Staging Of Cancer Patients Research Articles

Serum-based microRNA signatures in early diagnosis and prognosis prediction of colon cancer

Early detection of colorectal cancer is the main prerequisite for successful treatment and reduction of mortality. Circulating microRNAs were previously identified as promising diagnostic, prognostic and predictive biomarkers. The purpose of this study was to identify serum microRNAs enabling early diagnosis and prognosis prediction of colon cancer. In total, serum samples from 427 colon cancer patients and 276 healthy donors were included in three-phase biomarker study. Large-scale microRNA expression profiling was performed using Illumina small RNA sequencing. Diagnostic and prognostic potential of identified microRNAs was validated on independent training and validation sets of samples using RT-qPCR. Fifty-four microRNAs were found to be significantly deregulated in serum of colon cancer patients compared to healthy donors (P < 0.01). A diagnostic four-microRNA signature consisting of miR-23a-3p, miR-27a-3p, miR-142-5p and miR-376c-3p was established (AUC = 0.917), distinguishing colon cancer patients from healthy donors with sensitivity of 89% and specificity of 81% (AUC = 0.922). This panel of microRNAs exhibited high diagnostic performance also when analyzed separately in colon cancer patients in early stages of the disease (T1-4N0M0; AUC = 0.877). Further, a prognostic panel based on the expression of miR-23a-3p and miR-376c-3p independent of TNM stage was established (HR 2.30; 95% CI 1.44-3.66; P < 0.0004). In summary, highly sensitive signatures of circulating microRNAs enabling non-invasive early detection and prognosis prediction of colon cancer were identified.

The development of a liquid biopsy for head and neck cancers

Developing non-invasive diagnostic tools in the field of head and neck oncology has been a challenge. Analysis of circulating tumour derivatives in a patient’s blood has been explored in other solid cancers. This includes analysis of circulating tumour DNA, intact circulating tumour cells (CTCs) and exosomes. These circulating tumour derivatives provide avenues of investigation which can be representative of a patient’s primary tumour signature and can be assessed from a patient’s blood sample. In advanced stage cancer patients, these tumour derivatives are found in higher amounts, attributed to higher cellular turnover (apoptosis, autophagy), lysed CTCs and sloughing from necrotic tumours. Head and neck squamous cell carcinoma (HNSCC) patients often present with advanced disease associated with a poor 5-year survival of <50%. Outside of sophisticated imaging and clinical examination, there is a lack of available biomarkers to measure disease burden, and/or response to therapy. Implementation of a liquid biopsy in HNSCC through serial blood samples has the potential to detect metastatic events earlier, thereby allowing better selection of appropriate treatment choices, predict prognosis in patients with potentially curable disease, monitor systemic therapies and residual disease post-treatment.

Perspectives on Hospice and Palliative Care among the Family Caregivers of Cancer Patients in South Korea

Background/Objectives: The utilization of hospice and palliative care services has been limited yet in South Korea. The purpose of this study is to investigate perception and needs toward hospice and palliative care. Methods/Statistical Analysis: A cross-sectional design was used to examine perception and needs on hospice and palliative care. Data were collected from 19th August to 30th September in 2014. 250 family caregivers of cancer patients in South Korea were surveyed from cancer wards or hospice care units using a structured questionnaire. Chi-square tests were conducted to determine the differences in the perception and needs on hospice and palliative care according to participant's characteristics. Findings: Around 50% of the respondents replied that they had no or vague idea on hospice and palliative care services. Over 80% of the respondents perceived that hospice and palliative care is necessary and they want to use those services. Religion of the respondents, type of ward, dependence of patient, and length of caring were related to perception on Hospice and Palliative care. Type of ward, cancer stage of patient, dependence of patient, type of insurance, length of caring were related to need on those services. Those who had more awareness on hospice and palliative care were more likely to recognize the necessity of those services. Application/Improvements: These findings represent that caregivers' needs on hospice and palliative care services are high, but its perception is relatively low. To improve awareness about it, public education should be required.

