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The treatment of lung cancer is one of the major challenges in the field of oncology. According to statistics from the National Cancer Center of China in 2015, lung cancer has the highest incidence and mortality, with 733,300 new cases and 610,200 deaths across the country (1). About 85% of lung cancers are non-small cell lung cancer (NSCLC), of which 30% to 40% are considered resectable tumors, including most stage I-II and a small portion of stage IIIA tumors (2). Very early-stage NSCLC (IA) can be cured by surgery. However, more than 50% of NSCLC patients who undergo surgical treatment will relapse or metastasize within 5 years. Even if there is no lymph node metastasis and the primary

Soft tissue sarcomas (STS) represent a broad family of rare tumours for which surgery with radiotherapy represents first-line treatment. Recently, neoadjuvant chemo-radiotherapy has been increasingly used in high-risk patients in an effort to reduce surgical morbidity and improve clinical outcomes. An adequate understanding of the efficacy of neoadjuvant therapies would optimise patient care, allowing a tailored approach. Although response evaluation criteria in solid tumours (RECIST) is the most common imaging method to assess tumour response, Choi criteria and functional and molecular imaging (DWI, DCE-MRI and 18F-FDG-PET) seem to outperform it in the discrimination between responders and non-responders. Moreover, the radiologic-pathology correlation of treatment-related changes remains poorly understood. In this review, we provide an overview of the imaging assessment of tumour response in STS undergoing neoadjuvant treatment, including conventional imaging (CT, MRI, PET) and advanced imaging analysis. Future directions will be presented to shed light on potential advances in pre-surgical imaging assessments that have clinical implications for sarcoma patients.

Soft tissue sarcomas (STS) represent a broad family of rare tumours for which surgery with radiotherapy represents first-line treatment. Recently, neoadjuvant chemo-radiotherapy has been increasingly used in high-risk patients in an effort to reduce surgical morbidity and improve clinical outcomes. An adequate understanding of the efficacy of neoadjuvant therapies would optimise patient care, allowing a tailored approach. Although response evaluation criteria in solid tumours (RECIST) is the most common imaging method to assess tumour response, Choi criteria and functional and molecular imaging (DWI, DCE-MRI and 18F-FDG-PET) seem to outperform it in the discrimination between responders and non-responders. Moreover, the radiologic-pathology correlation of treatment-related changes remains poorly understood. In this review, we provide an overview of the imaging assessment of tumour response in STS undergoing neoadjuvant treatment, including conventional imaging (CT, MRI, PET) and advanced imaging analysis. Future directions will be presented to shed light on potential advances in pre-surgical imaging assessments that have clinical implications for sarcoma patients.

Background The benefit of chemotherapy (NAC) for patients with ER/PR positive, HER2 negative breast cancer is unclear. Our aim was to determine factors associated with histopathologic response and oncologic outcome following NAC in this group. Methods Consecutive female patients undergoing neoadjuvant therapy and surgery for locally advanced Luminal A breast cancer between 2010 and 2015 were studied. Multivariable linear, logistic, and Cox regression analysis was undertaken. Results 114 patients were studied. Pathological complete response (pCR) was achieved in 7.9% of patients, ypN0 in 25.5%, and downstaging in 33.6%. However, 43.9% exhibited a Sataloff C-D response. Tumor grade independently predicted pCR (P = 0.039), while PR score predicted ypN0 (P = 0.017) and downstaging (P=0.029). 5-year invasive disease-free (iDFS) and overall survival (OS) were 68.5 ± 4.7% and 77.7 ± 4.3%, respectively. Conclusion After NAC for Luminal A breast cancer, pCR rates are low. Patients with high grade tumors with weak PR expression exhibit the most promising response rates.

The management of oncological malignancies has significantly improved over the last decades. In modern medicine, new concepts and trends have emerged paving the way for the era of personalized and evidence-based strategies adapted to the patients’ prognostic variables and requirements. Several challenges do exist that are encountered during the management, including the difficulty to assess chemotherapy response with certainty. Having known that neoadjuvant chemotherapy might be the only solution for a proportion of patients with tumors that are unresectable at diagnosis, emergence of strategies that use risk group-directed therapy became an integral part in the management of oncological malignancies. Tumor histopathological change post neoadjuvant chemotherapy is one of the most important predictors of management outcome and is being used in many chemotherapy protocols as an essential determinant of the most suitable postoperative chemotherapy regimen. Bone tumors are the classic models of this approach; however, other childhood solid tumors show significant variations in outcome as a result of tumor histopathological response to neoadjuvant chemotherapy. The aim of this review is therefore to summarize the significance of histopathological responses seen after neoadjuvant chemotherapy in childhood solid tumors. Moreover, it suggests that the effect on tumor histopathology through modifying neoadjuvant chemotherapy and, on the other hand, toxicities from intensifying adjuvant chemotherapy might either necessitate the change of a number of arm groups in different protocol regimens or include newer chemotherapeutic agents adjuvantly for better outcome and lesser toxicities in poor tumor histopathological responders.

