Tumor Response Outcomes Research Articles

Outcome of hearing preservation related to tumor morphologic analysis in acoustic neuromas treated by gamma knife radiosurgery

BackgroundGamma Knife radiosurgery (GKRS) is an important part of the neurosurgical armamentarium in the treatment of acoustic neuromas. However, the treatment outcome related to the morphology of the tumor has not been rigorously studied. In this cohort, we evaluated the morphological features of the tumor in the tumor response and neurological outcomes after GKRS.Material and methodsFrom July 2003 to December 2008, there were 93 cases of acoustic neuromas treated upfront with GKRS with 64 cases with serviceable hearing and 29 cases without serviceable hearing to fulfill the margin dose of 12Gy with at least follow up 5 years.ResultsThe duration of symptom before GKRS in serviceable /no serviceable hearing was 7.9 ± 1.2 and 15.3 ± 3.1 months (p < 0.001) and associated no-hearing symptom was 70% and 35%, respectively (p < 0.001). There was 81.2% of hearing preservation after GKRS in serviceable hearing group including 27 cases of pear type (84%), 14 of linear type (70%), and 9 cases of sphere type (90%) (p < 0.01); however, there was no case of hearing improvement in the no-serviceable hearing group (0 of 29). There were 85% of patients with decreased tinnitus in serviceable hearing groups as compared to 61.5% of patients in no serviceable hearing group (p < 0.05). In multivariate analysis, the tumor morphology was highly correlated to hearing preservation rate (p < 0.01).ConclusionIn the limited case of this cohort, we found that the tumor morphology and timing of treatment was highly correlated to the rate of hearing preservation. The sphere type of tumor morphology was associated with the best chance of hearing preservation.

3:36 PMAbstract No. 287 - Tumor response and survival outcomes of very small drug-eluting beads used in trans-arterial chemoembolization for unresectable hepatocellular carcinoma

Poster: ECR 2017 / C-0973 / Tumor response and survival outcomes of very small drug eluting beads used in trans-arterial chemoembolization for unresectable hepatocellular carcinoma by: M. K. Abdel Aal1, S. Moawad2, M. M. Hanaoka3, T. Tatum2, B. Jackson2, C. Baalmann2, N. Ertel1, A. Abouarab2, S. Saddekni1; 1Birmingham, AL/US, 2Birmingham/US, 3Sao Paulo/BR

ED13.02 Tissue-Based Biomarkers

ED13.02 Tissue-Based Biomarkers

Human antigen R as a predictive marker for response to gemcitabine-based chemotherapy in advanced cisplatin-resistant urothelial cancer.

In patients with advanced urothelial cancer (UC), a combination of cisplatin (CDDP) and gemcitabine (GEM) is the most commonly used first-line systematic chemotherapy regimen. Although no standard regime for the treatment of CDDP-resistant UC has been established, GEM-based regimens are frequently used in these patients. In other types of cancer, human antigen R (HuR) status in cancer cells is closely associated with patient response to GEM. The aim of the present study was to establish the predictive potential of HuR expression for disease progression and survival in patients with UC who were treated with GEM-based regimens as a first or second-line chemotherapy. A total of 50 patients with advanced UC were enrolled in the current study. As first-line chemotherapy, methotrexate, vinblastine, epirubicin and CDDP (MVEC) combination therapy and GEM and CDDP combination therapy were administered in 34 (68.0%) and 16 patients (32.0%), respectively. Following progression, 45 patients (90.0%) were treated with combined GEM and paclitaxel therapy, and 5 patients (10.0%) were treated with GEM monotherapy. Cytoplasmic and nuclear HuR expression was evaluated using immunohistochemical techniques. The associations between HuR expression levels and local tumor response and treatment outcomes were analyzed. In first-line chemotherapy, no anticancer effects were observed to be significantly associated with nuclear or cytoplasmic HuR expression. In second-line chemotherapy nuclear HuR expression also exhibited no significant association with anticancer effects; however, the local tumor response was significantly improved if positive cytoplasmic HuR expression was present (P=0.002). Multivariate analyses revealed that cytoplasmic HuR expression levels were a significant predictive marker for longer OS (hazard ratio, 0.22; 95% confidence interval, 0.09-0.56; P=0.001). No significant association was observed between nuclear HuR expression levels and the overall survival. Therefore, cytoplasmic HuR expression is a significant predictive marker of response to GEM-based chemotherapy in patients with CDDP-resistant UC. Despite the limitations of a small and retrospective study, the results of the present study may facilitate the development of novel treatment strategies and provide a focus for additional basic and clinical studies.

