Diagnosis Of Metastatic Cancer Research Articles

Fab-conjugated PLGA nanoparticles effectively target cancer cells expressing human CD44v6

Targeting of CD44 isoforms containing exon v6 (CD44v6) represents a viable strategy for the therapy and/or early diagnosis of metastatic cancers of the epithelium (e.g. gastric and colorectal cancer). We developed and characterized poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) modified with polyethylene glycol (PEG) and engrafted, by site-directed conjugation, with an engineered human Fab that specifically target human CD44v6 (v6 Fab-PLGA NPs). The v6 Fab-PLGA NPs displayed spherical morphology around 300 nm and were negatively charged. They strongly bound to a CD44v6-derived peptide and, more importantly, to cells that endogenously and exogenously express CD44v6, but not to non-expressing cells and cells expressing the standard isoform of CD44. The v6 Fab-PLGA NPs also recognized CD44v6 in tumor sections from cells grown subcutaneously within mice. The NPs had nominal cytotoxicity at 50 µg/mL and withstood simulated intestinal fluid exposure. Interestingly, v6 Fab-PLGA NPs cryopreserved in 10% trehalose and stored maintained specific cell binding. In conclusion, we envision NPs targeting CD44v6 as potential in vivo diagnostic agents and/or as anti-cancer agents in patients previously stratified with CD44v6+ carcinomas. Statement of SignificanceThe v6 Fab-PLGA NPs displayed many favorable qualities as a potential CD44v6-targeted drug and/or diagnostic delivery agent. The NPs were designed for optimal ligand orientation and for immediate administration into humans.v6 Fab-PLGA NPs strongly bound to cells that endogenously and exogenously express CD44v6, but not to non-expressing cells and cells expressing the standard isoform of CD44. Binding ability was retained after freeze-drying and long-term storage, providing evidences on the stability of Fab-functionalized NPs.These NPs can potentially be used as an in vivo diagnostic from parenteral or oral/rectal administration.

A comprehensive gene mutation analysis of liquid biopsy samples from patients with metastatic colorectal cancer to the ovary: A case report.

Liquid biopsies of circulating tumor DNA (ctDNA) can detect molecular alterations, including tumor-specific mutations, and have recently been used as a non-invasive diagnostic, prognostic, and predictive tool. However, this technique is not commonly used in the gynecological field. Gene mutation profiling of liquid biopsy samples was performed using CAncer Personalized Profiling by deep Sequencing (CAPP-Seq), a novel next-generation sequencing-based approach to ultrasensitive ctDNA detection, in order to make it possible to molecularly diagnose metastatic colorectal cancer to the ovary. Liquid biopsy (plasma) samples and formalin-fixed paraffin-embedded tumor samples were obtained from two patients with ovarian tumors, who had a history of surgery for colorectal cancer, and comprehensive gene mutation profiling was conducted using CAPP-Seq. In patient 1, mutations were identified in the same three regions in both the ovarian tumor and preoperative plasma sample (in the KRAS G13D, APC E1306*, and TP53 H193Y genes). In patient 2, mutation was identified in the same one region in all the primary colorectal tumor, the ovarian tumor, and preoperative plasma sample (in APC R216* gene). These mutations are well-known genetic signatures of colorectal cancer, suggesting that the ovarian tumor was metastatic. Tthe gene mutation patterns of colorectal cancer were examined by subjecting liquid biopsy samples from patients with suspected metastatic ovarian tumors to CAPP-Seq. Gene mutation profiling of liquid biopsy samples can contribute to the preoperative differential diagnosis of metastatic ovarian cancer and its subsequent personalized treatment.