Abstract 506: Post-surgical resection monitoring in early stage colorectal carcinoma patients using a circulating cell-free DNA assay with ultra-high accuracy and specificity

Abstract Analysis of cell-free circulating tumor DNA (ctDNA) by next-generation sequencing (NGS) allows non-invasive real-time profiling of actionable genomic alterations. Liquid biopsy provides an option for disease monitoring in early stage cancer patients post surgical resection, with a potential to aid in adjuvant decision making. However, to be applicable, tests must cover a broad enough genomic footprint to not require a priori knowledge of mutations, have high specificity, and sensitivity higher than conventional methods. NGS is necessary, since inactivating mutations are the most common alteration type in many common cancer types such as colorectal carcinomas (CRC). Here we present a highly efficient and specific NGS assay for detection of ctDNA in early stage cancer patients, capable of detecting single molecule variants across a 12 kb gene panel with an analytical sensitivity of &amp;gt;0.02% for single nucleotide variants (SNVs) and indels. This panel was applied to a clinical study involving 14 early stage (II/III) CRC patients with both pre- and post-op blood draws (up to 7 days post surgery). A subset (6 patients) also had tumor samples collected at the time of the surgical resection of the tumor. Overall, the detection rate of ctDNA in pre-op blood draws was 93%. In the post-op blood draws ctDNA was detectable in 43% of cases. The estimated average minor allele frequency (MAF) is 0.58% (± 0.82%) in pre-op, 0.18% (±0.21%) in post-op, and 40% (±18%) in tumor samples. When tumor tissue was available and used as a reference, the clinical sensitivity, specificity, and accuracy in pre-op blood samples were 83%, 99.995%, and 99.99%, respectively. SNVs with MAF as low as 0.04% were confirmed in tissue data. The clinical specificity of variants detected in post-op blood samples using pre-op samples as the reference is 99.996%. Cohort expansion to 50 patients and follow-up for clinical recurrence in both cohorts is ongoing. In conclusion, we have developed an assay with ultra-high accuracy and specificity, for the detection of ctDNA in early stage CRC patients that is capable of detecting alterations present in the tumor post-surgical resection. This technology allows for a promising non-invasive route for molecular monitoring of residual disease post surgery and for early detection of relapse compared to traditional methodologies. Citation Format: Stefanie A. Mortimer, Katharine Dilger, Stephen Fairclough, Diana Abdueva, Darya Chudova, Ankit Sarin, Jim Leng, Jeeyun Lee, Helmy Eltoukhy, AmirAli Talasaz. Post-surgical resection monitoring in early stage colorectal carcinoma patients using a circulating cell-free DNA assay with ultra-high accuracy and specificity. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 506.

Abstract 2369: Molecular profile of a GM-CSF overexpressing breast cancer whole-cell vaccine with systemic anti-tumor activity

Abstract BACKGROUND AND PURPOSE OF STUDY: The allogeneic whole-cell cancer vaccine BriaVax(TM) (formerly SV-BR-1-GM) is an ER/PR negative, HER2/neu positive breast cancer cell line (SV-BR-1) we engineered to stably overexpress GM-CSF. BriaVax, rendered proliferation incompetent by irradiation, has thus far been applied to 4 advanced stage cancer patients (3 subjects with breast cancer, 1 subject with ovarian cancer). One breast cancer subject responded to BriaVax with complete remission of a measurable lung lesion and near complete remission of multiple breast lesions after only 3 inoculations. Nevertheless, she relapsed 3 months after completing the protocol, with brain metastases as well as multiple breast lesions. We obtained FDA permission to resume vaccinations, and, upon doing so, all metastatic sites responded with a prompt tumor regression after only 3 inoculations. To prospectively identify patients with a high likelihood of benefiting from BriaVax therapy we began a program to identify molecular factors of diagnostic potential. Here, we describe a gene expression signature that might both be informative about BriaVax’ mechanism of action and helpful for developing diagnostic or monitoring biomarkers. METHODS: To prospectively identify patients with tumors responsive to BriaVax we began a molecular analysis of both the BriaVax cell line and cells obtained from the special clinical responder's blood. BriaVax gene expression profiles were obtained through Illumina BeadArray and NanoString nCounter technologies and compared to gene expression data sets publically available through the Gene Expression Omnibus (GEO; National Center for Biotechnology Information) portal. RESULTS: BriaVax expresses a gene signature consistent with a mechanism of action involving not only the activation of cytotoxic T cells but also the induction of a humoral response. In addition, BriaVax expresses known cancer antigens. Notably, blood-derived cells of the special clinical responder expressed genes complementing BriaVax’ gene expression signature, thus possibly explaining the unusually prompt and robust clinical response to BriaVax. CONCLUSIONS: Our findings suggest that BriaVax exerts its therapeutic effects via multiple modes. We identified both candidate immunogens overexpressed in BriaVax compared to normal breast cells and unraveled a potential mechanism of action explaining the encouraging clinical response observed. Citation Format: Markus Daniel Lacher, Charles L. Wiseman, Joseph Wagner. Molecular profile of a GM-CSF overexpressing breast cancer whole-cell vaccine with systemic anti-tumor activity. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2369.