The aim of this prospective pilot study was to investigate the potential of serial FLT-PET/CT compared to FDG-PET/CT to provide an early indication of esophageal cancer response to concurrent neoadjuvant chemoradiation therapy. Five patients with biopsy-proven esophageal adenocarcinomas underwent neoadjuvant chemoradiation (Tx) prior to minimally invasive esophagectomy. The presence of residual tumor was classified histologically using the Mandard et al. criteria, categorizing patients as pathologic responders and non-responders. Participants underwent PET/CT imaging 1 h after intravenous administration of FDG and of FLT on two separate days within 48 h of each other. Each patient underwent a total of 3 scan “pairs”: (1) pre-treatment, (2) during treatment, and (3) post-treatment. Image-based response to therapy was measured in terms of changes in SUVmax (ΔSUV) between pre- and post-therapeutic FLT- and FDG-PET scans. The PET imaging findings were correlated with the pathology results after surgery. All tumors were FDG and FLT avid at baseline. Lesion FLT uptake was lower than with FDG. Neoadjuvant chemoradiation resulted in a reduction of tumor uptake of both radiotracers in pathological responders (n = 3) and non-responders (n = 2). While the difference in the reduction in mean tumor FLT uptake during Tx between responders (ΔSUV = − 55%) and non-responders (ΔSUV = − 29%) was significant (P = 0.007), for FDG it was not, [responders had a mean ΔSUV = − 39 vs. − 31% for non-responders (P = 0.74)]. The difference in the reduction in tumor FLT uptake at the end of treatment between responders (ΔSUV = − 62%) and non-responders (ΔSUV = − 57%) was not significant (P = 0.54), while for FDG there was a trend toward significance [ΔSUV of responders = − 74 vs. − 52% in non-responders (P = 0.06)]. The results of this prospective pilot study suggest that early changes in tumor FLT uptake may be better than FDG in predicting response of esophageal adenocarcinomas to neoadjuvant chemoradiation. These preliminary results support the need to corroborate the value of FLT-PET/CT in a larger cohort.

e17539 Background: Neoadjuvant chemotherapy (NACT) with interval debulking surgery is considered for patients with advanced-stage ovarian carcinoma (OC) who are not ideal candidates for primary debulking surgery due to advanced age, frailty, poor performance status, comorbidities, or who have disease unlikely to be optimally resected. Moreover, response to NACT may be a suitable surrogate end point for long-term clinical outcome in ovarian cancer. The aim of the present study is to evaluate the utility of a three-tier Chemotherapy Response Score (CRS) and validate whether residual disease or evidence of regression following NACT may provide prognostic information in ovarian cancer. Methods: We conducted a retrospective single-institution study of patients who received NACT with carboplatin and paclitaxel for FIGO stage III/IV ovarian cancer. Response to NACT was graded as no or minimal tumor response (CRS1); appreciable tumor response amid readily identifiable viable tumor (CRS2); or complete/near-complete response with no residual tumor or minimal scattered tumor foci (CRS3) as described previously (Böhm S, et al. J Clin Oncol 33:2457-2463). Multivariate progression free survival (PFS) and overall survival (OS) analyses were performed accounting for age, FIGO stage and BRCA status. Results: Of the 86 patients accrued to date, median age was 65 years, 62% had stage IV disease and 16% had a somatic/germline BRCA mutation. CRS scores 1, 2 and 3 were found in 26 (30%), 43 (50%) and 17 (20%) of cases, respectively, and were associated with PFS (log rank p = 0.002). A high CRS score predicted improved PFS and OS (CRS 2/3 vs 1; median PFS 17.3 vs. 11.8 mo, adjusted hazard ratio (HR), 0.33; 95%CI 0.17-0.62; p < 0.001; median OS 47.9 vs. 38.3 mo, adjusted HR 0.36, 95%CI 0.15-0.88, p = 0.026). Similarly, when comparing CRS 3 with 1/2, the high score predicted improved outcome for PFS but not OS (median PFS 17.3 vs. 14.7 mo, adjusted HR, 0.42; 95%CI 0.19-0.95; p = 0.037; median OS 48.6 vs. 46.5 mo, adjusted HR 0.43, 95%CI 0.14-1.35, p = 0.149). Conclusions: In this study, we validate a simple three-tier chemotherapy response scoring system for assessing histopathologic response of OC to NACT. Residual disease and evidence of complete/near complete regression following NACT provides prognostic information in OC. CRS may serve as a potential surrogate marker for long-term outcome and be a useful alternative intermediate end point in future clinical trials.

Assessment of tumor response after chemotherapy using (18)F-FDG PET metrics is gaining acceptance. Several studies have suggested that the parameters metabolically active tumor volume (MTV) and total lesion glycolysis (TLG) are superior to SUVmax for measuring tumor burden. However, the measurement of MTV and TLG is still controversial; the most common method uses an absolute threshold of 42% of SUVmax Recently, we implemented a background-adaptive method to determine the background-subtracted lesion activity (BSL) and the background-subtracted volume (BSV). In this study, we investigated the correlation between such PET metrics and histopathologic response in non-small cell lung carcinoma (NSCLC).Forty-four NSCLC patients were retrospectively identified. Their PET/CT data on both types of scan before and after neoadjuvant chemotherapy were analyzed regarding SUVmax, MTV, TLG, BSL, and BSV, as well as the relative changes in these parameters. The tumor regression score as an indicator of histopathologic response was scored on hematoxylin- and eosin-stained sections of the surgical specimens using a 4-tiered scale (scores 1-4). The correlation between score and the absolute and relative PET metrics after chemotherapy was analyzed using Spearman rank correlation tests.Tumors that demonstrated a good response after neoadjuvant chemotherapy had significantly lower (18)F-FDG activity than nonresponding tumors (scores 3 and 4: SUVmax, 4.2 [range, 1.8-7.9] vs. scores 1 and 2: SUVmax, 8.1 [range, 1.4-40.4]; P = 0.001). The same was found for change in SUVmax and score (P = 0.001). PET volume metrics based on a 42% fixed threshold for SUVmax did not correlate with score (TLG, P = 0.505; MTV, P = 0.386). However, both of the background activity-based PET volume metrics-BSL and BSV-significantly correlated with score (P0.001 each).PET volume metrics based on background-adaptive methods correlate better with histopathologic tumor regression score in NSCLC patients under neoadjuvant chemotherapy than algorithms and methods using a fixed threshold (42% SUVmax).

