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Introduction: Earlier, we documented that a combination of vitamins A and D3 synergistically inhibited the growth of MCF-7, T48:A18 and SKBR3 breast cancer cells with the best activity seen in the ER+ cell line MCF-7. Transcriptomic analysis of treated MCF-7 cells also showed that the combination significantly upregulated the apoptosis and unfolded protein response canonical pathways, and reduced estrogen signaling. Objective: This study aimed to explore the impact of increasing vitamin A and D3 dose combinations over time in a postmenopausal model of breast cancer using ovariectomized athymic female mice bearing MCF-7 xenografts and further analyze mechanisms of action in MCF-7 cells using RNA-seq analysis. Methods: MCF-7 breast cancer cells were grown in culture for the xenograft experiments. Athymic female mice were injected with MCF-7 cells (1 x 10^6 in 100 µl of 50% Matrigel mixed with sterile PBS) via subcutaneous injection. Once the tumors reached an average volume of 100 mm³, the mice were randomly divided into four groups and treated with different vitamin A and D3 combinations. Tumor sizes and mouse body weights were monitored on a biweekly basis. After the treatment period, the mice were euthanized, and the tumors were surgically removed and measured. RNA-seq data from the treated MCF-7 cells were then further evaluated using IPA. Results: As compared with controls, treatment with vitamin A (25,000 IU) and vitamin D (10,000 IU) led to a significant reduction in tumor volume >70%, (p < 0.05-0.01) in OVX athymic mice with MCF-7 xenografts as determined by a twotailed Student T test. Over the treatment period, the tumor volume in mice treated with vitamin A (10,000 IU) and vitamin D (5,000 IU) or vitamin A (25,000 IU) and vitamin D (5,000 IU) also trended downward and was statistically significant using one-way analysis of variance (ANOVA) followed by Dunnett's multiple comparison test (p<0.05 and p<0.0001, respectively) but was not significant using a two-tailed Student T test. In cultured MCF-7 cells, Ingenuity Pathway Analysis of mRNA-seq data showed that the vitamin A and D combination significantly altered the expression of 101 genes out of 864 in the molecular mechanisms in cancer canonical pathway, downregulating gene expression in the integrin/P13K/Akt/mTOR pathway. Conclusions: The findings showed that the combination of vitamins A and D3 effectively reduced tumor burden in a postmenopausal MCF-7 xenograft mouse model, with effects that were both dose-dependent and time-dependent. The combination also significantly altered the expression of genes in the molecular mechanisms of cancer canonical pathway in cultured MCF-7 cells. These preclinical data support the use of vitamins A and D3 in the management of estrogendependent breast cancers, with the caveat that higher doses and longer treatment periods may be needed to observe anti-tumor effects. [ABSTRACT FROM AUTHOR]

Simple Summary: The optimal selection of patients with advanced high-grade serous ovarian cancer (HGSOC) who are likely to benefit from upfront cytoreductive surgery remains challenging. With the results of the TRUST trial, the fifth randomized phase III trial comparing oncologic outcomes of primary versus interval cytoreductive surgery, expected to be presented soon, there is a high unmet clinical need to define novel biomarkers to optimize pretherapeutic patient assessment and allow for more personalized clinical decision making. Building on the growing evidence of the predictive and prognostic value of fibrinogen in various solid cancers, this study is the first to observe an independent association between the "Fibrinogen–Albumin-Ratio Index" (FARI) and surgical outcomes in patients with advanced HGSOC undergoing primary cytoreductive surgery. Given that the FARI seems to act as a surrogate for intra-abdominal tumor load, the further clinical validation of this cost-effective and readily available biomarker appears promising. Background/Objectives: The present study evaluates predictive implications of the pretherapeutic Fibrinogen–Albumin-Ratio Index (FARI) in high-grade serous ovarian cancer (HGSOC) patients undergoing primary cytoreductive surgery. Methods: This retrospective study included 161 patients with HGSOC International Federation of Gynecology and Obstetrics (FIGO) stage ≥ IIb, who underwent primary cytoreductive surgery followed by platinum-based chemotherapy. Associations between the FARI and complete tumor resection status were described by receiver operating characteristics, and binary logistic regression models were fitted. Results: Higher preoperative FARI values correlated with higher ascites volumes (r = 0.371, p < 0.001), and higher CA125 levels (r = 0.271, p = 0.001). A high FARI cut at its median (≥11.06) was associated with lower rates of complete tumor resection (OR 3.13, 95% CI [1.63–6.05], p = 0.001), and retrained its predictive value in a multivariable model independent of ascites volumes, CA125 levels, FIGO stage, and Charlson Comorbidity Index (CCI). Conclusions: The FARI appears to act as a surrogate for higher intra-abdominal tumor load. After clinical validation, FARI could serve as a readily available serologic biomarker to complement preoperative patient assessment, helping to identify patients who are likely to achieve complete tumor resection during primary cytoreductive surgery. [ABSTRACT FROM AUTHOR]

