Pathologic Response In Patients Research Articles

Magnetic resonance imaging for prediction of pathologic response to neoadjuvant chemotherapy in triple-negative breast cancer

BACKGROUND: The ability of breast MRI to predict pathologic response to neoadjuvant chemotherapy varies across biological subtypes. We sought to determine how well breast MRI findings following initial treatment on the phase III BrighTNess trial correlated with pathologic response in patients with triple negative breast cancer (TNBC).

Comparison of Clinico-pathological and Radiological Parameters of Response to Neoadjuvant Chemotherapy in Breast Cancer

Complete histological response following neo-adjuvant chemotherapy (NACT) for breast cancer has great prognostic value. This study would access rates of complete clinical, radiological and pathological response in patients of breast cancer treated with neo-adjuvant chemotherapy. To Access Rates of Complete Clinical, radiological And Pathological Response in Patients of Breast Carcinoma Being Treated with NACT.

Re: Pathologic Response in Patients Receiving Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer: Is Therapeutic Effect Owing to Chemotherapy or TURBT?

Re: Pathologic Response in Patients Receiving Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer: Is Therapeutic Effect Owing to Chemotherapy or TURBT?

Early metabolic response to chemoradiotherapy by interim FDG PET/CT is associated with better overall survival and histological response in esophageal cancers

BackgroundEarly assessment of response to neoadjuvant chemoradiotherapy (CRT) is crucial in determining the most suitable treatment strategy in locally advanced oesophageal cancer (LAEC). AimsWe evaluated the impact of early metabolic response during CRT on overall survival (OS) and histological response. MethodsPatients with biopsy-proven oesophageal carcinoma underwent FDG PET/CT with evaluation of the standardized uptake value (SUV) before any treatment and during CRT after 20 Gy. Results116 patients (Male: 66.4%, Median age: 63; squamous cell carcinomas (SCC): 70%) met inclusion criteria. Median OS was 21.7 months. There was a significant positive correlation between interim metabolic response and OS. In multivariate analysis, only metabolic response using the 50% cut-off value remained significantly associated with OS (IC95% = 0.28–0.73; p = 0.001). In this statistical analysis, surgery (p = 0.007) and T stage (p = 0.023) were also correlated with OS. There was a significant correlation between early metabolic response and local recurrence (Chi-squared test p = 0.0001). ConclusionsEarly metabolic response using FDG PET/CT is associated with better OS, disease-free survival, local control and pathological response in patients treated by CRT for LAEC.

Pathological Response and Survival in Triple-Negative Breast Cancer Following Neoadjuvant Carboplatin plus Docetaxel.

Prognostic value of pathologic complete response (pCR) and extent of pathologic response attained with anthracycline-free platinum plus taxane neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) is unknown. We report recurrence-free survival (RFS) and overall survival (OS) according to degree of pathologic response in patients treated with carboplatin plus docetaxel NAC. One-hundred and ninety patients with stage I-III TNBC were treated with neoadjuvant carboplatin (AUC6) plus docetaxel (75 mg/m2) every 21 days × 6 cycles. pCR (no evidence of invasive tumor in breast and axilla) and Residual cancer burden (RCB) were evaluated. Patients were followed for recurrence and survival. Extent of pathologic response was associated with RFS and OS using the Kaplan-Meier method. Median age was 51 years, and 52% were node-positive. pCR and RCB I rates were 55% and 13%, respectively. Five percent of pCR patients, 0% of RCB I patients, and 58% of RCB II/III patients received adjuvant anthracyclines. Three-year RFS and OS were 79% and 87%, respectively. Three-year RFS was 90% in patients with pCR and 66% in those without pCR [HR = 0.30; 95% confidence interval (CI), 0.14-0.62; P = 0.0001]. Three-year OS was 94% in patients with pCR and 79% in those without pCR (HR = 0.25; 95% CI, 0.10-0.63; P = 0.001). Patients with RCB I demonstrated 3-year RFS (93%) and OS (100%) similar to those with pCR. On multivariable analysis, higher tumor stage, node positivity, and RCB II/III were associated with worse RFS. Neoadjuvant carboplatin plus docetaxel yields encouraging efficacy in TNBC. Patients achieving pCR or RCB I with this regimen demonstrate excellent 3-year RFS and OS without adjuvant anthracycline.