Serum Biomarkers Predict Outcomes in Advanced Hodgkin Lymphoma Independent of International Prognostic Score (IPS) and Treatment: Correlative Analysis from a Large North American Cooperative Group Trial

Introduction: Progress in the treatment of patients with classical Hodgkin lymphoma (cHL) depends on identifying methods to better risk-stratify patients and assess prognosis and treatment response. While prognostic scores based on clinical characteristics have utility, inflammatory markers and signaling proteins may better reflect tumor biology, the microenvironment, or host response and might serve as prognostic factors. Increased expression of tumor-associated macrophage markers in tumor tissue, such as CD68 or CD163, has been shown to be associated with inferior survival outcomes in cHL patients. Blood-based markers are more practical in that specimens are readily and serially obtainable. Such markers, if shown to track with tumor response and/or prognosticate outcomes, can be used throughout treatment and follow-up. Some soluble markers, such as TARC (chemokine (C-C motif) ligand (CCL)-17) and soluble CD163 (sCD163), have been shown to reflect tumor burden and active disease, and markers such as soluble CD30 (sCD30), interleukin (IL)-6, chemokine (C-X-C motif) ligand (CXCL)-10/IP10, and IL-2 receptor have been associated with failure-free survival (FFS).Methods: Newly diagnosed cHL patients with locally extensive or advanced stage disease were prospectively enrolled in the Intergroup E2496 randomized controlled trial, which compared ABVD with Stanford V chemotherapy. A panel of serum cytokines, chemokines, and other soluble markers including TARC, CCL22, CCL24, sCD30, sCD163, CXCL10/IP10, CXCL13, soluble CD14 (sCD14), IL-6, IL-10, IL-12, and IL-13, IL1-receptor antagonist (IL1RA)) were measured in pretreatment serum specimens from 301 cHL patients (out of 854 on study) using multiplex (Luminex) bead array immunoassay (R&D Systems). Serum marker values were log-transformed for all analyses. Epstein-Barr virus (EBV) tumor status was determined by EBER in situ hybridization. A linear regression model was used to assess the association between pre-treatment serum marker levels and baseline clinical characteristics. A stratified Cox proportional hazards regression model was used to evaluate the association between serum marker levels as continuous variables and survival outcomes, including FFS (time from registration to disease progression/relapse or death) and overall survival (OS). Patients were divided into quartile groups based on serum marker levels and Kaplan-Meier curves were constructed with comparison using the stratified log-rank test. Three stratification factors were used in all modeling/testing include: stage I-II bulky vs. stage III-IV; IPS 0-2 vs 3-7; and treatment arms (Stanford V vs. ABVD). Two-sided p-values were reported.Results: Increased pre-treatment levels of CCL24, sCD30, sCD163, IP10, sCD14, IL-6, and IL-10 were associated with the presence of B symptoms, independent of age, tumor histology, and disease stage, in multivariate analysis. Higher sCD163 and IP10 levels were associated with EBV positive tumors and higher TARC, CCL22, and CXCL13 levels were associated with EBV negative tumors, after adjusting for age and histology. Several markers were associated with factors in the International Prognostic Score (Table 1). Adjusting for IPS, stage and treatment arms, high levels of IL1RA, sCD30, sCD163, IP10, and IL-10, were significantly (p<0.05) associated with inferior FFS. While high levels of TARC (p=0.02, hazard ratio (HR) 0.88, 95% confidence interval (CI) 0.79-0.98), and CXCL13 (p=0.04, HR 0.84, 95% CI 0.72-0.99) were associated with better OS, high levels of CD14 (p=0.02, HR 2.2, 95% CI 1.11-4.38), IP10 (p<0.0001, HR 2.22, 95% CI 1.64-3.00) and sCD163 (p=0.0002, HR 2.89, 95% CI 1.65-5.06) were associated with significantly inferior OS (Figure 1). Conclusion: These findings support prior work demonstrating the prognostic significance of markers such as CD163 in cHL tumor tissue with similar findings using a more readily available (blood-based) method of assessment. The study expands upon the number of blood-based markers shown to be prognostic in cHL, and associates high pre-treatment levels of several markers with IPS factors and other baseline clinical characteristics. Further, and most importantly, IP10 and sCD163 predict inferior FFS and OS independent of IPS and treatment. [Display omitted] [Display omitted] DisclosuresCheson:Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Research Funding; Acerta: Membership on an entity's Board of Directors or advisory committees, Research Funding. Winter:Pharmacyclics: Research Funding; Medivation: Other: Provision of investigational agent for clinical trial; GSK: Research Funding; Seattle Genetics: Research Funding. Friedberg:Bayer: Honoraria, Other: Data Safety Monitoring Board. Kahl:This study was coordinated by the ECOG-ACRIN Cancer Research Group (Robert L. Comis, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported by the National Cancer Institute of the National Institutes of Health under the following award number: Research Funding.

Clinical outcomes according to molecular subtypes in stage II-III breast cancer patients treated with neoadjuvant chemotherapy followed by surgery and radiotherapy.

