Predictive Factors In Multivariate Analysis Research Articles

Abstract PO3-03-04: Metaplastic breast cancer: a single center retrospective study

Abstract Background: Metaplastic breast cancer (MBC) is a rare malignancy that accounts for up to 1% of all primary invasive breast carcinomas (BC). It is histologically heterogeneous, usually presents with a triple-negative phenotype and comprises low-grade and high-grade (HG) variants. HG variants have a higher risk of recurrence and a shorter disease-free and overall survival compared to other BC subtypes. Our research aimed to estimate the prevalence of HG-MBC among the Slovenian population and determine the characteristics of patients (pts) and tumours and the disease outcome. Patients and methods: Our retrospective study included pts diagnosed with HG-MBC at the Institute of Oncology Ljubljana from January 1983 until January 2021. Clinicopathologic characteristics such as tumour subtype, size and grade, nodal status, hormonal receptors (HR) and HER-2 status, lymphovascular invasion (LVI), tumour-infiltrating lymphocytes (TIL) and presence of germline BRCA mutation status were determined. The survival analyses were performed using the Kaplan-Meier method. The Cox proportional hazard model examined the association between risk factors and survival outcomes. Results: We evaluated 113 HG-MBC pts among a total of 27700 pts diagnosed with BC over 38 years (0.41%). The median age was 61.6 years (range 29.7 -93.9), majority of pts were postmenopausal (78.69%). The median follow-up was 15.5 years. The most common tumour subtype in our cohort was mixed MBC (53 cases, 46.9%), followed by MBC with mesenchymal differentiation (24 cases, 21.2%), squamous cell carcinoma (20 cases, 17.7%) and spindle cell carcinoma (16 cases, 14.2%). From the 113 evaluated pts, we obtained data about the stage in 105 pts, pathological tumour size in 100 pts, number of positive lymph nodes in 99 pts, HR status in 95 pts, HER2 status in 76 pts, grade in 97 pts, LVI in 85 pts, MIB-1 in 41 pts and TIL in 77 pts. At diagnosis, 17/105 pts (16.2%) had stage I disease, 59/105 pts (56.2%) stage II, 25/105 pts (23.8%) stage III and 4/105 pts (3,8%) stage IV. Most tumours were poorly differentiated (90/97, 92.2%) without LVI (60/85, 70.6%). Only 6/95 (6,3%) pts had positive HR, 7/76 (9.2%) pts had positive HER-2 status and 8/77(10.4%) pts intensive TIL. Overall, 13 pts were tested for BRCA germline mutation, among which only 1 (7,7%) had BRCA1 mutation. Modified radical mastectomy was the most frequent type of surgery (63.5%); 49.5% of the patients received radiotherapy. In total, 66/113 pts received CT: from 1983 to 2000, 16/36 (44.4%), and after 2000 50/77 (74.9%). In the first period, most pts received CMF (14/16; 87.5%) and anthracyclines and taxanes (27/50; 54%) in the second period. The disease progressed at 37 pts. At 19 pts, new malignancies were found. 55 pts died, 37 of them because of BC. Five- and 10-year disease-free survival (DFS) was 61.7% and 54.1%, while 5-and 10-year overall survival (OS) was 67.1 % and 56.7%, respectively. However, DFS and OS did not differ between the pre-2000 and post-2000 periods. The best outcome was found in pts with squamous cell carcinoma (5- and 10-year DFS 83.5% and 77.0% and 5-and 10- year OS 89.4 % and 83.0%). A subtype of MBC (squamous cell vs other) was the only predictive factor in multivariate analysis for both DFS (HR 0.21; 95% CI 0.05-0.92; p = 0.038 and OS (HR 0.27; 95%CI 0.09-0.78; p = 0.016), no association was seen between survival and tumour size, nodal status, stage, HR and HER2 status, grade, LVI and TILs. Visceral organs were the most common localization of distant metastases (21/37, 56.8%). Metastases in CNS occurred in 9/37 (24.3%) pts. Median OS after the first progression was only 0.9 years. Conclusions: The proportion of HG-MBC in our cohort of pts is 0.41%. Disease outcomes are poor; the 10-year OS of pts with early HG-MBC is only 56.6% and has not improved during the last decades. Squamous cell differentiation predicts a better outcome and is the only independent predictive factor of DFS and OS among HG-MBC pts. Citation Format: Maša Auprih, Gorana Gasljevic, Eva Setina, Anja Zizek, Simona Borstnar. Metaplastic breast cancer: a single center retrospective study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-03-04.