Correlation of Radiologic and Pathologic Response in Patients Receiving Neoadjuvant Radiotherapy for Soft Tissue Sarcoma

Correlation of Radiologic and Pathologic Response in Patients Receiving Neoadjuvant Radiotherapy for Soft Tissue Sarcoma

PS02.242: SIGNET-RING CELL PERCENTAGE MAY INFLUENCE PATHOLOGICAL RESPONSE TO CHEMOTHERAPY IN ESOPHAGO-GASTRIC JUNCTION SIGNET RING CELL CARCINOMA

Abstract Background Like in gastric cancer, the incidence of signet-ring cell carcinoma (SRCC) is rising also in esophago-gastric junction (EGJ) adenocarcinoma Siewert type I and II. SRCC is much more studied in gastric cancer and WHO classification divides poorly cohesive gastric cancer in two subtypes, depending on the percentage of signet-ring cells: real SRCC (percentage of signet-ring cell more than 50%) and poorly cohesive non-SRCC (less than 50%). Real SRCC seems to have higher chemosensitivity and better prognosis than poorly cohesive non-SRCC. Recently, a new classification for SRCC has been proposed, which subdivides SRCC based on different cut-off percentages of signet ring cells (less than or equal to 90% vs more than 90%). Aim of this study was to compare pathological response in patients with EGJ SRCC treated with neoadjuvant chemotherapy. Methods Study population comprised 11 patients with Siewert I and II EGJ SRCC treated with neoadjuvant chemotherapy and surgery. We analyzed differences in pathological response to therapy between ‘pure’-SRCC (more than 90% of SRC) and ‘non-pure’-SRCC (less than or equal to 90%). Tumor regression grade (TRG) was used to define response to treatment, with TRG 1–2 defining good response to treatment and TRG 3–5 poor or absent response to treatment. Results Among the 11 patients with EGJ SRCC, 6 had ‘pure’-SRCC histology and 5 ‘non-pure’-SRCC. Response to treatment in ‘pure’-SRCC patients was equally splint into good and poor responders: 3 had good response to treatment (TRG 1–2) and 3 poor or absent response (TRG 3–5). On the contrary most of ‘non-pure’-SRCC had poor or absent response: 4 out of 5 patients had TRG 3–5. Conclusion Although the case series was too small to perform statistical analyses, our results suggest that signet-ring cell percentage may influence the outcome of neoadjuvant therapy. Probably a larger case series would allow to better define cut-offs of percentage of signet-ring cell carcinoma of the EGJ. Moreover it would allow to inspect other factors related to response to treatment. This is only a preliminary investigation and further studies are needed to better understand the characteristics of these rising in incidence types of cancer. Disclosure All authors have declared no conflicts of interest.

Impact of Neoadjuvant Chemotherapy on Pathologic Response in Patients With Upper Tract Urothelial Carcinoma Undergoing Extirpative Surgery.

Neoadjuvant chemotherapy (NAC) has been increasingly adopted in the management of high-grade upper tract urothelial carcinoma (UTUC), largely extrapolating from level I evidence in urothelial carcinoma of the bladder. Studies examining pathologic outcomes in patients with UTUC receiving NAC are mostly limited to retrospective, single-center studies with limited sample size, with results of a phase II trial recently presented. Hypothesizing that NAC is associated with improved pathologic response (PR), we compared pathologic outcomes in patients with high-grade UTUC who did and did not receive NAC before extirpative surgery. A total of 6174 patients with nonmetastatic, high-grade UTUC who underwent extirpative surgery from 2006 to 2014 were identified from the National Cancer Database. Patients were stratified by NAC status. PR was defined as pathologic stage less than clinical stage. Univariate and multivariable logistic regression analysis was employed to identify predictors of PR. Two hundred sixty (4.2%) patients received NAC. A higher incidence of PR was observed in patients receiving NAC (25.2% vs. 1.8%; P< .001), with complete PR observed in 6.1% of patients receiving NAC and 0.4% of patients undergoing surgery alone. NAC (odds ratio [OR], 19.8; 95% confidence interval [CI], 11.8-33.5), nonwhite race (OR, 3.2; 95% CI, 1.7-6.3), and ureteral tumor location (OR, 1.6; 95% CI, 1.02-2.6) were independently associated with PR. Examining a large national cancer registry, we observed a higher incidence of PR in patients with UTUC receiving NAC, validating findings of prior studies. Our findings support consideration of NAC in high grade UTUC. Prospective trials will better define the impact of NAC on pathologic and survival outcomes.