We evaluated the tumor response and clinical outcomes according to molecular subtypes in stage II-III breast cancer patients who received neo-adjuvant chemotherapy (NAC) followed by surgery and radiotherapy. We retrospectively analyzed 329 patients with clinical stage II-III breast cancer who received NAC followed by surgery and radiotherapy. Luminal A and B, HER2-enriched and triple-negative subgroups were identified. The overall pathologic complete response (pCR) rate after NAC was 20.1% and the HER2-enriched subgroup had the highest pCR rate (43.6%), whereas luminal A showed the lowest rate of pCR (4.6%). The median follow-up duration was 55 months (range, 5-98 months). The 5-year overall survival (OS) and disease-free survival (DFS) rates were 88.9% and 72.9%, respectively. In subgroup analysis, according to the pathologic response (pCR vs non-pCR), the triple-negative subtype exhibited a significant difference in 5-year OS rate (100.0% vs 71.6%, P = 0.005) and 5-year DFS rate (93.1% vs 55.1%, P < 0.001). A distinct survival difference according to molecular subtype was found, particularly in the non-pCR group (5-year OS and DFS, P < 0.001, respectively). The non-pCR group showed significantly decreased 5-year OS and DFS rates compared to the pCR group, especially in triple negative and HER2-enriched breast cancer patients. A significant difference in survival rates and molecular subtypes was found in patients who failed to attain pCR.

Neuroendocrine tumor liver metastases treated with yttrium-90 radioembolization

ObjectiveYttrium-90 (Y-90) radioembolization is an emerging treatment option for unresectable neuroendocrine liver metastases (NELM). However, the data regarding this treatment are currently limited. This study evaluates the efficacy and tolerability of Y-90 radioembolization and identifies prognostic factors for radiographic response and survival. Methods and materialsThirty-eight patients underwent Y-90 radioembolization for NELM at our institution between April 2004 and February 2012. Patients were assessed radiographically (RECIST criteria, enhancement), serologically, and clinically at 1month, and then at every 3months after treatment for tumor response, toxicity, and survival outcomes. ResultsMedian length of follow-up was 17.0months (IQR, 9.0–37.0). Median survival was 29.2months. Three patients (9%) had a radiographic complete response to treatment, 6 (17%) had a partial response, 21 (60%) had stable disease, and 5 (14%) developed progressive disease. Two factors were significantly associated with a good radiographic response (complete/partial response): islet cell histological subtype (p=0.043) and hepatic tumor burden ≥33% (p=0.031). Multivariate analysis revealed that patients requiring multiple Y-90 treatments (HR 2.9, p=0.035) and patients who had previously failed systemic therapy with octreotide/chemotherapy (HR 4.4, p=0.012) had worse survival. Grade 3 serologic toxicity was observed in 2 patients (5%; hyperbilirubinemia, elevated alkaline phosphatase) after treatment. Grade 3 non-serologic toxicities included abdominal pain (11%), fatigue (11%), nausea/vomiting (5%), ascites (5%), dyspnea (3%), diarrhea (3%), and peripheral edema (3%). No grade 4 or 5 toxicity was reported. ConclusionsY-90 radioembolization is a promising treatment option for inoperable NELM and is associated with low rates of grade≥3 toxicity.

Survival and Tumor Response Outcomes in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN): A Systematic Literature Review

Survival and Tumor Response Outcomes in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN): A Systematic Literature Review

Improved tumor response and survival outcomes with post-transplant bortezomib (Btz) consolidation versus observation (Obs) alone in patients with newly diagnosed multiple myeloma (MM): Results from a randomized, open-label, multicenter, parallel-group phase 2 study

