Malignancies In Cancer Patients Research Articles

Abstract 6407: Identification of novel chemotherapy-related CHIP variations in patients with high-grade serous ovarian cancer

Abstract Background: Hematopoietic lineage differentiation is subjected to genetic mutations that, due to fitness advantages, might give rise to clonally expanded populations. Clonal hematopoiesis of indeterminate potential (CHIP) is defined as the outgrowth of a single clone driven by acquired somatic mutations in hematopoietic stem cells (HSCs), in the absence of hematological abnormalities. Previous studies have shown the association of CH with aging and a higher risk of developing secondary hematologic malignancies in cancer patients treated with chemotherapy agents. It is therefore of great interest to study CH incidence prior to and post chemotherapy exposure and its association with the evolution of hematologic malignancies. We aimed to characterize CHIP variants of a highly selected group of patients with high-grade serous ovarian cancer (HGSC) who underwent neoadjuvant chemotherapy (NACT). Methods: Comprehensive ultra-high-depth whole exome sequencing, employing unique molecular barcode technologies, was performed using plasma-derived cell-free DNA (cfDNA) and matched white blood cells (WBC) DNA and tumor DNA from pre-NACT (n=10) and post-NACT (n=10) samples of patients with HGSC. CHIP variants were defined as heterozygous variants found in both the WBC and cfDNA samples from the same patients with variant allele frequency less than 5% in the WBC and higher than 0.5% in cfDNA samples. Results: Our analysis identified 93,088 variants, impacting 13,780 genes. Among them, 463 variants were already known and published, and 5,548 variants were common to the COSMIC genes signature. The number of CHIP variants significantly decreased after chemotherapy (p = 0.004). We then focused on CHIP variants enriched after chemotherapy and identified 77 that showed higher VAF in post-NACT cfDNA samples, which may be associated with the development of therapy-related acute myeloid leukemia/myelodysplastic syndrome (t-AML/MDS). Among them, interestingly, we found a missense mutation with protein change in CDK12 (chr17_39492765_G_T). We noticed that 38% of the CHIP variants found in cfDNA samples, were also found in matched tumor samples. Among these, another CDK12 missense mutation (chr17_39492768_A_T) showed higher VAF in post-NACT tumors. Conclusions: Our innovative approach detected a higher number of CHIP variants than currently characterized. Analysis of cfDNA from HGSC patients consistently demonstrated a reduction in CHIP mutations post-NACT. The subset of variants with increased VAF post-NACT may be associated with therapy-related t-AML/MDS. The detection of cfDNA CHIP variants in matched tumors highlights the potential predictive role of CHIP in t-AML/MDS development, emphasizing its consideration in therapeutic protocols. Citation Format: Sara Corvigno, Amma Asare, Jun Yao, Li Zhao, Nicole Fleming, Joseph Celestino, Richard A. Hajek, Ency A. Arboleda Goette, Ridge T. Rogers, Tri V. Nguyen, Raymond N. Montoya, Karen H. Lu, Amir A. Jazaeri, Shannon N. Westin, Anil K. Sood, Sanghoon Lee. Identification of novel chemotherapy-related CHIP variations in patients with high-grade serous ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6407.

Abstract 5473: Genomic profiling of chemotherapy-related clonal hematopoiesis in patients with high-grade serous ovarian cancer