Objective: To investigate the correlation between changes in tumor burden and the dose of intraoperative radiation therapy (IORT) for unresectable pancreatic cancer within 60 days of treatment evaluated using imaging parameters. Methods: A total of 32 cases of unrespectable pancreatic cancer treated with IORT at the Sichuan Cancer Hospital from April 2017 to July 2020 were retrospectively included. The imaging parameters of the tumor were recorded 7 days before IORT and 60 days after IORT: the longest axis (LA), shortest axis (SA), largest cross-sectional area (A), absolute value changes of each parameter (Δ), and change rate (Δ%). Different tumor load groups (shrinking/stabilizing/increasing) were differentiated, and the relationship between each parameter, IORT radiation dose, and tumor response time was analyzed. Results: The LA of unresectable pancreatic cancer after IORT was lower than that before IORT, with significant differences observed. The SA and A values of unresectable pancreatic cancer after IORT were lower than those before IORT, with no statistical significance observed. Based on ΔLA of the pancreatic tumor, the three groups, shrinkage, stability, and enlargement, were divided, with a corresponding tumor response time of (39.57±11.77) d, (38.08±12.87) d, (41.17±42) d, respectively. There were no significant differences in LA, SA, and A among the three groups before IORT, while significant differences were observed in LA, SA, and A after IORT. The ΔLA of the three groups was statistically significant before and after IORT. There was a moderate negative correlation between ΔLA and IORT dose levels in unrespectable pancreatic cancer (r=−0.47,). There was a moderate and high correlation between ΔLA and IORT dose in the stable group and ΔA and IORT dose in the enlargement group, respectively (r=0.66 vs. 0.90). There was no significant correlation between the response time and imaging parameters in these groups, except for a moderate negative correlation between ΔSA and response time in the stability group (r=−0.68). Conclusion: ΔLA can be used to evaluate changes in tumor load within 60 days of IORT for unresectable pancreatic cancer. The efficacy of pancreatic cancer could be correlated with the IORT irradiation dose, whereas the tumor burden could not be affected by the tumor response time.

Objective: To evaluate the influence of endogenous testosterone density (ETD) and tumor load density (TLD) in the surgical specimen of prostate cancer (PCa) patients. Methods: ETD was assessed as the ratio of endogenous testosterone (ET) to prostate volume (PV). TLD was calculated as the ratio of tumor load (TL) to prostate weight. Preoperative prostate-specific antigen relative densities (PSAD) and percentage of biopsy-positive cores (BPCD) were also assessed. The association of high TLD (above the first quartile) with clinical and pathological factors was assessed by the logistic regression model (univariate and multivariate analysis). Results: Between November 2014 and December 2019, ET was measured in 805 cases treated with radical prostatectomy (RP). Median (IQR) of ET and ETD was 412 (321.4–519 ng/dL) and 9.8 (6.8–14.4 ng/(dLxmL)) as well as for TL and TLD was 20 (10-30%) and 0.33 (0.17-0.58%/gr), respectively. As a result, high TLD was detected in 75% of cases. A positive independent association was found between high TLD and ETD. Accordingly, as ETD levels increased, the risk of detecting high TLD in the surgical specimen increased, regardless of PSAD and BPCD. Conclusions: At diagnosis of PCa, a positive independent association was found between ETD and risk of high TLD. Subjects with increasing ETD levels were more likely to have high TLD, associated with unfavorable pathology features. The positive association between ETD and TLD in the prostate microenvironment might adversely influence PCa's natural history. [ABSTRACT FROM AUTHOR]