NRG Oncology BR005: Phase II trial assessing accuracy of tumor bed biopsies (Bx) in predicting pathologic response in patients (Pts) with clinical/radiological complete response (CR) after neoadjuvant chemotherapy (NCT) in order to explore the feasibility of breast-conserving treatment (BCT) without surgery.

TPS604Background: The increased use of neoadjuvant chemotherapy (NCT) has enabled higher rates of breast-conserving surgery (BCS) as well as provided prognostic information for women with breast ca...

MP28-03 CONTRAST MEDIA ENHANCEMENT REDUCTION PREDICTS TUMOR RESPONSE TO PRESURGICAL MOLECULAR-TARGETING THERAPY IN PATIENTS WITH ADVANCED RENAL CELL CARCINOMA

You have accessJournal of UrologyKidney Cancer: Epidemiology & Evaluation/Staging I1 Apr 2018MP28-03 CONTRAST MEDIA ENHANCEMENT REDUCTION PREDICTS TUMOR RESPONSE TO PRESURGICAL MOLECULAR-TARGETING THERAPY IN PATIENTS WITH ADVANCED RENAL CELL CARCINOMA Shogo Hosogoe, Shingo Hatakeyama, Hirotake Kodama, Ayumu Kusaka, Noriko Tokui, Hayato Yamamoto, Tohru Yoneyama, Atsushi Imai, Takahiro Yoneyama, Yasuhiro Hashimoto, Takuya Koie, and Chikara Ohyama Shogo HosogoeShogo Hosogoe More articles by this author , Shingo HatakeyamaShingo Hatakeyama More articles by this author , Hirotake KodamaHirotake Kodama More articles by this author , Ayumu KusakaAyumu Kusaka More articles by this author , Noriko TokuiNoriko Tokui More articles by this author , Hayato YamamotoHayato Yamamoto More articles by this author , Tohru YoneyamaTohru Yoneyama More articles by this author , Atsushi ImaiAtsushi Imai More articles by this author , Takahiro YoneyamaTakahiro Yoneyama More articles by this author , Yasuhiro HashimotoYasuhiro Hashimoto More articles by this author , Takuya KoieTakuya Koie More articles by this author , and Chikara OhyamaChikara Ohyama More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.903AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES A quantitative tumor response evaluation to molecular-targeting agents in advanced renal cell carcinoma (RCC) is debatable. We aimed to evaluate the relationship between radiologic tumor response and pathological response in patients with advanced RCC who underwent presurgical therapy. METHODS Between March 2012 and December 2016, we prospectively enrolled 34 locally advanced and/or metastatic RCC who underwent presurgical molecular-targeting therapy followed by radical nephrectomy. Primary endpoint was comparison of radiologic tumor response among Response Evaluation Criteria in Solid Tumors (RECIST), Choi, and contrast media enhancement reduction (CMER). Secondary endpoint included pathological downstaging, treatment related adverse events, postoperative complications, Ki67/MIB1 status, and tumor necrosis. RESULTS f 34 patients, 31 underwent scheduled radical nephrectomy. Presurgical therapy agents included axitinib (n = 26), everolimus (n = 3), sunitinib (n = 1), and axitinib followed by temsirolimus (n = 1). The major presurgical treatment-related adverse event was grade 2 or 3 hypertension (44%). The median radiologic tumor response by RECIST, Choi, and CMER were -19%, -24%, and -49%, respectively. Among the radiologic tumor response tests, CMER showed a higher association with tumor necrosis in surgical specimens than others. Ki67/MIB1 status was significantly decreased in surgical specimens than in biopsy specimens. The magnitude of the slope of the regression line associated with the tumor necrosis percentage was greater in CMER than in Choi and RECIST. CONCLUSIONS CMER may predict tumor response after presurgical molecular-targeting therapy. Larger prospective studies are needed to develop an optimal tumor response evaluation for molecular-targeting therapy. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e357 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Shogo Hosogoe More articles by this author Shingo Hatakeyama More articles by this author Hirotake Kodama More articles by this author Ayumu Kusaka More articles by this author Noriko Tokui More articles by this author Hayato Yamamoto More articles by this author Tohru Yoneyama More articles by this author Atsushi Imai More articles by this author Takahiro Yoneyama More articles by this author Yasuhiro Hashimoto More articles by this author Takuya Koie More articles by this author Chikara Ohyama More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Obesity as an independent predictive factor for pathologic complete response after neoadjuvant chemoradiation in rectal cancer.

