bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurological morbidity in survivors of childhood acute lymphoblastic leukemia (ALL)
Authors: Morris B. , Khan R. , Ledet D. , Howell C. , Pui C. , Hudson M. , Ness K.
Published: August 2020

9529

Background: The majority of children diagnosed with ALL over the past two decades have achieved long-term survival. This remarkable success is attributed in part to intensive central nervous system (CNS)-directed therapy that effectively prevents CNS relapse. Because treatment-related neurological morbidity is recognized but poorly characterized, the objective of this cross-sectional study was to estimate the prevalence of neurological symptoms and signs in long-term survivors of childhood ALL. Methods: After obtaining IRB approval, all long-term ALL survivors (≥ 5 years since diagnosis) aged 6–28 years who remained active patients at our institution were identified. All participants completed a questionnaire consisting of independent (and when possible validated) instruments designed to identify various neurological symptoms, as well as, a comprehensive and standardized neurologic examination by a board-certified neurologist. Results: Of the 433 potentially eligible subjects, 162 (37.4%) were enrolled. Participant demographic information and previous treatment exposure were similar to those not enrolled in the study. The rates of endorsed neurological symptoms were: neuropathy (40.1%), dizziness (33%), back pain (22.8%), fatigue (19.1%), falls (15.4%), headache (14.8%), seizures (10.5%), urinary incontinence (8.6%), and stroke (1.2%). Neurological examination confirmed an underlying sensory neuropathy in 44 patients (27.3%). Otherwise, signs of chronic cranial nerve dysfunction (1.9%) and motor weakness (5.6%) were rare. Conclusions: Symptoms and signs of a chronic sensory neuropathy, presumably from previous vincristine exposure, were evident in many patients. Complaints of fatigue, dizziness, and chronic back pain were also relatively common. The number of patients who routinely fall is of concern. Whether these falls are associated with symptoms/signs of neuropathy, weakness, and/or dizziness will require further analysis. Although headache was a common complaint, its prevalence may not differ significantly from a normal age-matched population.

No significant financial relationships to disclose.
How often is adjuvant FOLFOX (Adj FOLFOX) discontinued for toxicity among colon cancer patients in the routine care setting?
Authors: Romanus D. , Weiser M. , TerVeer A. , Skibber J. , Wilson J. , Rajput A. , Wong Y. , Benson A. , Niland J. , Schrag D.
Published: August 2020

9530

Background: Although 12 cycles of Adj FOLFOX are recommended for stage III and high risk stage II colon cancer, toxicity may preclude completion of treatment. We used the NCCN Colorectal Cancer Outcomes Database to identify how frequently Adj FOLFOX is discontinued prematurely for toxicity in a non-clinical trial population. Methods: Newly diagnosed stage II-III colon cancer pts treated with Adj FOLFOX at 7 NCI-designated comprehensive cancer centers between 9/05–12/07 were identified. We assessed completion of the prescribed adjuvant chemotherapy (AC) course, including Adj FOLFOX and 5FU-based adjuvant treatment alone subsequent to discontinuation of oxaliplatin (oxal). Dose limiting toxicity (DLT) of Adj FOLFOX was defined as premature discontinuation of Adj FOLFOX due to toxicity. We evaluated potential predictors of Adj FOLFOX DLT, including older age and history of diabetes in a multivariable logistic model controlling for stage and center. We measured the duration of Adj FOLFOX use in weeks, from first to last dose. Results: 293 pts began Adj FOLFOX. Pts who experienced DLT (40%) had a shorter duration of Adj FOLFOX and were less likely to complete AC, even after oxal was discontinued. The only significant predictor of experiencing a DLT was a history of diabetes. Conclusions: Our analysis of patients treated outside of a clinical trial demonstrated a notably high rate of discontinuation of Adj FOLFOX due to DLT, particularly in pts with diabetes. The results underscore the need for systematic assessment of toxicity especially among diabetics.

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Correlation between docetaxel-induced skin toxicity and the use of steroids and H2 blockers: A multi-institution survey
Authors: Kawaguchi K. , Ishiguro H. , Morita S. , Nakamura S. , Ohno S. , Masuda N. , Iwata H. , Aogi K. , Kuroi K. , Toi M.
Published: August 2020

9536

Background: Docetaxel is a standard drug used for adjuvant or neoadjuvant chemotherapeutic treatment of early breast cancer. With appropriate management of chemotherapy-induced bone marrow toxicity, skin toxicities such as hand-foot syndrome (HFS) and facial erythema (FE) have become dose-limiting. Steroids and H2 blockers are commonly used to provide supportive care to patients being treated with taxane-containing chemotherapeutic regimens, but their effects on skin toxicity are poorly understood. Methods: We asked institutions belonging to the JBCRG to complete a questionnaire regarding the occurrence of grade 2 or higher HFS and FE among patients treated with docetaxel as an adjuvant or neoadjuvant chemotherapeutic treatment for breast cancer between April 2007 and March 2008. Data collected were docetaxel dose, other chemotherapeutic agents administered, dosage regimens for the steroids and H2 blockers (if used), and incidences of grade 2 or higher HFS or FE. Statistical analyses were performed using the chi-squared test. Results: We obtained data for 989 patients from 22 institutions. Most patients received docetaxel at a dose of 75 mg/m2 and 852 patients were treated with docetaxel monotherapy. HFS and FE occurred in 18% and 13% of patients, respectively. The relationships between the incidence of skin toxicity and (i) chemotherapy regimen and (ii) use of H2 blockers are shown below ( Table ). Conclusions: Our data suggest that use of H2 blockers as premedication in breast cancer patients treated with docetaxel significantly increases the risk of both HFS and FE.