In multiple myeloma and its precursor stages, precise quantification of tumor load is of high importance for diagnosis, risk assessment, and therapy response evaluation. Both whole-body MRI, which allows to investigate the complete bone marrow of a patient, and bone marrow biopsy, which is commonly used to assess the histologic and genetic status, are relevant methods for tumor load assessment in multiple myeloma. We report on a series of striking mismatches between the plasma cell infiltration estimating the tumor load from unguided biopsies of the bone marrow at the posterior iliac crest and the tumor load assessment from whole-body MRI. [ABSTRACT FROM AUTHOR]

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Abstract Multiple myeloma (MM) is the second common hematologic malignancy manifesting as a clonal proliferation of plasma cells in the bone marrow. In recent years, high expression and activity of pim kinase have been found to be associated with both the progression and prognosis of a significant proportion of malignant diseases. Therefore, pim kinase has become a potential therapeutic target in the treatment of MM and some pim kinase inhibitors have demonstrated good efficacy in clinical trials. Based on nearly the entire literature searched from PubMed in the field of pim kinase in MM, the paper concluded how pim kinase got involved in the proliferation of myeloma cells, the progression of bone disease infiltration, and even in the regulation of the immune microenvironment. Next as a very promising drug, the effectiveness of pim kinase inhibitors as single agents or in combination with other drugs in the treatment of MM was also summarized. Our analysis will guide the clinical use of pim kinase inhibitors for managing tumor load and bone disease in MM patients.

Chimeric antigen receptor (CAR) T cell therapies have resulted in profound clinical responses in the treatment of CD19-positive hematological malignancies, but a significant proportion of patients do not respond or relapse eventually. As an alternative to CAR T cells, T cells can be engineered to express a tumor-targeting T cell receptor (TCR). Due to HLA restriction of TCRs, CARs have emerged as a preferred treatment moiety when targeting surface antigens, despite the fact that functional differences between engineered TCR (eTCR) T and CAR T cells remain ill-defined. Here, we compared the activity of CAR T cells versus engineered TCR T cells in targeting the B cell malignancy-associated antigen CD20 as a function of antigen exposure. We found CAR T cells to be more potent effector cells, producing higher levels of cytokines and killing more efficiently than eTCR T cells in a short time frame. However, we revealed that the increase of antigen exposure significantly impaired CAR T cell expansion, a phenotype defined by high expression of coinhibitory molecules and effector differentiation. In contrast, eTCR T cells expanded better than CAR T cells under high antigenic pressure, with lower expression of coinhibitory molecules and maintenance of an early differentiation phenotype, and comparable clearance of tumor cells.

To test the hypothesis of associations between the ABO blood group system (ABO-bg) and prostate cancer (PCa) features in the surgical specimen of patients treated with robot-assisted radical prostatectomy (RARP). Between January 2013 and October 2020, 1114 patients were treated with RARP. Associations of ABO-bg with specimen pathological features were evaluated by statistical methods. Overall, 305 patients were low risk (27.4%), 590 intermediate risk (50%) and 219 high risk (19.6%). Pelvic lymph node dissection was performed in 678 subjects (60.9%) of whom 79 (11.7%) had cancer invasion. In the surgical specimen, tumor extended beyond the capsule in 9.8% and invaded seminal vesicles in 11.8% of cases. Positive surgical margins (PSM) were detected in 271 cases (24.3%). The most frequently detected blood groups were A and O, which were equally distributed for both including 467 patients (41.9%), followed by groups B (127 cases; 11.4%) and AB (53 subjects; 4.8%). Among specimen factors, the ABO-bgs associated only with the risk of PSM, which was higher for blood group O (30.4%) compared with group A (19.5%) after adjusting for other standard clinical predictors (odds ratio, OR = 1.842; 95% CI 1.352–2.509; p < 0.0001). Along the ABO-bgs, the risk of PSM was increased by group O independently by other standard preoperative factors. The ABO-bgs may represent a further physical factor for clinical assessment of PCa patients, but confirmatory studies are required. [ABSTRACT FROM AUTHOR]

