (T4 ipsi. nod.) NSCLC, randomized in main (n = 33) and control (n = 32) groups with comparable clinical and pathological characteristics: m 23 (69.7) vs. 23 (71.8%), W 10 (30,3%) vs. 9 (28.2%); stage IIB - 8 (24.4%) vs. 9 (28.6%), IIIA - 22 (66.6%) vs. 19 (59.4%), IIIB - 3 (9%) vs. 4 (12.5%); 40-49 years 5 (15,5%) vs. 5 (15,6%), 50-59 14 (42,4%) vs.15 (46,8%), 60 years and older 14 (42,4%) vs. 12 (37,8%). Pts. of the control group received 2 iCT cycles: cisplatin 75 mg / m2 i.v. 1 day and gemcitabine 1000 mg / m2 i. v. 1 and 8 days; pts. of the main group additionally received recombinant tumor necrosis factor coupled with thymosin (TNF-T Farmaclon Russia) 50. 000 ED / m2i.v. 3, 5 and 7 days of the cycle. The direct results were evaluated 3 weeks after completion of induction. Pts. who underwent radical surgery received 2 cycles of platinum-based adjuvant CT. DFS was studied by the method of Kaplan-Meier. Results: 3-year DFS in the main group was 72% vs. 48% in the control group (p = 0.10603). Conclusions: Clinical trial of the effectiveness of iCIT with using immune drug TNF-T demonstrated a tendency to improve 3-year DFS by 24%, which favors further studies on a larger number of pts.

Identification of proteins differentially expressed by Chlamydia trachomatis treated with chlamydiaphage capsid protein VP1 during intracellular growth

Chlamydia trachomatis infection is one of the most prevalent sexually transmitted diseases. Our research pertains to the inhibitory effect and molecular mechanism of the chlamydiaphage capsid protein VP1 on the growth of Chlamydia trachomatis. In this research, the capsid protein VP1 of the guinea-pig conjunctivitis chlamydiaphage phiCPG1 was expressed, purified and identified, and then, it was applied to the cultivation of different serovars of Chlamydia trachomatis and Chlamydia psittaci. The inhibitory effect was observed in each serovar of Chlamydia trachomatis (D, E, F, G, H, I, K, and L2) and Chlamydia psittaci inoculated with VP1 protein. The inhibition affection of VP1 on the growth of Chlamydia trachomatis was caused by the changes of expressions of some related proteins including 36 proteins up-regulated and 81 proteins down-regulated in the development cycle of Ct through the label-free test, and the transcription levels of these proteins, including Hc1, pmpD, and MOMP, were confirmed by RT-PCR. It provides information that is essential for understanding the mechanism of chlamydiaphage capsid protein VP1 on chlamydia and a new direction for further clinical treatment of chlamydial infection.

Abstract P1-01-02: Circulating tumor cells (CTC) and endothelial cells (CEC) prognostic value in HER2 negative metastatic breast cancer patients treated with first line weekly paclitaxel and bevacizumab: First results of a prospective cohort from the French Breast Cancer InterGroup Unicancer (UCBG): COMET study

