bluuebunny/crossref_metadata_2025 huggingface dataset:
Mucositis in cancer patients: Prototypic semi-mechanistic kinetic model
Authors: Peterson D. E. , Lalla R. V. , Srivastava R. , Loew L. M.
Published: March 2020

19617

Background: Recent research advances have helped (i) define pathobiology of alimentary tract mucosal injury secondary to cancer therapy and (ii) link molecular mechanisms with clinically important outcomes. Recently-developed computational biology modeling may further enhance these advances. Semi-mechanistic (SM) modeling allows one to approach quantitative analysis of a biochemical system that is incompletely determined. In this study, data from sequential oral mucosal biopsies in 3 patients developing oral mucositis secondary to hematopoietic stem cell transplantation (HSCT) conditioning were utilized to establish a prototypic computational model for this toxicity. Methods: Plasma and oral mucosal biopsy specimens were obtained from 3 autologous HSCT patients before and after administration of conditioning chemotherapy: Day -10, +10, +28 and +100; Day 0 was day of transplant. Full-thickness tissue samples were measured by RT- PCR for COX-1, COX-2, IL-1β and TNF-a. Plasma samples were measured by ELISA for PGE2 and PGI2, markers of COX-2 activity. The SM model was implemented as a system of 6 ordinary differential equations with 15 parameters. Parameter estimation and simulations were conducted based on experimental results, using a combination of Mathematica, Berkeley Madonna and Virtual Cell software packages. Results: The SM model captured the behavior of COX-1, IL-1β and PGE2 dynamics, predicting an exponential decay for each of these species. Half-lives relative to average steady-state values were found to be 9.7 days, 8.7 days and 9.3 days for COX-1, IL-1β and PGE2 respectively. Correlation ratios for each of these species were calculated to be 0.62, 0.61 and 0.90 respectively. Conclusions: This prototypic model provides a basis for development of a detailed mathematical model for quantifying relevant components of the mucositis pathway. This combination of modeling and experiment could also identify gaps in the pathway that would be important targets for new hypotheses, including possible feedback mechanisms relative to inflammatory cytokines.

No significant financial relationships to disclose.
Treatment profiles in patients with cancer aged 80 years or more
Authors: Noonan A. M. , Horgan A. M. , Grogan L. , Breathnach O. S.
Published: March 2020

19620

Background: There is much criticism about the omission of very elderly patients (>80 years old) from clinical trials. The question is raised as to whether results of clinical trials performed with younger pts (usually <75 years) can be extrapolated to the very elderly population. The most recent Irish census predicts that those aged =80 yrs is set to rise dramatically from the 2001 level of 98,000 to a projected 323,000 in 2036. Accordingly oncologists will have to plan carefully to appropriately treat these pts. Methods: A retrospective review of all new pts referrals aged =80 years was performed for the period Sept. 2005 to Sept. 2006. Pts records were analysed for age, cancer diagnosis, co-morbidities, treatment plan and complications. Results: A total of 52 referrals were identified but records were available for only 49 pts. The average age was 83.7 years (80–93yrs). The M:F ratio was 1.04:1. The 4 most common cancers were Colorectal (20%), lung (18%), oesophageal (12%) and breast (10%). The mean number of co-morbidities was 5. 13 pts (26%) had a previous unrelated cancer diagnosis. 19 patients (38.8%) received cancer treatment (see table ). Three other pts were offered chemotherapy but declined citing age and fear of side effects as their reasons. 68% of patients receiving cancer treatment had a performance status (PS) of ECOG =1. The main reasons cited for not giving cancer treatment were poor PS (21), comorbidities (13), or patient preference (3). 75% of patients receiving chemotherapy were on schedule with no delays. Only 25% (2) of patients experienced delays due to toxicity. Conclusion: In this diverse group of very elderly cancer pts, those that received cancer treatment tolerated it reasonably well. However, 55% of pts were deemed unfit for cancer treatment at presentation due to poor performance status or compromising co-morbidities. This fact must be taken into account when setting recruitment targets for this age group when planning oncology clinical trials.

No significant financial relationships to disclose.