Background: Patients with hepatic metastatic uveal melanoma still have a poor outcome. Purpose: To evaluate overall survival (OS), progression-free survival (PFS), and response predictors in these patients treated with chemosaturation by percutaneous hepatic perfusion with melphalan (CS-PHP). Material and Methods: Between June 2015 and March 2020, a total of 29 patients (median age 69.7 years; age range 30–81 years; 60% women; median BMI 25.7 kg/m2; range 18.7–35.3kg/m2; 1–6 procedures per patient) were treated with 53 CS-PHPs. All patients received cross-sectional imaging for initial and follow-up examinations. Baseline tumor load, extrahepatic tumor load, tumor response, PFS, and OS were assessed. Non-parametric statistics were used. Results: After the initial CS-PHP, a partial response was observed in 11 patients (41%), stable disease in 12 patients (44%) and progressive disease in 4 patients (15%); two patients died before the response was evaluated. After initial CS-PHP, median OS was 12.9 ± 7.4 months and median PFS was 7.1 ± 7.4 months. OS after one year was 50%. After the second CS-PHP, median PFS was 7.9 ± 5.7 months. Seven patients had a liver tumor burden >25%, associated with a significantly shorter OS (6.0 ± 2.4 vs. 14.1 ± 12.7 months; P = 0.008). At the time of first CS-PHP, 41% (12/29) of the patients had extrahepatic metastases that did not affect OS (11.1 ± 8.4 months vs. 12.9 ± 13.6 months; P = 0.66). Conclusion: CS-PHP is a safe and effective treatment for the hepatic metastatic uveal melanoma, especially for patients with a hepatic tumor burden <25%. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) T cell therapies have resulted in profound clinical responses in the treatment of CD19-positive hematological malignancies, but a significant proportion of patients do not respond or relapse eventually. As an alternative to CAR T cells, T cells can be engineered to express a tumor-targeting T cell receptor (TCR). Due to HLA restriction of TCRs, CARs have emerged as a preferred treatment moiety when targeting surface antigens, despite the fact that functional differences between engineered TCR (eTCR) T and CAR T cells remain ill-defined. Here, we compared the activity of CAR T cells versus engineered TCR T cells in targeting the B cell malignancy-associated antigen CD20 as a function of antigen exposure. We found CAR T cells to be more potent effector cells, producing higher levels of cytokines and killing more efficiently than eTCR T cells in a short time frame. However, we revealed that the increase of antigen exposure significantly impaired CAR T cell expansion, a phenotype defined by high expression of coinhibitory molecules and effector differentiation. In contrast, eTCR T cells expanded better than CAR T cells under high antigenic pressure, with lower expression of coinhibitory molecules and maintenance of an early differentiation phenotype, and comparable clearance of tumor cells. [ABSTRACT FROM AUTHOR]

Background: Talimogene laherparepvec (T-VEC) is a genetically modified herpes simplex type 1 virus and known as an effective oncolytic immunotherapy for injectable cutaneous, subcutaneous and nodal melanoma lesions in stage IIIB-IVM1a patients. This study set out to identify prognostic factors for achieving a complete response that can be used to optimize patient selection for T-VEC monotherapy. Methods: Patients with stage IIIB-IVM1a melanoma, treated with T-VEC at the Netherlands Cancer Institute between 2016–12 and 2020–01 with a follow-up time > 6 months, were included. Data were collected on baseline characteristics, responses and adverse events (AEs). Uni- and multivariable analyses were conducted, and a prediction model was developed to identify prognostic factors associated with CR. Results: A total of 93 patients were included with a median age of 69 years, median follow-up time was 16.6 months. As best response, 58 patients (62%) had a CR, and the overall response rate was 79%. The durable response rate (objective response lasting > 6 months) was 51%. Grade 1–2 AEs occurred in almost every patient. Tumor size, type of metastases, prior treatment with systemic therapy and stage (8Th AJCC) were independent prognostic factors for achieving CR. The prediction model includes the predictors tumor size, type of metastases and number of lesions. Conclusions: This study shows that intralesional T-VEC monotherapy is able to achieve high complete and durable responses. The prediction model shows that use of T-VEC in patients with less tumor burden is associated with better outcomes, suggesting use earlier in the course of the disease. [ABSTRACT FROM AUTHOR]