and showed evidence of disease in 145 (93%). After a median follow-up of 3.5 years, the median OS for the entire group was 7 months. Untreated and treated patients had median OS of 2 and 8 months, respectively. At least one previous line of therapy for MM and > 1 cytogenetic abnormality were independently associated with worse OS. The median OS for patients with 0, 1 and 2 of these risk factors were 25 months, 5.5 months and 2 months, respectively. Conclusion: Neurological manifestations observed in patients with MM should raise a suspicion of CNS involvement. The diagnosis of CNS MM should be based on imaging studies and CSF cytology and flow cytometry. Although prognosis is generally poor, especially in patients with a long history of chemotherapy and unfavorable cytogenetic profile, survival of individuals free from these negative prognostic factors can be prolonged due to administration of systemic treatment and/or radiotherapy. Prospective multi-institutional studies are warranted to improve the outcome of patients with CNS MM. PO-089 Improved tumor response and survival outcomes with post-transplant bortezomib (Btz) consolidation versus observation (Obs) alone in patients with newly diagnosed multiple myeloma (MM): Results from a randomized, open-label, multicenter, parallel-group phase 2 study O. Sezer, E. Terpos, R. Hajek, G. Sucak, S. Cagirgan, W. Linkesch, O.M. Akay, G. Armbrecht, T. Plesner, J.A. Snowden, H. Nahi, Z. Gulbas, A. Potamianou, C. Couturier, R. Olie, C. Feys, N. Allietta, M. Beksac Department of Hematology and Stem Cell Transplantation, Memorial Hospital, Istanbul, Turkey; Department of Clinical Therapeutics, University of Athens School of Medicine, Alexandra General Hospital, Athens, Greece; Internal Medicine and Hematooncology, Masaryk University Hospital Brno and Faculty of Medicine University Hospital Ostrava, Czech Republic; Department of Hematology, Faculty of Medicine, Gazi University, Ankara, Turkey; Department of Hematology and BMT Center, Izmir Medicalpark Private Hospital, Izmir, Turkey; Department of Hematology, Medical University Clinic, Medical University of Graz, Graz, Austria; Hematology Department, Eskisehir Osmangazi University, Eskisehir, Turkey; Centre for Muscle and Bone Research, Charite e Campus Benjamin Franklin, Berlin, Germany; Department of Hematology, Vejle Hospital, Vejle and IRS/ SDU, Denmark; Department of Haematology, Royal Hallamshire Hospital, Sheffield, UK; Haematology Centre, Karolinska University Hospital, Stockholm, Sweden; Bone Marrow Transplantation Department, Anadolu Health Center, Kocaeli, Turkey; Janssen-Cilag Pharmaceutical SACI, Athens, Greece; Janssen-Cilag, Issy-lesMoulineaux, France; Janssen-Cilag AG, Zug, Switzerland; Janssen Research & Development, Division of Janssen Pharmaceutica NV, Beerse, Belgium; Covance for Janssen-Cilag, Issy-les-Moulineaux, France; Department of Hematology, Ankara University, Ankara, Turkey Background: Induction therapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) is a standard frontline treatment for eligible MM patients (pts). PostASCT consolidation can improve depth of response and long-term outcomes. This phase 2 study evaluated the effects of Btz consolidation vs Obs alone on MM-related bone disease; pre-specified secondary endpoints of disease status (myeloma response), PFS, and OS are reported here. Methods: Eligible pts were adults with newly diagnosed MM who had achieved PR after single/double ASCT. Pts were randomized 1:1 (stratified by baseline bisphosphonate use and age) to receive 4 x 35-d cycles of Btz 1.6 mg/m2 IV on d 1, 8, 15, and 22, or Obs alone, followed by 18-mos’ follow-up for disease status and survival monitoring. Response was investigator-assessed per IMWG 2009 criteria. A last observation carried forward approach was used for missing assessments. PFS and OS were estimated using Kaplan-Meier analysis; exploratory p-values were determined using the log-rank test. Results: Between July 2009 and May 2012, 106 pts were randomized (52 Btz, 54 Obs). 2 pts were withdrawn prior to d 1, thus the modified intent-to-treat (mITT) population included 104 pts (51 Btz, 53 Obs): median age 58 vs 57 yrs; 71% vs 66% prior Btz-based induction. 41 (79%) and 46 (85%) pts completed the respective Btz consolidation and Obs phases as planned. CR+sCR rates at screening were 16% (Btz) and 15% (Obs). After the treatment/Obs phase, response rates were (Btz vs Obs): CR+sCR 22% vs 11%; VGPR 80% vs 68%; PD 8% vs 23%. PFS appeared longer with Btz consolidation vs Obs, both from randomization (median 44.9 vs 21.8 mos) and from first antiMM treatment (median 50.7 vs 35.0 mos) (Figure). After 21 (20%) deaths (11 Btz; 10 Obs), mean OS from randomization was 40.1 vs 36.6 mos and from first anti-MM treatment was 51.7 vs 47.1 mos; median OS was not reached in either arm at both time points. Pvalues for between-arm differences in response rates, PFS, and OS were all >0.05, likely due to small sample size. Conclusion: Compared with Obs alone, Btz consolidation was associated with trends for improved response depth and longer PFS and OS in newly diagnosed MM pts. Our response and PFS findings compare favorably with recent phase 3 data of Btz consolidation vs Obs in 15th International Myeloma Workshop, September 23-26, 2015 e129

Gene Expression in Hepatocellular Carcinoma: Pilot Study of Potential Transarterial Chemoembolization Response Biomarkers