Methods for identifying health state transitions from administrative data: the case of metastasis in prostate cancer

IntroductionHealth administrative data are a rich source of population-based information, useful for building state transition models for medical decision making. These models require identification of health state transitions and associated times. Indirect methods are needed to predict this information, as it is rarely available in administrative data.
 Objectives and ApproachWe considered a set of criteria to identify transitions to metastasis for prostate cancer patients in administrative data, utilizing dates of diagnostic and medical billing codes for secondary malignancy, palliative radiation therapy, chemotherapy and bone disorders or procedures. We evaluated the criteria using the true date of metastasis from medical charts of 195 patients linked to health care administrative data in Ontario, Canada. We also built a recursive partitioning tree to optimally combine these criteria and construct rules for identifying metastatic patients. For the evaluation, both misclassification and discrepancy between true and predicted dates for the true positives were considered.
 ResultsCriteria involving chemotherapy drugs or hospital visits with secondary malignancy ICD10 diagnosis gave the best results, with high sensitivity and specificity. Criteria involving bone related problems, radiation therapy or diagnosis of metastatic cancer in physician billing data were very specific but not sensitive. The criterion involving prescriptions for narcotics was sensitive but not specific. The fitted tree was parsimonious involving only two of the criteria, while improving the accuracy over individual criteria. Most criteria gave a “delayed” prediction, with criterion based on chemotherapy giving on average the smallest delay, as well as exhibiting the least variability. Criteria involving narcotics and bone related problems predicted metastasis date very prematurely, probably triggered by conditions other than prostate cancer.
 Conclusion/ImplicationsSeveral criteria from administrative databases satisfactorily classified prostate cancer patients with metastasis. A classification tree was built and improved the results over single criteria, demonstrating the added benefits in using advanced statistical learning methods for this task. However, “transition to metastasis” dates were predicted inaccurately, often with significant delay.

Impact of Time to Start Systemic Therapy on the Outcomes of Patients with Metastatic Colorectal Cancer Treated with First Line FOLFOX Chemotherapy; a Patient-Level Pooled Analysis of Two Clinical Trials

ABSTRACTBackground: Impact of time to start first-line systemic chemotherapy following diagnosis of metastatic colorectal cancer (mCRC) needs to be studied.Methods: This is a pooled analysis of the raw data of the comparator arms of two randomized studies (NCT00272051; NCT00305188). Univariate and multivariate analyses of predictors of overall and progression-free survival were conducted through Cox regression analysis. Factors with statistically significant P value (P < 0.05) in the univariate part of the analysis were included in the multivariate analysis.Results: In univariate analysis, time to start systemic therapy did not affect overall or progression-free survival (P=0.694; P= 0.891 respectively). In multivariate analysis for overall survival, the following factors were predictive of worse overall survival: younger age (P = 0.019), higher ECOG performance score (P = 0.001), more than one site of metastatic disease (P = 0.002), colon site of the primary tumor (P = 0.004), and no oncologic surgery to the primary tumor (P < 0.001). Likewise, in multivariate analysis for progression-free survival, the following factors were predictive of worse progression-free survival: no oncologic surgery to the primary (P < 0.001), more than one organ of metastatic disease (P < 0.001), and no concurrent bevacizumab administration (P = 0.015).Conclusion: Time to start systemic chemotherapy does not appear to impact overall or progression-free survival among mCRC patients.

Gynecologic Oncologists’ Perceptions of Palliative Care and Associated Barriers: A Survey of the Society of Gynecologic Oncology

Objectives: Gynecologic oncologists frequently care for patients at the end of life with the aid of palliative care (PC) specialists. Our primary objectives were to identify perceived barriers to integrating specialty PC into gynecologic cancer care. Materials and Methods: Members of the Society of Gynecologic Oncology (SGO) were invited to participate in an anonymous online survey. A Likert scale captured perceptions regarding primary and specialty PC, frequent barriers to use of PC, and potential interventions. Results: A total of 174 (16%) gynecologic oncologists completed the survey. The majority (75%) agreed or strongly agreed that PC should be integrated into cancer care at diagnosis of advanced or metastatic cancer. The most frequently perceived PC barriers included patients’ unrealistic expectations (54%), limited access to specialty PC (25%), poor reimbursement (25%), time constraints (22%), and concern of reducing hope or trust (21%). The most agreed upon potential intervention was increased access to outpatient PC (80%). Conclusions: According to this cohort of SGO members, families’ or patients’ unrealistic expectations are the most frequent barriers to specialty PC. Understanding this communication breakdown is critically important.