Long-term outcomes after haploidentical stem cell transplantation for hematologic malignancies

AbstractThe introduction of posttransplant cyclophosphamide (PTCy)–based graft-versus-host disease (GVHD) prophylaxis lead to significant improvements in haploidentical stem cell transplantation (haplo-SCT) outcomes over the past decade. We retrospectively assessed long-term outcomes of patients who had their first haplo-SCT between February 2009 and March 2019. Long-term survivors were defined as patients who were alive and disease-free at 2 years after transplant. Three hundred thirty-five patients with a median age of 48 years (range, 18-72) were identified. Of these, 142 patients were disease-free and alive at 2 years after transplant. The 4-year progression-free survival (PFS) and overall survival (OS) for all study patients were 42% and 47%, respectively. With a median follow-up of 52 months for the long-term survivor group, the 4-year PFS and OS were 94% and 96%, respectively. The 4-year cumulative incidence of relapse and non-relapse mortality (NRM) were 2.9% and 3.3%, respectively. Age ≥55 years was the only predictive factor in multivariate analysis for inferior PFS (hazard ratio [HR], 3.41; 95% confidence interval [CI], 1.21-9.60; P = .020) and OS (HR, 3.31; 95% CI, 1.08-10.18; P = .037). Thirteen patients (9%) died in the long-term survivor group, only 2 of whom died of relapsed disease. Secondary primary malignancy was the most frequent cause of NRM (n = 4), followed by infection (n = 2). For haplo-SCT with PTCy–based GVHD prophylaxis, our findings suggest an excellent long-term survival for patients who were disease-free and alive at 2 years after transplant. Late relapses were rare, and age was the only predictive factor for long-term outcomes.

The highest percentage of Gleason Pattern 4 is a predictor in intermediate-risk prostate cancer.

This study aims to clarify the clinicopathological significance of several novel pathological markers, including the percentage of Gleason pattern 4 and small/non-small cribriform pattern, in intermediate-risk Gleason score 3+4=7 prostate cancer. Two-hundred and twenty-eight patients with Gleason score 3+4=7 intermediate-risk prostate cancer who underwent radical prostatectomy between 2009 and 2019 at our institute were selected. Preoperative clinicopathological characteristics, including serum prostate-specific antigen level, clinical T stage, percentage of cancer-positive cores at biopsy, small/non-small cribriform pattern, the highest percentage of Gleason pattern 4, the total length of Gleason pattern 4 and percentage of Gleason score 7 cores were examined in univariate/multivariate logistic regression analysis to determine their predictive value for postoperative adverse pathological findings, defined as an upgrade to Gleason score 4+3=7 or higher, pN1 or pT3b disease. Fifty-four cases (23.7%) showed adverse pathological findings. Although a non-small cribriform pattern, highest Gleason pattern 4 percentage and total length of Gleason pattern 4 were predictive of adverse pathological findings in univariate analysis, only the highest Gleason pattern 4 percentage was an independent predictive factor in multivariate analysis (odds ratio: 1.610; 95% confidence interval: 1.260-2.070; P= 0.0002). The highest Gleason pattern 4 percentage was a potent predictive parameter for Gleason score 3+4=7 intermediate-risk prostate cancer and should be considered in the risk classification scheme for prostate cancer.

AML-528 Long-Term Outcomes After Haploidentical Stem Cell Transplantation (Haplo-SCT) for Hematologic Malignancies

Allogeneic SCT is curative for large proportion of patients with high-risk hematologic malignancies. The introduction of posttransplant cyclophosphamide (PTCy)-based graft versus host disease (GVHD) prophylaxis led to significant improvements in haplo-SCT outcomes and a remarkable increase in its use in the past decade. We aimed from this study to assess long-term outcomes of patients who underwent haplo-SCT. We included all consecutive adult patients who had their first haplo-SCT between 2/2009 and 3/2019. Long-term survivors defined as patients who were alive and disease free at 2 years after transplant. PFS and OS. cumulative incidence of relapse (CIR) and non-relapse mortality (NRM). Age, gender, KPS, DRI, HCT-CI, conditioning regimen, CMV status, and history of GVHD were included in the predictive risk-factor analysis for long-term outcomes. 336 patients were identified: AML/MDS, n=196; ALL, n=55; lymphoid malignancy, n=48; MPNs, n=37. Of these, 144 patients with a median age of 45 (range, 18-72) years were disease-free at 2 years after transplant. Thirty-three percent of patients with ≥55 years, 28% had high/very-high DRI, and 30% had high HCT-CI >3. Majority received reduced intensity conditioning (88%). Prior history of acute grades 2-4 and chronic GVHD were 54 (37%) and 28 (19%) patients, respectively. The 4-year PFS and OS for all study patients were 42% and 47%, respectively. With a median follow-up of 52 months for the long-term survival group, the 4-year PFS and OS were 92% and 96%, respectively. The 4-year CIR and NRM were 4% and 3%, respectively. Age ≥ 55 was the only predictive factor in multivariate analysis for inferior PFS (HR 2.63, 95% CI: 1.01-6.84; p=0.047) and OS (HR 3.33, 95% CI: 1.08-12.23; p=0.036). Thirteen patients (9%) died in the long-term survivor group, only two of which died of relapsed disease. Secondary primary malignancy was the most frequent cause of NRM (n=4), 2 patients died from infection, 1 patient each from GVHD and sudden death, and 3 unknowns. Our findings suggest an excellent long-term survival for patients who were disease-free at 2 years after haplo-SCT. Late relapses were low, and age was the only predictive factor for survival.

Prognostic Significance of PNI in Patients With Pancreatic Head Cancer Undergoing Laparoscopic Pancreaticoduodenectomy.