The present investigation evidences the analysis of the compatibility of the dental tissue with the biomaterial and the consequent infections; Developing a technical procedure of valuation of these at statistical and laboratory level. The scientific problem that was considered was: What are the in - vivo differences in the histopathological response and antibacterial effect of dental materials: resin vs amalgam in the cavity preparations of Canis familiaris from the Faculty of Veterinary Medicine - Pedro National University Ruiz Gallo - Lambayeque, 2015? Presenting as hypothesis: The in - vivo difference of histopathological response and antibacterial effect of dental materials: resin vs amalgam is statistically significant in the molar cavity preparations of Canis familiaris, which was tangible in the control and experiment groups, taking as sample selected teeth from the canines. Regarding the compatibility of the biomaterial with the dental tissue, it was observed at 90 days that the bone resorption is of the active type and a greater neoformation is achieved, achieving some integration in both. There were histological changes at the apical, periodontal and bone tissue levels: when comparing experimental groups based on teeth at 30 and 60 days, there were no significant differences between the inflammatory processes (acute and chronic) in the studied groups, however It should be noted that at 90 days it was found that there are already inflammatory patterns in response to the adhesive systems applied in the cavity preparations of Canis familiaris (resin vs. amalgam) molars presenting a chronic inflammation in 100% of amalgam treated dental pieces And 25% for resin treated dental pieces; And in the case of superinfections these were not evidenced assuming an equivalent antibacterial effect for both substances. La presente investigación evidencia el análisis de la compatibilidad del tejido dental con el biomaterial y las infecciones devinientes; desarrollando un procedimiento técnico de valoración de estos a nivel estadístico y de laboratorio. El problema científico que se consideró fue: ¿Cuáles la diferencia in – vivo de la respuesta histopatológica y del efecto antibacteriano de los materiales dentales: resina vs amalgama en las preparaciones cavitarias de molares de Canis familiaris de la Facultad de Medicina Veterinaria –Universidad Nacional Pedro Ruiz Gallo - Lambayeque, 2015? Presentando como hipótesis: La diferencia in – vivo de la respuesta histopatológica y del efecto antibacteriano de los materiales dentales: resina vs amalgama es significativa estadísticamente en las preparaciones cavitarias de molares de Canis familiaris, lo cual fue tangible en los grupos testigo y experimento, tomando como muestra dientes seleccionados de los caninos. En cuanto a la compatibilidad del biomaterial con el tejido dental se observó a los 90 días, que la reabsorción ósea es de tipo activo y se presenta una mayor neoformación logrando cierta integración en ambos. Hubieron cambios histológicos a nivel del tejido apical, periodontal y óseo: al comparar los grupos de experimentación basados en piezas dentarias a los 30 y 60 días no se presentaron diferencias significativas entre los procesos inflamatorios (agudo y crónico) en los grupos estudiados, sin embargo se debe señalar que a los 90 días se encontró que ya existen patrones inflamatorios como respuesta a los sistemas adhesivos aplicados en las preparaciones cavitarias de molares de Canis familiaris (resina vs amalgama) presentando una inflamación crónica en un 100% de piezas dentales tratadas con amalgama y un 25% para piezas dentales tratadas con resina; y en el caso de sobreinfecciones estas no se evidenciaron asumiendo un efecto antibacteriano equivalente para ambas sustancias.

PURPOSE: In the current study we examined the ability of diffusion MRI (dMRI) to predict pathologic response in pancreatic cancer patients receiving neoadjuvant chemoradiation. METHODS: We performed a prospective pilot study of dMRI in patients with resectable pancreatic cancer. Patients underwent dMRI prior to neoadjuvant chemoradiation. Surgical specimens were graded according to the percent tumor cell destruction. Apparent diffusion coefficient (ADC) maps were used to generate whole-tumor derived ADC histogram distributions and mean ADC values. The primary objective of the study was to correlate ADC parameters with pathologic and CT response. RESULTS: Ten of the 12 patients enrolled on the study completed chemoradiation and had surgery. Three were found to be unresectable at the time of surgery and no specimen was obtained. Out of the 7 patients who underwent pancreaticoduodenectomy, 3 had a grade III histopathologic response (> 90% tumor cell destruction), 2 had a grade IIB response (51% to 90% tumor cell destruction), 1 had a grade IIA response (11% to 50% tumor cell destruction), and 1 had a grade I response (> 90% viable tumor). Median survival for patients with a grade III response, grade I-II response, and unresectable disease were 25.6, 18.7, and 6.1 months, respectively. There was a significant correlation between pre-treatment mean tumor ADC values and the amount of tumor cell destruction after chemoradiation with a Pearson correlation coefficient of 0.94 (P = .001). Mean pre-treatment ADC was 161 × 10− 5 mm2/s (n = 3) in responding patients (> 90% tumor cell destruction) compared to 125 × 10− 5 mm2/s (n = 4) in non-responding patients (> 10% viable tumor). CT imaging showed no significant change in tumor size in responders or non-responders. CONCLUSIONS: dMRI may be useful to predict response to chemoradiation in pancreatic cancer. In our study, tumors with a low ADC mean value at baseline responded poorly to standard chemoradiation and would be candidates for intensified therapy.