Being Present: A single-arm feasibility study of audio-based mindfulness meditation for colorectal cancer patients and caregivers.

A metastatic cancer diagnosis is associated with high levels of distress in patients and caregivers. Mindfulness interventions can reduce distress and improve quality of life in cancer patients. However, standard mindfulness training relies on in-person instruction, which is often not practical for either patients receiving chemotherapy or their caregivers. In the Being Present single arm pilot study, we designed and tested an 8-week audio-based mindfulness meditation program for patients with metastatic colorectal cancer receiving chemotherapy with or without a participating caregiver. The study accrued 33 of 74 (45%) eligible patients consenting together with 20 family caregivers (53 participants total) within nine months. Forty-one participants were evaluable (77%); 10 of 12 cases of attrition were attributable to hospitalization or death. Median participant age was 51 (range 21–78 years); 38% were men. Baseline levels of distress were similar in patients and caregivers. The top reasons for participation cited in pre-intervention interviews were to increase relaxation/calm, improve mood/emotions, and reduce stress/anxiety. In measures of adherence, 59% of responses to weekly texts asking: “Have you practiced today?” were “Yes” and 59% of interviewees reported practicing >50% of the time. Compared to baseline, post-intervention surveys demonstrated significantly reduced distress (p = 0.01) and anxiety (p = 0.03); as well as increased non-reactivity (p<0.01), and feeling at peace (p<0.01). Post-intervention qualitative interviews, where 71% of participants reported benefit, were consistent with quantitative findings. In the interviews, participants spontaneously described reduced stress/anxiety and increased relaxation/calm. Benefits appeared to be accentuated in patient-caregiver pairs as compared to unpaired patients. Seventy-nine percent of participants reported plans for continued practice after study completion. We conclude that the Being Present audio-based mindfulness meditation program is of interest to, feasible, and acceptable for patients with metastatic colorectal cancer and caregivers, with initial evidence of efficacy. These results will guide plans for a follow-up study.Trial registration: ClinicalTrials.gov NCT02423720

Effectiveness of palliative care services: A population-based study of end-of-life care for cancer patients

Background: Multiple studies demonstrate substantial utilization of acute hospital care and, potentially excessive, intensive medical and surgical treatments at the end-of-life. Aim: To evaluate the relationship between the use of home and facility-based hospice palliative care for patients dying with cancer and service utilization at the end of life. Design: Retrospective, population-level study using administrative databases. The effect of palliative care was analyzed between coarsened exact matched cohorts and evaluated through a conditional logistic regression model. Setting/participants: The study was conducted on the cohort of 34,357 patients, resident in Emilia-Romagna Region, Italy, admitted to hospital with a diagnosis of metastatic or poor-prognosis cancer during the 6 months before death between January 2013 and December 2015. Results: Patients who received palliative care experienced significantly lower rates of all indicators of aggressive care such as hospital admission (odds ratio (OR) = 0.05, 95% confidence interval (CI): 0.04–0.06), emergency department visits (OR = 0.23, 95% CI: 0.21–0.25), intensive care unit stays (OR = 0.29, 95% CI: 0.26–0.32), major operating room procedures (OR = 0.22, 95% CI: 0.21–0.24), and lower in-hospital death (OR = 0.11, 95% CI: 0.10–0.11). This cohort had significantly higher rates of opiate prescriptions (OR = 1.27, 95% CI: 1.21–1.33) (p < 0.01 for all comparisons). Conclusion: Use of palliative care at the end of life for cancer patients is associated with a reduction of the use of high-cost, intensive services. Future research is necessary to evaluate the impact of increasing use of palliative care services on other health outcomes. Administrative databases linked at the patient level are a useful data source for assessment of care at the end of life.