BackgroundRecently, several prognosis indicators based on inflammatory and nutritional factors, such as the neutrophil-to-lymphocyte ratio (NLR), plated-to-lymphocyte (PLR), lymphocyte-to-monocyte (LMR) and prognosis nutritional index (PNI), have been proposed as prognosis factors for several cancers. However, few studies have looked into PNI. The goal of this research was to see if preoperative PNI had any predictive value in patients with pancreatic head cancer who were having a laparoscopic pancreaticoduodenectomy.MethodsFrom February 11, 2018 to May 31, 2019, two hundred and fifty-one pancreatic head carcinoma patients were retrospectively enrolled. The receiver operator characteristic (ROC) curve was used to determine the cut-off value. Patients were divided into two groups: PNI > 45.1 (high PNI group) and PNI < 45.1 (low PNI group), and clinic-pathological data was compared between the two groups. The link between PNI and NLR, PLR, and LMR, and their effect on overall survival. In addition, the factors of postoperative survival were analyzed univariate and multivariate.ResultsPNI, NLR, PLR and LMR cut-off values were 45.1, 3.7,287.2 and 3.6, respectively. Between the two groups of patients, the low PNI group exhibited considerably higher PLR and lower LMR. PNI had a negative correlation with PLR and NLR (r = −0.329, p < 0.001 and r = 0.170, p = 0.014), but a positive correlation with LMR (r = 0.476, p < 0.001). The high PNI group had a considerably greater survival rate than the low PNI group (median survival days, 217 vs. 468, log-rank = 45.92, p < 0.001). PNI < 45.1(HR: 0.357, 95 percent CI, 0.263–0.485, p < 0.001) and LMR <3.6(HR: 0.705, 95 percent CI, 0.528–0.942, p < 0.018) were revealed to be possible predictive variable in univariate analysis. Only PNI <45.1 was found to be an independent predictive factor in multivariate analysis (HR: 0.359, 95%CI,: 0.256–0.502, p < 0.001).ConclusionsOur findings shoe that PNI is linked to a variety of systemic inflammatory response and can be used to predict survival in individuals with pancreatic head cancer.

CD19+ B Lymphocytes Are Predictive for Anti-Sars-Cov-2 Vaccination Response in Multiple Myeloma Patients

CD19+ B Lymphocytes Are Predictive for Anti-Sars-Cov-2 Vaccination Response in Multiple Myeloma Patients

The role of fluorodeoxyglucose-PET/computed tomography as a predictor of breast cancer characteristics and prognosis.

Fluorodeoxyglucose-PET/computed tomography (FDG-PET/CT) affects the management of patients with breast cancer. Our study aimed to determine the predictive ability of characteristics such as lymph node involvement or subtype and the prognostic value of pretreatment FDG-PET/CT in breast cancer. A total of 270 patients who were confirmed with breast cancer histopathologically and underwent pretreatment FDG-PET/CT were enrolled in the study. Nuclear medicine specialists obtained the readings and measured the maximum standardized uptake value (SUVmax) of the images. Tumor and lymph node SUVmax were evaluated according to lymph node metastasis and subtype status. Survival outcomes were analyzed by the Kaplan-Meier method. The lymph node SUVmax and the lymph node/tumor SUVmax ratio were significantly higher in the subgroup of patients with lymph node metastasis than in those without lymph node metastasis. High cutoff lymph node SUVmax value and lymph node/tumor SUVmax ratio were confirmed as significant predictive factors in multivariate analysis. In a comparison of the tumor SUVmax values, the more biological aggressive subtype showed higher tumor SUVmax values. In survival analysis, tumor SUVmax and lymph node SUVmax were significant predisposing factors for disease-free survival in breast cancer. In subgroup analysis, tumor SUVmax was a more significant prognostic factor in patients who had breast cancer with tumor sizes of ≤2 cm. The lymph node SUVmax was more a significant prognostic factor in patients who had breast cancer with lymph node metastasis. In this study, we showed that the SUVmax of FDG-PET/CT was a useful predictor of lymph node metastasis and breast cancer prognosis.

Predictors of efficacy of corticosteroid switching from abiraterone plus prednisone to dexamethasone in patients with metastatic castration-resistant prostate cancer.

Corticosteroid switching can reverse abiraterone resistance in some patients with metastatic castration-resistant prostate cancer (mCRPC). Here, we investigated the potential biomarkers for predicting the efficacy of corticosteroid switching during treatment with abiraterone acetate (AA). We retrospectively analyzed 101 mCRPC patients receiving corticosteroid switching from West China Hospital and Sun Yat-Sen University Cancer Center between January 2016 and December 2018. All cases received AA plus prednisone as first-line therapy during mCRPC. Primary end points were biochemical progression-free survival (bPFS) and overall survival (OS). The risk groups were defined based on multivariate analysis. A total of 42 (41.6%) and 25 (24.8%) patients achieved 30% and 50% decline in prostate-specific antigen (PSA), respectively, after corticosteroid switching. The median bPFS and median OS on AA plus dexamethasone were 4.9 (95% confidence interval [CI]: 3.7–6.0) months and 18.8 (95% CI: 16.2–30.2) months, respectively. Aldo-keto reductase family 1 member C3 (AKR1C3) expression (hazard ratio [HR]: 2.15, 95% Cl: 1.22–3.80, P = 0.008) and baseline serum alkaline phosphatase (ALP; HR: 4.95, 95% Cl: 2.40–10.19, P < 0.001) were independent predictors of efficacy before corticosteroid switching in the multivariate analysis of bPFS. Only baseline serum ALP >160 IU l−1 (HR: 3.41, 95% Cl: 1.57–7.38, P = 0.002) together with PSA level at switch ≥50 ng ml−1 (HR: 2.59, 95% Cl: 1.22–5.47, P = 0.013) independently predicted poorer OS. Based on the predictive factors in multivariate analysis, we developed two risk stratification tools to select candidates for corticosteroid switching. Detection of serum ALP level, PSA level, and tissue AKR1C3 expression in mCRPC patients could help make clinical decisions for corticosteroid switching.