Introduction This study's objectives were to determine whether tumor response measured by computed tomography (CT) and evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) correlated with overall survival (OS) in patients with non–small-cell lung cancer (NSCLC) after neoadjuvant chemotherapy and surgical resection. Methods We measured primary tumor size on CT before and after neoadjuvant chemotherapy in 160 NSCLC patients who underwent surgical resection. The relationship between CT-measured response (RECIST) and histopathologic response (⩽ 10% viable tumor) and OS were assessed by Kaplan-Meier survival, univariable, and multivariable Cox proportional hazards regression. Results There was a statistically significant association between CT-measured response (RECIST) and OS ( p = 0.03). However, histopathologic response was a stronger predictor of OS ( p = 0.002), with a more pronounced separation of the survival curves when compared with CT-measured response. In multivariable Cox regression analysis, only pathologic stage and histopathologic response were significant predictors of OS. A 41% overall discordance rate was noted between CT RECIST response and histopathologic response. CT RECIST classified as nonresponders a subset of patients with histopathologic response (8 out of 30 points, 27%) who demonstrated prolonged survival after neoadjuvant chemotherapy. Conclusion We were unable to show that CT RECIST is a reliable predictor of OS in patients with NSCLC undergoing surgical resection after neoadjuvant chemotherapy. The failure of CT RECIST to predict long-term outcome may be because of the inability of CT imaging to consistently identify patients with histopathologic response. CT RECIST may have only a limited role as an efficacy endpoint after neoadjuvant chemotherapy in patients with resectable NSCLC.

Purpose This study evaluated the usefulness of the maximum standardized uptake value (SUVmax) as a measure of histologic response to neoadjuvant chemotherapy in patients with extremity osteosarcoma. The correlation between [18 F]FDG PET SUVmax values and histologic response to preoperative chemotherapy was also assessed prospectively using PET/MRI.

Background: Lymphocytic-plasmacytic enteritis (LPE) is a common cause of chronic vomiting and diarrhea in dogs. However, little information is available about endoscopic or histopathologic improvement after therapy in dogs with LPE. Hypothesis: The objective was to study the clinical, endoscopic, and histopathologic evolution of LPE during and after immunosuppressive treatment with prednisone and metronidazole. Most dogs also were treated symptomatically with metoclopramide and cimetidine. Animals: Sixteen dogs with LPE and normal serum protein concentrations diagnosed at the Veterinary Medical Teaching Hospital of the Complutense University of Madrid were monitored during and after drug treatment. The control group consisted of 9 dogs that had no gastrointestinal signs for the preceding 12 months. Methods: In this prospective clinical treatment trial, clinical, endoscopic, and histopathologic scores were evaluated to describe disease evolution during conventional therapy. Dogs with LPE were monitored for 120 days from the start of treatment. Re-evaluation was performed on post-treatment days 30, 60, 90 (end of treatment), and 120. Results: The average disease activity index observed in our study fell progressively from its initial value, and the decrease between consecutive re-evaluations was statistically significant until day 60 (P= .04). Our results indicate that 75% of the animals revealed improvement of endoscopic gastric lesions (defined as a reduction of the endoscopic score) after treatment, and 75% exhibited improvement of endoscopic duodenal lesions. Statistical analysis of the data revealed significant differences between pre- and post-treatment gastric and duodenal macroscopic endoscopic lesions (P < .05). On the other hand, treatment did not lead to any significant changes in the severity of the gastric and duodenal histopathologic lesions of the affected dogs. Conclusions and Clinical Importance: Treatment of nonhypoproteinemic dogs with LPE led to clinical and endoscopic improvement, but histopathologic lesions were unchanged during therapy.

Objective: To investigate prognostic impact of histopathologic response induced by neoadjuvant chemotherapy in patients with stage IIIA non-small cell lung cancer (NSCLC). Methods: Forty patients with stage IIIA NSCLC underwent two cycles of neoadjuvant chemotherapy with mitomycin, vindosine, and cisplatin followed by surgery. Histopathologic response in resection of the tumor was examined after surgery. Tumor regression was classified as grade IV, grade III, grade II, and grade I according to the extent of tumor necrosis and the extent of the vital tumor tissues. The tumor regression grading was correlated with the survival time of the patients. Results: After two cycles of chemotherapy, 19 (47.5%) of 40 patients had objective response (2 complete and 17 partial response). In 40 resected tumor specimens, 2 (5%) were classified as regression grade IV, 16 (40%) as regression grade III, 18 (45%) as regression grade II, and 4 (10%) as regression grade I. The rate of complete surgical resection was significantly higher in patients with tumor regression grade III-IV (

[(18)F]fluorodeoxyglucose positron emission tomography (FDG PET) is used to evaluate the metabolic activity of intermediate- to high-grade soft tissue sarcomas prior to the initiation of chemotherapy. FDG PET and MRI are repeated after chemotherapy to assess treatment response and to correlate this with the histologic response. This case report highlights discrepant results between the final histologic diagnosis (tumor response) and the percent change in maximum standard uptake variable (SUV(max)). Further investigation of the resected specimen identified the significant difference in tumor response assessment to be due to the heterogeneity of the tumor and heterogeneity in its response to treatment. FDG PET imaging has an important role in evaluating tumor metabolic activity and has played an increasingly important part in evaluating the response to neoadjuvant chemotherapy in sarcomas. Evaluating the heterogeneity of the tumor at baseline and after response to therapy can provide insight into prognosis and treatment planning.