PurposeThe predictive role of obesity on pathologic complete response (pCR) after neoadjuvant chemoradiation (nCRT) in rectal cancer remains controversial. This study aimed to evaluate the association between obesity and pathologic response in patients with rectal cancer following nCRT.MethodsA total of 320 patients with primary rectal cancer who underwent curative resection after nCRT between January 2010 and September 2014 were enrolled in this study. Obesity was defined as body mass index of ≥25 kg/m2. Clinicopathologic characteristics were analyzed to identify independent predictive factors for pCR.ResultsAmong the included patients, 23.4% (n = 75) were obese, and 14.7% (n = 47) showed pCR. Baseline characteristics were generally similar between obese and nonobese patients, except that women (P = 0.001) and cT2 tumors (P = 0.001) were more common in the obese group. Multivariate logistic regression analysis revealed that obesity (odds ratio [OR] = 2.051; 95% confidence interval [CI], 1.009–4.168), cT2 (OR, 3.614; 95% CI, 1.166–11.202), and pretreatment carcinoembryonic antigen <5 ng/mL (OR, 2.921; 95% CI, 1.365–6.253) were independent predictors for pCR. Obesity was not associated with disease-free survival or local recurrence-free survival.ConclusionObesity was an independent predictive factor for pCR following nCRT in rectal cancer, but was not associated with recurrence. Further studies are needed to clarify the association between obesity and prognosis of rectal cancer after nCRT.

Dynamic Diffuse Optical Tomography for Monitoring Neoadjuvant Chemotherapy in Patients with Breast Cancer.

Purpose To identify dynamic optical imaging features that associate with the degree of pathologic response in patients with breast cancer during neoadjuvant chemotherapy (NAC). Materials and Methods Of 40 patients with breast cancer who participated in a longitudinal study between June 2011 and March 2016, 34 completed the study. There were 13 patients who obtained a pathologic complete response (pCR) and 21 patients who did not obtain a pCR. Imaging data from six subjects were excluded from the study because either the patients dropped out of the study before it was finished or there was an instrumentation malfunction. Two weeks into the treatment regimen, three-dimensional images of both breasts during a breath hold were acquired by using dynamic diffuse optical tomography. Features from the breath-hold traces were used to distinguish between response groups. Receiver operating characteristic (ROC) curves and sensitivity analysis were used to determine the degree of association with 5-month treatment outcome. Results An ROC curve analysis showed that this method could identify patients with a pCR with a positive predictive value of 70.6% (12 of 17), a negative predictive value of 94.1% (16 of 17), a sensitivity of 92.3% (12 of 13), a specificity of 76.2% (16 of 21), and an area under the ROC curve of 0.85. Conclusion Several dynamic optical imaging features obtained within 2 weeks of NAC initiation were identified that showed statistically significant differences between patients with pCR and patients without pCR as determined 5 months after treatment initiation. If confirmed in a larger cohort prospective study, these dynamic imaging features may be used to predict treatment outcome as early as 2 weeks after treatment initiation. © RSNA, 2018 Online supplemental material is available for this article.

Abstract 3979: Immune correlates of pathologic response in bladder cancer patients undergoing neoadjuvant chemotherapy