[Table: see text]
Changes in iron parameters in patients (pts) with chemotherapy-induced anemia (CIA) receiving darbepoetin alfa (DA) every 3 weeks with and without intravenous iron supplementation
Authors: Suto T. , Vansteenkiste J. F. , Mossman T. , Pinter T.
Published: March 2020

19621

Background: There is growing interest in the use of intravenous (IV) iron supplementation in pts receiving erythropoiesis- stimulating agents (ESAs). We present an exploratory analysis of iron parameters in pts with CIA enrolled in a phase IIIb, randomized, open- label, study of DA administered with either IV iron or oral/no iron. Methods: Eligible pts had a non-myeloid malignancy and CIA (baseline Hb < 11g/dL). Pts received DA 500 mcg every 3 weeks (Q3W) using the Aranesp (darbepoetin alfa) prefilled SureClick autoinjector. Pts were randomly allocated (1:1) to receive either DA + 200 mg IV iron (200 mg Q3W with DA Q3W or two 100 mg doses within 3 weeks) or DA + oral/no iron. Randomization was stratified by tumor type and baseline Hb (< or = 10 g/dL). The primary endpoint was % pts achieving a hematopoietic response (Hb = 12 g/dL or increase = 2 g/dL). Results: 396 randomized pts received 1 dose of DA (IV-iron arm = 200; oral/no-iron arm = 196). Mean (SD) age was 61.0 (11.5) yrs; 61% (n = 240) were women; 28% (n = 111) had lung/gynecological tumors. Pt demographics were similar between arms. 44 (11%) pts had baseline iron deficiency (TSAT < 15%; serum ferritin < 100 μg/L); 5 (2%) in the IV iron arm and 23 (12%) in the oral/no-iron arm developed it. 141 (36%) pts had baseline functional iron deficiency (serum iron < 60 μg/dL; serum ferritin > 20 μg/L; TSAT < 20%); 54 (27%) in the IV arm and 67 (35%) in the oral/no-iron arm developed it. See table for iron parameters. Improved Hb-based responses in the IV-iron arm will be presented. Conclusions: Pts who received DA Q3W + IV iron appeared less likely to develop iron deficiency; iron deficiency may reduce responsiveness to ESAs. These pts also appeared to have a larger increase in mean serum ferritin levels. In contrast, mean serum iron, %TSAT, total iron binding capacity, and reticulocytes appeared to be similar in the 2 arms for most of the study period, suggesting that these iron parameters are not influenced by IV iron.

No significant financial relationships to disclose.

[Table: see text]
Pharmacokinetic effect of aprepitant on irinotecan in patients with colorectal cancer
Authors: Nieva J. J. , Webb W. , Siuzdak G.
Published: March 2020

19622

Background: Alterations in the activity of cytochrome P450 enzymes can affect the clearance of chemotherapeutic drugs. Aprepitant, a moderate inhibitor and inducer of cytochrome P450 3A4, is now increasingly used for the prevention of chemotherapy induced nausea and vomiting as an adjuct to irinotecan-containing chemotherapy. There is little published data on the potential interaction between these agents. We sought to determine if aprepitant impacts the clinical pharmacokinetics of irinotecan. Methods: Patients with colorectal cancer receiving FOLFIRI chemotherapy were eligible for enrollment. Each patient received 2 cycles of FOLFIRI chemotherapy with, and 2 cycles without, aprepitant as part of the anti-emetic regimen. Plasma was obtained for each chemotherapy cycle at: 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 24 and 48 hours. Irinotecan and its active metabolite SN-38 plasma levels were measured in duplicate by LC-FLD. Differences between groups were evaluated using a paired students t-test. Results: We administered 8 cycles of FOLFIRI chemotherapy for treatment of colorectal cancer to 2 patients. Median Cmax of irinotecan and SN-38 was 1,628 ± 1,565 ng/mL and 18.8 ± 9.7 ng/mL for aprepitant treated chemotherapy cycles compared with 1376 ± 1536 ng/mL and 23.5 ± 8.5 ng/mL for conventionally pre-medicated cycles. Median area under the concentration versus time curve (AUC) for irinotecan was 583.9 ± 317.6 μg/ml·min in aprepitant treated cycles and 682.6 ±266.5 μg/ml·min during conventionally treated cycles. Median AUC for SN-38 was 15.0 ± 7.5 μg/ml·min and 18.0 ± 9.0 μg/ml·min in aprepitant and conventionally premedicated chemotherapy cycles respectively. Conclusions: In this pilot study, aprepitant, as it is typically administered, did not have any significant effect on irinotecan pharmacokinetics in patients with colorectal cancer.