Abstract Background: increased levels of circulating tumor cells (CTC) are associated with worse progression-free survival (PFS) and overall survival (OS) in patients (pts) with metastatic breast cancer (MBC). It has been hypothesized that bevacizumab could modify CTC prognostic value. CEC variations to predict benefit of anti-angiogenic treatment is still controversial. Predictive markers for response to bevacizumab combined to chemotherapy in MBC remains a clinical unmet need. Patients &amp; methods: The French cohort COMET is a prospective study including first line HER2 negative patients (pts) receiving weekly paclitaxel and bevacizumab according to EMA approved combination. The aim of this cohort is to evaluate clinical, biological and radiological parameters associated with pts outcome (CTC, CEC, serum markers, ctDNA, pharmacogenomic polymorphisms, metabolomic parameters, visceral fat assessed by initial CTscan, serum estradiol level, and quality of life). We present here the first planned analysis on 203 pts evaluated for CTC and CEC using the FDA cleared CellSearch method. Results: For CTC substudy, 211 patients were included from 09/2012 to 5/2014. Median follow-up is 24 months. Median PFS was 10 months (CI95 9-12) and response rate was 57%. Median OS was not reached. 203 patients were evaluable for both CTC and CEC at baseline and first day of second cycle of CT (D1C2). At baseline, 97/203 (48%) pts had ≥ 5 CTC (median 4 (range 0-30,000). Median number CEC was 21 (0-2231) at baseline and 22 (1-881) at D1C2. LDH, CEA, CA15.3 and CYFRA 21 were above normal at baseline in 44%, 46%, 73% and 71% of the cases respectively. CTC level was not correlated with any patients' characteristics except a number of metastatic site &amp;gt;3. After one cycle of chemotherapy (D1C2) 37 pts (22%) had still ≥ 5 CTC: 36 pts with initial high level and only one patient with low CTC at baseline had increased CTC above 5. Prognostic factors for PFS at univariate analysis were visceral disease, number of metastatic sites (&amp;gt; 3), triple negative status, LDH, CTC level at baseline and CTC level after one cycle of chemotherapy (D1C2). None of serum marker nor CEC level at baseline or any variations had prognostic value. In multivariate analysis for PFS, CTC level after one cyle of chemotherapy predicts poor outcome Table 1 Multivariate analysis for PFSPts' characteristicsnRRCI 95%p-valueNumber of metastatic sites &amp;lt;3 sites971 &amp;gt;=3 sites1001.65[1.13 ; 2.41]0.010CTC D1C2 &amp;lt; 51321 &amp;gt;= 5372.17[1.43 ; 3.29]&amp;lt;0.001Hormonal status Luminal (HR+)1531 Triple negative372.86[1.85 ; 4.54]&amp;lt;0.001 Conclusion: We confirm in a large prospective series the lack of clinical validity of CEC to predict response to an antiangiogenic based treatment in MBC. A persistent elevated level of CTC after just one cycle of chemotherapy is a very strong and independent marker of poor outcome in a homogeneously bevacizumab-treated cohort of MBC patients. This marker could be used to stopped earlier an inefficient and costly treatment. Citation Format: Pierga J-Y, Tredant O, Chevrier M, Dubot C, Lorgis V, Romieu G, Goncalves A, Debled M, Levy C, Ferrero J-M, Jouannaud C, Luporsi E, Mouret-Reynier M-A, Dalenc F, Berger F, Lemonnier J, Proudhon C, Bidard F-C. Circulating tumor cells (CTC) and endothelial cells (CEC) prognostic value in HER2 negative metastatic breast cancer patients treated with first line weekly paclitaxel and bevacizumab: First results of a prospective cohort from the French Breast Cancer InterGroup Unicancer (UCBG): COMET study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-01-02.

Second-Line Palliative Chemotherapy in Advanced Gall Bladder Cancer, CAP-IRI: Safe and Effective Option.

Gall bladder cancer (GBC) has high prevalence in the Indo-Gangetic belt in India. While the first-line chemotherapy (CT1) has been established as gemcitabine-platinum doublet in advanced GBC, there is no standard recommendation or guidelines regarding feasibility of second-line therapy. We performed a retrospective analysis of all patients who received second-line of chemotherapy (CT2) at our institution from July 2012 to December 2014. Patient records were examined for efficacy and toxicity of administered CT2, along with response rates (RR) and survival. Potential prognostic factors were also evaluated. Eighty-seven patients received CT2 in the predefined period. Ninety-nine percent of patients had received a gemcitabine-based regimen as CT1 with a median progression-free survival (PFS) of 5months before CT2. 51.7% patients had undergone surgery prior with 5.7% patients having received radiotherapy previously. Prior to beginning CT2, PS was 0/1 in 67.8% patients, albumin was >4g% in 40.2% and CA 19.9 was raised in a majority (66.7%) patients, respectively. As per institution protocol, a majority of patients (89.6%) were administered CAP-IRI regimen. Overall RR and disease control rates(DCR) were 21.8 % and 41.3%, respectively. Median progression-free survival (PFS) and overall survival (OS) were 6 and 8months, with no significant differences between CAP-IRI and other regimens. Adverse effects were tolerable, with dose reduced upfront in 23% patients and 11.5% patients during subsequent cycles of CT. ECOG Performance Status (PS) of 0/1 was a significant prognostic variable for OS on multivariate analysis (p = 0.003). CAP-IRI is a well-tolerated second-line chemotherapeutic regimen in patients with advanced GBC. Careful selection of patients is required when administering second-line chemotherapy to advanced GBC patients, with particular emphasis on ECOG PS.