Abstract Introduction and Objective: The immune system is increasingly recognized as both a key player in cancer control and as druggable target. We hypothesized that the immune system impacts pathologic response in patients undergoing cisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer though the immune system. Methods: Whole exome sequencing (WES) was performed on tumor DNA from patients in two independent cohorts who underwent cisplatin-based NAC. The Memorial Sloan Kettering/Dana Farber Cancer Institute (n=50; 25 responders) and Philadelphia cohorts (n=48; 20 responders) were treated with gemcitabine / cisplatin or methotrexate / vinblastine / doxorubicin / cisplatin. Mutation analysis was performed using standard analytical pipelines. Macrohistocompatibility complex (MHC)-restricted neoantigens were identified with netMHCpan and PolySolver. High affinity neoantigens were defined to have ≤500 nM binding affinity (Kd). Pathologic response was defined as ≤ypTis cystectomy specimen. CIBERSORT was used to infer immune cell infiltrate based on DASL Illumina microarray expression profiles (n=41; 17 responders). Results: Chemoresponders had &amp;gt;twice as many putative neoantigens as nonresponders (471 vs 207 neoantigens respectively; p=1x10-6, Wilcoxon). This relationship maintained significance when neoantigens were limited to Kd≤100 nM or ≤50 nM, and when chemoresponse was defined as ypT0-only, or ≤ypT1. ERCC2 loss-of-function mutations were 36% sensitive in identifying chemoresponders but 96% specific. Above-median neoantigen burden was 81% sensitive in identifying chemoresponders and 78% specific. CD8+ cells were enriched in responders (13.5% vs 8.4% of infiltrate; p&amp;lt;0.008, t-test) as were activated NK cells (15.5% vs 12.7%; p=0.05). In 28 samples where WES and CIBERSORT data was available, the neoantigen burden was correlated to the CD8+ infiltrate value (R2=0.33, Pearson). Conclusions: Neoantigen burden and CD8+ infiltrate correlate strongly with chemoresponse. Neoantigen burden and CD8+ infiltrate are directly proportional. NAC may therefore exert known tumor cell autonomous effects and an extrinsic effect involving the immune system via neoantigens. Anti-neoantigen responses have been shown to impact immune checkpoint responses and a similar mechanism may mediate cytotoxic chemoresponse. Experiments are underway to directly and functionally characterize the effect of the immune system in chemoresponse. Citation Format: Philip H. Abbosh, David Liu, Woonyoung Choi, Wafik S. El-Deiry, Jonathan E. Rosenberg, David McConkey, Elizabeth R. Plimack, Eliezer M. Van Allen. Immune correlates of pathologic response in bladder cancer patients undergoing neoadjuvant chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3979. doi:10.1158/1538-7445.AM2017-3979

Prognostic effect of transarterial chemoembolization-induced complete pathological response in patients undergoing liver resection and transplantation for hepatocellular carcinoma.

Transarterial chemoembolization (TACE)-induced complete pathological response (CPR) is known to improve postresection outcomes of hepatocellular carcinoma (HCC). We aimed to assess the prognostic effects of CPR after preoperative TACE for HCC in patients who underwent hepatic resection (HR) or liver transplantation (LT). The clinical outcomes of patients showing CPR after HR (n = 110) or LT (n = 233) were analyzed. The control groups comprised patients with minimal recurrence risk as naïve single HCC ≤ 2 cm for HR (n = 476), and 1 or 2 HCCs ≤ 2 cm for LT (n = 184). Among HR study patients, 1-, 3-, and 5-year tumor recurrence rates were 18.5%, 50.6%, and 58.7% respectively, which were higher than those of controls (P < 0.001). The 1-, 3-, and 5-year patient survival rates were 97.8%, 82.0%, and 69.1%, respectively, which were lower than those of controls (P < 0.001). Among LT study patients, 1-, 3-, and 5-year tumor recurrence rates were 4.1%, 7.9%, and 7.9%, respectively, which were higher than those of controls (P = 0.019). The 1-, 3-, and 5-year patient survival rates were 92.7%, 89.2%, and 86.9%, respectively, which were not different than those of controls (P = 0.11). LT recipients had lower recurrence and higher survival rates compared with HR patients (P < 0.001). The tumor recurrence site was mainly intrahepatic in HR patients. There was no difference between the incidences of extrahepatic recurrence in the HR study group and all-site recurrence in the LT study group (P = 0.61). We concluded that the prognostic effect of TACE-induced CPR for HCC patients appears to be limited to downstaging. LT recipients benefited more from CPR than HR patients. Liver Transplantation 23 781-790 2017 AASLD.

A phase II study of atezolizumab as neoadjuvant and adjuvant therapy in patients (pts) with resectable non-small cell lung cancer (NSCLC).