No significant financial relationships to disclose.
A randomized comparison of darbepoetin alfa every three weeks with epoetin thrice weekly for chemotherapy induced anemia in nonhematological cancer patients
Authors: Kotsori A. A. , Vaslamatzis M. M. , Alexopoulos C. G.
Published: March 2020

19625

Background: A strong tendency exists nowadays in clinical practice to move from thrice weekly (TIW) to weekly (QW) and even every 3 weeks (Q3W) administration of erythropoetic therapy for chemotherapy induced anemia. Although head to head comparison of QW Darbepoetin with TIW Epoetin showed similar effectiveness between the two, such a study for Q3W Darbepoetin has not been published so far. Methods: We randomly compared Q3W Darbepoetin (500mcg, Group B) with TIW Epoetin, 10.000 U (20.000 U in nonresponders after 6 weeks, Group A) in 100 patients with chemotherapy induced anemia (Hb = 11gr). Evaluation was performed on week 6 and 12 including QOL assessment using FACT-An scale Results: At present, all patients have completed first evaluation and 94 second evaluation. All will have completed second evaluation by the end of January 2007. In group A, Hb increased from 10.31±0.81 at baseline to 11.5±1.8 at 6 weeks (p=.000) and to 12±2.27 at 12 weeks (p=0.000). No significant (p=.13) increase was observed between week 6 and 12. In group B, a non significant (p=.068) increase of Hb was observed from baseline (10.27±.78) to week 6 (10.68±.24) but Hb increased significantly (p=.005) to 11.12±1.7 at 12 weeks. It also increased between week 6 and 12 (p=.009). In all 100 patients, Hb increased from 10.30±.79 at baseline to 11.09±1.74 at 6 weeks (p= .000) and to 11.58±2.05 at 12 weeks (p=.000). It also increased between week 6 and 12 (p=.005). Seven of 31 (22%) responders in group A had to double Epoetin dose. Eight patients in group A required transfusions compared with 7 in group B (p=NS). On an intent to treat analysis, RR at 6 weeks was 52% for Epoetin versus 30% for Darbepoetin (p=.078) and 62% versus 46%, respectively at 12 weeks. QOL analysis will be presented. Conclusions: Q3W Darbepoetin is a very convenient scheme with comparable effectiveness with TIW Epoetin.

No significant financial relationships to disclose.
Octreotide for the treatment of symptoms of bowel obstruction in advanced cancer
Authors: Imamura S. , Maehara S.
Published: March 2020

19626

Background: Symptom of bowel obstruction are common and serious complications in terminal advanced cancer patients. Mechanisms of bowel obstructions include intraabdominal carcinomatosis, drug-induced intestinal immobility and intraluminal obstruction. Octreotide inhibits the release of the several gastrointestinal hormones thereby reducing GI tract secretion, and increase the GI tract absorption by slowing down intestinal mobility and decreasing the splanchnic blood flow. Methods: Objectives of this study evaluated efficacy of octreotide in terminal cancer patients with bowel obstruction. We treated all patients with recurrent or advanced cancer admitted to our palliative unit in last 2 years, who had continuous nausea and vomiting related to no surgically bowel obstruction. Octreotide started at a dose of 150 mcg/day in subcutaneous infusion or continuous intravenous infusion, and increase to a dose of 300 mcg/day depending on the symptom. Results: 52 patients with terminal cancer were included in this study. Primary tumor were 13 colon-rectum 13, gastric 8, pancreas 8, biliary tract 4, esophagus 2, gynecological 3 and others 12. The mean age of patients is 71 years of age. All patient have died from tumor progression. The mean dose is 232 mcg/day and the mean duration of treatment is 24 days. 23 patients (45%) were remarkably improved and can take a meal. 15 patients (29%) were improved and diminished vomiting. But 13 patients (25%) remained continuous vomiting. The patient with markedly efficacy lived 2 times longer than other groups. No serious side effects were present. Conclusions: Octreotide shows good efficacy in the management of symptom of malignant obstruction and can be used safely in this population.

No significant financial relationships to disclose.
Safety of transdermal fentanyl (TF) in front-line approach to severe cancer pain. Meta-analysis of randomized clinical trials
Authors: Maltoni M. , Scarpi E. , Poggi B. , Tassinari D.
Published: March 2020