Abstract Background: Clonal hematopoiesis (CH) is identified as the presence of clonal populations of hematopoietic stem cells (HSC). Hematopoietic lineage differentiation is subjected to genetic mutations that, due to fitness advantages, might give rise to clonally expanded populations. Clonal hematopoiesis of indeterminate potential (CHIP) is defined as the outgrowth of a single clone driven by acquired somatic mutation(s) in HSCs, in the absence of hematological abnormalities. Previous studies have been shown the association of CH with aging and a higher risk of developing secondary hematologic malignancies in cancer patients treated with chemotherapy agents. It is therefore of great interest to study CH incidence prior to and post chemotherapy exposure and its association with the evolution of hematologic malignancies. We aimed to characterize CHIP variants of a highly selected group of patients with high-grade serous ovarian cancer (HGSC) who underwent neoadjuvant chemotherapy; moreover, while previous CHIP studies are largely knowledge based and are limited to known hematologic genes or target gene panels, our study discovers novel CHIP mutations. Methods: Comprehensive ultra-high-depth whole exome sequencing using unique molecular barcode technologies was performed using plasma-derived cell-free DNA and matched white blood cells DNA and tumor DNA from pre-NACT (n=12) and post-NACT (n=12) samples of patients with HGSC who have excellent or poor response to NACT. Using spike-in mutated DNAs as positive controls, we detected variant alleles at 1% variant allele frequency. Results: We identified on average about 3,000 candidate CHIP variants in one patient. Among these, 1,977 variants affecting 1,375 genes were recurrently found in more than one patient. These CHIP genes include not only previous reported CHIP genes (e.g. DNMT3A, JAK2, TET2, and KMT2D) but also many novel CHIP candidates (such as RPTN, MTCH2, FAM186A, CACNA1A, FCGBP, and MUC3A). A number of CHIP mutations were uniquely found enriched in post-chemotherapy samples (e.g. ARID1A T290P, TP53 G245D, SMARCA4 G495D, and CIC T2456P). Interestingly, there is a strong enrichment of COSMIC cancer census genes in CHIP genes identified in every patient. Conclusions: Our findings corroborate the notion that CHIP mutations are present in nonmalignant blood cells of patients with HGSC, and some are enriched after chemotherapy. Moreover, our innovative sequencing approach allowed discovery of novel candidate CHIP genes. The systematic identification of CHIP in patients with HGSC might be an important new clinical consideration when establishing chemotherapy protocols. Citation Format: Sara Corvigno, Jun Yao, Li Zhao, Amma Asare, Joseph Celestino, Richard Hajek, Ency Arboleda Goette, Elaine Stur, Emine Bayraktar, Mark S Kim, Ping Song, Qingxiu Zhang, Xingzhi Song, Mohammad Mohammad, Kenna Shaw, Jianhua Zhang, Karen Lu, Amir Jazaeri, Shannon Westin, Sanghoon Lee, Anil Sood. Genomic profiling of chemotherapy-related clonal hematopoiesis in patients with high-grade serous ovarian cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5473.

Intravenous iron versus oral iron versus no iron with or without erythropoiesis- stimulating agents (ESA) for cancer patients with anaemia: a systematic review and network meta-analysis.

Intravenous iron versus oral iron versus no iron with or without erythropoiesis- stimulating agents (ESA) for cancer patients with anaemia: a systematic review and network meta-analysis.

Assessing the impact of hypercalcemia of malignancy on clinical outcomes in cancer patients admitted with acute pancreatitis.

e24049 Background: Hypercalcemia of malignancy is a well-recognized complication in cancer. Hypercalcemia itself is one of the etiologies of acute pancreatitis. Empiric data on how presence of both these entities affect hospitalization outcomes in cancer patients is lacking. We studied 5 common cancers - Lung cancer, multiple myeloma, diffuse large B-cell lymphoma, renal cell cancer and head & neck cancers with known hypercalcemia of malignancy and studied the outcomes if they developed acute pancreatitis versus not. Methods: Healthcare Cost and Utilization Project National Inpatient Sample (HCUP-NIS) 2016 – 2018 was queried to identify adult patients with known hypercalcemia of malignancy and any of the 5 cancers stated above. From this cohort we identified patients admitted with a principal diagnosis of acute pancreatitis. The frequency of various etiologies of acute pancreatitis in the defined population was assessed. Primary outcomes assessed were mortality, length of stay (LOS), and total hospitalization charges (THC). Secondary outcomes included diagnosis of septic shock, acute kidney injury (AKI), and acute respiratory failure (ARF). Statistics were performed using multivariate linear and logistic regression. Results: There were a total of 44,030 adult patient hospitalizations with history of hypercalcemia of malignancy and one of the 5 cancers of which 4,195 hospitalizations were for acute pancreatitis. The most common etiology for acute pancreatitis was idiopathic (69.4%), followed by biliary pancreatitis (15.7%), alcohol-associated pancreatitis (7.75%) and drug-induced pancreatitis (7.15%). The incidence of acute pancreatitis was higher in the hypercalcemia of malignancy group than those without (0.36% vs 0.28%). Hypercalcemia of malignancy group had significantly increased odds of mortality during admission for acute pancreatitis (15.63% vs 3.48%, aOR: 3.48, p = 0.043) and significantly higher THC ($122,184 vs $49,223, adjusted difference of $69,974.59, p = 0.049). There was a trend towards an increased LOS among patients with hypercalcemia of malignancy (10.7 vs 5.5 days), but it was not statistically significant (p = 0.069). Hypercalcemia of malignancy was also associated with an increased odds of AKI, 53.13% vs 16.85% (aOR: 6.15, p < 0.001). Other outcomes of septic shock and ARF were similar between groups. Conclusions: Despite the high prevalence of hypercalcemia of malignancy in certain at-risk cancer groups, the most common etiology of acute pancreatitis is idiopathic. The history of hypercalcemia of malignancy in cancer patients with acute pancreatitis was associated with a 3-fold increased odds of death, higher odds of AKI and a significant increase in THC. Cancer patients with history of hypercalcemia presenting with acute pancreatitis may need more aggressive management to prevent worse outcomes than patients without history of hypercalcemia.