Objectives: Plasma cell dyscrasias are diseases characterized by clonal proliferation and accumulation of cells producing monoclonal immunoglobulins. These diseases have not been studied in our region and we don't know if their behavior is similar to that reported in the literature. That's why we evaluated multiple characteristics in southern Colombia. Methods: analytical cross-sectional study of patients with confirmed diagnosis of a plasma cell dyscrasias were included. Results: 60 patients included in our study, 65% were men, with an average age of 58.8 years (CI 96% 55.8 - 61.93). Bone pain was the most frequent symptom (88%). The most frequent dyscrasia was multiple myeloma and in these patients we found a high percentage of hemoglobin less than 10 mg/dl, creatinine greater than 2 mg/dl and serum calcium higher than 11 mg/dl (77%, 38% and 37 %, respectively). Half of the patients had a time course of symptoms greater than 4 months and 43% had plasma cells in bone marrow greater than 60%. 65% of patients had elevated levels of serum B2-microglobulin (> 5.5 mg/L) and in-hospital mortality was 15%. We found a statistically significant association between mortality and gender (PR 6.5) and between mortality and hemoglobin (p = 0.039). Conclusion: Patients with plasma cell dyscrasia in southern Colombia are younger, consult late, in an advanced stage of their disease, with greater renal damage, hypercalcemia and anemia than reported in the literature, also a high tumor burden due to high plasma cell infiltration into bone marrow and high values of serum B2-microglobulin. [ABSTRACT FROM AUTHOR]

Complete removal of disease is the most important prognostic factor for patients with advanced epithelial ovarian carcinoma. However, the influence of carcinomatosis distribution on prognosis is unknown and the prognostic impact of implant size according to their location is poorly studied. Our objective was to assess the impact of peritoneal carcinomatosis quantitative and qualitative localizations on progression free survival (PFS) in patients with advanced epithelial ovarian carcinoma (AEOC) after complete cytoreductive surgery. We conducted a monocentric cohort study, retrospective from October 2001 to July 2014. Inclusion criteria were high-grade AEOC patients without residual disease (CC0) after primary debulking surgery (PDS) or after interval debulking surgery (IDS) following neoadjuvant chemotherapy (NACT). Peritoneal carcinomatosis was assessed according to qualitative criteria and quantitative criteria. One hundred and one patients were included. Median PFS was 21·2 months and median OS was 62·2 months. On the whole population, involvement of adipocytes-enriched areas tended to be associated with a decreased PFS and was significantly associated with a decreased OS. Any localization was associated with PFS or OS in the "IDS" subgroup. In the "PDS" subgroup, PCI score and involvement of the right mesocolic area were associated with a decreased PFS. Initial tumor load has not been found associated with PFS after complete surgery. Adipocytes-enriched areas and right mesocolic areas involvement were associated with poor prognosis in patients receiving primary debulking surgery. Larger-scale studies are needed to assess whether initial tumor load has a prognostic impact even after complete cytoreductive surgery is achieved. [ABSTRACT FROM AUTHOR]

Background: Bone metastatic involvement represents a leading cause of death in patients with advanced breast cancer (BC). At present, it is not clear whether the bone metastatic load might impact Overall Survival (OS) in patients with bone metastatic BC at diagnosis. For this purpose, we used the Bone Scan Index (BSI), which is a reproducible and quantitative expression of tumor load observed at bone scintigraphy., Objective: The aim of this study was to associate BSI with OS in bone metastatic BC patients., Methods: In this retrospective study, we enrolled BC patients with bone metastases at the scintigraphic bone scan performed for staging purposes. The BSI was calculated through the DASciS software, and statistical analysis was carried out. Other clinical variables relevant to OS analysis were taken into account., Results: Of a total of 94 patients, 32% died. In most cases, the histotype was ductal infiltrating carcinoma. The median OS from diagnosis was 72 months (CI 95%: 62-NA). The univariate analysis with COX regression showed that only hormone therapy significantly correlates with OS (HR 0.417, CI 95%: 0.174-0.997, p < 0.049). As concerning BSI, the statistical analysis showed that it does not predict OS in BC patients (HR 0.960, 95% CI: 0.416-2.216, p < 0.924)., Conclusion: Although the BSI significantly predicts OS in prostate cancer and in other tumors, we observed that the metastatic load of bone disease has not a key role in prognostic stratification in our population., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: To test hypothesized associations between the ABO blood group (ABO-bg) system and the pathological features of prostate cancer (PCa)., Material and Methods: Between January 2013 and September 2019, 1173 patients underwent radical prostatectomy. Associations between ABO-bg levels and pathological features were evaluated using statistical methods., Results: Overall, 1149 consecutive patients were evaluated using the ABO-bg system, which was represented by O-bg (42.8%) and A-bg (41.3%), followed by B-bg (11.1%) and AB-bg (4.8%). Only positive surgical margins (PSMs) was correlated with ABO-bg (Pearson correlation coefficient, r = 0.071; p = 0.017), and the risk was increased in group-O (odds ratio [OR], 1.497; 95% confidence interval, 1.149-1.950; p = 0.003) versus non-O-bg. In clinical and pathological models, O-bg was at increased risk of PSM after the adjustment for prostate-specific antigen, percentage of biopsy-positive cores, and high surgical volume (adjusted OR, 1.546; 95% confidence interval, 1.180-2.026; p = 0.002); however, the adjusted OR did not change after the adjustment for tumor load and stage as well as high surgical volume., Conclusions: In clinical PCa, the risk of PSM was higher in O-bg versus non-O-bg patients after the adjustment for standard predictors. Confirmatory studies are needed to confirm the association between ABO-bg and unfavorable PCa features., Competing Interests: No conflict of interest has been declared by the authors., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc.)