Abstract 5130: Immune profiling of malignant effusion from metastatic gastric cancer patients as a predictive biomarker for immune checkpoint inhibitors

Abstract Many types of cancers are able to circumvent immune surveillance by the host's immune system. It has been well established that many tumor infiltrating T cells are in a state of non-responsiveness due to the immune suppressive tumor microenvironment. The main mechanisms of T cells that confer suppressive anti-tumor immune response in tumor microenvironment could be regulatory T cells (Treg) and exhausted T cells. In advanced stage cancer patients, detailed evaluation of Treg cells in tumor microenvironment is hampered by limitation for enough tumor tissue, because surgical resection for sample is not standard treatment in these patients. In order to overcome this limitation of research, we performed the studies using lymphocytes and tumor cells isolated from malignant effusion including pleural effusion or ascites from advanced gastric cancer patients. We collected 25 malignant effusion specimens from advanced gastric cancer patients, including 20 paired peripheral blood samples. Lymphocytes from malignant effusions and peripheral bloods were analyzed for subtype of Memory, Activated T cell and Treg cells, and expressions of inhibitory molecule using by flow cytometry. To evaluate the expression of PD-L1, we used the tumor cells of malignant effusions. Firstly, the percentage of CD8+ T cells in malignant effusion seems to increase compared to those in peripheral blood, but the percentage of CD4+ T in malignant effusion were significantly lower than those in peripheral blood. Interestingly, the percentage of CD45RO+ (Memory) on CD4+ and CD8+ T cells was significantly higher in malignant effusion than peripheral blood. And Early activated molecule (CD69 and CD25) on CD4+ and CD8+ T cells was significantly higher in malignant effusion than peripheral blood. The percentage of PD-1 expression on CD8+ T cells was significantly higher in malignant effusion than peripheral blood (p = 0.017). And the percentage and MFI of Treg cells (Foxp3+/CD4 T cell) tend to increase in malignant effusion was comparable with those of peripheral blood but did not show the statistical significance. Collectively, we found that T cells derived from malignant effusion demonstrated the exhausted phenotype showing highly expression of PD-1, compared to those from peripheral blood. Finally, the PD-L1 expression on tumor cells from malignant effusions was 0.04∼12.78%. The upregulation of PD-1 on Treg cells and PD-L1 on tumor cell of malignant effusions could be a potential predictive marker and therapeutic target for immune checkpoint blockade. Citation Format: Woo Sun Kwon, So Jung Lim, Won Suk Lee, Eunji Jo, Hyun-jeong Kim, Kyung Hee Lee, Hyun Cheol Chung, Sun Young Rha. Immune profiling of malignant effusion from metastatic gastric cancer patients as a predictive biomarker for immune checkpoint inhibitors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5130.

Expression of Th1- Th2- and Th17-associated cytokines in laryngeal carcinoma.