PurposeTo perform a feasibility study to explore the relationship between hepatocellular carcinoma genetics and transarterial chemoembolization treatment response to identify potential biomarkers associated with enhanced treatment efficacy. Materials and MethodsIn this single-institution study, pretreatment hepatocellular carcinoma biopsy specimens for tumors in 19 patients (14 men, five women; mean age, 59 y) treated with chemoembolization between 2007 and 2013 were analyzed for a panel of 60 chemotherapy-sensitivity, hypoxia, mitosis, and inflammatory genes with the QuantiGene Plex 2.0 mRNA detection assay. Demographic, disease, and procedure data and tumor response outcomes were collected. Quantitative mRNA levels were compared based on radiologic response between tumors exhibiting complete response (CR) versus partial response (PR). ResultsThe study sample included 19 biopsy specimens from tumors (mean size, 3.0 cm; grade 1, n = 6; grade 2, n = 9; grade 3, n = 4) in patients treated with a mean of two conventional chemoembolization sessions. Thirteen and six tumors exhibited CR and PR, respectively, at a mean of 116 days after treatment. Tumors with CR showed a significant increase in (P < .05) or trend toward (P < .1) greater (range, 1.49–3.50 fold) pretreatment chemotherapy-sensitivity and mitosis (ATF4, BAX, CCNE1, KIF11, NFX1, PPP3CA, SNX1, TOP2A, and TOP2B) gene mRNA expression compared with tumors with PR, in addition to lower CXCL10 levels (0.48-fold), and had significantly (P < .05) higher (1.65-fold) baseline VEGFA levels. ConclusionsGenetic signatures may allow prechemoembolization stratification of tumor response probability, and gene analysis may therefore offer an opportunity to personalize locoregional therapy by enhancing treatment modality allocation. Further corroboration of identified markers and exploration of their respective predictive capacity thresholds is necessary.

4:51 PM Abstract No. 145 - Conventional ethiodized oil transarterial chemoembolization (C-TACE) for treatment of hepatocellular carcinoma (HCC): contemporary single-center review of clinical outcomes

4:51 PM Abstract No. 145 - Conventional ethiodized oil transarterial chemoembolization (C-TACE) for treatment of hepatocellular carcinoma (HCC): contemporary single-center review of clinical outcomes

Gene expression in hepatocellular carcinoma (HCC): pilot study of potential transarterial chemoembolization (TACE) response biomarkers

Genetic analysis is an encouraging approach to improve the understanding of biochemical mechanisms that underlie tumor therapeutic outcome. While gene assays have been previously applied to liver tissues to identify genetic signatures associated with cytotoxic and ischemic tissue insults, investigation of the association between HCC gene expression and TACE treatment outcomes has not been performed. This study was undertaken to explore the relationship between HCC genetics and TACE response in order to identify potential biomarkers associated with enhanced treatment efficacy. In this single-institution study, pre-treatment HCC biopsy specimens for tumors treated with TACE between 2007-2013 were analyzed for a panel of 60 chemosensitivity, hypoxia response, mitosis, and inflammatory mediator genes using the QuantiGene® Plex 2.0 mRNA detection assay (Affymetrix). Medical record and imaging review was used to collect demographic, disease, and procedure data, as well as tumor response outcomes, assessed using necrosis (EASL) criteria. Quantitative mRNA levels were compared between tumors exhibiting complete (CR) versus partial (PR) radiographic response. The study sample included 19 biopsied index tumors (mean size 3.0 cm) from 19 patients (14 men, 5 women; mean age 59 years) who underwent mean 2 TACE sessions using 1:1 chemotherapy to ethiodized oil ± particle embolization. Thirteen and 6 tumors exhibited CR and PR, respectively, at mean 116 days post-treatment. CR tumors showed a statistical increase (P<0.05) in or trend (P<0.1) toward higher pre-treatment chemosensitivity and mitosis (ATF4, BAX, CCNE1, KIF11, NFX1, PPP3CA, SNX1, TOP2A, and TOP2B) gene mRNA expression compared to PR tumors, lower CXCL10 levels, and statistically higher (P<0.05) baseline VEGF-alpha levels. Genetic signatures may allow pre-TACE stratification of tumor response probability, and gene analysis may thus offer an opportunity to personalize locoregional therapy by enhancing treatment modality allocation (e.g. TACE vs. yttrium-90 radioembolization vs. ablative therapy). Further confirmation of identified markers and exploration of their respective predictive capacity thresholds is necessary.

2:03 PM, Abstract No. 123 - Timing of imaging response after locoregional transarterial therapy (LRT): comparison between transarterial chemoembolization (TACE), and yttrium-90 radioembolization (Y-90 RE)