P53-dependent induction of P2X7 on hematopoietic stem and progenitor cells regulates hematopoietic response to genotoxic stress

Stem and progenitor cells are the main mediators of tissue renewal and repair, both under homeostatic conditions and in response to physiological stress and injury. Hematopoietic system is responsible for the regeneration of blood and immune cells and is maintained by bone marrow-resident hematopoietic stem and progenitor cells (HSPCs). Hematopoietic system is particularly susceptible to injury in response to genotoxic stress, resulting in the risk of bone marrow failure and secondary malignancies in cancer patients undergoing radiotherapy. Here we analyze the in vivo transcriptional response of HSPCs to genotoxic stress in a mouse whole-body irradiation model and, together with p53 ChIP-Seq and studies in p53-knockout (p53KO) mice, characterize the p53-dependent and p53-independent branches of this transcriptional response. Our work demonstrates the p53-independent induction of inflammatory transcriptional signatures in HSPCs in response to genotoxic stress and identifies multiple novel p53-target genes induced in HSPCs in response to whole-body irradiation. In particular, we establish the direct p53-mediated induction of P2X7 expression on HSCs and HSPCs in response to genotoxic stress. We further demonstrate the role of P2X7 in hematopoietic response to acute genotoxic stress, with P2X7 deficiency significantly extending mouse survival in irradiation-induced hematopoietic failure. We also demonstrate the role of P2X7 in the context of long-term HSC regenerative fitness following sublethal irradiation. Overall our studies provide important insights into the mechanisms of HSC response to genotoxic stress and further suggest P2X7 as a target for pharmacological modulation of HSC fitness and hematopoietic response to genotoxic injury.

English

Ever since it was first described by Billroth, there is an increasing incidence of multiple primary malignancies cases, due to increase in the survival rate of cancer patients and improvement of diagnostic tools. Incidence of second malignancies in cancer patients is 10 to 20%. A total of 10 patients who fulfilled the inclusion criteria were included. All the 10 patients’ case sheets were pursued, and the biochemical, radiological and histopathological reports were analyzed. Results revealed that out of the 10 patients, five were synchronous and the other five were metachronous with a median age of 59 years. Four male patients and six female patients are included. The most common malignancy sites were the stomach and breast, and the mean time interval between both the metachronous tumors is 7.2 years. Thus, a strong clinical suspicion is needed for detecting the multiple primary malignancies, anda treatment plan should be formulated individually for every case. Key words:  Neoplasm, multiple primary, synchronous neoplasm, metachronous neoplasm, therapeutics. &nbsp

Synchronous tumours detected during cancer patient staging: prevalence and patterns of occurrence in multidetector computed tomography.