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[Table: see text]
Incorporation of a Comprehensive Geriatric Assessment (CGA) into a randomized phase III trial for metastatic breast cancer: The PELICAN Study
Authors: de Wit M. , Harbeck N. , Scholz M. , Lerbs W. , Wedding U. , Honecker F.
Published: August 2020

9551

Background: The PELICAN trial is a randomized phase III trial evaluating efficacy and safety of pegylated liposomal doxorubicin (PLD) versus capecitabine as first-line therapy in patients (pts) with metastatic breast cancer who are not considered candidates for combination chemotherapy. Randomisation was stratified according to age (cut-off 65 years) and anthracycline pretreatment. CGA results and adverse events (AEs), dose reductions, and number of applied cycles were evaluated. Methods: CGA comprised data on activities of daily living (ADL), instrumental activities of daily living (IADL), ECOG and Karnofsky performance score, comorbidity (CIRS-G), and number of comedication. According to CGA, pts were classified into groups 1–3 (Balducci 2000). Associations of CGA groups and single CGA items with outcome measures were assessed using Fisher's exact test, Wilcoxon test, and logistic regression. Results: Results of 210 pts, mean age 61 years (SD 11; range 22–85) were analysed. According to CGA, 102 pts were considered fit (group 1, 72%), 21 compromised (group 2, 15%), and 19 frail (group 3, 13%). Age was associated neither with overall AEs, nor with dose reductions or number of applied cycles. However, the following significant associations were observed: any AE and number of comedication (p=0.026); less hand foot syndrome (HFS) and CGA group 2/3 (p=0.032); and more constitutional symptomes and age >=65 as well as CGA group 2/3 (p=0.002 and 0.015, respectively). Comedication was the variable most frequently associated with single AEs (dermatology other than HFS, p=0.038; gastrointestinal, p=0.035; constitutional symptomes, p=0.002; pain, p=0.001; pulmonary, p<0.0001; fatigue, p=0.01). Whereas no association between any item and dose reduction was found, CIRS-G grade 3–4 was associated with a reduced number of applied cycles (p=0.049). Conclusions: Incorporation of CGA into a phase III trial is feasible and yields information that would otherwise have been missed. Results of CGA should be validated prospectively in treatment algorithms for this population.

[Table: see text]
Retrospective claims database analysis of elderly compared with nonelderly patients (pts) with newly diagnosed hepatocellular carcinoma (HCC)
Authors: Sanyal A. J. , Moyneur E. , Barghout V.
Published: August 2020

9552

Background: HCC is the most common type of liver cancer in the US and its incidence has been rising. We assessed whether differences existed in risk factors and treatment practices in pts with HCC by age. Methods: De-identified, individual-level healthcare claims data from a database (MarketScan MedStat) covering all US census regions for ≥18 million lives in 2002–2008 were retrospectively analyzed. Pts had ≥2 claims for primary HCC (ICD9 155.0), continuous healthcare coverage, >180 days of coverage before HCC, and no prior claims for secondary liver cancer (ICD9 197.7). Pts were followed longitudinally from HCC diagnosis until end of healthcare coverage or 3/31/08. Pts were stratified by age (<65 or ≥65 y), and treatment was analyzed using prevalence and time to initiation. Results: Of 4,153 pts with HCC identified, 46.3% were ≥65 y. Risk factors in the groups were nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH, 59% for <65 vs 50% for ≥65), hepatitis C (32% vs 11%), diabetes (29% vs 40%), alcoholic cirrhosis (16% vs 7%), and hepatitis B (9% vs 3%). Treatments were similar between groups; however, more pts in the younger group received transplantation, IV chemotherapy, and hospice care ( Table ). Twice as many older pts did not receive any of the considered treatment compared with younger pts. Sorafenib, approved for unresectable HCC in 11/07, was used in a limited number of pts in the groups. Most noncurative treatment options were initiated sooner in pts ≥65 y than those <65 y, whereas the opposite holds for the 2 main curative treatments (transplantation and cancer removal surgery). Conclusions: Regardless of age, principal risk factors associated with HCC were NAFLD/NASH, diabetes, and hepatitis C. Based on this retrospective claims analysis, variations between treatment options and time to initiation did differ between the groups, suggesting that underlying comorbidities and practice patterns affect treatment options in elderly and nonelderly pts with HCC.

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Predictors of deep vein thrombosis (DVT) in newly diagnosed multiple myeloma (MM) patients with and without prophylactic recombinant erythropoietin (EPO) therapy
Authors: Coleman E. A. , Anaissie E. J. , Kennedy R. L. , Lockhart K. D. , Stewart C. B. , Bailey C.
Published: August 2020