Comparison of pretherapeutic osseous tumor volume and standard hematology for prediction of hematotoxicity after PSMA-targeted radioligand therapy

PurposeHematotoxicity is a potentially dose-limiting adverse event in patients with metastasized castration-resistant prostate cancer (mCRPC) undergoing prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT). We aimed to identify clinical or PSMA-targeted imaging-derived parameters to predict hematological adverse events at early and late stages in the treatment course.MethodsIn 67 patients with mCRPC scheduled for 177Lu-PSMA-617 RLT, pretherapeutic osseous tumor volume (TV) from 68Ga-PSMA-11 PET/CT and laboratory values were assessed. We then tested the predictive capability of these parameters for early and late hematotoxicity (according to CTCAE vers. 5.0) after one cycle of RLT and in a subgroup of 32/67 (47.8%) patients after four cycles of RLT.ResultsAfter one cycle, 10/67 (14.9%) patients developed leukocytopenia (lymphocytopenia, 39/67 [58.2%]; thrombocytopenia, 17/67 [25.4%]). A cut-off of 5.6 × 103/mm3 for baseline leukocytes was defined by receiver operating characteristics (ROC) and separated between patients with and without leukocytopenia (P < 0.001). Baseline leukocyte count emerged as a stronger predictive factor in multivariate analysis (hazard ratio [HR], 33.94, P = 0.001) relative to osseous TV (HR, 14.24, P = 0.01). After four cycles, 4/32 (12.5%) developed leukocytopenia and the pretherapeutic leukocyte cut-off (HR, 9.97, P = 0.082) tended to predict leukocytopenia better than TV (HR, 8.37, P = 0.109). In addition, a cut-off of 1.33 × 103/mm3 for baseline lymphocytes separated between patients with and without lymphocytopenia (P < 0.001), which was corroborated in multivariate analysis (HR, 21.39, P < 0.001 vs. TV, HR, 4.57, P = 0.03). After four cycles, 19/32 (59.4%) developed lymphocytopenia and the pretherapeutic cut-off for lymphocytes (HR, 46.76, P = 0.007) also demonstrated superior predictive performance for late lymphocytopenia (TV, HR, 5.15, P = 0.167). Moreover, a cut-off of 206 × 103/mm3 for baseline platelets separated between patients with and without thrombocytopenia (P < 0.001) and also demonstrated superior predictive capability in multivariate analysis (HR, 115.02, P < 0.001 vs.TV, HR, 12.75, P = 0.025). After four cycles, 9/32 (28.1%) developed thrombocytopenia and the pretherapeutic cut-off for platelets (HR, 5.44, P = 0.048) was also superior for the occurrence of late thrombocytopenia (TV, HR, 1.44, P = 0.7).ConclusionsPretherapeutic leukocyte, lymphocyte, and platelet levels themselves are strong predictors for early and late hematotoxicity under PSMA-directed RLT, and are better suited than PET-based osseous TV for this purpose.

Efficacy of Sleeve Gastrectomy with Duodenal-Jejunal Bypass for the Treatment of Obese Severe Diabetes Patients in Japan: a Retrospective Multicenter Study.

The incidence of obesity with type 2 diabetes (T2DM) is increasing in Japan. The main bariatric surgery procedures in Japan are laparoscopic sleeve gastrectomy (LSG) and LSG with duodenal-jejunal bypass (LSG/DJB) because of the high incidence of gastric cancer and difficulty exploring a remnant stomach after gastric bypass. However, few studies have compared the antidiabetic effect of LSG/DJB with LSG alone. The purpose of this study is to compare the antidiabetic effect of LSG/DJB with that of LSG alone in Japanese obese diabetic patients. This was a retrospective multicenter study including 298 cases: 177 and 121 LSG and LSG/DJB cases, respectively. We investigated the antidiabetic effect of these two procedures at 12months after surgery. Univariate and multivariate analyses were done to evaluate the predictive factors of T2DM remission. The diabetes remission rate at 12months after surgery was 80.8% for LSG and 86.0% for LSG/DJB. Insulin use and HbA1c ≤6.7% were significant predictive factors in multivariate analysis for all patients. In patients with ABCD score ≥6, the diabetes remission rate was 94.8% and there was no difference between procedures. Only duration of diabetes and insulin use were significant predictive factors both in univariate and multivariate analyses. However, in cases with ABCD score ≤5, the remission rate was 70.3% and procedure type was the most significant predictive factor for diabetes remission (odds ratio [OR] 5.140). Although both LSG and LSG/DJB have good antidiabetic effects in Japanese obese patients, LSG/DJB is more effective for patients with lower ABCD scores.

Ocular morbidities of juvenile idiopathic arthritis-associated uveitis in adulthood: results from a tertiary center study.