T-helper (Th) 0 cell differentiation into Th1 or Th2 cells is dependent on a number of transcription factors that act at specific time points to regulate gene expression. Th17 cells, a subset of interleukin (IL)-17-producing T cells distinct from Th1 or Th2 cells, are considered to exhibit a critical function in inflammation and autoimmune diseases, as well as cancer development. In the present study, the expression of Th1-, Th2- and Th17-associated cytokines in laryngeal cancer and pericarcinoma tissues obtained from 57 laryngeal carcinoma patients was investigated. The association between Th1, Th2 and Th17 infiltration and tumor development was also evaluated. Reverse transcription-polymerase chain reaction and western blotting results revealed that the mRNA and protein expression of Th2 cytokines was lower, while the expression of Th1 and Th17 cytokines was higher in tumor tissues than in pericarcinoma tissues. Furthermore, the early stage cancer patients exhibited a higher level of interferon-γ, IL-2 and IL-17 mRNA expression than those at advanced stages. Cancer tissues exhibited higher Th17 cytokine expression than pericarcinoma tissues. By contrast, Th1 cytokine expression was increased in pericarcinoma tissues compared with cancer tissues. These results indicate that high expression of Th1- and Th17-associated cytokines in laryngeal carcinoma may contribute to suppression of cancer development and a relatively good prognosis.

TP53 mutations on circulating cell-free DNA

Detection of cancer by analysis of circulating cell-free DNA (cfDNA) has received enormous attention over the past years (Alix-Panabieres and Pantel, 2016). cfDNA is released into the blood circulation by apoptotic and necrotic cells, and cancer patients have increased concentrations of cfDNA (Schwarzenbach et al., 2011). With the development of novel technologies it is now possible to detect tumor-associated mutations on cfDNA and monitor the evolution of cancer progression in patients (Bettegowda et al., 2014). However, the detection of very low amounts of circulating tumor-derived DNA (ctDNA) in blood samples from early stage cancer patients is still a challenge. ctDNA was revealed in only 48–73% of patients with localized cancers including lung cancer (Bettegowda et al., 2014, Newman et al., 2014).

Recurrent amplification of RTEL1 and ABCA13 and its synergistic effect associated with clinicopathological data of gastric adenocarcinoma.

BackgroundDespite progression in treatment of gastric cancer, prognosis of patients remains poor, in part due to the low rate of diagnosis during its early stages. This paradigm implies the necessity to identify molecular biomarkers for early gastric cancer diagnosis, as well as for disease monitoring, thus contributing to the development of new therapeutic approaches. In a previous study, performed by array-Comparative Genomic Hybridization, we described for the first time in literature recurrent amplification of RTEL1 and ABCA13 genes in gastric cancer. Thus, the aim of the present study was to validate recurrent amplification of RTEL1 and ABCA13 genes and associate CNV status with clinicopathological data.FindingsResults showed RTEL1 and ABCA13 amplification in 38 % of samples. Statistical analysis demonstrated that RTEL amplification is more common in older patients and more associated with intestinal type and ABCA13 amplification increases the risk of lymph node metastasis and is more common in men. Co-amplification of these genes showed a significant association with advanced staging.ConclusionsaCGH is a very useful tool for investigating novel genes associated with carcinogenesis and RTEL1 amplification may be important for the development of gastric cancer in older patients, besides being a probable event contributing for chromosomal instability in intestinal gastric carcinogenesis. ABCA13 amplification may have age-specific function and could be considered a useful marker for predicting lymph node metastasis in resected gastric cancer patients in early stage. Lastly, RTEL1 and ABCA13 synergistic effect may be considered as a putative marker for advanced staging in gastric cancer patients.

Is aortic lymphadenectomy indicated in locally advanced cervical cancer after neoadjuvant chemotherapy followed by radical surgery? A retrospective study on 261 women