Trends of Earlier Palliative Care Consultation in Advanced Cancer Patients Receiving Palliative Radiation Therapy

ContextThe American Society of Clinical Oncology recommends that all patients with metastatic disease receive dedicated palliative care (PC) services early in their illness, ideally via interdisciplinary care teams. ObjectivesWe investigated the time trends of specialty palliative care consultations from the date of metastatic cancer diagnosis among patients receiving palliative radiation therapy (PRT). A shorter time interval between metastatic diagnosis and first PC consultation suggests earlier involvement of palliative care in a patient's life with metastatic cancer. MethodsIn this IRB-approved retrospective analysis, patients treated with PRT for solid tumors (bone and brain) at a single tertiary care hospital between 2010 and 2016 were included. Cohorts were arbitrarily established by metastatic diagnosis within approximately two-year intervals: 1) 1/1/2010–3/27/2012, 2) 3/28/2012–5/21/2014, and 3) 5/22/2014–12/31/2016. Cox proportional hazards regression modeling was used to compare trends of PC consultation among cohorts. ResultsOf 284 patients identified, 184 patients received PC consultation, whereas 15 patients died before receiving a PC consult. Median follow-up time until an event or censor was 257 days (range: 1900). Patients in the most recent cohort had a shorter median time to first PC consult (57 days) compared to those in the first (374 days) and second (186 days) cohorts. On multivariable analysis, patients in the third cohort were more likely to undergo a PC consultation earlier in their metastatic illness (hazard ratio: 1.8, 95% CI: 1.2–2.8). ConclusionOver a six-year period, palliative care consultation occurred earlier for metastatic patients treated with PRT at our institution.

Relationship of healthcare costs and disease progression in patients with HER2+ breast cancer.

e13013 Background: Reducing disease recurrence with better treatments in the adjuvant setting may alleviate the economic burden associated with metastatic disease in HER2 positive breast cancer (BC). Analyses were performed to complement existing literature on the cost of metastatic HER2+ breast cancer given the introduction of new treatment options since 2012. Methods: We performed a retrospective cohort study using Truven Marketscan 2011-2016 commercial and Medicare administrative claims data. Metastatic BC patients were followed for up to three years and healthcare costs (hospital stays, prescription costs, outpatient services) were analyzed. An additional matched cohort analysis was performed for recurrent patients, selecting adjuvant treated patients who did not progress with similar age, year of initial anti-HER2 treatment, anti-HER2 treatment duration and follow-up duration. Results: Three year costs following a diagnosis of metastatic BC cancer were $470,240. The matched cohort analysis showed patients with metastatic BC incurred costs greater than $240,000 vs. less than $20,000 for a cohort of adjuvant treated patients who did not progress in the first year post-index date. Average Healthcare Costs After Metastasis in HER2+ Breast Cancer Conclusions: Total healthcare costs in the first year after metastatic diagnosis was high in HER2+ breast cancer patients. Relative to healthcare costs in patients treated in the early BC setting who did not progress, metastatic BC costs were over $240,000 vs less than $20,000 for a comparable cohort of patients. Reducing recurrences with better treatment in the adjuvant setting may be important in alleviating the economic burden associated with HER2 positive metastatic breast cancer Sample Costs in the 1st year after metastasis Mean (SE) Costs in 2 years after metastasis Mean (SE) Costs in 3 years after metastasis Mean (SE) Pts with at least 1yr follow-up (N = 1,799) 267,485 (3,737) Pts with at least 2yr follow-up (N = 910) 257,316 (5,257) 382,115 (8,704) Pts with at least 3yr follow-up (N = 391) 248,759 (7,904) 366,811 (13,383) 470,240 (18,672)

Metastasis of gastric adenocarcinoma in the endometrium and the cervix. Сlinical case

Comprehensive approach and a highly qualified morphological analysis are important conditions for timely diagnosis and development of tactics of pathogenetic treatment of cancer patients. This clinical case demonstrates a multimodal approach to the differential diagnosis of metastatic cancer. Due to oncological alertness, the clinical data, qualitative morphological study and close cooperation of all participants in a multidisciplinary group a metastasis of the gastric signet-ring cell carcinoma was diagnosed in the cervix, allowing to optimize treatment of the patient.