To describe the clinical and visual outcomes of juvenile idiopathic arthritis (JIA)-associated uveitis in adults and to examine risk factors for ongoing inflammation in adulthood. Medical records were reviewed for patients with JIA-associated uveitis who were >16years old at the final visit (the last visit prior to data collection). In total, 135 eyes of 77 patients (70 female, 7 male) were included. The mean age of patients at the final visit was 29.72 ± 11.27years. The number of eyes with visual acuity of ≤20/50 and ≤20/200 at the final visit was 37 (28%) and 20 (15%), respectively; at least one ocular complication was present in 72% of eyes. Band keratopathy was the most frequent complication (42%), followed by cataract (25%), posterior synechiae (22%), maculopathy (22%), ocular hypertension (13%), and hypotony (5%). At the final visit, patients who were >16years of age at presentation to the Massachusetts Eye Research and Surgery Institution had more ocular complications and a greater degree of vision loss than patients who were ≤16years of age. Ongoing inflammation at the final visit was noted in 40 patients (52%). The presence of posterior synechiae, hypotony, cataract at presentation, and a history of cataract surgery prior to presentation were predictive of ongoing inflammation in adulthood in univariate analysis. The presence of hypotony and posterior synechiae at the initial visit were predictive factors in multivariate analysis. JIA-associated uveitis may be associated with ongoing inflammation, ocular complications, and severe visual impairment in adulthood. The presence of posterior synechiae and hypotony at the initial visit is predictive of ongoing inflammation.

Severe Jaundice Increases Early Severe Morbidity and Decreases Long-Term Survival after Pancreaticoduodenectomy for Pancreatic Adenocarcinoma

The influence of jaundice on outcomes after pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) is debated. This study aimed to determine, in a large multicentric series, the influence of severe jaundice (serum bilirubin level ≥250 μmol/L and 300 μmol/L) on early severe morbidity and survival after PD. From 2004 to 2009, twelve hundred patients (median age 66 years, 57% male) with resectable PDAC underwent PD. Patients who received preoperative biliary drainage for neoadjuvant treatment or cholangitis were excluded. Pre- and intraoperative data were collected by a standardized form. Serum bilirubin level and creatinine clearance were analyzed as categorical variables. Predictive factors of severe complications and poor survival (Kaplan-Meier method) were identified by univariate and multivariate analysis. Median follow-up was 21 months (95% CI, 19-23). Operative mortality was 3.9% (n = 47), with no predictive factors in multivariate analysis. Severe complications (Dindo-Clavien grade III to IV) occurred in 22% (n = 268), with male sex (p = 0.025), America Society of Anesthesiologists score 3 to 4 (p = 0.022), serum bilirubin level ≥300 μmol/L (p = 0.034), and creatinine clearance <60 mL/min/1.73 m(2) (p = 0.013) identified as predictive factors in multivariate analysis. Overall 3-year survival rate was 41% (95% CI, 37-45%). In multivariate analysis, serum bilirubin level ≥300 μmol/L (p = 0.048), low-volume center (p < 0.001), venous resection (p = 0.014), N1 status (p < 0.01), R1 status (p < 0.001), and absence of adjuvant treatment (p < 0.001) negatively impacted survival. There was a negative relationship between survival at 12 months or later and higher rates of bilirubin. Presence of a biliary stent did not influence early or long-term results. In this multicentric study, serum bilirubin level ≥300 μmol/L increased severe morbidity and decreased long-term survival after PD for PDAC. These findings suggest that biliary stenting is appropriately indicated before PD in patients with PDAC and severe jaundice.

Determining a Magnetic Resonance Imaging Inflammatory Activity Acceptable State Without Subsequent Radiographic Progression in Rheumatoid Arthritis: Results from a Followup MRI Study of 254 Patients in Clinical Remission or Low Disease Activity

To assess the predictive value of magnetic resonance imaging (MRI)-detected subclinical inflammation for subsequent radiographic progression in a longitudinal study of patients with rheumatoid arthritis (RA) in clinical remission or low disease activity (LDA), and to determine cutoffs for an MRI inflammatory activity acceptable state in RA in which radiographic progression rarely occurs. Patients with RA in clinical remission [28-joint Disease Activity Score-C-reactive protein (DAS28-CRP) < 2.6, n = 185] or LDA state (2.6 ≤ DAS28-CRP < 3.2, n = 69) with longitudinal MRI and radiographic data were included from 5 cohorts (4 international centers). MRI were assessed according to the Outcome Measures in Rheumatology (OMERACT) RA MRI scoring system (RAMRIS). Statistical analyses included an underlying conditional logistic regression model stratified per cohort, with radiographic progression as dependent variable. A total of 254 patients were included in the multivariate analyses. At baseline, synovitis was observed in 95% and osteitis in 49% of patients. Radiographic progression was observed in 60 patients (24%). RAMRIS synovitis was the only independent predictive factor in multivariate analysis. ROC analysis identified a cutoff value for baseline RAMRIS synovitis score of 5 (maximum possible score 21). Rheumatoid factor (RF) status yielded a significant interaction with synovitis (p value = 0.044). RF-positive patients with a RAMRIS synovitis score of > 5 vs ≤ 5, had an OR of 4.4 (95% CI 1.72-11.4) for radiographic progression. High MRI synovitis score predicts radiographic progression in patients in clinical remission/LDA. A cutoff point for determining an MRI inflammatory activity acceptable state based on the RAMRIS synovitis score was established. Incorporating MRI in future remission criteria should be considered.