ObjectivesThe aim of this study was to estimate the rate of aortic lymph nodes (LN) metastases/recurrences among patients affected by locally advanced stage cancer patients (LACC), treated with neoadjuvant chemotherapy (NACT) and radical surgery. MethodsRetrospective evaluation of consecutive 261 patients affected by LACC (stage IB2–IIB), treated with NACT followed by radical surgery at National Cancer Institute, Milan, Italy, between 1990 and 2011. ResultsStage at presentation included stage IB2, IIA and IIB in 100 (38.3%), 50 (19.2%) and 111 (42.5%) patients, respectively. Squamous cell carcinoma accounted for more than 80%, followed by adenocarcinoma or adenosquamous cancers (20%). Overall, 56 women (21.5%) had LN metastases. Four out of 83 women (5%) who underwent both pelvic and aortic LN dissection had aortic LN metastases, and all women had concomitant pelvic and aortic LN metastases. Only one woman out of 178 (0.5%) who underwent pelvic lymphadenectomy only, had an aortic LN recurrence. Overall 2% of women (5/261) had aortic LN metastases/recurrence. ConclusionsOur data suggest that aortic lymphadenectomy at the time of surgery is not routinely indicated in LACC after NACT, but should reserved in case of bulky LN in both pelvic and/or aortic area. The risk of isolated aortic LN relapse is negligible. Further prospective studies are warranted.

WE‐AB‐207B‐04: A Preliminary Investigation of Indicators for Treatment Outcomes of CT Guided Cervical Cancer Brachytherapy

Purpose:To identify indicators for recurrence in cervical cancer patients treated with high‐dose‐rate brachytherapy (HDR‐BT).Methods:A total of 37 biopsy proven uterine cervical cancer patients of stage IB‐IVA treated between 2011 and 2015 were included in this study. All patients were treated with 37.8–52.2Gy of external beam radiotherapy (EBRT) plus 5 × 5.0–6.5Gy of HDR‐BT. Patient age, standard deviation of high‐risk clinical tumor volume (HR‐CTVSD) collected throughout HDR‐BT, and D90 (EQD2, α/β=10Gy) of the HR‐CTV were investigated as potential indicators for local/distant recurrence using ROC analysis. The optimal cutoff value was identified through the Youden index and was subsequently used to obtain a group assignment for all patients. Another two comparing groups were defined per evidence of post‐EBRT tumor shrinkage based on the pre‐HDR MR scan. Kaplan‐Meier curves were generated for recurrence‐free proportions for comparing groups where time was measured from the final HDR treatment date to the date of the final follow‐up exam and compared through Cox regression.Results:Patients had a median follow‐up of 12 months, where 16% had local pelvic recurrence and 16% had distant recurrence. HR‐CTVSD was identified as a statistically significant indicator for recurrence (AUC=0.802, p=0.007) compared to D90 (AUC=0.655, p=0.167) and patient age (AUC=0.683, p=0.103). HR‐CTVSD of 6.26cc was chosen as the optimal cutoff value, which was used as the basis for patient group assignment. Patients with HR‐CTVSD&gt;6.26cc had a hazard ratio of 3.92 (95% CI‐1.37, 11.24; p=0.011) for recurrence compared to HRCTVSD≤ 6.26cc. Patients without evidence of post‐EBRT tumor shrinkage compared to those with had a hazard ratio of 4.28 (95% CI‐1.14, 16.15; p=0.032) for recurrence.Conclusion:HR‐CTVSD was identified as an indicator for recurrence and an optimal value of 6.26cc was established in our study. In addition, patients without evidence of post‐EBRT tumor shrinkage demonstrated an increased recurrence rate.

進行・再発治療期のがん患者・家族に対する訪問看護師の看護実践上の困難と学習ニーズ

進行・再発治療期のがん患者・家族に対する訪問看護師の看護実践上の困難と学習ニーズ

Clinical significance of pancreatic circulating tumor cells using combined negative enrichment and immunostaining-fluorescence in situ hybridization.