19627

Background: To assess the safety of TF when compared with Slow Releasing Oral Morphine (SROM) in the front-line approach to severe cancer pain. Methods: A systematic review of literature in the MEDLINE and EMBASE data bases from 1966 to October 2006, using “Administration, Cutaneous” [MeSH term], “Administration, Oral” [MeSH term], “Analgesic, Opioid/*administration & dosage/adverse effects” [MeSH term], “Delayed-Action Preparations” [MeSH term], “Fentanyl/*administration & dosage/adverse effects” [MeSH term], “Cancer Pain/*drug therapy” [MeSH term], “Morphine/*administration & dosage/adverse effects” [MeSH term] as search terms was performed independently by two authors (DT and MM). All the randomized phase III trials comparing TF and SROM were considered eligible and included into the analysis. The overall side effects odds ratio (OR) was the primary end point of the analysis; overall gastrointestinal side effects, constipation, nausea, somnolence, the patient's preference and the trial withdrawal pooled ORs the secondary ones. Heterogeneity between the trials was analysed using the Mantel-Haenszel test, and the outcome analysis was performed using a fixed effects model and an alpha error lower than 5%. Results: 3 trials met the selection criteria and were included into the analysis. The safety of TF and SROM was analysed in 373 patients (188 and 185 respectively treated with TF and SROM). A significant difference in favour of TF was observed for constipation (OR=0.42, p=0.002), somnolence (OR=0.559, p=0.018) and the preference of the patient (OR=0.39, p<0.001): no significant differences were observed for overall side effects (OR=0.82, p=0.51), overall gastrointestinal side effects (OR=0.87, p=0.6), nausea (OR=1.2, p=0.446) and trial withdrawal (OR=0.62, p=0.59). No heterogeneity was documented between the trials. Conclusion: Although no differences exist between TF and SROM in efficacy (with equianalgesic doses) and safety (when assessed as overall safety profile) on the whole, the differences in the peculiar safety profile of the two opiates seems to favour TF in patient's preference in the choice of front-line treatment of severe cancer pain.

No significant financial relationships to disclose.
The academic oncology hospitalist—a model for improved teaching and patient care
Authors: Denes A. E. , DiPersio J. F. , Ellis M. J.
Published: March 2020

19630

Background: The care of hospitalized cancer patients in academic institutions is usually assigned to residents and fellows with supervision by a “rotating” attending oncologist. This approach ensures that, at a minimum, each patient’s care is reviewed and supervised by an attending physician. This model, however, has several shortcomings including: 1) lack of continuity of care 2) limited time for teaching 3) limited knowledge of diseases outside of the research or clinical interests of the attending 4) lack of consistent clinical leadership and 5) communication problems when the attending physician is in clinic, meetings, or research activities. Methods: We felt that a model in which a senior medical oncologist with an interest in patient care, teaching, and clinical research serves as the full time director of the inpatient oncology service would address these challenges. The organizational chart for this model will be presented. In this model, the attending oncologist meets with the “post call” intern/resident team, fellow, and hospitalist each morning to review and discuss all patients admitted to the service in the prior 24 hrs. The afternoons are spent visiting patients, reviewing the status of all patients on the service, and evaluating high acuity new admissions. An oncology core curriculum lecture series was developed with daily lectures. The trainees are encouraged to attend additional conferences as time permits. Results: The program was initiated in November 2005 and has been a universal success. Patient satisfaction has improved significantly and the number of graduating residents pursuing fellowships in oncology has increased from 3–4 to 7–8 per year. The attending physicians are able to continue their clinic schedules and research activities without interruption. We are planning to review this experience to evaluate additional changes in patient outcome such as length of stay, efficacy of symptom control, and readmission rates. Conclusions: Our model of inpatient oncology care has improved patient satisfaction, teaching, and faculty utilization. It lends itself to develop clinical trials of inpatient cancer care. We suggest it be considered in academic cancer centers to achieve similar goals.

No significant financial relationships to disclose.
RESPOND - Raising awareness of anemia in oncology centers through computer algorithm driven guidelines: Assessment of intraclass correlation metrics for the accuracy of algorithmic definitions
Authors: Foubert J. , Aapro M. , Soubeyran P. , Bokemeyer C. , Van Erps J. , Muenzberg M. , Turner M. , MacDonald K. , Abraham I.
Published: March 2020