Variation in imaging follow-up practices within the interventional radiology (IR) community demands an evidence basis to dictate suitable follow-up approaches. The timing of follow-up imaging after treatment should ideally be timed to capture tumors at maximal expected response, and it not known whether response manifestations occur at similar time frames for different therapies. This study aimed to characterize and compare temporal features of tumor imaging response to transarterial chemoembolization (TACE), and yttrium-90 radioembolization (Y-90 RE). The index tumors for this single-center, IRB-approved retrospective study were drawn from 188 patients who underwent conventional TACE and 56 patients treated with Y-90 RE for hepatocellular carcinoma (HCC) between 2007-2013. Medical record and imaging review was used to collect demographic and disease data and tumor response outcomes, calculated from time of first treatment. Time-to-best imaging response was compared between TACE and Y-90 RE patients in groups delineated by tumor size: small (<3 cm), intermediate (3-5 cm), and large (5-7 cm). The TACE cohort included 140 men and 48 women (mean age 60 years) with 207 index tumors (mean size 4.0 cm) treated with mean 1.5 TACE sessions. The Y-90 RE cohort included 47 men and 9 women (mean age 62 years) with 58 index tumors (mean size 6.7 cm) treated with mean 1.4 Y-90 RE sessions. 152 TACE treated tumors and 36 Y-90 RE treated tumors achieved adequate clinical follow-up for assessment. Objective response rates by necrosis (EASL) criteria were 84% among TACE patients and 89% among Y-90 RE patients. Tumor diameters were generally similar among size groups (2.0 vs. 2.3 cm, P=0.129; 3.8 vs. 4.0 cm, P=0.294; 5.5 vs. 6.0 cm, P=0.013); Time-to-best response did not differ within size groups (small: 103 vs. 103 days, P=0.990; intermediate: 98 vs. 80 days, P=0.536; large: 206 vs. 108 days, P=0.117). No differences in tumor response times were identified between TACE versus Y-90 RE treated HCC, suggesting that the same imaging follow-up protocols may be used for both. These results serve as a first step toward generating evidence to establish post-procedure follow-up guidelines.

First-line treatment with modified FOLFOX6 (mFOLFOX6) + panitumumab (pmab) or bevacizumab (bev) in wild-type (WT) RAS metastatic colorectal carcinoma (mCRC): Tumor response outcomes beyond RECIST.

660 Background: In the PEAK study, pmab + FOLFOX6 was associated with longer OS than bev + FOLFOX6 in first-line RAS WT mCRC. RECIST overall response rates (ORR) were similar between treatment arms. Here, we report exploratory analyses of tumour assessments beyond RECIST. Methods: PEAK was a randomised phase II study of first-line pmab + mFOLFOX6 vs bev + mFOLFOX6 in previously untreated mCRC. ORRs (investigator assessed), median duration of response (DoR; from first confirmed response to disease progression or death [secondary endpoint]) and depth of response (DpR; defined as the percentage of tumour shrinkage at nadir or progression) in RAS WT pts were calculated by treatment. Early tumour shrinkage (ETS) was defined as the proportion of patients with ≥30% tumour shrinkage at week 8 (exploratory analysis). Results: Overall, 169 pts withRAS WT mCRC were included in the ORR analysis and 154 had tumour-shrinkage data available at baseline and week 8. Significantly more pts in the pmab + mFOLFOX6 arm had ETS at week 8 vs. the bev + mFOLFOX6 arm (Table). ORRs were similar in the two arms, while DoR was significantly longer and DpR significantly greater with pmab + mFOLFOX6 (Table). ≥30% vs. &lt;30% tumour shrinkage at week 8 was associated with longer median PFS (HR: 0.52 [95% CI: 0.29–0.92] and HR: 0.65 [95% CI: 0.38–1.13]) and OS (HR: 0.44 [95% CI: 0.15–1.32] and HR: 0.23 [95% CI: 0.08–0.66]) for pmab + mFOLFOX6 and bev + mFOLFOX6, respectively. Conclusions: Although ORR appeared to be similar or only numerically improved in the pmab arm of PEAK, the responses observed appeared to occur earlier, last longer and be deeper in our exploratory analyses. This is consistent with the observed OS and PFS benefit, and with data reported earlier from the FIRE3 study. Clinical trial information: NCT00819780. [Table: see text]

Interval between neoadjuvant treatment and definitive surgery in locally advanced rectal cancer: impact on response and oncologic outcomes

The optimal waiting period between neoadjuvant treatment completion and surgery in locally advanced rectal cancer (LARC) is controversial. The specific purpose of this study was to evaluate the effect of prolonging this interval on the pathologic response, postoperative morbidity, and long-term oncologic outcomes. Retrospective data analysis is reported from LARC patients who had been treated with chemoradiation followed by surgery and intra-operative radiotherapy, between February 1995 and December 2012. In total, two groups were studied, according to the time elapsed between neoadjuvant treatment and surgery: conventional interval (CI; <6 weeks) and delayed interval (DI; ≥6 weeks). Clinicopathological data related to tumor response, postoperative morbidity, and oncologic outcomes were compared. This study included 335 consecutive LARC patients. There was a higher proportion of patients with clinical staging nodal involvement (cN+) in the DI group (76.6 vs. 64.1 %; p = 0.01). The pathologic complete response (pCR) was not significantly different among groups (8.8 vs. 12.1 %; p = 0.34). Longer intervals did not affect complication incidence or severity or hospital admission length. Certain postneoadjuvant tumor effect parameters were significantly increased in the DI group, including N-downstaging and T-downsizing. After a median follow-up of 71 months, patients in the DI group presented with superior 5-year overall survival (OS) (55.9 vs. 70.4 %, p = 0.014); however, no statistically significant differences were observed in 5-year disease-free survival (DFS) or 5-year local control (LC) (69.9 vs. 74.9 %, p = 0.223; 90.4 vs. 94.5 %, p = 0.123, respectively). A modest surgical interval delay (≥6 weeks) did not increase postoperative complications and was identified as a favorable prognostic factor for OS, although no differences were observed in pCR, LC, or DFS. Innovative multidisciplinary strategies incorporating further time extension of the surgical interval can be safely explored.