BackgroundCirculating tumor cells (CTCs) hold great potential in both clinical application and basic research for the managements of cancer. However, it remains to be an enormous challenge to obtain efficient detection of pancreatic CTCs. New detection platforms for the detection of pancreatic CTCs are urgently required.MethodsIn the present study, we applied a newly-developed platform integrated subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH) to analyze clinical significance of pancreatic CTCs. Immunostaining of CK, CD45, DAPI and FISH with the centromere of chromosome 8 (CEP8) were utilized to identify CTCs. Cells with features of CK+/CD45-/DAPI+/CEP8 = 2, CK+/CD45-/DAPI+/CEP8 > 2, CK-/CD45-/DAPI+/CEP8 > 2 were defined as pancreatic CTCs. The Kaplan-Meier method and Cox proportional hazards model were used to analyze the relationship of CTC level and other clinicopathological factors with pancreatic cancer clinical outcomes.ResultsCTC count in pancreatic cancer was higher than healthy individuals (median, 3 vs 0 per 7.5 ml; P < 0.001). SE-iFISH platform yielded a sensitivity of 88 % and specificity of 90 % in pancreatic cancer at the cutoff value of 2 cells/7.5 ml. Pancreatic cancer patients with lower CTC count (<3/7.5 ml) had substantially better overall survival (OS) compared with these with higher CTC count (≥3/7.5 ml) (15.2 vs 10.2 months, P = 0.023). Multivariate analysis indicated that higher CTC count was a strong indicator for worse OS (HR = 4.547, P = 0.016).ConclusionOur current data showed that CTCs could be detected in pancreatic cancer patients in various stages, whether localized, locally advanced and metastatic. Besides, CTCs have shown the potential implication in predicting prognosis of pancreatic cancer.

Loneliness of oncology patients at the end of life.

Terminal stage cancer patients experience anxiety about death and pessimism about the future. They usually fear that as they approach death, their pain will increase, they will lose their reputation, and they will be alone. However, few studies have evaluated the loneliness that these cancer patients feel. This was a cross-sectional and definitive study that evaluated the feeling of loneliness in terminal cancer patients. In total, 55 cancer patients with terminal cancer who were hospitalised for palliative therapy between 14 November 2014 and 14 January 2015 in the Okmeydanı Training and Research Hospital were included in the study. The patients were given a questionnaire form that included sociodemographic properties and University of California Los Angeles Loneliness Scale to collect data. Loneliness was detected as 53.61±9.29. There was no relationship between sociodemographic data and loneliness (p>0.05). Regression analysis revealed that family support and sharing of emotional stress were related to the level of loneliness (p<0.05). More than half of the patients needed psychological support because they could not handle the situation. Terminal stage cancer patients felt lonely in general, and patients with a lack of visitors and family support experienced a higher level of loneliness.

Abstract P6-08-08: Expression and role of ING3 gene in breast cancer

Abstract Background: Inhibitor of growth (ING) tumor suppressor gene family has been discovered over the past decade and five different genes have been identified from ING1 to ING5. They have some functions like cell transcription regulation, cell cycle control, DNA repair and apoptosis. Because of the fact that ING3 gene expression has not been studied in breast cancer so far, we aimed to determine whether there was a relationship between ING3 gene expression and breast cancer prognostic factors. Methods: 46 female breast cancer patients in different stages were enrolled to our study. ING3 gene expressions obtained from tumoral and healthy breast tissue samples of patients were evaluated together with pathological and histological parameters. Results: The median age of the patients was 49 years. ING3 expression rate has been significantly higher in the tumor tissue compared to normal tissue and was statistically significant (p=0.001). In estrogen receptor (ER) and progesterone receptor (PR) positive patients, gene expression ratio was significantly higher than negative ones (p&amp;lt;0.001 and p&amp;lt;0.001, respectively). ING3 expression in tumor tissues of the patients with advanced disease (stage 3-4) was detected higher than ones with early stage disease and it was found to be statistically significant at the border (p=0.048). Moreover, there were no significant changes when ING3 gene expressions were compared with c-erbB2 (Receptor tyrosine-protein kinase erbB-2) status and tumor grade (p&amp;gt; 0.05). Conclusions: This study was the first study on ING3 gene expression in breast cancer. ING3 gene expression has been shown to be associated with the receptor positivity and advanced stage disease. Further studies should be conducted on the prognostic significance of ING3 gene in breast cancer. Citation Format: Kalender ME, Cakir M, Ergun S, Oztuzcu S, Cengiz B, Ulasli M, Sevinc A, Camci C. Expression and role of ING3 gene in breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-08-08.