TPS8580 Background: Trials of neoadjuvant and adjuvant chemotherapy have demonstrated an absolute survival benefit of 5% for patients with early stage disease. Atezolizumab is a humanized IgG1 monoclonal antibody that inhibits PD-L1 from binding to its receptors PD-1 and B7.1, thereby restoring anti-tumor immune response. In the OAK trial, a randomized phase III trial of patients with metastatic NSCLC who progressed on platinum based chemotherapy, atezolizumab improved overall survival in patients regardless of PD-L1 expression compared with docetaxel (13.8 months vs. 9.6 months, HR 0.73 [95% CI 0.62 – 0.87]) with a manageable safety profile. Methods: NCT02927301 is a phase II, open-label, single-arm study designed to evaluate the efficacy and safety of atezolizumab as a neoadjuvant and adjuvant therapy in patients with Stage IB, II, or IIIA NSCLC prior to curative-intent resection. Approximately 180 patients with NSCLC will be enrolled in this study at 15 academic medical centers in the United States. The study has two parts: the primary part will evaluate the ability of neoadjuvant atezolizumab to produce pathologic responses in patients with early stage NSCLC. Atezolizumab 1200 mg IV will be given every 3 weeks for two doses. Surgical resection of tumors following treatment will allow determination of pathologic response rates and potential predictive biomarkers. Part 2 is exploratory and will evaluate atezolizumab adjuvant therapy for up to 12 months in patients who demonstrate clinical benefit in Part 1. The primary endpoint is major pathologic response rate (defined as ≤ 10% of viable tumor tissue) based on surgical resection. Secondary end points include overall response rate by status of mutation load, neoantigen score and gene expression signatures. OS and DFS are exploratory end points. This trial presents a unique opportunity to evaluate exploratory biomarkers given the availability of pre- and post-treatment biopsy specimens for assessment of evolution of immune related markers associated with response. The study opened to accrual in January 2017. Clinical trial information: NCT02927301.

Contrast media enhancement reduction predicts tumor response to presurgical molecular-targeting therapy in patients with advanced renal cell carcinoma.

Background and ObjectiveA quantitative tumor response evaluation to molecular-targeting agents in advanced renal cell carcinoma (RCC) is debatable. We aimed to evaluate the relationship between radiologic tumor response and pathological response in patients with advanced RCC who underwent presurgical therapy.ResultsOf 34 patients, 31 underwent scheduled radical nephrectomy. Presurgical therapy agents included axitinib (n = 26), everolimus (n = 3), sunitinib (n = 1), and axitinib followed by temsirolimus (n = 1). The major presurgical treatment-related adverse event was grade 2 or 3 hypertension (44%). The median radiologic tumor response by RECIST, Choi, and CMER were −19%, −24%, and −49%, respectively. Among the radiologic tumor response tests, CMER showed a higher association with tumor necrosis in surgical specimens than others. Ki67/MIB1 status was significantly decreased in surgical specimens than in biopsy specimens. The magnitude of the slope of the regression line associated with the tumor necrosis percentage was greater in CMER than in Choi and RECIST.Materials and MethodsBetween March 2012 and December 2016, we prospectively enrolled 34 locally advanced and/or metastatic RCC who underwent presurgical molecular-targeting therapy followed by radical nephrectomy. Primary endpoint was comparison of radiologic tumor response among Response Evaluation Criteria in Solid Tumors (RECIST), Choi, and contrast media enhancement reduction (CMER). Secondary endpoint included pathological downstaging, treatment related adverse events, postoperative complications, Ki67/MIB1 status, and tumor necrosis.ConclusionsCMER may predict tumor response after presurgical molecular-targeting therapy. Larger prospective studies are needed to develop an optimal tumor response evaluation for molecular-targeting therapy.