PurposeThe incidental detection of one or more additional primary tumours during computed tomography (CT) staging of a patient with known malignancy is rare but possible. This occurrence should be considered by the radiologist when a new lesion is detected, especially if the lesion location is atypical for metastases. The purpose of this report was to document the usefulness of total body CT scan to detect synchronous primary malignancies in cancer patients undergoing a staging workup.Material and methodsThis was done by reviewing the staging CT studies of the adult patients with a newly diagnosed cancer evaluated during a five-year period in a single cancer institute in order to identify any possible correlation, establishing which tumours are more frequently combined with a second tumour and which second tumours are more commonly present.ResultsAmong the patients with a second tumour, the most frequent first primary tumours were melanoma (eight patients, 17.8%), lymphoma (seven patients, 15.6%), and prostate carcinoma (seven patients, 15.6%). The most frequent incidentally detected second tumours were hepatocellular carcinoma (nine patients, 20% of 45 incidental tumours), renal carcinoma (eight patients, 17.8%), lung carcinoma (seven patients, 15.6%), and bladder carcinoma (four patients, 8.9%). One patient had three primary tumours synchronously.ConclusionsWe believe that the radiologist’s knowledge of the prevalence and pattern of occurrence of these multiple primary malignancies represents added diagnostic value.

Diagnostic accuracy of 18-F FDG-PET/CT in evaluation of malignant neuronal involvement in neurologically manifested cancer patients

Aim and objectivesThe aim of this study was to assess the role of 18-F FDG-PET/CT in evaluating the peripheral malignant neuronal affection as well as perineural tumoral spread that occurs in patients with cancers. Methodology50 patients with clinical symptoms of neurological deficits (34 male and 16 female) were included, their ages ranged from 17 to 74 with a mean of 45 years. PET/CT was done for all patients followed by clinical correlation after anti-inflammatory drugs and chemotherapy. ResultsInterpretation of the PET/CT studies and clinical correlation revealed 10 true positive cases with malignant neuronal involvement, 4 false positive cases diagnosed clinically as radiotherapy-induced neuropathy, 34 true negative cases and 2 false negative cases with negative PET/CT study and clinical evidence of nerve affection with sensitivity 83.33%, specificity 89.47%, PPV 71.43%, NPV 94.44% and diagnostic accuracy 88%. P-value > 0.05 was considered statistically significant. ConclusionPET/CT has a significant role in detection of neuronal involvement by malignancy in cancer patients. Correlation between PET/CT and clinical outcome after chemotherapy improves the accuracy of diagnosis.

Therapy-associated myelodysplastic syndrome with monosomy 7 arising in a Muir-Torre Syndrome patient carrying SETBP1 mutation.

Muir-Torre Syndrome (MTS) is a rare hereditary autosomal dominant cancer syndrome and is linked to hereditary non-polyposis colorectal carcinoma (Lynch Syndrome). Individuals develop various skin neoplasms in addition to colorectal, endometrial and upper gastrointestinal malignancies. Therapy-associated myelodysplastic syndrome (T-MDS) is an aggressive hematologic malignancy and is considered a pre-leukemic phase. T-MDS is associated with prior exposure to chemo- and radiotherapy that potentially results in DNA damage. The current case report presents a 74-year-old male MTS patient with prior history of solid tumors and radiation therapy with new onset cytopenia. A subsequent bone marrow biopsy revealed multilineage dysplasia with a high blast count and a diagnosis of high grade T-MDS was rendered. FISH and G-banded karyotype analyses revealed 5q deletion and monosomy 7. This is a unique case of T-MDS arising in the setting of MTS. Secondary malignancies including MDS and acute leukemia may occur in cancer survivors and are often associated with an unfavorable prognosis. This case demonstrates the need to be aware of the risk of secondary hematologic malignancies in cancer patients and a thorough clinical and lab work-up are warranted in patients with persistent or transfusion requiring cytopenia(s).

Dexrazoxane Averts Idarubicin-Evoked Genomic Damage by Regulating Gene Expression Profiling Associated With the DNA Damage-Signaling Pathway in BALB/c Mice.

Idarubicin is an anthracycline antileukemic agent widely used in the treatment of hematological malignancies. However, cardiotoxicity and secondary leukemia have been reported after idarubicin treatment. Dexrazoxane is the only medication approved by FDA to prevent anthracycline-evoked cardiotoxicity. However, lack of information on the genomic damage caused by the combination of these 2 drugs prompted us to conduct the current study. We treated mice with different doses of idarubicin and/or dexrazoxane. Genomic DNA damage, apoptosis, and reactive oxygen species (ROS) were evaluated in the bone marrow cells. Our results demonstrate that mice pretreated of with dexrazoxane had significant lower genomic damage, apoptosis and ROS generation compared with that of mice treated with idarubicin alone, an effect that was dependent on dexrazoxane dose. The expression of 84 genes implicated in DNA damage-signaling pathways was quantified using an RT2 Profiler PCR Array. Idarubicin treatments altered the expression of 58 genes, and 16 of those were expressed at significantly different level. In treatments combining idarubicin and dexrazoxane, substantial restorations of mRNA expression of these genes were observed. RT-qPCR was performed for selected genes and the alteration of these genes was confirmed. Alterations in mRNA expression of a subset of genes were further proved by Western blotting analysis of protein levels, which nearly showed similar alterations. Conclusively, dexrazoxane can be safely co-administered with idarubicin. Moreover, dexrazoxane minimizes idarubicin-evoked genomic damage via its radical scavenging and DNA repair-enhancing activities. Thus, dexrazoxane may help avert secondary malignancies in cancer patients in remission who are exposed to idarubicin.