Background: The purpose of this single-center study was to determine the practicability of the intra-operative use of one-step nucleic acid amplification (OSNA) as the only method for detection of SLN. The OSNA system has been well described and is supposed to be as accurate as conventional histology. Methods: Three hundred and thirty SLNs from 143 breast cancer patients were analyzed in an intra-operative setting. The CK19-copy number was determined by OSNA and divided into 3 results ('−' no metastasis; '+' micrometastasis; '++' marcometastasis). If OSNA gave a positive result, an axillary lymph node dissection was carried out during the same session. The central 1-mm slice of each node was obtained for permanent histology. Additionally, the results were correlated to clinicopathological factors, and the time for the intra-operative use was evaluated. Results: Thirty-nine of the 143 patients were OSNA positive, 22 with macrometastatic and 17 with micrometastatic spread. The mean time for the OSNA run with one SLN was 34.4 min. We could show a correlation between the tumor size and OSNA positivity as well as between the numbers of OSNA positive SLNs with the tumor load of associated non-SLNs. Furthermore, we found that a cutoff CK19 copy number of 7,900/μL indicates a positive non-SLN result with the highest sensitivity (91 %) and specificity (61 %). Conclusion: We found OSNA to be very helpful for the intra-operative determination of the tumor load of a SLN as a basis for decision-making concerning further surgical axillary intervention. OSNA allows precise differentiation of micro- from macrometastasis, and the CK19 copy number predicts the probability of tumor load in other axillary lymph nodes and might help to find adequate adjuvant treatment options. This objective method is well suitable for everyday use and may reduce the pathologic workload and the risk of secondary operative interventions with all associated costs and stress for the patients. [ABSTRACT FROM AUTHOR]