Abstract P2-02-13: The clinical significance of breast MRI in the management of ductal carcinoma in situ diagnosed on needle biopsy

Abstract Background: About 10-40% of ductal carcinoma in situ (DCIS) cases diagnosed on needle biopsy have invasive disease in the surgical specimens, which require surgical axillary staging. However, there is controversy regarding which subgroups should be indicated for sentinel lymph node biopsy (SLNB) because of the upstage on final diagnosis. Therefore, our aim is to identify the associated factors with invasive disease in DCIS diagnosed on needle biopsy by analyzing breast MRI findings with the histopathological factors of biopsy specimens. Methods: Seventy-five consecutive DCIS patients diagnosed on needle-biopsy in our institution who underwent preoperative MRI were retrospectively reviewed. The morphological features and kinetic curves were assessed using the ACR BI-RADS MRI lexicon. We measured the signal intensity (SI) of detected breast lesions and surrounding normal breast tissue on dynamic MRI and calculated the SI ratio as the SI of detected lesion divided by that of surrounding normal breast tissue. The MRI and histopathological variables were assessed between pure DCIS and invasive breast cancer (IBC) diagnosed on surgical specimens. Multivariable-analyses were performed to determine the independent factors for invasion using logistic-regression-model. Results: On dynamic MRI, 60 cases of 75 (80%) were classified as non-mass-like enhancement (NMLE) type and 15/75 (20%) were Mass type. In NMLE, 11/60 (18%) were ultimately diagnosed as IBC. Lesion size (P = 0.027), signal intensity (SI) ratios (calculated as the SI of detected lesions divided by the SI of surrounding normal breast tissue) (P = 0.032) on MRI and the number of biopsy-cores containing cancer nests (cancer-cores) (P = 0.012) were each independently associated with invasion. Table 1. Comparison of MRI findings and clinicopathological factors between pure DCIS and IBC groups in NMLE type.VariablesDCIS (n = 49)IDC (n = 11)P value (univariate)P value (multivariate)Age (years) 0.0480.067Median5544 Range34-7639-66 Lesion size on MRI (mm) 0.0180.027Median1634 Range5-606-59 Signal intensity ratio 0.0010.032Median1.352.01 Range1.04-2.891.56-2.55 The number of Cancer-cores 0.0050.012Median32 Range1-101-7 According to the ROC and statistical analyses performed for these independent factors, the area under the curve (AUC) was 0.72 for lesion size on MRI, 0.92 for the SI ratio and 0.80 for the number of cancer-cores (Table 2). Among these three factors, the SI ratio was the most accurately correlated with the presence of invasive disease. Table 2. The statistical results of the predictive factors in multivariate analysis for NMLE type.VariablesAUCCut-off valueSensitivitySpecificityPPVNPVLesion size on MRI (mm)0.723164%84%47%92%Signal intensity ratio0.921.7691%88%63%98%The number of Cancer-cores0.80282%80%47%95% In Mass type, there were no statistically significant differences between the DCIS and IBC cases. Conclusion: Our study demonstrated that needle biopsy-proven DCIS cases of NMLE type might be sufficiently managed using breast MRI features such as enhanced lesion size and signal intensity, incorporating the number of cancer-cores at needle biopsy specimen in the clinical setting. (Jpn J Clin Oncol. 2013 Epub ahead of print). Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-02-13.

The Effects of Azacitidine On Quality of Life: A Prospective Longitudinal Assessment