9554

Background: DVT, a complication among newly diagnosed MM patients, is most common during the first 3–4 months of therapy. EPO, given to treat anemia in patients receiving chemotherapy, has been associated with increased DVT risk and the mechanism, thought to be related to rise in hemoglobin, remains unknown. Methods: All 604 patients with newly diagnosed MM who completed the induction phase (∼ 3–4 months) of treatment were included. Induction consisted of multiagent chemotherapy with upfront randomization to thalidomide (THAL) or no THAL. 122 patients were also enrolled in an exercise study that included prophylactic EPO. Venous thromboembolism, defined as Doppler confirmed DVT and/or pulmonary embolus during induction, was the primary endpoint. Univariate analyses provided group comparisons. Logistic regression analysis determined predictors of DVT. Results: EPO and No EPO groups were similar for THAL use, age, race, gender, BMI, DVT history, and key baseline laboratory values except for lower cytogenetics risk score (p = 0.010) and higher albumin (p = 0.005), hemoglobin (p = 0.025) and fibrinogen (p = 0.0005) in the EPO group. EPO patients had a higher incidence of DVT 25 (20.5%) vs. 47 (9.8%) (p = 0.001). Risk factors for DVT by univariate analysis were THAL (p =0.001) and baseline platelets > 350,000/μL (p = 0.018) but not hemoglobin (at baseline or throughout study). There were no significant differences in MM response or survival between the groups with and without DVT. Compared to the No EPO group, EPO-treated patients had a better MM response (p = 0.023) and a higher survival (p = 0.0005). The main predictors of DVT by logistic regression were THAL and prophylactic EPO. Conclusions: THAL and prophylactic EPO predict for higher risk of DVT among newly diagnosed MM patients. Hemoglobin levels were not related to higher risk of DVT. DVT and EPO did not decrease treatment response or survival.

No significant financial relationships to disclose.
Childhood, adolescent, and young adult cancer survivors (CAYACS) research program of British Columbia: Data linkage: Results to date
Authors: Rogers P. C. , Lorenzi M. , Broemeling A. , Glickman V. , Goddard K. , Pritchard S. , Sheps S. , Siegel L. , Spinelli J. , McBride M.
Published: August 2020

9555

Background: Long-term survivors of childhood and adolescent cancers are at risk for late mortality and morbidity. Using database linkages we assessed the extent of these issues and health care utilization in a population based cohort in British Columbia. Methods: Retrospective cohorts of 3,483 survivors (>5 years from diagnosis), and representative comparison groups, have been identified from population-based registries. Linkages were made with administrative databases of risk factors and outcomes. Late mortality, second cancers, late morbidity, health services utilization, continuity of care, and educational outcomes, among those diagnosed before age 20 between 1970 to 1995, and followed to 2000, have been examined. Results: Survivors experienced a 9-fold increase in mortality (SMR 9.1, 95% CI 7.8–10.5). Risk of developing a second cancer was 5 times higher than in the general population (SIR 5.0, 95% CI 3.8–6.5). Survivors had three times the odds of being hospitalized (OR 2.97, 95% CI 2.56–3.45) in a three-year period (1998–2000). Survivors were significantly more likely than the population group to consult any physician (excluding oncologists) (adj. RR 1.61, 95% CI 1.51–1.70). Survivors were found to experience a drop in continuity of primary health care as they aged and transitioned into adult care. Survivors were significantly more likely than their peers to receive special education (32.5% vs. 14.1%), most significantly among CNS survivors who received cranial irradiation. Conclusions: Survivors of childhood and adolescent cancers have severe long term health issues and increased health care utilization. Survivors of CNS tumors were at highest risk of poor health and educational outcomes measured. Data linkage provides useful insights for survivorship research.

No significant financial relationships to disclose.
Prevalence of renal insufficiency in cancer patients: Data from the IRMA-2 study
Authors: Janus N. , Oudard S. , Beuzeboc P. , Gligorov J. , Ray-Coquard I. , Morere J. , Spano J. , Pourrat X. , Deray G. , Launay-Vacher V.
Published: August 2020

9559

Background: The IRMA-1 study reported the high prevalence of renal insufficiency (RI) in 4,684 cancer patients, with a glomerular filtration rate (GFR) <90 and <60 ml/min/1.73m2 for 52.9% and 12.0%, respectively. Furthermore, almost 80% of patients were receiving nephrotoxic drugs or drugs necessitating dosage adjustment. The IRMA-2 study was started one year later, in different patients, and consisted of 2 phases: 1) a cross-sectional study, similar to IRMA-1, and 2) a 2-year retrospective follow-up of the patients to describe the evolution of their renal function along with time. Data from the phase 1 were compared to the results of IRMA-1 in terms of RI prevalence. Methods: Data were collected for cancer patients presenting at one of the 19 IRMA-2 centers in March 2005: type of tumour, sex, age, weight, serum creatinine (SCR), and anticancer drugs. Dialysis, myeloma and lymphoma patients were not included. The prevalence of SCR>110 μmol/L was assessed. GFR was estimated with the aMDRD formula, anticancer drugs necessitating dosage adjustment and those potentially nephrotoxic were identified. Results: 4,945 patients (breast 1816, colorectal 747, lung 463, ovarian 294, prostate 251) were included in the IRMA-2 study. Median age 60.0, mean weight 66.2, 62.8% were women. The prevalence of an elevated SCR (SCR>110μmol/l) was 7.2% (vs. 7.2% in IRMA-1), that of a GFR < 90 ml/min/1.73m2 was 50.2% (vs. 52.9%) and that of a GFR < 60 ml/min/1.73m2 was 11.9% (vs. 12.0%) ( Table ). 73.2% of treated patients (n=3882) were receiving at least one drug needing dosage adjustment and 75.5% received at least one nephrotoxic drug (vs. 79.9 and 80.1%, respectively). Conclusions: The results of IRMA-2 and IRMA-1 confirm the high prevalence of RI in cancer patients, on 2 different cohorts of nearly 5,000 cancer patients each. This underlines that estimating renal function in cancer patients is mandatory and that this highly frequent co-morbidity should be considered.