636 Background: The histopathological response to pre-operative chemotherapy is associated with clinical outcome in patients (pts) undergoing secondary resection of CRCLM. Three different histopathological growth patterns (HGPs) of CRCLM have been described: desmoplastic (i.e. with a capsule of stroma separating tumor and normal cells), pushing (i.e. with limited infiltration of normal hepatic plates by tumor cells) and replacement (i.e. with abundant infiltration of normal hepatic plates by tumor cells and vessel cooption). Methods: Histopathological parameters of response were evaluated in specimens from 159 pts who underwent secondary resection of CRCLM, after receiving triplet (FOLFOXIRI or COI) plus bev (N = 103) or anti-EGFR (N = 56) in 5 first-line clinical studies (TRIBE, MOMA, MACBETH, COI-B and COI-E). The aims of this analysis were to evaluate the prognostic role of histopathologic response and to investigate the prognostic role of HGPs and their potential different sensitivity to targeted agents. Results: When compared with partial (TRG 3) and no (TRG 4-5) pathologic response (N = 118), major response (TRG 1-2, N = 41) was associated with longer RFS (mRFS: 28.0 versus 11.0 mos, HR = 0.57, 95%CI = 0.39–0.86; p = 0.007) and OS (mOS: unreached versus 42.1 mos, HR = 0.54, 95%CI = 0.31-0.93; p = 0.027). No association of baseline clinical characteristics and RAS and BRAF status with major response was found. Major response was more frequent among pts treated with bev than with anti-EGFRs (OR = 2.83, 95%CI = 1.20–6.65; p = 0.015) and was associated with deepness of response as a continuous variable (HR = 1.02, 95% CI = 1.00–1.04; p = 0.011). In the desmoplastic HGP (N = 28) a higher percentage of major response was reported (57% vs 17% in pushing and 22% in replacement HGP, p < 0.001) and a numerical advantage from anti-EGFR vs bev was evident in terms of both major response and RFS. Conversely, in the pushing HGP (N = 66) a significant benefit from bev vs anti-EGFR in major response and RFS was observed. No difference was described in the replacement HGP (N = 65). Conclusions: The assessment of HGPs may be useful to predict benefit from available targeted agents.

11014 Background: Two large phase III studies have shown an improved overall survival in soft-tissue sarcoma (STS) pts treated with neoadjuvant chemotherapy. The prognostic impact of pathologic response is not known neither the clinical, radiological and genetic features associated with response. Methods: Data from pts with localized STS of the extremities or trunk wall and treated with anthracyline-based NAC at Institut Bergonie (Bordeaux, France) were reviewed. Central pathology (diagnosis, histological response) and radiology (MRI, DCE-MRI) reviews were performed for all the cases. A good histological response (GR) was defined as 20 cm). Median OSwas 10.3 year [IC95 : 5.8 ; 14.9]. On multivariate analysis, only GR (HR= 0.36, 95%CI 0.184-0.703, p=0.0028) and performance status (PS) (HR= 3.799, 95%CI 1.72-8.387, p=0.001 for PS=2-3) were prognostic factors for OS. Early DCE- MRI parameters (after 2 cycles of treatment) such as, area under the contrast concentration vs. time curve for 90 seconds after contrast injection ( IAUC90) were strongly associated with histological response (p=0.027) whereas RECIST 1.1 was not. Conclusions: As for bone sarcomas, histological response to NAC is a crucial prognostic factor in STS. Multiparametric MRI parameters obtained post-2nd cycle of NAC are predictive of histological response and should be considered to adjust the therapeutic strategy. Genetic features (including the CINSARC signature) associated with response to NAC will be presented at the meeting.

Introduction: The purpose of this study was to evaluate the clinical and histopathologic response of photoaged skin to a series of combined Jessner solution and 53% resorcinol paste chemical peels. Materials and Methods: Five women aged 40–53 years were treated with 5 peels at weekly intervals. The peels consisted of applying Jessner solution followed by the application of 53% resorcinol paste for 1 minute initially. This was increased according to the patient's tolerance. Pre-, intra-, and posttreatment clinical signs were tabulated. Skin biopsies were taken before treatment and again 3 days after the fifth peel. Results: Both the clinical and histopathologic signs of photoaging were improved by the peels. Side effects and negative sequelae were minimal, consisting of pruritus and desquamation. Discussion: The peels were well tolerated and resulted in improvement of aged skin. The clinical and histopathologic evaluations indicate that the peel process, performed as presented, results in biological changes in the deep papillary to upper reticular dermis.

The mouse ear inflammation model was used to establish simple endpoints of skin injury following cutaneous exposure to sulfur mustard (bis(2- chloroethyl)sulfide, HD). Mouse ear edema and histopathologic response to a single topical application of 5 muL of 8, 16, 32, 64, or 128 mg/mL HD in dichloromethane was evaluated at 12, 18, and 24 h postexposure. Edema response was determined from weighed 8 mm diameter skin punch biopsies taken from the center of exposed and control ears. Key light microscopic histopathologic changes assessed on the inner (exposed side) and outer surfaces (contralateral side) of the exposed ear included epidermal necrosis (EN) and epidermal-dermal separation (subepidermal blister, SEB). HD produced statistically significant (p