The diagnostic efficacy of whole body 18F-FDG PET CT in detection of unexpected second primary malignancy in cancer patients

Purposeto assess the efficacy of FDG PET/CT in detecting unexpected additional primary malignant neoplasms in patients being evaluated by PET/CT for known malignancies compared to conventional staging work-up (CSW). Patients and methodsOf 1889 patients referred for whole-body FDG PET/CT in the period from February 2015 to May 2016, only 273 were included in this prospective study. Patients included are those with histopathologicaly proven primary malignancy and sent for initial tumor staging before treatment within 1month of CSW that was performed for the patients according to the site and cell type of the primary tumor. Histopathologic examination was performed for lesions indicating additional primary cancer detected by either PET/CT or CSW. ResultsIn 13 out of 273 patients included in the study (4.76%) only were proved to have additional primary cancer, the PPV of PET/CT for detecting an additional primary cancer was 56.5%. Also, it showed high sensitivity of 89.2%, which was significantly higher than 23% from the CSW (P<0.005). ConclusionPET/CT is more accurate than CSW for detecting additional primary cancer with a higher sensitivity and positive predictive value, which consequently affect further management.

Diagnostic Performance of Whole-Body PET/MRI for Detecting Malignancies in Cancer Patients: A Meta-Analysis.

BackgroundAs an evolving imaging modality, PET/MRI is preliminarily applied in clinical practice. The aim of this study was to assess the diagnostic performance of PET/MRI for tumor staging in patients with various types of cancer.MethodsRelevant articles about PET/MRI for cancer staging were systematically searched in PubMed, EMBASE, EBSCO and the Cochrane Library. Two researchers independently selected studies, extracted data and assessed the methodological quality using the QUADAS tool. The pooled sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were calculated per patient and per lesion. The summary receiver-operating characteristic (SROC) curves were also constructed, and the area under the curve (AUC) and Q* estimates were obtained.ResultsA total of 38 studies that involved 753 patients and 4234 lesions met the inclusion criteria. On a per-patient level, the pooled sensitivity and specificity with 95% confidence intervals (CIs) were 0.93 (0.90–0.95) and 0.92 (0.89–0.95), respectively. On a per-lesion level, the corresponding estimates were 0.90 (0.88–0.92) and 0.95 (0.94–0.96), respectively. The pooled PLR, NLR and DOR estimates were 6.67 (4.83–9.19), 0.12 (0.07–0.21) and 75.08 (42.10–133.91) per patient and 10.91 (6.79–17.54), 0.13 (0.08–0.19) and 102.53 (59.74–175.97) per lesion, respectively.ConclusionAccording to our results, PET/MRI has excellent diagnostic potential for the overall detection of malignancies in cancer patients. Large, multicenter and prospective studies with standard scanning protocols are required to evaluate the diagnostic value of PET/MRI for individual cancer types.

Why do breast cancer patients visit the emergency department?

e12046 Background: Breast cancer (BC) is the second most common malignancy in cancer patients presenting to the emergency department (ED). Very few studies investigated this population’s ED utiliza...