European guidelines on perioperative venous thromboembolism prophylaxis: Cardiovascular and thoracic surgery.

: None of the predictive models for venous thromboembolism (VTE) prophylaxis have been designed for and validated in patients undergoing cardiothoracic and vascular surgery. The presence of one or more risk factors [age over 70 years old, transfusion of more than 4 U of red blood cells/fresh frozen plasma/cryoprecipitate, mechanical ventilation lasting more than 24 h, postoperative complication (e.g. acute kidney injury, infection/sepsis, neurological complication)] should place the cardiac population at high risk for VTE. In this context, we suggest the use of pharmacological prophylaxis as soon as satisfactory haemostasis has been achieved, in addition to intermittent pneumatic compression (IPC) (Grade 2C). In patients undergoing abdominal aortic aneurysm repair, particularly when an open surgical approach is used, the risk for VTE is high and the bleeding risk is high. In this context, we suggest the use of pharmacological prophylaxis as soon as satisfactory haemostasis is achieved (Grade 2C). Patients undergoing thoracic surgery in the absence of cancer could be considered at low risk for VTE. Patients undergoing thoracic surgery with a diagnosis of primary or metastatic cancer should be considered at high risk for VTE. In low-risk patients, we suggest the use of mechanical prophylaxis using IPC (Grade 2C). In high-risk patients, we suggest the use of pharmacological prophylaxis in addition to IPC (Grade 2B).

European Guidelines on perioperative venous thromboembolism prophylaxis: Executive summary.

European Guidelines on perioperative venous thromboembolism prophylaxis: Executive summary.

Three-dimensional graphene biointerface with extremely high sensitivity to single cancer cell monitoring

We developed a three-dimensional biointerface of graphene-based electrical impedance sensor for metastatic cancer diagnosis at single-cell resolution. Compared with traditional impedance sensor with two-dimensional interface, the graphene biointerface mimiced the topography and somatotype features of cancer cells, achieving more comprehensive and thorough single cell signals in the three-dimensional space. At the nodes of physiological behavior change of single cell, namely cell capture, adhesion, migration and proliferation, the collected electrical signals from graphene biointerface were about two times stronger than those from the two-dimensional gold interface due to the substantial increase in contact area and significant improvement of topographical interaction between cells and graphene electrode. Simultaneous CCD recording and electrical signal extraction from the entrapped single cell on the graphene biointerface enabled to investigate multidimensional cell-electrode interactions and predict cancerous stage and pathology.

Development and evaluation of a CEACAM6-targeting theranostic nanomedicine for photoacoustic-based diagnosis and chemotherapy of metastatic cancer.

Metastasis is the leading cause of cancer-related deaths. A number of chemotherapeutic and early diagnosis strategies, including nanomedicine, have been developed to target metastatic tumor cells. However, simultaneous inhibition and imaging of metastasis is yet to be fully achieved.Methods: To overcome this limitation, we have developed human serum albumin-based nanoparticles (tHSA-NPs) with photoacoustic imaging capability, which target carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6). CEACAM6 is highly expressed in metastatic anoikis-resistant tumor cells.Results: In vitro, the CEACAM6-targeting tHSA-NPs efficiently targeted CEACAM6-overexpressing metastatic anoikis-resistant tumor cells. In vivo, CEACAM6-targeting tHSA-NPs administered intravenously to BALB/c nude mice efficiently inhibited lung metastasis in circulating anoikis-resistant tumor cells compared to the controls. In addition, anoikis-resistant tumor cells can be successfully detected by photoacoustic imaging, both in vitro and in vivo, using the intrinsic indocyanine green-binding affinity of albumin.Conclusion: In summary, the CEACAM6-targeting albumin-based nanoparticles allowed the delivery of drugs and photoacoustic imaging to metastatic anoikis-resistant tumor cells in vitro and in vivo. Based on the expression of CEACAM6 in a variety of tumors, CEACAM6-targeting nanomedicine might be used to target various types of metastatic tumor cells.