The aim of this study was to evaluate imaging-based response to standardized neoadjuvant chemotherapy (NACT) regimen by dynamic contrast-enhanced magnetic resonance mammography (DCE-MRM), whereas MR images were analyzed by an automatic computer-assisted diagnosis (CAD) system in comparison to visual evaluation. MRI findings were correlated with histopathologic response to NACT and also with the occurrence of metastases in a follow-up analysis.Fifty-four patients with invasive ductal breast carcinomas received two identical MRI examinations (before and after NACT; 1.5T, contrast medium gadoteric acid). Pre-therapeutic images were compared with post-therapeutic examinations by CAD and two blinded human observers, considering morphologic and dynamic MRI parameters as well as tumor size measurements. Imaging-assessed response to NACT was compared with histopathologically verified response. All clinical, histopathologic, and DCE-MRM parameters were correlated with the occurrence of distant metastases.Initial and post-initial dynamic parameters significantly changed between pre- and post-therapeutic DCE-MRM. Visually evaluated DCE-MRM revealed sensitivity of 85.7%, specificity of 91.7%, and diagnostic accuracy of 87.0% in evaluating the response to NACT compared to histopathology. CAD analysis led to more false-negative findings (37.0%) compared to visual evaluation (11.1%), resulting in sensitivity of 52.4%, specificity of 100.0%, and diagnostic accuracy of 63.0%. The following dynamic MRI parameters showed significant associations to occurring metastases: Post-initial curve type before NACT (entire lesions, calculated by CAD) and post-initial curve type of the most enhancing tumor parts after NACT (calculated by CAD and manually).In the accurate evaluation of response to neoadjuvant treatment, CAD systems can provide useful additional information due to the high specificity; however, they cannot replace visual imaging evaluation. Besides traditional prognostic factors, contrast medium-induced dynamic MRI parameters reveal significant associations to patient outcome, i.e. occurrence of distant metastases.

The purpose of this study was to use color Doppler flow imaging to predict the response to preoperative chemotherapy in patients with Ewing's sarcoma or high-grade osteosarcomas early in treatment.Color Doppler flow imaging was done in 31 patients before, during, and after chemotherapy. In each phase of treatment, semiquantitative changes in intratumoral blood flow, changes in maximum intratumoral Doppler shifts, and changes in resistive indexes of arteries feeding limbs that contained tumors relative to contralateral normal arteries were compared with the histopathologic response, as evaluated on the resected specimens.Before chemotherapy, pathologic flow was found in the extraosseous component of all but two patients. Resistive indexes in arteries that fed tumors were significantly lower (p.001) than the resistive indexes in the contralateral normal arteries. Histopathologic response could not be predicted on the basis of the initial measurements of Doppler shifts and resistive indexes taken before or after the first cycle of chemotherapy. Histopathologic response could be predicted after the second cycle of chemotherapy. After the second cycle of chemotherapy, the resistive index in the arteries that fed tumors increased in eight of nine good respondents but did not change or decreased in eight of nine poor respondents (p = .03). Lower intratumoral Doppler shifts were measured in six of 10 good respondents but also in five of 13 poor respondents (p = .07). After the full course of chemotherapy, persistent lower resistive indexes were measured in the arteries that fed tumors in all poor respondents but one. Intratumoral flow and Doppler shifts further decreased in all good respondents but one. Changes in Doppler shifts (p = .001) and resistive indexes (p.001) were statistically significant between good and poor respondents, irrespective of the tumor type studied.Decreased or unaltered resistive index in the arteries that feed tumors in addition to persistent intratumoral flow and high-frequency Doppler shifts after two cycles of chemotherapy suggest poor histologic response to chemotherapy in osteosarcoma and Ewing's sarcoma. An increased resistive index after two cycles is indicative of good response.

PURPOSE: To evaluate previously described radiologic prognostic factors in extremity osteosarcoma. MATERIALS AND METHODS: In 47 pediatric patients, available images were evaluated for seven prognostic factors at diagnosis and seven additional factors after preoperative chemotherapy. These factors were correlated with histopathologic response and clinical outcome. The association of histopathologic response and outcome was also evaluated. RESULTS: Metastases at presentation and a > 20-cm-diameter soft-tissue mass were predictive of a poor outcome but occurred in few patients. Factors most predictive of < 90% tumor necrosis after chemotherapy included an increase or no change in soft-tissue mass size and increased bone destruction. Although a significant relationship (P < .05) was found between histopathologic response and outcome, no factors predictive of histopathologic response were also predictive of outcome. The accuracy of pathologic response in predicting outcome was 66%. CONCLUSION: Radiologic studi...

PURPOSE To evaluate more accurately the effectiveness of preoperative chemotherapy in the treatment of patients with Ewing's sarcoma, we studied histopathologically the chemotherapeutic response and correlated it to oncologic outcome. PATIENTS AND METHODS Between June 1983 and December 1989, 68 patients with nonmetastatic Ewing's sarcoma of the extremities were treated at our institute with preoperative chemotherapy (without radiation therapy) and surgery. The specimens were retrospectively evaluated for areas of viable tumor cells and graded from I to III (macroscopic, microscopic, or no residual disease, respectively) in a blinded fashion. Clinical follow-up data were available on all patients for a mean of 60 months (range, 32 to 111). RESULTS This histopathologic analysis was strongly correlated with oncologic outcome (P = .004). Patients who demonstrated grade III response (no identifiable viable tumor nodules present) had improved 5-year disease-free survival rates as compared with patients with grade II (microscopic nodes present; P = .023; 90% v 53%) and grade I responses (macroscopic nodules present; P = .0003; 90% v 32%). Patients with grade II necrosis had statistically improved survival rates over those with grade I necrosis (53% v 32%; P = .074). CONCLUSION This new histopathologic analysis technique for the evaluation of neoadjuvant chemotherapy effectiveness (which does not rely on tumor volume for its assessment) is a valuable prognostic indicator for patients with Ewing's sarcoma treated with surgery. Based on this preliminary report, cases of grade I or II chemotherapeutic tumor response should be considered clinical failures and a different, more aggressive postoperative chemotherapy regimen should be considered.