[Table: see text]

No significant financial relationships to disclose.
Coping with cancer: Associations between coping methods and use of intensive life-prolonging care near death
Authors: Phelps A. C. , Maciejewski P. K. , Nilsson M. , Balboni T. A. , Wright A. A. , Trice E. , Block S. D. , Prigerson H. G.
Published: August 2020

9575

Background: Cancer patients cope with advanced illness in a variety of ways, including relying on their religious beliefs. Religious coping has been associated with preference for aggressive care near death, yet little is known about how religious and other coping mechanisms effect the use of intensive life-prolonging care at the end-of-life (EOL). We sought to determine how patient coping mechanisms affect the use of intensive life-prolonging EOL care among advanced cancer patients. Methods: The Coping with Cancer Study is a US multi-site, prospective, longitudinal cohort of 345 advanced cancer patients enrolled January, 2003 -August, 2007. The Brief COPE assessed active coping (e.g., problem solving), emotional-support based coping (e.g., getting comfort from others), and behavioral disengagement (e.g., giving up the attempt to cope). The Brief RCOPE assessed positive religious coping (e.g., seeking a strength and guidance from God) and negative religious coping (e.g., believing illness is God's punishment). Patients were followed until death, a median of 122 days after baseline assessment. The main outcome was receipt of intensive life-prolonging care, defined as receipt of ventilation or resuscitation in the last week of life. Results: Greater use of positive religious coping prospectively predicted receipt of intensive life-prolonging care (AOR, 5.43; p<0.001), ventilation (AOR, 4.40; p<0.01), resuscitation (AOR, 5.19; p<0.05), and death in the intensive care unit (AOR, 2.76; p<0.05) in the last week of life, controlling for confounding factors and other examined coping styles. In analyses that adjusted for significant confounding influences, behavioral disengagement was associated with DNR order completion (AOR, 2.80; p<0.01), and prospectively predicted lower rates of intensive life-prolonging care (AOR, 0.20; p<0.05), and ventilation (AOR 0.13, p<0.05). Conclusions: The manner in which patients cope with advanced cancer predicts receipt of intensive life-prolonging care at the EOL. Specifically, positive religious coping predicts the receipt of aggressive medical care near death.

No significant financial relationships to disclose.
Prevalence and risk factors of vitamin D insufficiency in cancer
Authors: Hauser K. A. , Karafa M. , Seyidova-Khoshknabi D. , Davis M. P. , Walsh D.
Published: August 2020

9581

Background: Low vitamin D has been linked to increased cancer incidence and reduced prognosis. Little is known about prevalence and risks of insufficiency in cancer. Methods: Electronic medical records of all adult solid tumor patients treated at The Cleveland Clinic in 2006–2007 were reviewed. Data extracted: demographics (age, gender, race), cancer site (primary and metastatic, ICD-9 codes) and first 25 hydroxy vitamin D level [25OHD] during the study period. Laboratory data (calcium, hepatic and renal function), medications prescribed (anticonvulsants, antineoplastic, corticosteroids, vitamin D) and treatment procedures (chemotherapy and radiotherapy) in 2 months preceding vitamin D were recorded. Clinical factors were compared between those tested for 25OHD vs not, and those insufficient (25OH D ≤30ng/ml) vs not (25OH D >31ng/ml) by Chi square or T-tests. Stepwise logistic regression identified independent predictors of vitamin D insufficiency. Results: n=39,254. 19,030 (48%) were female, mean age 63 (± 14), 86% Caucasian. Most common cancers: breast (19%), prostate (18%), skin (13%). 2,100 (5%) had vitamin D tested. They were more likely female (66% vs 47%), and to have breast, hepatobiliary, skin or thyroid cancer, than those not tested (both p<0.001). 1446 (69%) were insufficient, and 200 (10%) were frankly deficient (25OHD ≤12ng/ml). Insufficiency was associated with male gender, race (African American), month of test (Feb-Apr, Oct), cancer type (hepatobiliary, genitourinary, pancreas, upper gastrointestinal), metastatic disease, low albumin, high bilirubin and AST, and lack of antineoplastic or vitamin D medication (all p<0.01). Multivariable predictors were cancer type, test month, African American race, low albumin, and lack of antineoplastic or vitamin D medication (all p<0.01). Conclusions: Vitamin D insufficiency is highly prevalent among cancer patients tested. This study is limited by selection bias but indicates need for prospective vitamin D evaluation in cancer.

No significant financial relationships to disclose.
Risk of bleeding in cancer patients treated with the angiogenesis inhibitor bevacizumab: A meta-analysis
Authors: Sher A. F. , Chu D. , Wu S.
Published: August 2020