MP88-11 IMMUNE CORRELATES OF PATHOLOGIC RESPONSE IN BLADDER CANCER PATIENTS UNDERGOING NEOADJUVANT CHEMOTHERAPY

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology IV1 Apr 2017MP88-11 IMMUNE CORRELATES OF PATHOLOGIC RESPONSE IN BLADDER CANCER PATIENTS UNDERGOING NEOADJUVANT CHEMOTHERAPY Philip Abbosh, David Liu, Woonyoung Choid, Wafik El-Deiry, Jonathan Rosenberg, David McConkey, Elizabeth Plimack, and Eliezer Van Allen Philip AbboshPhilip Abbosh More articles by this author , David LiuDavid Liu More articles by this author , Woonyoung ChoidWoonyoung Choid More articles by this author , Wafik El-DeiryWafik El-Deiry More articles by this author , Jonathan RosenbergJonathan Rosenberg More articles by this author , David McConkeyDavid McConkey More articles by this author , Elizabeth PlimackElizabeth Plimack More articles by this author , and Eliezer Van AllenEliezer Van Allen More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2736AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The immune system is increasingly recognized as both a key player in cancer control and as druggable target. We hypothesized that the immune system impacts pathologic response in patients undergoing cisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer though the immune system. METHODS Whole exome sequencing (WES) was performed on tumor DNA from patients in two independent cohorts who underwent cisplatin-based NAC. The Memorial Sloan Kettering / Dana Farber Cancer Institute (n=50; 25 responders) and Philadelphia (n=48; 20 responders) cohorts were treated with gemcitabine / cisplatin or methotrexate / vinblastine / doxorubicin / cisplatin. Mutation analysis was performed using standard analytical pipelines. Macrohistocompatibility complex (MHC)-restricted neoantigens were identified with netMHCpan and PolySolver. High affinity neoantigens were defined to have ≤500 nM binding affinity (Kd). Pathologic response was defined as ≤ypTis cystectomy specimen. CIBERSORT was used to infer immune cell infiltrate based on DASL Illumina microarray expression profiles (n=41; 17 responders). RESULTS Chemoresponders had >twice as many putative neoantigens as nonresponders (471 vs 207 neoantigens respectively; p=1x10-6, Wilcoxon). This relationship maintained significance when neoantigens were limited to Kd≤100 nM or ≤50 nM, and when chemoresponse was defined as ypT0-only, or ≤ypT1. ERCC2 loss-of-function mutations were 36% sensitive in identifying chemoresponders but 96% specific. Above-median neoantigen burden was 81% sensitive in identifying chemoresponders and 78% specific. CD8+ cells were enriched in responders (13.5% vs 8.4% of infiltrate; p<0.008, t-test) as were activated NK cells (15.5% vs 12.7%; p=0.05). In 28 samples where WES and CIBERSORT data was available, the neoantigen burden was correlated to the CD8+ infiltrate value (R2=0.33, Pearson). CONCLUSIONS Neoantigen burden and CD8+ infiltrate correlate strongly with chemoresponse. Neoantigen burden and CD8+ infiltrate are directly proportional. NAC may therefore exert known tumor cell autonomous effects and an extrinsic effect involving the immune system via neoantigens. Anti-neoantigen responses have been shown to impact immune checkpoint responses and a similar mechanism may mediate cytotoxic chemoresponse. Experiments are underway to directly and functionally characterize the effect of the immune system in chemoresponse. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1178 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Philip Abbosh More articles by this author David Liu More articles by this author Woonyoung Choid More articles by this author Wafik El-Deiry More articles by this author Jonathan Rosenberg More articles by this author David McConkey More articles by this author Elizabeth Plimack More articles by this author Eliezer Van Allen More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Abstract P3-02-11: Clinical examination and breast MRI as predictors of pathologic complete response post neoadjuvant therapy in HER2 overexpressed subtypes and triple negative breast cancer

Abstract Background: Preoperative identification of pathologic complete response (pCR) is important to decrease surgical morbity. The objective of this study was to determine diagnostic validity of clinical examination and magnetic resonance imaging (MRI) in determining pathologic response in patients with breast cancer subtypes HER 2 overexpressed and triple negative after neoadjuvant therapy. Methods: This is a cross- sectional study, with a sample comprising 72 patients woman with HER-2 overexpressed or triple negative breast submitted to neoadjuvant treatment at Hospital Sirio Libanês between January 2005 and December 2012. All patients were clinically evaluated by a group of seven breast surgeons. Double reading of breast MRI was performed in three periods: at the beginning of treatment, after the second cycle of chemotherapy and after treatment. Photographic record of the breast was done before and after chemotherapy. HER-2 and hormone receptors were assessed using immunohistochemistry. Sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (VNP) were estimated using pathology as the gold standard. Area under ROC curve and the corresponding 95% confidence intervals (95% CI) were calculated. Results: Thirty- two patients (44,4%) had triple negative tumors while 40 (55.6%) overexpressed HER-2. Among those with triple negative tumors, clinical examination evidenced a completed response in 31.2% (10/32) of the cases. pCR was observed in 3 patients (9.4%). Diagnostic validity measures for clinical examination were: Se= 100%, Sp=75.9%, PPV=42.9% and NPV=100%. In this group, MRI detected a complete response in 7 cases (21.9%). Therefore, MRI presented a Se=66.8%, Sp=82.8%, PPV 28.6% and NPV= 96%. Area under ROC curve was 0.88 (95% CI 0.80-0.96) and 0.75 (95% ci 0.41-1.00) for clinical examination and MRI, respectively. Among woman with tumors over expressing HER-2, complete response was observed through clinical examination in 45% (18/40) of these cases, showing Se= 100%, Sp=71%, PPV=100% and NPV=70,9%. In this group, complete radiological response was noted in 8 cases (20%). Therefor, MRI had Se=33.3%, Sp=83.9%, PPV 37.5% and NPV=96%. Area under ROC curve was 0.85 (95% CI 0.77-0.94) and 0.59 (95% CI 0.41-0.76) for clinical examination and MRI, respectively. Conclusions: Our findings demonstrate that clinical examination is superior to MRI to predict pCR for woman wth tumor overexpressing HER-2, while for tumor patients with triple negative tumors the two methods were equivalent. Therefore, clinical examination can be used with MRI to monitor tumor response to neoadjuvant chemotherapy and also to determine the best course of surgical action. Monitoring and assessment, however, are better when both methods are associates. Citation Format: Andrade FEM, De Barros ACS, Docema MF, Heinzen RN, De Andrade JZ, Nimir C, Mano MDS, Gianotti D, Ribeiro KDCB. Clinical examination and breast MRI as predictors of pathologic complete response post neoadjuvant therapy in HER2 overexpressed subtypes and triple negative breast cancer [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 P3-02-11.