To evaluate whether 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) more accurately predicts the histopathologic response to neoadjuvant chemotherapy (NAC) than magnetic resonance imaging (MRI) in patients with head and neck squamous cell carcinoma (HNSCC).Sixteen patients with HNSCC underwent FDG-PET/CT and MRI scans before and after one cycle of NAC, followed by surgical resection. The 26 surgically resected specimens of the 16 patients were analyzed. Decreases in maximum standardized uptake value (SUV(max)) or in tumor maximum size (diameter(max)) were calculated, and their accuracies for the prediction of histopathologic response were evaluated.In histopathologic responders (n = 7), percent decreases in SUV(max) were significantly higher (P 0.001) than in non-responders (n = 19). Applying a cut-off point of 55.5%, the histopathologic response could be predicted with a sensitivity and specificity of 86% and 95%, respectively.FDG-PET/CT can predict histopathologic NAC responses with higher accuracy than MRI in HNSCC patients.

Purpose. The aim of this study was to prospectively evaluate whether FDG-PET allows an accurate assessment of histopathologic response to neoadjuvant treatment in adult patients with primary bone sarcomas.Methods. Twelve consecutive patients with resectable, primary high grade bone sarcomas were enrolled prospectively. FDG-PET/CT imaging was performed prior to the initiation and after completion of neoadjuvant treatment. Imaging findings were correlated with histopathologic response.Results. Histopathologic responders showed significantly more pronounced decreases in tumor FDG-SUVmax from baseline to late follow up than non-responders (64±19% versus29±30%, resp.;P=.03). Using a 60% decrease in tumor FDG-uptake as a threshold for metabolic response correctly classified 3 of 4 histopathologic responders and 7 of 8 histopathologic non-responders as metabolic responders and non-responders, respectively (sensitivity, 75%; specificity, 88%).Conclusion. These results suggest that changes in FDG-SUVmax at the end of neoadjuvant treatment can identify histopathologic responders and non-responders in adult primary bone sarcoma patients.

Purpose To evaluate positron emission tomography (PET) using [18F]fluorodeoxyglucose (FDG) for prediction of histopathologic response early during primary systemic therapy of large or locally advanced breast cancer. Patients and Methods In a prospective multicenter trial, 272 FDG-PET scans were performed in 104 patients at baseline (n = 104) and after the first (n = 87) and second cycle (n = 81) of chemotherapy. The level and relative changes in standardized uptake value (SUV) of FDG uptake were assessed regarding their ability to predict histopathologic response. All patients underwent surgery after chemotherapy, and histopathologic response defined as minimal residual disease or gross residual disease served as the reference standard. Results Seventeen (16%) of 104 patients were histopathologic responders and 87 were (84%) nonresponders. All patients for whom baseline SUV was less than 3.0 (n = 24) did not achieve a histopathologic response. SUV decreased by 51% ± 18% after the first cycle of chemotherapy in histopathologic responders (n = 15), compared with 37% ± 21% in nonresponders (n = 54; P = .01). A threshold of 45% decrease in SUV correctly identified 11 of 15 responders, and histopathologic nonresponders were identified with a negative predictive value of 90%. Similar results were found after the second cycle when using a threshold of 55% relative decrease in SUV. Conclusion FDG-PET allows for prediction of treatment response by the level of FDG uptake in terms of SUV at baseline and after each cycle of chemotherapy. Moreover, relative changes in SUV after the first and second cycle are a strong predictor of response. Thus, FDG-PET may be helpful for individual treatment stratification in breast cancer patients.

Percutaneous left atrial appendage (LAA) closure technology is a novel therapeutic strategy for stroke prevention in patients with atrial fibrillation. The histopathologic response following mechanical LAA closure with the next generation WATCHMAN (WM) FLX device (Boston Scientific Corporation

e14656 Background: The RECIST criteria may be limited in assessing response to biologic agents such as bevacizumab (BVZ). Retrospective studies of patients (pts) with colorectal liver metastases (C...

Red-backed salamanders (Plethodon cinereus) were exposed to four different concentrations of 1,3,5-trinitrohexahydro-1,3,5-triazine (RDX) in soil under controlled laboratory conditions for 28 days. Wild-caught P. cinereus (N = 20/treatment) were exposed to target concentrations of 5,000, 1000, 100, 10, and 0 mg RDX/kg soil (dry wt) using a microcosm design. Animals were fed 5 to 10 uncontaminated mutant Drosophila flies every 3 days and monitored daily. Animals were weighed 1 day before being placed in treatment and weekly thereafter. RDX concentrations in soil were analytically determined after the compound was added and mixed at the beginning, the midpoint, and the end of exposure. RDX soil concentrations were relatively stable throughout the exposure period. Signs of overt toxicity were observed primarily in the highest exposure group. Salamanders exposed to 5,000 mg RDX/kg soil exhibited signs of neuromuscular effects (lethargy, gaping, hypersensitivity, tremors) and exhibited significant weight loss. A single moribund animal from this group lost >20% of its original body weight and was killed. Animals in this exposure group also lost weight relative to animals in other treatments. Histopathologic evaluations, including an evaluation of melanomacrophage parameters, indicated no strong treatment-related findings. This study provided information regarding the effects from subchronic dermal exposure of a terrestrial amphibian species to RDX in soil and provides a microcosm approach to the evaluation of toxicity of contaminants in soil to a terrestrial vertebrate.