Objective: In routine practice, axillary lymph node dissection is performed in early invasive breast cancer patients with positive sentinel node biopsy. However, sentinel node is the only involved axillary node in 40-70% of patients, and determining factors that predict axillary non-sentinel node involvement will therefore prevent unnecessary axillary lymph node dissection and decrease morbidity. Material and Method: In this study, 119 invasive breast cancer patients with sentinel node metastasis who underwent axillary lymph node dissection between 1998-2009 at our institution were studied. Primary tumor characteristics and features of the metastatic tumors in sentinel nodes, such as microanatomic location, size of metastasis, and the ratio of metastatic tumor area to the total sentinel node area were evaluated. Student's t-test and multivariate logistic regression were used for statistical analysis. Results: The mean age of the patients was 50.7 years (28-80). Forty-three patients (36%) had invasive ductal and 25 patients (21%) had invasive lobular carcinoma. Most of the patients had either pT1 (44%) or pT2 (54%) tumors. Fifty-four patients (45%) had no further positive nodes in the axilla. The metastatic deposits in the sentinel node were subcapsular in 16 patients (13%). The percent area of sentinel node occupied by tumor (p<0.001), number of sentinel nodes (p=0.041), and microanatomic location of metastatic tumor (p=0.002) were significantly associated with non-sentinel node metastasis in univariate analysis. The percent area of sentinel node occupied by tumor (p<0.001) and number of sentinel nodes (p=0.033) remained significantly associated with non-sentinel node involvement in multivariate analysis. Conclusion: In patients with invasive breast cancer and positive sentinel node, area percent of sentinel node occupied by tumor, and the number of sentinel nodes removed are independently predictive of non-sentinel node involvement. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Define subgroups of patients at highest risk for major morbidity and mortality after a traditional approach of maximal surgical efforts followed by chemotherapy for advanced ovarian cancer (AOC). Methods: Preoperative health, intra-operative findings and outcomes were assessed in consecutive patients with primary AOC from 4 centers. Initial tumor dissemination was stratified into 3 groups based on volume of disease. Surgery was categorized using a previously described surgical complexity score (SCS). Statistical analysis was directed toward validating a multivariable risk-adjusted model. Results: 576 patients with stage IIIC (N=447, 77.6%) or IV AOC (N=129, 22.4%) were analyzed. Age (HR (per year): 1.02; 95%CI: 1.01–1.03), high tumor dissemination (HTD) (HR: 1.73; 95%CI: 1.19–2.56), residual disease (RD) >1cm (HR: 2.46; 95%CI: 1.74–3.53), and stage IV (HR: 1.93; 95% CI: 1.51–2.45), independently correlated with OS. We identified a small subgroup of patients who comprised a high-risk group (N=38, 6.6%) characterized by all of the following characteristics: high initial tumor dissemination (HTD) or stage IV plus poor performance or nutritional status plus age≥75. In this group, high SCS to achieve low RD was associated with morbidity of 63.6% and limited survival benefit. Conclusions: Optimal management of AOC requires accurate, risk-adjusted predictors of outcomes allowing a tailored approach starting with primary therapy. Complex surgical procedures to render low RD improve survival, and in the majority of cases, the benefits of such surgery appear to outweigh the morbidity. However careful analysis identifies a subgroup of patients in whom an alternative approach may be the better strategy. [ABSTRACT FROM AUTHOR]

Background: The need for routine axillary lymph node dissection (ALND) in patients with invasive breast cancer and low-volume sentinel node (SN) involvement is questionable. Accurate prediction of second echelon lymph node involvement could identify those patients most likely to benefit from ALND. Methods: A consecutive series of 317 patients with invasive breast cancer and a tumor positive axillary SN followed by ALND was reviewed. Clinicopathologic features of the primary tumor and the SN were assessed as possible predictors of second echelon lymph node involvement. Results: Second echelon metastases were found in 116/317 cases (36.6%). Frequency of second echelon lymph node involvement in patients with isolated tumor cells (ITC, N=23), micro- (N=101) and macrometastases (N=193) was 13%, 20% and 48%, respectively (p<0.001). Based on the area % of SN occupied by tumor no subgroup of patients could be selected with less than 20% second echelon lymph node involvement. However, none of the patients with SN ITC or micrometastases and a primary tumor size ≤1 cm (N=12, 3.8%) had second echelon lymph node involvement. Conclusions: Accurately measured SN tumor load predicts second echelon lymph node involvement. However, even in patients with ITC, the second echelon lymph nodes are involved in 13% justifying ALND. [ABSTRACT FROM AUTHOR]

Background: The soluble transferrin receptor (sTfR) is a parameter of erythropoietic activity and iron deficiency. Increased levels have also been described in hematological malignancies, especially in chronic lymphocytic leukemia (CLL). Methods: We investigated the value of sTfR in the assessment of tumor mass in 61 previously untreated CLL patients. Both hemolysis and iron deficiency were excluded. sTfR was measured nephelometrically (normal 0.81–1.75 mg/L). Results: All Binet A patients had normal sTfR values (1.36±0.22 mg/L). In Binet B patients, the sTfR was increased (3.08±1.70 mg/L, p<0.0001) compared to Binet A patients. Binet B patients with normal sTfR had a small tumor load and no abdominal involvement. A further increase of sTfR in Binet C (3.75± 2.32 mg/L) was not significant compared to Binet B patients. sTfR values decreased or even normalized after successful treatment, whereas relapse or disease progression was associated with another increase of sTfR. Conclusions: The sTfR concentration directly reflects the tumor burden in CLL. Therefore, sTfR may be of clinical value in monitoring disease activity, response to treatment and disease progression. Clin Chem Lab Med 2007;45:1313–8. [ABSTRACT FROM AUTHOR]