9584

Background: Bleeding is a serious adverse event associated with bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF) used extensively in the treatment of cancer. Currently the overall risk of bleeding remains unclear. This study was conducted to determine the overall risk of bleeding associated with bevacizumab in cancer patients by a meta-analysis of randomized controlled trials (RCT). Methods: Databases from PUBMED and the Web Science from January 1966 until July 2008 and abstracts presented at the American Society of Clinical Oncology (ASCO) conferences from January 2000 to through July 2008 were searched to identify relevant studies. Eligible studies included prospective RCTs in which standard anti-neoplastic therapy was administered with and without the use of bevacizumab with available data of bleeding. Summary incidence rate, relative risk (RR), and 95% confidence interval (CI) were calculated employing fixed- or random-effect models based upon the heterogeneity of the included studies. Results: A total of 13048 patients with a variety of solid tumors from 20 RCTs were included for analysis. Among patients receiving bevacizumab, the incidence of all-grade bleeding was 36.3% (95% CI: 28.0 - 45.5), and the RR was 3.1 (95% CI: 2.4 - 4.1) as compared to controls. The incidence of high grade (grade 3 or above) bleeding with bevacizumab was 2.7% (95% CI: 2.0 - 3.6%), and the RR was 1.8 (95% CI: 1.2 - 2.7). The risk of bleeding varied with the dose of bevacizumab, with RR of 3.0 (95% CI: 2.4 - 3.6) at 5mg/kg/week and 1.6 (95% CI: 1.3 - 2.0) at 2.5mg/kg/week. The risk of bleeding with bevacizumab may vary with tumor type, with higher risk seen in patients with colorectal cancer (RR=6.6, 95% CI: 3.6–12.2) and renal cell cancer (RR=3.7, 95% CI: 2.6–5.5). Bevacizumab is associated with different patterns of bleeding, with epistaxis being the most common. The incidence of all grade epistaxis with bevacizumab was 33.8% (95% CI 24.5–44.6) with a RR of 3.1 (95% CI 2.4 - 4.0). Conclusions: There is a significant increase in the risk of bleeding in cancer patients receiving bevacizumab. The risk may vary with the dose of bevacizumab and tumor type.

No significant financial relationships to disclose.
Impact of renal insufficiency on cancer survival: Results of the IRMA-2 study
Authors: Launay-Vacher V. , Janus N. , Spano J. , Gligorov J. , Ray-Coquard I. , Beuzeboc P. , Morere J. , Pourrat X. , Deray G. , Oudard S.
Published: August 2020

9585

Background: Data are scant on the potential impact of renal insufficiency (RI) on the morbidity and mortality of cancer patients. The IRMA-2 study was started to evaluate the potential association between RI and cancer survival. Methods: Data were collected for cancer patients presenting at one of the 19 IRMA-2 centers in March 2005. Data included: sex, age, weight, serum creatinine, type of tumour, metastasis (bone and/or visceral). GFR was estimated with the abbreviated MDRD (aMDRD) formula at the inclusion. RI was defined as an aMDRD <60 mL/min/1.73m2. Patients were retrospectively followed during 2 years after the inclusion. Survival analyses were performed with the log-rank test, survival median with the Mann-Whitney test, multivariate analysis with the Cox regression. Results: 4267 cancer patients (breast 1601, colorectal 575, lung 407, ovarian 269, prostate 224) with available data (aMDRD and follow-up) were included in the analysis. Median age 59.0, mean weight 66.2, 62.9% were women. 51.2% of these patients were alive at the end of the follow-up. RI was strongly linked to mortality (p<0.0001), when analysing all type of patients and tumors. When the same analysis was performed for non-metastatic patients (n=2382), RI was also associated with mortality (p<0.0001). Similar results were found when comparing the survival medians of the same populations ( table ). Finally, 2 Cox models adjusted for sex, age, and the 5 main types of tumor were associated with a significant increase in the risk of death for patients with aMDRD<60 as compared to patients without ( Table ). Conclusions: IRMA-2 is the first large scale study reporting an association between RI and a reduced cancer survival. Cancer patients with aMDRD<60 seemed to be more at risk of death for the following 2 years even in non metastatic patients. IRMA-2 underlines that assessing, monitoring and managing renal function in cancer patients is crucial in order to prevent or at least minimise renal dysfunction because of its potential impact on survival.

[Table: see text]

No significant financial relationships to disclose.
Characteristics of patients who refuse medically appropriate do not resuscitate orders (DNR) upon admission to a palliative care (PC) unit in a comprehensive cancer center
Authors: Parsons H. A. , de La Cruz M. , Delgado-Guay M. O. , Akitoye A. E. , Chacko R. , Poulter V. , Bruera E.
Published: August 2020

9589

Background: Cardiopulmonary resuscitation (CPR) has limited benefit in advanced cancer patients (pts). Refusal of medically appropriate DNR (maDNR) may cause harm and distress for pts, families, and the medical team. We conducted a retrospective study to determine the frequency of refusals of maDNR in a tertiary PC unit in a comprehensive cancer center, and characterize the differences between maDNR acceptors (A) and refusers (R). Methods: We reviewed 2538 consecutive admissions to the PC unit to find refusals of maDNR. Data were collected regarding demographical/clinical factors, 0–10 Edmonton Symptom Assessment System, DNR, CPR, and death for the first 100 R and 200 A pts. Results: DNR was considered medically appropriate for 2530/2538 (99%) admissions. 2374/2530 admissions were of unique pts, and 100/2374 (4%) refused maDNR. 3/3 (100%) R pts who coded underwent CPR versus 0/87 A pts who coded (0%, p<0.0001). 2/3 CPR pts survived code and were discharged but died in less than 10 days. Median age (62), female gender (54%), and religious affiliation were not different between R and A. African-Americans and pts with head and neck malignancies were more frequently R than others (OR=1.99, CI=1.13–3.51, p=0.02 and OR=2.62, CI=1.05–6.56, p=0.04, respectively). A had more hematological malignancies and advance directives (OR=2.66, CI=1.07–6.63, p=0.02, and OR=2.80, CI=1.68–4.66, p<0.0001, respectively). Multivariate regression analysis revealed that pts with hematologic malignancies (OR 2.69, CI=1.05–6.90 p= 0.04) and advance directives (OR 1.46, CI=1.46–4.27, p= 0.001) were associated with A. R pts presented with median (interquartile range, IR) pain of 7(4–9) vs 5(3–8, p=0.0005) nausea of 2(0–7) vs 1(0–4, p=0.05), and dyspnea of 1(0–5) vs 4(0–7, p=0.002). Median (IR) time between PC consult and death and discharge and death were 143 (49–329) days for R vs 25(10–77) for A (p<0.0001) and 85 (25–206) for R and 18 (8–35) for A (p<0.0001). Conclusions: DNR refusal in pts after PC consult is low, more frequent among African Americans, pts with head and neck cancers, pts with more pain or nausea, and is associated with longer survival. This study demonstrates possible predictors of complicated DNR discussions.