The role of denosumab in the prevention of hypercalcaemia of malignancy in cancer patients with metastatic bone disease

BackgroundWe compared the activity of denosumab with zoledronic acid for delaying or preventing hypercalcaemia of malignancy (HCM) in patients with advanced cancer and bone metastases or with multiple myeloma. MethodsPatient-level data were combined from two identically designed, randomised, double-blind, active-controlled, phase III trials of advanced cancer patients with breast cancer and other solid tumours (excluding breast or prostate cancer) or multiple myeloma. End-points included time to first on-study HCM, time to first and subsequent on-study HCM, proportion of patients experiencing HCM and proportion of patients experiencing recurrent HCM. ResultsDenosumab significantly delayed the time to first on-study HCM, representing a 37% reduction in the hazard ratio (HR) compared with zoledronic acid (HR, 0.63; 95% confidence interval (CI): 0.41–0.98; P=0.042) and reduced the risk of developing recurrent HCM (time to first and subsequent on-study HCM) by 52% (rate ratio, 0.48; 95% CI: 0.29–0.81; P=0.006). The median time on study was 12.9months. Fewer patients receiving denosumab compared with zoledronic acid experienced an HCM event (1.7% versus 2.7%; P=0.028). Of the 84 patients experiencing an HCM event, 40% of those receiving zoledronic acid experienced >1 event of HCM compared with 31% of those receiving denosumab. ConclusionDenosumab treatment was more efficacious than treatment with zoledronic acid in delaying or preventing HCM in advanced cancer patients with breast cancer, other solid tumours or multiple myeloma.

Fibrous dysplasia mimicking vertebral bone metastasis on 18F-FDG PET/computed tomography in a patient with tongue cancer

A 50-year-old man presented to our hospital with complaints of back pain. He had been following with the diagnosis of tongue cancer for 2 years. The physical examination and laboratory findings were normal. Bone scintigraphy was done to rule out bone metastasis. Bone scintigraphy showed focally increased radiotracer uptake in the fifth thoracal vertebrae and right sixth rib, suspicious for metastasis. 18F-FDG PET-computed tomography was done for metastasis to other organs. On PET images, hypermetabolicfocuswasseenintheregionsdetectedonbonescintigraphy(Figs.1and2).Percutaneoustrucutbiopsywasperformed for the accurate diagnosis, and the diagnosis of fibrous dysplasia (FD) was made after a pathologic examination. Fibrous dysplasia is a benign and slowly progressive disorder in which normal bone is replaced by abnormal fibroosseous tissue [1]. The ribs, femur, tibia, calvarium, long bones, spine, and pelvis are the most frequently involved sites in FD [2]. Patients are often asymptomatic and the disease is detected incidentally on radiologic and scintigraphic examinations made for other reasons. Benign and malign bone conditions can show increased 18F-FDG uptake on PET-computed tomography, and increased FDG uptake may mimic bone metastasis of primary malignancy in cancer patients with FD [2,3]. Bone lesions should be carefully evaluated in patients with known malignancies, and FD should be given as a differential diagnosis.

A rare case of a synchronous anaplastic carcinoma thyroid with ductal carcinoma breast.

Dual malignancy was first reported by Billroth in 1889. Incidence of second malignancy in cancer patients is as high as 10%, but synchronous anaplastic thyroid cancer along with breast tumor is a rare entity. We present a case of a 61-year-old female with a synchronous anaplastic carcinoma thyroid with ductal carcinoma breast. The plausible association of breast cancers with thyroid carcinomas should thus be evaluated in larger cohort studies. More importantly, this report is to highlight the unusual synchronous occurrence of anaplastic thyroid cancer with ductal breast cancer and the therapeutic challenges involved in such cases.

Performance of Whole-Body PET/CT for the Detection of Distant Malignancies in Various Cancers: A Systematic Review and Meta-Analysis

At present, there is no ideal imaging modality for the diagnosis of distant metastases and second primary cancers in cancer patients. We aimed to assess the accuracy of whole-body PET/CT for the overall assessment of distant malignancies in patients with various cancers. Studies about whole-body PET/CT for the detection of distant malignancies in cancer patients were systematically searched in MEDLINE and EMBASE. We determined sensitivities and specificities across studies, calculated positive and negative likelihood ratios, and constructed summary receiver operating characteristic curves using hierarchical regression models for whole-body PET/CT. Across 41 studies (4,305 patients), the sensitivity and specificity of whole-body PET/CT were 0.93 (95% confidence interval [CI], 0.88-0.96) and 0.96 (95% CI, 0.95-0.96), respectively. Subgroup analysis showed that the sensitivity and specificity of whole-body PET/CT for various cancers, respectively, were as follows: head and neck cancer, 0.90 (95% CI, 0.83-0.95) and 0.95 (95% CI, 0.94-0.96); lung cancer, 0.91 (95% CI, 0.76-0.97) and 0.96 (95% CI, 0.94-0.98); breast cancer, 0.97 (95% CI, 0.93-0.99) and 0.95 (95% CI, 0.90-0.97); and cancer of digestive system, 0.92 (95% CI, 0.68-0.98) and 0.97 (95% CI, 0.91-0.99). Whole-body PET/CT has excellent diagnostic performance for the overall assessment of distant malignancies in patients with various cancers, especially head and neck cancer, breast cancer, and lung cancer.