Abstract P2-01-04: A method for comprehensive genomic analysis of cell free DNA

Abstract Circulating tumor DNA (ctDNA) is released from tumor tissue into the blood, carries tumor specific genetic alterations, and can be analyzed through noninvasive "liquid biopsy" approaches to identify genetic alterations in cancer patients. Liquid biopsies offer a considerable advantage as they may eliminate the need for invasive tissue biopsies and allow for the detection of alterations in multiple metastatic lesions throughout the course of therapy. However, the fraction of ctDNA obtained from a blood sample is often very low (&amp;lt;1.0%) and can be difficult to detect. Additionally, most methods to evaluate circulating tumor DNA (ctDNA) interrogate single hot spot mutations or few genetic alterations. The next generation of ctDNA assays must interrogate multiple gene regions from a single sample with high precision and accuracy and need to evaluate all forms of actionable genomic alterations including point mutations, amplifications, and translocations. To address these issues, we have developed a ctDNA approach called PlasmaSelect to detect somatic sequence mutations, amplifications and translocations at low allele frequencies in the circulation of cancer patients. Utilizing digital genomic approaches, PlasmaSelect achieves high sensitivity and specificity while interrogating &amp;gt;250,000 nucleotides spanning 63 well-established cancer genes. In addition to sequence mutations in the entire coding region of 18 genes and the exons of 40 genes that are frequently mutated in cancer, PlasmaSelect also performs a comprehensive genomic analysis of amplifications in 57 genes and translocations in 10 genes significant in cancer tumorigenesis. To evaluate the PlasmaSelect approach, we performed dilution series using tumor-derived DNA, containing well-characterized somatic mutations, in the presence of wild-type DNA. PlasmaSelect was able to detect genetic alterations with high specificity and a lower level of detection of 0.10% for sequence mutations and translocations, as well as a focal amplification of ERBB2 with a lower level of detection of 0.20%. We evaluated the clinical utility of PlasmaSelect for detection of genetic alterations in the plasma and matched tissue biopsy specimens from late stage cancer patients. These analyses demonstrated high concordance between the somatic sequence mutations, amplifications, and translocations identified in the tumor sample and those identified directly in the plasma, including alterations in both driver genes as well as those related to acquired resistance to targeted therapies. PlasmaSelect provides a non-invasive platform to enable liquid biopsy detection of clinically relevant genetic alterations across a large number of genomic loci. Citation Format: Parpart-Li S, Angiuoli SV, Chesnick B, Galens K, Jones S, Kadan M, Kann L, Lytle K, Murphy D, Nesselbush M, Phallen J, Riley D, Shukla M, Zhang T, Husain H, Velculescu V, Diaz, Jr LA, Sausen M. A method for comprehensive genomic analysis of cell free DNA. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-01-04.

Predictors of physicians’ satisfaction with their management of uncertainty during a decision-making encounter with a simulated advanced stage cancer patient

ObjectivesTo optimize their training, predictors of physicians’ satisfaction with their management of uncertainty should be examined. This study investigated these predictors by using a simulated advanced stage cancer patient. MethodsPhysicians (n=85) rated their satisfaction with their management of uncertainty (Visual Analog Scale-100mm) after a decision-making encounter. Communication predictors were examined with the: Observing Patient Involvement scale (OPTION), Multidimensional analysis of Patient Outcome Predictions (MD.POP) and Communication Content Analysis Software (LaComm). Psychological predictors were assessed with the: Intolerance of Uncertainty Inventory (IUI), Physicians’ Reactions to Uncertainty scale (PRU), Decisional Conflict Scale (DCS), and Jefferson Scale of Physician Empathy (JSPE). ResultsPhysicians’ satisfaction (mean=67mm; standard deviation=17mm) was not predicted by their communication, but by their anxiety due to uncertainty (PRU) (β=−.42; p=<.001) and their perceived empathy (JSPE) (β=.26; p=.009). These variables accounted for 25% of variance in physicians’ satisfaction. ConclusionsPhysicians’ satisfaction with their management of uncertainty was not affected by their communication performance, but by their psychological characteristics. Practice implicationsTraining programs should increase physicians’ awareness regarding the communication performance required in decision-making encounters under conditions of uncertainty.