Disease-specific graded prognostic assessment lung cancer update

Lung cancer accounts for almost 30% of cancer deaths. Length of survival after diagnosis of metastatic lung cancer, however, spans a significant range today. While some patients still only survive in the order of a few weeks to months, an increasing percentage are living years due to the recognition of different types of lung cancer genetics and the ability to treat patients in a personalized fashion with targeted therapies.

Integrated Multifunctional Electrochemistry Microchip for Highly Efficient Capture, Release, Lysis, and Analysis of Circulating Tumor Cells.

The circulating tumor cells (CTCs) in the blood allow the noninvasive analysis of metastatic mechanisms, cancer diagnosis, prognosis, disease monitoring, and precise therapy through "liquid biopsies". However, there is no integrated and robust multifunctional microchip, which not only could highly efficient capture CTCs, but also fast release and lyse cells on one single chip without using other biochemical agents for downstream biomedical analysis. In this work, we integrated the three functions in one electrochemical microchip (echip) by intentionally designing a cactus-like, topologically structured conductive array consisted of a PDMS micropillar-array core and an electroconductive gold coating layer with hierarchical structure. The echip presented a capture efficiency of 85-100% for different cell lines in both buffer solution and whole blood. Moreover, the validity of the echip was further evaluated by using non-small-cell lung cancer patient samples. The electrochemical released cells or lysed-cell solutions could be obtained within 10 min and have been successfully used for mutant detection by DNA sequencing or RT-PCR. The fast release at a relative low voltage (-1.2 V) was originating from an electrochemical cleavage of the Au-S bonds that immobilized antibody on the chip. The electrochemical lysis took place at a high voltage (20 V) with an admirable performance. Thus, the highly integrated multifunctional echip was well demonstrated and promised a significant application in the clinical field.

Characteristics of urgent palliative cancer care consultations encountered by radiation oncologists.

135 Background: Palliative radiation therapy(PRT)is often employed in patients with advanced cancers requiring urgent consultation given the rapidity of presentation.We report on characteristics of urgent palliative oncologic issues encountered by radiation oncologists(RO). Methods: We prospectively evaluated patterns of presentation in162 consecutive consultations for urgent PRT at 3 centers from 5/19/14 to 9/26/14.Survey of palliative care issues was completed by physicians/nurse practitioners including assessment of reasons for urgent radiation oncology consultation,disease presentation characteristics and site of RT delivery.Response rate was 86% with 140 of 162 responses received. Results: Median age of patients was 63 years(29-89)with 39% &gt; 65, 41% from 50-65 and 20% &lt; 50 years;56% were males and 44% females. Most were married(62%)and 30% non-Caucasians.48% had ECOG PS 0-1,whereas it was 2, 3 and 4 in 24%,9% and 3%.Primary cancer diagnoses were lung (28%),breast(13%),prostate(10%),melanoma(10%),sarcoma(7%) and other diagnoses in 32%.Pain was predominant reason for consult(57%)followed by brain metastases(29%),spinal cord/cauda compression (13%),dyspnea (10%),bleeding (8%),bone fracture(4%)and dysphagia(2%).Clinicians managed pain (69%),neurologic symptoms(51%),fatigue (49%),intestinal(21%),respiratory (19%) symptoms,bleeding (14%),insomnia (13%),nausea/vomiting(12%)and dysphagia(6%).Patients presented at all stages 79% at the time of their diagnosis of metastatic cancer,63% with an established ( &gt; 1 month) metastatic cancer diagnosis and continuing to further cancer therapies and 17% proceeding to hospice care without further anti-cancer therapy after PRT. Conclusions: Radiation oncologists care for patients across time course of metastatic cancer diagnosis managing variety of urgent oncologic issues,most commonly metastases causing pain followed by brain metastases and cord compression.They also manage cancer-related symptoms,mostly pain,neurological symptoms and fatigue.These findings point to need for palliative care to be well integrated into radiation oncology practice including education and systems of care.