Abstract 4938The effect of azacitidine (AZA) on health related quality of life (QOL) compared with best supportive care in MDS patients has been evaluated by Kornblith A. et al (JCO 2002) in a prospective randomized CALGB trial. The study demonstrated improved fatigue, dyspnea, physical functioning and psychological state in patients receiving AZA. One limitation is the relatively short follow up (last QOL measured at 8. 6 months) and the lack of validation in a non-trial setting. We have been conducting prospective assessments of QOL in all patients registered at our MDS clinic using the instruments EORTC QLQ-C30, FACT-Fatigue, EQ-5D and a global fatigue scale. We present longitudinal data on 56 registered patients registered in our program who were treated with AZA, 50 with serial QOLs. Methods:We examined and compared QOL scores at AZA start (baseline) and over time in all patients. We considered the following co-variates’ potential impact on QOL scores: age, sex, IPSS, time from diagnosis, being a responder, # cycles and transfusion dependence. We used univariate linear regression analysis for continuous variables and analysis of variance (ANOVA) for categorical variables to determine their relationship with QOL scores at baseline and over time. For time-dependent covariates, linear mixed model was performed with random intercept and unstructured covariance matrix. Clinically significant (CS) score differences were considered 10 points for the QLQ-C30, 4 for the FACT-Fatigue and 0. 08 for the EQ-5D (7 for the visual analog score). The impact of baseline covariates on the QOL scores for global health, fatigue and dyspnea were determined by backward selection procedure of regression analysis using the Bonferroni adjusted P value of <0. 01 for multiple comparisons. Patients provided informed consent for this REB approved study. Results:56 MDS patients consented to our registry have been treated with AZA between Oct 2008 and July 2012. The median age was 72, 60% were male and 77% had int-2/high risk IPSS MDS. 64 % were transfusion dependent (TD) at baseline. With a median time to death or last follow up of 16 months (range 1. 5–45) a median of 11 cycles of AZA were administered with 34% remaining on drug for a median of 25 cycles (IQR 8–32). The overall response rate (ORR) was 62%: 25% CR; 5% MCR; 4% PR; 28% HI. Stable disease (SD) was seen in 26% and not considered a response. 53% became transfusion independent (TI). 59% have died and 61% developed leukemia or progressed to > 30% blasts at a median time of 13 months. Overall survival was 18 months (95% CI 14. 5–26). 50 were evaluable for HrQOL with a median time between each serial QOL of 13 weeks (IQR 10–18). QOL was assessed at baseline (within 12 weeks pre-AZA start) in 50 patients, 2x in 44, 3x in 32, 4x in 22 and 5x in 14 patients (exceeding 52 weeks follow up). Looking at all 50 patients, overall, function and symptom domains remained stable over time in all instruments. At baseline, there were no statistically significant differences in QOL scores between responders and non responders. Nevertheless, clinically important differences were seen in physical, role, cognitive and social functioning, global health status (all higher in responders). Assessing QOL changes over time and considering baseline and time-dependent predictive factors in multivariate analysis, responders had significantly superior global health status (p=. 001) and EQ-5D scores (p=. 0002) and lower levels of fatigue (p<. 0001). If transfusion dependence status at time of QOL was included in the model, this often supplanted response as predictive of higher scores over time, likely representing the strong relationship between response and transfusion dependence. Conclusions:In addition to validating the clinical outcomes of AZA-001 study, we validate the importance of clinical response on QOL in MDS patients treated with AZA. Unlike the CALGB study, we observed relative stability in global health status and fatigue scores in responding patients and overall declines in non-responding patients. The higher scores at baseline in the patients destined for response raises the intriguing possibility that QOL at AZA start may be independently predictive of response perhaps because of improved tolerability and ability to remain on drug for the requisite number of cycles to achieve response. [Display omitted] Disclosures:Wells:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Buckstein:Celgene: Honoraria, Research Funding.

Expression of TIP60 (tat‐interactive protein) and MRE11 (meiotic recombination 11 homolog) predict treatment‐specific outcome of localised invasive bladder cancer

What's known on the subject? and What does the study add? Several studies have shown that defects in DNA-damage response are associated with good survival after chemotherapy and radiotherapy. Furthermore, loss of cell cycle regulators may be prognostic indicators of poor survival after cystectomy. However, the potential clinical impact of previous findings is hampered by insufficient validation of significant results in suitable cystectomy and radiotherapy cohorts. Here we use a large cohort of patients receiving radiotherapy to successfully validate the importance of MRE11 as a predictive marker of disease-specific survival (DSS). Furthermore, using two independent patient cohorts we show for the first time that TIP60 is a predictive marker of DSS after cystectomy. We show that combined use of TIP60 and MRE11 may hold the potential to guide treatment decisions. • To determine the association between the proteins: tat-interactive protein 60 kDa (TIP60), p16, meiotic recombination 11 homolog (MRE11), phosphorylated ataxia telangiectasia mutated (ATM), retinoblastoma protein (Rb), Ki67, and p53 and clinical outcome in invasive lymph node-negative bladder cancer. • Protein expression was measured by immunohistochemistry in cancer specimens from two independent cohorts of patients with bladder cancer treated with cystectomy (162 patients and 273) and one cohort of patients receiving radiotherapy (148). • Disease-specific survival (DSS) was used as the outcome measure, and patients with no disease-specific death were followed for a minimum of 36 months. • TIP60 was significantly correlated with DSS in both cystectomy cohorts (hazard ratio [HR] 0.42, 95% confidence interval [CI] 0.26-0.68, P < 0.001 and HR 0.45, 95% CI 0.28-0.72, P = 0.001). • MRE11 was significantly correlated with DSS in the cohort receiving radiotherapy (HR 0.64, 95% CI 0.47-0.86, P = 0.005). • P16 was significantly correlated with DSS in all three cohorts (HR 0.46, 95% CI 0.30-0.75, P = 0.032; HR 0.60, 95% CI 0.37-0.97, P = 0.032; HR 0.52, 95% CI 0.28-0.96, P = 0.001). • Rb was significantly correlated with DSS in one cystectomy cohort (HR 1.71, 95% CI 1.13-2.75, P = 0.017). • Ki67, p53, and pATM were not significantly correlated with DSS in any of the cohorts. • TIP60 protein expression was a predictive marker for DSS after cystectomy in two independent cohorts. This novel marker was the strongest predictive factor in multivariate analysis in patients receiving cystectomy. • MRE11 was shown to be a predictive marker for DSS after radiotherapy. • We have shown that TIP60 and MRE11 hold the potential to guide patients with invasive bladder cancer to either cystectomy or radiotherapy. This study was based on retrospective material and consequently we suggest that these markers should be validated in a prospective study.