3051 POSTER Effect of Denosumab Treatment on Prevention of Hypercalcemia of Malignancy in Cancer Patients With Metastatic Bone Disease

3051 POSTER Effect of Denosumab Treatment on Prevention of Hypercalcemia of Malignancy in Cancer Patients With Metastatic Bone Disease

Clinical manifestations and prognostic factors in cancer patients with bacteremia due to extended-spectrum β-lactamase-producing Escherichia coli or Klebsiella pneumoniae

Clinical information about bacteremia due to extended-spectrum β-lactamase (ESBL)-producing pathogens in cancer patients was limited. The study was aimed to identify the clinical manifestations and risk factors for mortality in ESBL-producer bacteremia in cancer patients. A retrospective study of bacteremia caused by ESBL-producing Escherichia coli or Klebsiella pneumoniae in adults with cancer in National Cheng Kung University Hospital and National Taiwan University Hospital from July 2002 to August 2007 was conducted. Clinical characteristics, initial manifestations, and antimicrobial therapy were analyzed for their association with crude mortality at 14 days after bacteremia onset. A total 113 episodes of bacteremia caused by E coli (59.3%), K pneumoniae (39.8%) or both (0.9%) were included. Patients with hematological malignancy were younger (55 ± 22 vs. 69 ± 14 years, p < 0.003) and had less co-morbidity, but were more likely to have neutropenia (73.1% vs. 4.6%, p < 0.001) than those with solid tumor. By the univariate analysis in 113 episodes of ESBL-producer bacteremia, several risk factors, including pneumonia or soft-tissue infection as the bacteremia source, initial manifestations with high Pitt bacteremia scores, shock, respiratory failure or severe sepsis, and inappropriate definitive therapy were associated with 14-day crude mortality. By multivariate analysis, only pneumonia [adjusted odds ratio (AOR), 5.2; 95% confident interval (CI), 1.3-21.0; p = 0.021], severe sepsis (AOR, 24.3; 95% CI, 5.6-105.0; p < 0.001), and inappropriate definitive therapy (AOR, 11.3; 95% CI, 1.7-72.8; p = 0.011) were independently associated with a fatal outcome. The presence of neutropenia or underlying hematological malignancy in cancer patients with ESBL-producer bacteremia was not associated with an increase in the mortality rate. Appropriate definitive antimicrobial therapy will be beneficial in improving clinical outcome.

Assessment of Anti-Cytogenotoxic Effects of Quercetin in Animals Treated with Topotecan

The present investigation was directed to study the possible chemoprotective activity of orally administered quercetin against topotecan-induced cyto- and genotoxicity towards mouse somatic cells in vivo. DNA strand breaks, micronuclei formation, and mitotic activity were undertaken in the current study as markers of cyto- and genotoxicity. Oxidative stress markers such as intracellular reactive oxygen species generation, lipid peroxidation, and reduced and oxidized glutathione were assessed in bone marrow as a possible mechanism underlying this amelioration. Quercetin was neither cytotoxic nor genotoxic in mice at doses tested. Pretreatment of mice with quercetin significantly reduced topotecan-induced genotoxicity and cytotoxicity in bone marrow cells, and these effects were dose dependent. Moreover, prior administration of quercetin ahead of topotecan challenge ameliorated oxidative stress markers. In conclusion, quercetin has a protective role in the abatement of topotecan-induced cyto- and genotoxicity in the bone marrow cells of mice that resides, at least in part, on its antioxidant effects. Based on the data presented, strategies can be developed to decrease the topotecan-induced bone marrow suppression and secondary malignancy in cancer patients and medical personnel exposing to topotecan.