Does radiologic response correlate to pathologic response in patients undergoing neoadjuvant therapy for borderline resectable pancreatic malignancy?

In patients with borderline resectable pancreas cancers, clinicians frequently consider radiographic response as the primary driver of whether patients should be offered surgical intervention following neoadjuvant therapy (NT). We sought to determine any correlation between radiographic and pathologic response rates following NT. Between 2005 and 2015, 38 patients at a tertiary care referral center underwent NT followed by pancreaticoduodenectomy for borderline resectable pancreas cancer. Radiographic response after the completion of NT and pathologic response after surgery were graded according to RECIST and Evans' criteria, respectively. Preoperatively, 50% of patients underwent chemotherapy alone and 50% underwent chemotherapy and chemoradiation. Radiographically, one patient demonstrated a complete radiologic response, 68.4% (n = 26) of patients had stable disease (SD), 26.3% (n = 10) demonstrated a partial response, and one patient had progressive. Among patients without radiographic response, 77.7% (n = 21) achieved a R0 resection. Of patients with SD on imaging, 26.9% (n = 7) had Evans grade IIB or greater pathologic response. Our data indicate that approximately one-fourth of patients who did not have a radiologic response had a grade IIB or greater pathologic response. In the absence of metastatic progression, lack of radiographic down-staging following NT should not preclude surgery.

Sequential PET/CT with [18F]-FDG Predicts Pathological Tumor Response to Preoperative Short Course Radiotherapy with Delayed Surgery in Patients with Locally Advanced Rectal Cancer Using Logistic Regression Analysis.

Previous studies indicate that FDG PET/CT may predict pathological response in patients undergoing neoadjuvant chemo-radiotherapy for locally advanced rectal cancer (LARC). Aim of the current study is evaluate if pathological response can be similarly predicted in LARC patients after short course radiation therapy alone. Methods: Thirty-three patients with cT2-3, N0-2, M0 rectal adenocarcinoma treated with hypo fractionated short course neoadjuvant RT (5x5 Gy) with delayed surgery (SCRTDS) were prospectively studied. All patients underwent 3 PET/CT studies at baseline, 10 days from RT end (early), and 53 days from RT end (delayed). Maximal standardized uptake value (SUVmax), mean standardized uptake value (SUVmean) and total lesion glycolysis (TLG) of the primary tumor were measured and recorded at each PET/CT study. We use logistic regression analysis to aggregate different measures of metabolic response to predict the pathological response in the course of SCRTDS. Results: We provide straightforward formulas to classify response and estimate the probability of being a major responder (TRG1-2) or a complete responder (TRG1) for each individual. The formulas are based on the level of TLG at the early PET and on the overall proportional reduction of TLG between baseline and delayed PET studies. Conclusions: This study demonstrates that in the course of SCRTDS it is possible to estimate the probabilities of pathological tumor responses on the basis of PET/CT with FDG. Our formulas make it possible to assess the risks associated to LARC borne by a patient in the course of SCRTDS. These risk assessments can be balanced against other health risks associated with further treatments and can therefore be used to make informed therapy adjustments during SCRTDS.