The impact of dose/time modification in irinotecan- and oxaliplatin-based chemotherapies on outcomes in metastatic colorectal cancer

This study was designed to evaluate (1) the impact of relative dose intensity (RDI) on tumor response and survival outcomes and (2) the influence of dose reduction and schedule modification on outcomes in patients with metastatic colorectal cancer (mCRC). Pooled datasets from two previous phase II trials of FOLFIRI (CCOG-0502; n = 36) and mFOLFOX6 (CCOG-0704; n = 30) in patients with mCRC were analyzed retrospectively. The RDIs of irinotecan and oxaliplatin were compared to response rate (RR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). To assess the effects of dose reduction and schedule modification, the effects of dose index (DI) and time index (TI) on outcomes were evaluated. The median RDIs of irinotecan in FOLFIRI and oxaliplatin in mFOLFOX6 were 80 and 79 %, respectively. Higher RDI of irinotecan in FOLFIRI was associated with significant improvements in RR (65 vs. 6 %, p < 0.01), DCR (100 vs. 59 %, p < 0.01), PFS (9.9 vs. 5.6 months, p < 0.01) and OS (26.7 vs. 12.9 months, p = 0.01) and was the only independent factor associated with PFS [hazard ratio (HR) 8.48, p < 0.01). Higher RDI of oxaliplatin in FOLFOX was significantly associated with DCR (65 vs. 6 %, p < 0.01), and higher TI of oxaliplatin was the only independent factor associated with PFS (HR 2.74, p = 0.04). RDIs of irinotecan and oxaliplatin affected clinical outcomes. Dose reductions in irinotecan, as indicated by DI, and time delays in oxaliplatin, as indicated by TI, were the only independent prognostic factors predicting PFS in patients receiving FOLFIRI and FOLFOX6, respectively.

Neuroendocrine Tumor Liver Metastases Treated With Yttrium-90 Radioembolization

Surgical resection remains the only curative option for neuroendocrine tumor liver metastases (NETLM). However, 90% of patients have unresectable disease. Limited data currently exists for yttrium-90 radioembolization (Y90-RE), an emerging treatment option for unresectable NETLM. This study evaluates the efficacy and tolerability of Y90-RE as well as prognostic factors in a group of NETLM patients treated with Y90-RE. Thirty-eight patients underwent glass-based Y90-RE from April 2004-February 2012. Patients were assessed radiographically (both RECIST criteria and change in tumor enhancement), serologically, and clinically at 1 month and then every 3 months post-treatment for tumor response, toxicity, and survival outcomes. Median length of follow-up was 17 months (IQR, 9-37). Median survival was 29 months. On imaging follow-up, 3 patients (9%) had a complete response (CR) to treatment, 6 (17%) had a partial response (PR), 21 (60%) had stable disease (SD), and 5 (14%) developed progressive disease (PD). Univariate analysis identified 2 significant factors associated with a good treatment response (CR/PR): location of primary tumor (p = 0.036) and histological subtype (p = 0.050). Trends towards improved survival were observed in patients who received systemic therapy before Y90-RE (p = 0.070) and in patients who received octreotide before treatment (p = 0.052). Patients requiring >1 Y90-RE treatment had worse survival (17.3 vs 39.7 months, p = 0.040). Grade 3 serologic toxicity was observed in 2 patients (one elevated bilirubin, one elevated alkaline phosphatase) after Y90-RE. No portal hypertension, liver abscess, or bilomas were reported. Grade 3 non-serologic toxicities included abdominal pain (11%), fatigue (11%), nausea/vomiting (5%), ascites (5%), dyspnea (3%), diarrhea (3%), and peripheral edema (3%). Our institutional experience demonstrates Y90-RE to be an efficacious, safe, and tolerable treatment for NETLM.

The role of chemotherapy in advanced solitary fibrous tumors: a retrospective analysis