No significant financial relationships to disclose.
Utilization of antineoplastic therapy (ANT) in advanced cancer patients admitted to an acute palliative care unit (APCU) at a comprehensive cancer center
Authors: Hui D. , Bruera E. , Li Z. , Palmer J. L. , de la Cruz M. , Elsayem A.
Published: August 2020

9590

Background: Cancer patients admitted to a palliative care unit generally have a poor prognosis. The role of ANT (chemotherapy and targeted agents) in these patients is unclear. We examined the frequency, trends, factors and survival associated with ANT use in hospitalized patients who required an APCU stay. Methods: All patients admitted to APCU between September 1, 2003 and August 31, 2008 were included. Demographics, cancer diagnosis and ANTs utilization from day of hospitalization to discharge, and survival information were retrieved retrospectively. Results: 2604 cancer patients had the following characteristics: median age 59 (range 18–101), male 51%, hematologic malignancy 11%, median hospital stay 11 (Q1-Q3 8–17) days, median APCU stay 7 (Q1-Q3 4–10) days and median survival 22 days. During hospitalization, 393 patients (15%) received ANTs, including chemotherapy (N=297, 11%) and targeted therapy (N=155, 6%). No significant change in frequency of ANTs was detected over the 5 year period. Multivariate logistic regression analysis ( Table ) revealed that younger age, cancer primaries and longer admissions were associated with ANT use. Patients with hematologic malignancies received more chemotherapy (38% vs. 8%, p<0.001) and targeted agents (18% vs. 4%, p<0.001) compared to patients with solid tumors. ANT use was associated with longer overall survival in univariate analysis (median 25 days vs. 21 days, p=0.001); however, this was no longer significant in multivariate Cox regression analysis. Conclusions: The use of ANT during hospitalization that included an APCU stay was limited to a highly selected group of patients, and did not increase overtime. ANT use was associated with younger age, specific cancer primaries, longer admissions, and no significant improvement in survival. The APCU at our cancer center facilitates simultaneous care where patients access palliative care while on ANT. [Table: see text]

No significant financial relationships to disclose.
Evaluation of the Edmonton Symptoms Assesment Scale (ESAS) symptoms improvement (SI) assessment as a prognostic factor for survival in advanced cancer patients (pts) undergoing palliative care (PC): An observational prospective study
Authors: Gamucci T. , Narducci F. , Sperduti I. , Mentuccia L. , Trapasso T. , Magnolfi E. , Grande R. , Cianci G. , Gemma D. , Trombetta G.
Published: August 2020

9591

Background: ESAS is a validated tool for physical symptoms assessment in PC practice which evaluates symptoms through a numeric scale ( 0–10). The use of SI as a prognostic factor is controversial. To this purpose, an observational prospective study in advanced cancer pts previously treated with anti-cancer treatments and now undergoing only PC was conducted. Methods: Pts were considered eligible if no longer able to receive any anticancer treatment; they were scheduled to undergo ESAS assessment: 1) at the hospitalization time-point (TH); 2) at the hospital discharge time-point (TD). Symptoms’ scores were divided into 3 severity-classes (SC): mild (0–3, MI), moderate (4–6, MO) and severe (≥7, S). Differences across symptoms’ classes between TH and TD was analyzed with the paired-data McNemar-test, according to tumor types. KM method was used for survival calculation, according to ESAS score classes, and logrank test for curves comparison. Uni/multi-variate survival analysis including age, sex, tumour, symptoms number and score class, PaP (Palliative Prognostic)-score, KPS, were carried out using the Cox regression model. Results: ESAS was administered to 68 pts, gastrointesinal (GI)/lung (NSCLC): 39/29, median age: 69-yrs, KPS ≤50/>50: 27 (39.7 %)/ 41 (60.3%), PaP-score A/B/C: 26 (38.2%)/37 (54.4%)/C (7.4%). A statistically significant reduction of S-SC rates was observed, as shown in the Table . SI correlates with survival improvement: PaP score (HR 2.95, 95% CI 1.35–6.41, p=0.006) and anorexia (HR 3.21, 95% CI 1.33–7.72, p=0.009) appear to be prognostic factors for survival at the multivariate analaysis for GI pts; asthenia is the only significant variable (HR 5.11 CI 95% 1.86–14.03, p=.0.002) for NSCLC pts. Conclusions: SI according to ESAS after PC treatment represents an important prognostic factor for survival in pts no longer suitable to receive any anticancer active therapies. [Table: see text]

No significant financial relationships to disclose.
Association between inflammatory markers, symptom burden, hypogonadism, and survival in cancer patients with cachexia
Authors: Del Fabbro E. , Hui D. , Nooruddin Z. , Dalal S. , Freer G. , Palmer L. , Bruera E.
Published: August 2020