Eyelid metastasis as first presentation of renal cell carcinoma

Abstract Case report An 87-year-old male presented with a slow-growing, painless and well defined nodule in the upper eyelid. The tumor measured 1 cm, and was pigmented and adhered to deep planes. The histopathology analysis was compatible with renal cell carcinoma. The extension study showed a tumor mass in each kidney, as well as multiple pulmonary metastases. Discussion The ophthalmologist can play an important role in the diagnosis of metastatic cancer when eye disease is present. Therefore, the importance of a biopsy should be noted in those suspicious and/or recurrent lesions of the eyelid.

Goals of care documentation in advanced cancer.

58 Background: Documenting goals of care (GOC) is integral to patient centered care, decision making and quality performance. Studies show patients value conversations about GOC after receiving a terminal diagnosis. Positive effects have been demonstrated for survival, quality of life, disease management and healthcare savings. The ASCO QOPI recommends documentation within 3 visits from diagnosis of metastatic cancer. For hospital inpatients, GOC are more often integrated into care planning, as admissions frequently reflect changes in illness trajectory, yet documentation remains poor. This Quality Improvement (QI) initiative aims to increase GOC documentation for ambulatory patients and referral rates to Palliative Medicine. Methods: A retrospective cohort receiving palliative chemotherapy for metastatic lung, pancreas, colorectal and breast cancers during 2010-2015 were identified from pharmacy records at a Canadian Regional Cancer Centre. Inclusion criteria required a minimum of 4 clinic visits post treatment. Clinical notes of Oncologists and Palliative Medicine Physicians were reviewed for GOC documentation and referrals to Palliative Medicine. Baseline data determined improvement target rates. A clinical practice QI initiative applied passive and active phases, beginning May 2016. Passive phase included the development of a guideline, documentation template and referral process. The active phase is the implementation process (ongoing). Results: A cohort included 456 patients with metastatic cancer, 63% lung cancer. Oncologists documented GOC in 6% (26/456) and referred 47% to Palliative Medicine. GOC rate was 48% post-referral. Improvement target rates were set at 40% and for referrals 70% by March 2017. Analysis during the passive phase showed Oncologists’ GOC documentations increased to 15%. Analysis of the active phase is ongoing and preliminary results will be presented. Conclusions: Low rates of GOC documentation and referrals to Palliative Medicine persist. The passive phase of engaging physicians in the QI development positively influenced GOC documentation. This QI initiative will inform the sustainability of GOC documentation, Palliative Medicine referrals and standardization of institutional guidelines.

Metastatic Cancer in the Middle Age: The Possible Case of a Female Skeleton from Bormio (Italy)

AbstractSecondary signs of cancer are difficult to assess in the archaeological context, as other lesions may mimic metastases on dry bones. Furthermore, the low life expectancy, lower level of environmental cancer risk factors and pollution than the present times can contribute in limiting the frequency of signs of cancer in archaeological populations.This study focuses on a female adult skeleton from the necropolis of Bormio (North Italy), dating back to Middle Ages, which shows multiple lytic lesions on cranium, upper limbs, ribs and pelvis; lesions are oval in shape, with a diameter ranging from 1–2 to 80 mm. The lesions appearance and distribution at macroscopic and radiographic level, together with sex and age indications, suggest the diagnosis of metastatic cancer. Possible diagnostic hypotheses of the possible sites of original cancer were performed as well, based on modern epidemiological data. Copyright © 2017 John Wiley &amp; Sons, Ltd.