BackgroundPatients with advanced solitary fibrous tumors (SFTs) have a poor prognosis; treatment options for recurrent disease are particularly limited. Several novel targeted agents have recently shown promise against advanced SFTs, but the relative efficacy of new agents is difficult to assess because data on the efficacy of conventional chemotherapy for SFTs are limited. We thus sought to estimate the efficacy of conventional chemotherapy for SFTs by reviewing data on tumor response to therapy and progression-free survival from SFT patients who received this therapy.MethodsWe retrospectively analyzed the clinical outcomes of 21 patients with grossly measurable, advanced SFTs (unresectable metastatic disease or potentially resectable primary tumors) who received conventional chemotherapy and follow-up at The University of Texas MD Anderson Cancer Center between January 1994 and June 2007. Best tumor response to therapy was assessed using the Response Evaluation Criteria In Solid Tumors 1.1. The Kaplan-Meier method was used to estimate median progression-free survival (PFS) duration.ResultsOf 21 patients, 4 received more than 1 regimen of chemotherapy, for a total of 25 treatments. Doxorubicin-based chemotherapy was given in 15 cases (60%), gemcitabine-based therapy in 5 cases (20%), and paclitaxel in 5 cases (20%). First-line chemotherapy was delivered in 18 cases (72%). No patients had a complete or partial response, 16 (89%) had stable disease, and 2 (11%) had disease progression. Five patients (28%) maintained stable disease for at least 6 months after first-line treatment. The median PFS duration was 4.6 months. The median overall survival from diagnosis was 10.3 years.ConclusionConventional chemotherapy is effective in controlling or stabilizing locally advanced and metastatic SFTs. Our findings can serve as a reference for tumor response and clinical outcomes in the assessment of novel treatments for SFTs.

8:32 AM Abstract No. 63 - Tumor response and patient outcomes of radioembolization for hepatic GI metastasis as it relates to hypervascularity pattern on spect

Purpose Radioembolization has shown promising results in the treatment of unresectable metastatic gastrointestinal cancer to the liver, however the tumor response is unpredictable. The importance of predicting the outcome of selective internal radiotherapy (SIRT) in these patients cannot be over emphasized. This retrospective review was conducted to determine if the radionuclide uptake on SPECT can predict the outcome in these patients treated with Yttrium-90 glass microsphere radioembolization. Materials and Methods 26 patients with known history of SIRT for hepatic metastasis from GI tumors (colorectal, pancreatic etc.) were included in the study. Baseline and post-SIRT CT images (1 month, 3 months and 6 months post-SIRT) were analyzed to find out the progression free survival (PFS). Overall Survival(OS) was also calculated.The radionuclide uptake was then stratified into one of the four categories: Hypovascular tumor, Halo of activity around the tumor, peripheral activity within the tumor and Central/diffuse activity. Kaplan-Meier methods were used to estimate survival curves. Results Twenty-six patients (64% M; average age of 60 years) were included in the study. On evaluation of the SPECT characteristics, 15 pts (57.7%) had a halo of activity around the lesion, 8 pts (30.8%) demonstrated peripheral activity within the tumor itself, 2 patients (7.7%) demonstrated diffuse/central activity and only 1(3.8%) was hypovascular with no significant activity. No statistically significant correlation was demonstrated between the SPECT characteristics and OS and PFS. 17 (68%) patients demonstrated increase in the size of the target lesions after one month of SIRT, thus demonstrating progression according to the RECIST 1.1 criteria. Conclusion There is no significant correlation between the hypervascularity pattern on SPECT and overall survival. 68% of the lesions demonstrated increase in the size after one month of therapy, though many of these patients had prolonged survival; thus, RECIST 1.1 criteria may not be sufficient to access tumor progression in these patients.

Neoadjuvant Therapy and Mini-Invasive Total Mesorectal Excision for Rectal Cancer: Feasibility and Outcome Analysis from a Single Institution Prospectively Collected Data Base

Neoadjuvant treatment for rectal adenocarcinoma improves local control and represents the standard for locally advanced disease. Laparoscopic and robotic total mesorectal excision has been increasingly adopted. It provides magnified visualization of the pelvic cavity, thereby facilitating the mesorectal dissection. Consecutive patients with locally advanced/ultralow rectal adenocarcinoma received neoadjuvant treatment and mini-invasive total mesorectal excision at our center. We retrospectively reviewed the clinical records by using a prospectively collected data base and focusing on feasibility, tumor response and treatment outcomes. In a 13-year period, 117 rectal adenocarcinoma patients (80 males and 37 females) received neoadjuvant treatment and mini-invasive total mesorectal excision. Median age at diagnosis was 67 years; pre-treatment stage was I in 10 (9%); IIA in 58 (50%); IIC in 5 (4%); IIIA in 10 (9%); IIIB in 31 (26%) and IV in 3 (2%) patients. All patients received external beam radiation therapy, 79 (67%) combined with fluorouracil-based chemotherapy. One-hundred and three patients underwent laparoscopic surgery and 14 robotic surgery. Overall, 90 patients (77%) had anterior resection and 27 (23%) had abdominoperineal resection. Down-staging was obtained in 70 patients (66%). No major intraoperative nor delayed surgical complications were observed. At a median follow up of 52 months, 8 patients (7%) had a local relapse, 7 of them along with distant relapse, and 16 (14%) had distant relapse. The 5-year relapse-free survival was 76.5%. Our data suggest that in a community hospital mini-invasive surgery after neoadjuvant treatment is feasible in real clinical practice and achieves consistent results in term of disease control rate.