9594

Background: Cancer cachexia is characterized by muscle wasting, anorexia, and elevated inflammatory markers. Similarly, in patients without cancer, hypogonadism is associated with lower lean body mass, increased symptom burden and decreased survival. Hypogonadism in cancer cachexia could exacerbate symptom distress, facilitate a pro-inflammatory state and decrease survival. Currently, there are no guidelines for testosterone replacement therapy in cancer patients. We evaluated the relationship between hypogonadism, symptom severity, inflammation and survival in patients with cachexia. Methods: A retrospective chart review of 159 consecutive patients (61 females, 98 males) referred to a specialized cachexia clinic at a comprehensive cancer center. 98 patients (62%) had C-reactive protein (CRP) levels measured, and 68(69%) males had serum total testosterone evaluated. Testosterone levels were not evaluated in female patients. Symptoms were assessed by the Edmonton Symptom Assessment Scale (ESAS). Results: All patients reported weight loss of >5% within the preceding 6 months; Median age was 62, CRP 26mg/L and in males median total testosterone186ng/dL (normal level≥240 ng/dL). Spearman correlation revealed higher CRP levels (r=0.57, p<0.01) increased dyspnea (r=0.27, p<0.05) and poorer sleep scores (r=0.29, p<0.05) in males with low testosterone. In 46 males and females who underwent CRP testing within 30 days of their ESAS evaluation, pain (r=0.48, p<0.01), fatigue (r=0.39, p<0.01), poor appetite (r=0.49, p<0.01), insomnia (r=0.42, p<0.01), anxiety (r=0.29, p<0.05), and dyspnea (r=0.31, p<0.05) correlated with an elevated CRP. Survival of male patients with testosterone<186 ng/dL was decreased compared to those with levels ≥ 186ng/dL (13 vs.62 weeks, p=0.004). Patients with CRP>10 mg/L had decreased survival compared to those <10 mg/L (30 vs. 66 weeks, p=0.017). Conclusions: Elevated C-RP levels in cancer cachexia are associated with poorer survival and increased symptom burden. Low testosterone is strongly associated with decreased survival in cachectic male patients and correlates inversely with CRP levels, dyspnea and insomnia.

No significant financial relationships to disclose.
Survival prediction in terminally ill cancer patients: Description and validation of a new predictive score
Authors: Jimenez Gordo A. M. , Feliu J. , Dominguez J. , Molina R. , Camara J. C. , Alonso A. , Madero R. , De Castro J. , Espinosa E. , Gonzalez-Baron M.
Published: August 2020

9595

Background: Determining an accurate prognosis for terminally ill cancer patients is one of the biggest challenges that confronts a physician. Correct predictions can be done in only 20–40% of all cases. Although the current prognostic scales are helpful, they have significant limitations. Our objective consists of determining the potential indicators that influence the survival of these patients and develop and validate a new predictive model. Methods: A prospective, multicentric and observational study was conducted in 880 terminally ill cancer patients. At first, 40 clinical, demographic and laboratory variables were recorded in 406 patients. A forward stepwise regression method was applied for the multivariate survival analysis. Hence, a predictive model was constructed. Subsequent validation was performed in 474 patients. Results: Median age was 66.4 years (range 18–95). The median overall survival was 21 days in the first 406 patients studied and 19 days in the validation group. A prognostic model with 9 variables was constructed (age, ECOG, the amount of time between initial diagnosis up to being considered terminal phase, nauseas, anorexia, cognitive impairment, lymphocytes, LDH and albumin). Afterwards, to simplify the model, 4 variables that were considered more objective and with greater Odds ratio were selected and assigned one point per each prognostically poor category. We obtained a survival model that discriminates 3 prognostic categories: Good prognoses (score 0) with a median survival of 95 days (44–146), intermediate prognoses (score 1–2) with a median survival of 33 days (26.8–39.2) and bad prognoses (score 3–4) with a median survival of 15 days (11.1–18.9). In the validation group, median survival times were 60 (47.1–72.8), 27 (22.8–31.1) and 11 days (9.2–12.7) respectively. Conclusions: We propose a predictive score model that is objective and easy to use to help in accurately predicting life expectancy in terminally ill cancer patients. Its effectiveness has been validated in a group of independent centers.

No significant financial relationships to disclose.
Factors for choosing prostate cancer treatment and resulting impact on health related quality of life
Authors: Rice K. , Peay K. , Hudak J. , Elsamanoudi S. , Travis J. , Lockhart R. , Jennifer C. , Black L. , Hogue S. , Brassell S.
Published: August 2020