The role of the induction chemotherapy followed by RCT in advanced rectal cancer assessed by MRI.

e15133 Background: Induction chemotherapy (IC) followed by concurrent radiochemotherapy (RCT) and total mesorectal excision (TME) is a treatment option for loco-regionally advanced rectal carcinomas (T3/T4 N0 and any T with positive adenopathies). Postoperatively, depending on the findings of the histopathological examination performed on the excision sample, patients shall undertake or not adjuvant CT. Induction chemotherapy (IC) has major benefits: rapid symptomatic response, early treatment of micrometastases, high compliance of patients with the treatment, decreased acute and chronic toxicity as compared to adjuvant CT. Concurrent RCT has shown a decrease in local recurrence rate, possibility of performing sphincter-preserving surgery or even full sterilization of surgical sample. Methods: The patients enrolled in the study have undertaken 4-6 cycles of induction CT with CapeOx and concurrent preoperative RCT. All patients have been preoperatively restaged based on MRI, for the purpose of assessing the efficacy of the induction treatment, translated through the decrease of the PT dimension, the numerical and size decrease of N and the decrease of the distance between the lower pole of the PT against the anus and the correlation of MRI response to neoadjuvant therapy with the histopathological examination of the resection sample. Results: During January-September 2015, 27 patients who had received clinical and imaging diagnosis of rectum adk, stage cTNM II and III, have been included in a prospective phase 2 trial. All patients have concluded the neoadjuvant therapy. This trial has shown the efficacy of induction CT based on an objective response rate of 72.84%. The MRI reassessment following RCT has shown an objective response rate of 90.91% and negative MRF in 61.81% of the patients. R0 resection margin has been 100% until now. Out of the 27 patients, TME has been performed up to present day in 13 of the patients, obtaining a pCR in 4 of them and a partial response in 5 of them. Conclusions: The efficacyof induction chemotherapy with CapeOx followed by concurrent RCT has been proved by the substantial reduction of the primary tumour size, the numerical and size decrease of adenopathies.

PROGNOSTIC IMPACT OF NEOADJUVANT CHEMOTHERAPY ON JUVENILE NASOPHARYNGEAL CARCINOMA.