Rôle pronostique des emboles vasculaires tumoraux dans les tumeurs des voies excrétrices urinaires supérieures : analyse rétrospective monocentrique

To analyze the prognostic impact of lymphovascular invasion (LVI) in case of urothelial carcinoma of upper urinary tract (UUT-UC).Retrospective study of 83 consecutive patients treated surgically for UUT-UC between January 1998 and October 2008. Prognostic interest of histopathological factors (stage, grade, LVI, CIS, tumor architecture, location, nodal status and surgical margins) was assessed in univariate and multivariate Cox regression model. Specific survival (SS), recurrence-free survival (RFS) and metastasis-free survival (MFS) were calculated using Kaplan-Meier method and Log-Rank test.LVI was observed in 26.5% of patients after histopathologic reviewing. The SS, RFS and MFS at 2 years were 93%, 76% and 96% respectively in group without LVI compared to 40%, 13% and 38% in group with LVI (P<0.001). In univariate analysis, pathological stage, LVI and margin status were predictive of SS (P<0.05). Pathological stage, LVI and surgical margin status were predictive of RFS (P<0.05). LVI, tumor architecture and status of surgical margins were predictive of MFS (P<0.05). LVI was the only independent predictive factor in multivariate analysis for all survival (P=0.002, 0.002 and 0.001 respectively for the SS, RFS and MFS).LVI was a poor prognostic factor in cases of UUT-UC. This criteria should be routinely sought and included in the pathology report.

In situ immune response after neoadjuvant chemotherapy for breast cancer predicts survival

Accumulating preclinical evidence suggests that anticancer immune responses contribute to the success of chemotherapy. However, the predictive value of tumour-infiltrating lymphocytes after neoadjuvant chemotherapy for breast cancer remains unknown. We hypothesized that the nature of the immune infiltrate following neoadjuvant chemotherapy would predict patient survival. In a series of 111 consecutive HER2- and a series of 51 non-HER2-overexpressing breast cancer patients treated by neoadjuvant chemotherapy, we studied by immunohistochemistry tumour infiltration by FOXP3 and CD8 T lymphocytes before and after chemotherapy. Kaplan-Meier analysis and Cox modelling were used to assess relapse-free survival (RFS) and overall survival (OS). A predictive scoring system using American Joint Committee on Cancer (AJCC) pathological staging and immunological markers was created. Association of high CD8 and low FOXP3 cell infiltrates after chemotherapy was significantly associated with improved RFS (p = 0.02) and OS (p = 0.002), and outperformed classical predictive factors in multivariate analysis. A combined score associating CD8/FOXP3 ratio and pathological AJCC staging isolated a subgroup of patients with a long-term overall survival of 100%. Importantly, this score also identified patients with a favourable prognosis in an independent cohort of HER2-negative breast cancer patients. These results suggest that immunological CD8 and FOXP3 cell infiltrate after treatment is an independent predictive factor of survival in breast cancer patients treated with neoadjuvant chemotherapy and provides new insights into the role of the immune milieu and cancer.

Operative Risk Factors in Gastric Cancer Surgery for Elderly Patients

PurposeGastric cancer surgery is a common operation in East Asia, such as Korea and Japan, and there has been a significant increase in the need for this procedure due to the aging population. As a result, surgery for the treatment of gastric cancer for elderly patients is expected to increase. This study examined the effect of old age on gastric cancer surgery, and analyzed the operative risk factors for elderly patients.Materials and MethodsFrom November 2008 to August 2010, 590 patients, who underwent a curative resection for gastric cancers, were enrolled. Patients who underwent palliative or emergency surgery were excluded. A retrospective analysis of the correlation between surgical outcomes and age was performed. The elderly were defined as patients who were over the age of 65 years.ResultsThe mean age of all patients was 58.3 years, and complications occurred in 87 cases (14.7%). The most common complication was wound infection and severe complications requiring surgical, endoscopic, or radiologic intervention developed in 52 cases (8.8%). The rate of complications increased with increasing age of the patients. Univariate analysis revealed age, comorbidity, extent of resection, operation time, and combined resection to be associated with surgical complications. In particular, age over 75 years old, operation time, and comorbidity were predictive factors in multivariate analysis. In the elderly, only comorbidity was associated with surgical complications.ConclusionsThe patients' age is the most important factor for predicting surgical complications. Surgeons should pay an attention to the performance of gastric cancer surgery on elderly patients. In particular, it must be performed carefully for elderly patients with a comorbidity.

Predictive factors of sorafenib in the treatment of metastatic renal cell carcinoma

Objective To analyze the effect and related factors of sorafenib in the treatment of metastatic renal cell carcinoma(MRCC), and identify the potential predictive factors of sorafenib re-sponse. Methods The data of 51 MRCC patients who received sorafenib therapy, with or without combination with interferon or chemotherapy were retrospectively reviewed. After two cycles of treat-ment, patients were evaluated for progression or response. Pearson Chi-square test and Logistic re-gression test were performed respectively as univariate and multivariate analyses of sorafenib response. Results The overall objective response rate was 29.4%(95% confidence interval 16.9% to 41.9%, with 1(2.0%) complete response and 14(27.4%) partial responses. Twenty-nine(56.9%) had stable disease, and 7 (13.7%) had progression disease (PD). Significant independent predictive factors asso-ciated with good response in multivariate analysis were lung metastasis only(P=0.021, HR=5.127). Conclusions Sorafenib is effective in MRCC patients. Lung metastasis only is predictive factor in mul-tivariate analysis for sorafenib response. Key words: Carcinoma, renal cell; Predictive factors; Sorafenib