9601

Background: The equivalence of surgery (RP), external beam radiation (EBRT), and expectant management (EM) on overall survival of prostate cancer (PCa) patients and their respective impact on health-related quality of life (HRQoL) is controversial. Thus, the benefit of screening has been raised. There is a scarcity of information on demographic factors that influence patient treatment choice and the resulting impact treatment has on HRQoL. Methods: Patients presenting to an equal access military multi-disciplinary PCa clinic are enrolled in a HRQoL database after informed consent. Surveys are administered prior to treatment and at 3, 6, 9, and 12 months. The instruments are the EPIC, EPIC Demographic, and the MOS Short-Form 36. Chi-square analysis compared frequency of race, income, and education level by treatment choice. Multivariate analysis was used to predict changes in HRQoL outcomes over time. Results: The study consisted of 538 patients. Caucasians chose EM twice as frequently as African Americans (AA) (p=0.0033). Caucasians were 3 times more likely to choose RP over EBRT, whereas AA were more evenly divided. Patients who earned over $100,000 annually disproportionately chose RP while the other treatment groups were disproportionately represented by those earning less than $100,000 (p<0.0001). Those having a graduate school degree disproportionately chose RP while the other treatment options were disproportionately represented in those with college education or less (p<0.0001). Mean age for RP, EBRT, and EM was 58, 67, and 69 respectively. Patients undergoing RP had significantly worse HRQoL outcomes in the following domains: urinary function, sexual function, and sexual bother at 12 months despite having the highest baseline scores (p<0.0001). The only domain that differed between patients undergoing EBRT and EM was bowel bother (p<0.0001). Conclusions: Patients choosing RP tend to be younger Caucasians with higher income and educational levels. This cohort chose the option with the greatest impact on HRQoL, which gives evidence that patients with certain demographics may emphasize other factors in their treatment decisions. HRQoL between EBRT and EM differed in only one domain. EBRT may be offered to older patients with minimal HRQoL impact.

No significant financial relationships to disclose.
Is a diagnosis of invasive breast cancer an effective motivational factor for lifestyle change?
Authors: Ellsworth R. , Sann N. J. , Kvecher L. , Ellsworth D. L. , Shriver C. D.
Published: August 2020

9602

Background: While survival rates for patients diagnosed with invasive breast cancer have increased dramatically, survivors often face a host of adverse health effects. Factors such as obesity, physical activity and tobacco may contribute to decreased survival and quality of life. Here, we evaluated behavioral risk factors in patients with and without breast cancer to determine whether a diagnosis of invasive disease was sufficient motivation to modify lifestyle choices. Methods: The dataset included patients undergoing surgical procedures between 2001 and 2006 and diagnosed with malignant (n=299) or benign (n=130) breast disease and who had baseline and 1-year follow-up information available. Changes in BMI, fat intake, exercise frequency, alcohol and tobacco use, caffeine consumption and frequency of breast self exam (BSE) were assessed. Results: At baseline (diagnosis), significantly more (P<0.005) invasive patients (70%) were menopausal compared to benign patients (48%), no other patient characteristics were significantly different between malignant and benign groups at baseline; a majority in both groups were overweight, non (current) smokers, and consumed high fat diets, ∼40% reported exercising >3 times/week, >60% had high (>500 mg/day) levels of caffeine and consumed low (<1 drink/month) levels of alcohol. The only modifiable behavior that showed a significant change (P<0.05) between baseline and 1-year from diagnosis was compliance with recommended BSE frequency in invasive patients, improving from 61% of patients at baseline to 72% one year later; a concomitant change was not seen in benign patients. No other behaviors changed either from baseline to 1-year or between invasive and benign patients. Conclusions: The paucity of behavioral changes after a diagnosis of breast cancer suggests that a diagnosis of breast cancer is not sufficient motivation to promote healthier lifestyles. Our data suggest a need for increased health-related behavioral counseling and support systems to successfully modify personal behaviors. Development and implementation of lifestyle recommendations have the potential to improve the health and quality of life of breast cancer survivors.

No significant financial relationships to disclose.
Health-related quality of life (HRQOL) in non-small cell lung cancer (NSCLC): An update of a systematic review on methodological issues in randomized controlled trials (RCTs)
Authors: Claassens L. , van Meerbeeck J. , Coens C. , Quinten C. , Wang X. S. , Velikova G. , Bottomley A.
Published: August 2020

9604

Background: NSCLC is a prevalent cancer site and RCTs frequently assess patient HRQOL, given the modest survival gains. This study is an update of a systematic review (JCO, 2003) on the HRQOL methodology in NSCLC RCTs. The objective was gaining insight into the evolution of HRQOL methodology over the last decades to help understand if the quality of reporting—and its benefit for clinical-decision making—has improved. Methods: A systematic literature review was undertaken through Medline. RCTs including newly diagnosed NSCLC patients with age ≥ 18, who underwent chemotherapy and/or radiotherapy; comprising patient-reported HRQOL endpoints; and published in English from 2002 to end 2008 were eligible. Two independent reviewers evaluated demographics, trial design, HRQOL measurements and statistical analysis. Results: Forty-five RCTs including 16,382 patients were selected, versus 29 trials between 1980 and 2002. Overall, the quality of HRQOL methodology reported was adequate, although no improvement over time was noticed. Comparisons to the former review led to similar results (p > .05): Of the 45 RCTs, HRQOL end points were primary objectives in 20%. Significant HRQOL between-treatment differences were found in 60% of the RCTs. Adequacy of result presentation was found for a majority (71%). Few studies paid attention to clinically meaningful differences (36%). The EORTC and FACIT tools and the LCSS were most commonly applied in 56%, 18% and 13% respectively. There was sufficient detailing on domains, time points and patient compliance (> 70%), but little on instrument administration methods (18%). However, HRQOL hypothesis (9%); instrument rationale (11%); verification of the cultural validity (29%); and impact of missing data (31%) were addressed to a significantly less extent than before 2002 (p < .05). Conclusions: The number of RCTs incorporating HRQOL assessments in the NSCLC population has increased considerably. Despite the acceptable quality of the HRQOL methodology reporting, certain aspects remain poorly addressed. Our findings suggest the need for international standardization of HRQOL reporting, similar to the CONSORT guidelines for clinical findings.

No significant financial relationships to disclose.