Applications of Artificial Neural Networks: A Review

Objectives: The objective of this research paper is study the different methods related to artificial neural network used for prediction and detection of the lung cancer in its early stages so that survival rate of lung cancer patients can be increased. Methods: Lung cancer is the leading cause of death in India so early detection of lung cancer is very important. The detection and prediction of lung cancer was determined with image prepossessing method where segmentation, smoothing and enhancement steps were processed and features were extracted from images and stages of lung cancer were identified with suitable artificial neural network model and also survival rate of lung cancer patients was determined. Findings: Artificial neural network has a significant role in medical area. In these days most of the disease cure methods are process with the help of artificial intelligence to increase the performance of output. In lung cancer disease the artificial neural network model is very useful because detection of lung cancer in its early stages can be determine and it is very important to cure this disease initially because with the increasing stages of lung cancer it is very difficult to cure this disease and also the survival rate of lung cancer patients in higher stages is very low Improvements: The ultimate goal of this paper is to study different methods of Artificial Neural Networks model that can help for detection, prediction and find the survival rate of lung cancer patients.

Physical activity communication between oncology providers and patients with early stage breast, colon or prostate cancer.

171 Background: National guidelines recommend that patients with a cancer diagnosis engage in regular physical activity (PA) to reduce cancer-related fatigue, maintain quality of life and physical function, and improve overall prognosis and survival. This study investigates oncology provider communications about PA during routine clinic visits with early stage breast, colon or prostate cancer patients. Methods: Retrospective chart review for documentation of communications (inquiries or recommendations) pertaining to PA in clinician notes and after visit patient summaries. Mixed methods analysis. Results: In a 1-month period, 55 oncology providers had 361 encounters (clinic visits) with early stage cancer patients. Of these encounters, 35% included a provider communication about “physical activity”, “exercise” or “activity”. Encounters with a medical oncologist resulted in a PA communication 55% of the time as compared to 20% of encounters with other clinician specialties (p &lt; 0.0001). Older patients were more likely than younger patients to have a PA communication (p &lt; 0.001). When the encounter was with a patient who was being seen for surveillance, chemotherapy or endocrine treatment, the rate of PA communications was significantly higher (46%, 37%, 58% respectively) as compared to when the visit was during radiation treatment or surgery (6%, 19% respectively) (p &lt; 0.0001). Four PA themes emerged from our analysis of provider communications: (1) level and types of engagement in PA, (2) restrictions on PA either by the provider or perceived by patients, (3) encouragement or recommendations, or (4) relationships between PA and weight, nutrition, pain, and fatigue. There were no significant differences in PA communication rates by clinician gender, clinician training, patient gender, patient race, or disease site. Conclusions: This study shows it is feasible for oncology providers to have PA communications during routine clinic visits; however, the frequency of PA communications varies among providers. Interventions are needed to remind all oncology providers to encourage of their patients with early stage cancer to be physically active.

Physical activity interests and preferences of cancer patients with brain metastases: a cross-sectional survey.

BackgroundPhysical activity has been shown to positively impact cancer-related fatigue, physical functioning and quality of life outcomes in early stage cancer patients, however its role at the end stage of cancer has yet to be determined. Brain metastases are amongst the most common neurological complications of advanced cancer, with significant deterioration in fatigue and quality of life. The purpose of the present study was to examine the physical activity interests and preferences of cancer patients with brain metastases initiating palliative whole brain radiotherapy.MethodsThirty-one patients aged 18 years or older, cognitively intact, diagnosed with brain metastases, and with Palliative Performance Scale scores of greater than 30 %, were recruited from a multidisciplinary outpatient brain metastases clinic. An interviewer-administered survey was used to assess physical activity interests and preferences of participants who were embarking upon palliative whole brain radiotherapy.Results87 % (n = 27) of participants felt that physical activity was important, however there was limited interest in participating in a structured program at the onset of palliative whole brain radiotherapy. Lung cancer diagnosis was associated with being less interested in participating in a physical activity program, and feeling less able to participate in a physical activity program at the onset of palliative whole brain radiotherapy.ConclusionsCancer patients with brain metastases demonstrate limited interest and varied preferences for physical activity during palliative whole brain radiotherapy. Additional pilot work with this patient population is needed before physical activity interventions can be tested in clinical research.