The basic electrical rhythm (BER) of the intestine is known to decrease during mesenteric ischaemia. Some studies have reported the relationship between the BER and the pathologic changes that occur in the bowel during vascular injury. However, these changes have not been completely elucidated. This study describes the histopathologic pattern when the rabbit small intestine was subjected to ischaemia of varying time lengths (30 – 150 minutes) and subsequent reperfusion for six hours. Intestinal biopsies were taken at baseline, at the end of ischaemia, and at hourly intervals during reperfusion. Microscopic examination of the biopsies revealed evidence of progressive infarction of the mucosa during ischaemia. There was an acute worsening of the pathology during reperfusion, the severity being greater when reperfusion was preceded by longer periods of ischaemia. These changes were statistically significant. The observed pattern in this study shows clearly that reperfusion injury is reflected in the histopathologic response and that this is worse in severity than the response to ischaemia. Studies of longer duration should further clarify the picture during recovery in ischaemia/reperfusion injuries of the bowel. Keywords: Mesenteric, Ischaemia, Reperfusion, Pathology. Resume Le rythme electrique normal (Basic Electrical Rhythm, BER) de l'intestin diminue pendant la deficience de sang. Quelques etudes ont releve une relation entre le rythme electrique normal (BER) et les changements pathologiques qui se produisent dans la cavite intestinale lors de l'injurie vasculaire. Neanmoins ces changements n'ont pas ete completement elucides. Cette etude decrit le type histopathologique quand l'intestin grele du cobaye etait soumis a la deficience pendant un temps varie (30 – 150mn) et la reperfusion subsequent de six heures. Les biopsies intestinales etaient portees a la baseline a la baseline a la fin de la deficience et a intervals d'une heure durant la reperfusion. L'examen microscopique des biopsies revele l'evidence d'infarction progressive de muchose durant la deficience. Il y avait une detoriation accrue de la pathologie durant la reperfusion la severite etait plus grande que quand la reperfusion etait precedee par une plus longue periode de deficience. Ces changement etaient significants statistiquement. Le model observe dans cette montre clairement que l'injurie de reperfusion est reflectee dans la reponse histopathologique et que ca s'empire en severite que dans la reponse a la deficience. Les etudes d'une duree plus longue peuvent clarifier l'image durant le retablissement de l'injurie de la deficience reperfusion de la cavite intestinale. West African Journal of Medicine Vol.22(1) 2003: 59-62

e14636 Background: Recent studies imply that positron emission tomography with fludeoxyglucose F 18(FDG-PET) correlates with histopathologic response and survival in patients with esophageal cancer undergoing neoadjuvant chemoradiotherapy (CRT) followed by surgical resection. To evaluate the rating system of FDG-PET after the completion of neoadjuvant CRT for the assessment of histopathologic response and prognosis inthe multimodality treatment of patients with esophageal cancer. Methods: Seventy patients (58 men, 12 women; median age, 61 years) with locally advanced esophageal squamous cell carcinoma who received neoadjuvant CRT underwent FDG-PET before chemoradiotherapy and transthoracic en bloc esophagectomy in evaluation of pathologic response to CRT and postoperative survival. Lack of FDG uptake was defined as primary tumors with SUVmax at least 2.5, and FDG-PET complete response after CRT (PET-CR) was defined as SUVmax

3583 Background: Tumor regression grade (TRG) is a measure of histopathologic response of rectal cancer to preoperative chemoradiation (CRT) and correlates with outcomes. Several TRG systems have been reported including Mandard (5, 3 tier), Dowrak/Rodel (5, 3 tier), Memorial Sloan Kettering Cancer Center (MSKCC), and American Joint Committee of Cancer (AJCC). The purpose of this study is to compare the different TRG systems and determine which one(s) best predict recurrence and survival. Methods: Review of prospective maintained database from 1998 to 2007 identified 563 patients with locally advanced rectal cancer (T3/4 and/or N1) and treated with long-course CRT followed by total mesorectal excision. TRG was determined by measuring proportion of tumor mass replaced by fibrosis. Patients were then classified into the various TRG schemes which were compared by analyzing association with recurrence and survival using concordance index (CI) and reclassification index. CI is a measure that summarizes the predictive strength of a marker. Computing and contrasting CI across several markers is a way of selecting the best prognostic marker. Results: 75% of patients were noted to have clinical stage III disease by endorectal ultrasound or rectal MRI. Following resection with median follow-up of 39.3 months, 2% developed local recurrence and 17% developed distant metastasis. The median interval time between completion of CRT and surgery is 48 days. 20% demonstarted complete pathological response. CI of the 3 tier Mandard, 3 tier Dowrak/Rodel, MSKCC and AJCC are 0.665, 0.653, 0.683, and 0.694, respectively (higher number indicates better prediction). The AJCC was significantly more accurate in predicting recurrence than the 3- tier Mandard (p=0.002), and Dowrak/Rodel (p=0.006). AJCC had a higher CI than MSKCC although it did not reach significance (p=0.068). Comparing the 3 tier systems, MSKCC was most accurate and correctly reclassified 17 % and 23 % of the patients Mandard and Dowrak/Rodel systems, respectively. Conclusions: TRG predicts recurrence and survival following combined modality therapy for rectal cancer. The TRG system that recently was proposed in the 7thAJCC staging is currently the most accurate predictor.