ABSTRACT Objective: To study the efficiency of neoadjuvant chemotherapy (NACT) and the impact of CT response on prognosis of juvenile nasopharyngeal carcinoma (NPC). Materials and Methods: From 1995 to 2005, 108 non-metastatic NPC patients younger than 25 years old were treated with NACT at Salah Azaiz Institute.The Median age of patients was 17 year-old and the male/female ratio was 1.6. According to the 2002 TNM staging system, T3-T4 tumors and N3 nodal status rates were 64% and 52%, respectively. All patients had undifferentiated carcinoma and received three cycles of CT combining doxorubicin and cisplatin followed by conventional RT with a total dose of 70 Gy to the primary tumor and the cervical areas initially involved, and 54 Gy to the remaining cervical areas. Tumor response to NACT was assessed after the third cycle on the basis of clinical examination (100%) and CT-scan of the nasopharynx (66%). Response was evaluated according to WHO criteria. Results: The overall CT response rate was 88% at cervical lymph node (complete response (CR): 35%, partial response (PR): 53%) and 83% at primary tumor (CR: 20%, PR: 63%). A complete remission at the end of the treatment program was observed in 91% of cases. Five-year DFS and OS rates were 75% and 81%, respectively. A no response (NR) or progressive disease (PD) after NACT at both cervical nodes and primary tumor had a statistically significant pejorative impact on DFS (p<0.001 and p=0.04, respectively) and OS (p<0.001 and p=0.037). Five-year DFS and OS rates of patients in CR after initial CT at cervical nodes was significantly better than the other patients (PR, NR, or PD) (94% vs. 66% and 94% vs. 73%, respectively). Conclusion: Our results showed that NPC is a very chemosensitive neoplasm and suggest that a regimen of induction CT followed by RT is feasible and can provide excellent antitumor effect in juvenile NPC. The prognosis was influenced by response to initial CT; the DFS and OS were better in patients with a good response to CT. RT dose reduction to good responders could be an interesting therapeutic approach in order to limit long-term sequelae.

Predictors of Outcome in HIV-associated Primary Effusion Lymphoma

25 (64.1%), stage I was 22 (56.4%), stage II were 17 (43.6%), B symptoms were 14 (35.9%), LDH above normal were 16 (41%), 6 patients received 1-3 CT cycles (15.4%), and 33 patients received 4-6 cycles(84.6%). Twenty-nine (74.4%) of 39 patients achieved CR. The group 1 had 76.0% (19/25) of CR, the group 2 had 75.0% (9/12), and the group 3 had 50% (1/2). Univariate analysis identified LDH and number of CT cycles, as significant predictors of CR (both P <0.05). On multivariate analysis, only number of CT cycles showed statistically significant, received 1-3 cycles of CHOP-based CT had an odds ratio (OR): 17.085, P ¼0.026 being independent predictor. Conclusion: The number of CT cycles was the only CR predictor, and the fact of having received CT followed by RT or radiotherapy followed by CT as first-line did not influence the response. Keywords: Natural Killer/T-cell lymphoma; Prognostic index; chemotherapy.

Predictors of Survival of Natural Killer/T-cell Lymphoma (NKTL), nasal type in a Peruvian Population at a Cancer Institute

S66 we divided in three groups, the first group had 25 patients who received CHOP (10)/CHOEP (15) follow by external beam radiation, the second group had 12 patients who received external beam radiation followed by CHOP (8) or CHOEP (4)-based chemotherapy and the third group only had two patients who received concurrent radiotherapy plus CHOP-based chemotherapy. Variables were analyzed using univariate and multivariate analyses with CR as the dependent variable; it used Chi-square for comparing the risks among patient’s characteristics. Results: The mean of age was 37.72 years (14-68), males were 14 (35.9%), females were 25 (64.1%), stage I was 22 (56.4%), stage II were 17 (43.6%), B symptoms were 14 (35.9%), LDH above normal were 16 (41%), 6 patients received 1-3 CT cycles (15.4%), and 33 patients received 4-6 cycles(84.6%). Twenty-nine (74.4%) of 39 patients achieved CR. The group 1 had 76.0% (19/25) of CR, the group 2 had 75.0% (9/12), and the group 3 had 50% (1/2). Univariate analysis identified LDH and number of CT cycles, as significant predictors of CR (both P <0.05). On multivariate analysis, only number of CT cycles showed statistically significant, received 1-3 cycles of CHOP-based CT had an odds ratio (OR): 17.085, P1⁄4 0.026 being independent predictor. Conclusion: The number of CT cycles was the only CR predictor, and the fact of having received CT followed by RT or radiotherapy followed by CT as first-line did not influence the response.

Abstract P4-01-12: Circulating tumor cells (CTC) and endothelial cells (CEC) changes in HER2 negative metastatic breast cancer (MBC) patients treated with first line weekly paclitaxel and bevacizumab: Preliminary results of a prospective cohort from the French Breast Cancer

Abstract Background: increased levels of circulating tumor cells (CTC) are associated with worse progression-free survival (PFS) and overall survival (OS) in patients (pts) with MBC (Bidard FC et al, Lancet Oncol 2014). The failure of chemotherapy to reduce CTCs to levels below five CTCs per 7.5 mL whole blood at first follow-up after initiating a new systemic therapy for MBC predicts shorter time to progression and OS. It has been hypothesized that bevacizumab could modify CTC prognostic value due to extravasation or epithelio-mesenchymal transition induction. CEC variations to predict benefit of anti-angiogenic treatment is still controversial. Patients &amp; methods: the French cohort COMET is a prospective study including first line HER2 negative pts receiving weekly paclitaxel and bevacizumab according to EMEA approved combination. The aim of this cohort is to evaluate clinical, biological and radiological parameters associated with pts outcome (CTC, CEC, VEGFA levels, ctDNA, pharmacogenomic polymorphisms, metabolomic parameters, visceral fat assessed by initial CTscan, serum estradiol level, and quality of life). We present here the first planned analysis on 206 patients evaluated for CTC and CEC using the FDA cleared CellSearch method. Results: inclusions started in 09/2012. At time of analysis, 219 patients were included, 211 were evaluable for CTC at baseline (failure rate 4%) and 207 for CEC at baseline (failure rate 5%). Due to short follow-up, 173 pts and 166 pts were evaluable for both CTC and CEC at baseline and first day of second cycle of CT (D1C2) respectively. At baseline, 100/211 (47%) pts had ≥ 5 CTC (median 4 (range 0-30,000) and 30% had no detectable CTC (0 CTC). After one cycle of chemotherapy (D28) 38 pts (22%) had still ≥ 5 CTC: 37 pts with initial high level and only one patient with low CTC at baseline had increased CTC above 5. Median number CEC was 21 (0)-2231) at baseline and 22 (1-881) at D1C2. CEC increased in 16% and decreased in 15% of the cases. CTC &amp; CEC changes after one cycleCTC BaselineCTC at D1C2CEC BaselineCEC at D1C2≥ 5≥ 537 (21%)&amp;gt;20&amp;gt;2065 (39%)≥ 5&amp;lt;545 (26%)&amp;gt;20≤ 2025 (15%)&amp;lt;5≥ 51 (&amp;lt;1%)≤ 20&amp;gt;2027 (16%)&amp;lt;5&amp;lt;590 (52%)≤ 20≤ 2049 (30%)Total173166 CTC number at baseline line and CTC D1C2 were correlated (p&amp;lt;0.01) (Spearman test). There was no correlation between CEC at baseline or at D1C2 with CTC or CTC changes. Final analysis will be completed when 206 couples for both CTC and CEC at baseline and D1C2 will be available. Accrual is still ongoing. Conclusion: this 22% rate of failure to reduce CTC &amp;lt; 5 after one cycle of first line CT in a homogeneously bevacizumab-treated cohort of MBC patients did not differ from previous series. As second lines of chemotherapy do not improve the poor prognosis of this group of patients according to the SWOG 500 study results (Smerage et al, JCO 2014), trials of novel therapeutic agents should be considered at the time of progression. Citation Format: Jean-Yves Pierga, Isabelle Vaucher, Maya Gutierrez, Olivier Tredan, Séverine Guiu, Gilles Romieu, Anthony Goncalves, Marc Debled, Christelle Levy, Jean-Marc Ferrero, Christelle Jouannaud, Elisabeth Luporsi, Marie-Ange Mouret-Reynier, Florence Dalenc, Bernard Asselain, Jerome Lemonnier, Francois-Clement Bidard. Circulating tumor cells (CTC) and endothelial cells (CEC) changes in HER2 negative metastatic breast cancer (MBC) patients treated with first line weekly paclitaxel and bevacizumab: Preliminary results of a prospective cohort from the French Breast Cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-01-12.