19633

Background: Publication of evidence-based (EB) practice guidelines (EBPGs) does not assure their application in patient care. Computerized clinical decision support systems (CDSSs) incorporating EBPGs may promote EB decision-making about individual patients. Most CDSSs are knowledge-, not evidence-based. Effective CDSSs are those integrated into workflow, providing point of care guidance, and offering actionable recommendations. Few are validated in terms of algorithmic operationalization. RESPOND is a CDSS based on the 2006 update of the European Organisation for Research and Treatment of Cancer (EORTC) EBPGs for erythropoietic proteins in cancer-related anemia. Method: Descriptive study. Panel of five experts (three physicians, two nurses) rated the 27 algorithms derived from the EORTC EBPGs in terms of accuracy (binary: yes/no). If not judged accurate, experts were asked to explain and propose correction. Objective was to attain intraclass correlation coefficient (ICC) >0.90 for each operationalization in a maximum of three iterations. Table 1 . Example of operationalization of guideline Hb, hemoglobin Results: In iteration 1, three experts agreed with all 27 sets; one disagreed with one set and one with four sets; therefore ICC = 1.00 for 22 sets; ≤0.90 for five sets. Three sets concerned additional output to be generated, and one a substantive inaccuracy; all were corrected. One set concerned a suggestion not supported by evidence, hence not incorporated. In iteration 2, all five experts agreed with all sets, thus ICC = 1.00 for 27 sets. Conclusions: The RESPOND CDSS being developed and validated is based on algorithms that accurately specify, in the form of conditional dependency rules, the EORTC EBPGs for erythropoietic proteins.

[Table: see text] [Table: see text]
A post-treatment individualized prescriptive exercise and recreation therapy intervention for breast cancer patients
Authors: Groff D. G. , Battaglini C. L. , Peppercorn J.
Published: March 2020

19637

Background: The number of breast cancer survivors is increasing due to early detection and advancements in treatment leading to increased concern with long term side effects and quality of life after therapy for early stage breast cancer. The Get REAL & HEEL Breast Cancer Program addresses the physiological and psychological declines experienced by breast cancer survivors post-treatment through combined exercise (EX) and recreation therapy (RT) to strengthen the body and mind of survivors and improve overall QOL. Methods: Women with early stage breast cancer within 6 months from completion of initial therapy were recruited to participate in a combined EX and RT intervention. The EX consisted of cardiovascular endurance (VO2 Max), muscular endurance (ME) and flexibility (FL) training. The RT included activities such as leisure counseling, bio-feedback, heart-math, crafts, and a ropes course. Each participant engaged in an individually prescribed intervention for 8 weeks, 3 times per week, for approximately 1.5 hour per therapy session. A battery of fitness and psychological assessments including, VO2 Max, body composition (BC), ME, FL, fatigue (F), depression (D), QOL were used to assess baseline parameters and outcomes. Descriptive statistics presenting the results of baseline and final assessments were used to evaluate program outcomes. Results: Fifteen subjects, age 30 to 75, volunteered for the program. At initial analysis, clinically relevant changes in physiological and psychological parameters were observed. Improvements in VO2 Max, BC, and ME were observed for all subjects. Positive changes in psychological parameters were also observed in all of subjects including decreased F and D accompanied by increased QOL. Conclusions: The results of this pilot program are promising and suggest that further evaluation of this novel combination of EX and RT to improve physical and emotional functioning, and overall QOL after breast cancer treatment are warranted.

No significant financial relationships to disclose.
Comprehensive geriatric assessment (CGA) in elderly women with early breast cancer
Authors: Girones R. S. , Torregrosa D. M. , Torró J. , Aguiló J. , Maestu I. , Diaz Beveridge R.
Published: March 2020

19641

Background: Advancing age is a major risk factor for breast cancer. Long-term follow up is recommended after diagnosis and treatment of early breast cancer. With older age, the risk of comorbid conditions and functional impairment is increased. A useful tool in the management and follow-up of these elderly patients could be a CGA Methods: Purpose of the study: Descriptive, transversal study of the prevalence of other comorbidities and of the functional impairment in elderly patients on follow-up after curative treatment of early breast cancer. Patients: Women aged ≥ 70 years at time of diagnosis, with removed early breast cancer. Attended in a outpatient unit from January 2005 to June 2006. No disease recurrences were allowed. Methods: CGA was conducted in an oncology unit. The assessment used usual screening instruments (ADL, IADL, POMA, GDS, MMSE, MNA) as well as the performance status (PS). Co-morbidity was classified using the Charlson score. Results: 91 pts underwent CGA. Mean age at surgery of primary tumour: 76 (70–92). Mean age at time of CGA: 80 (71–95). > 75% of patients had more than 84 years at time of GCA: Median follow up: 5 years (1–12). 47% PS 0. 9% PS 2. 83% were fully independent for ADL and 71% for IADL. IADL most affected was the ability to drive/use public transport. Median Charlson Score was 2 (1–6). ≥ 75% of patients had score ≥4. Most frequent comorbidity: cardiovascular disease (hypertension). Cognitive deterioration: 15%, depression: 16%. Only 28% were thin (BMI< 22). 75% were polymedicated (> 6 drugs). 28% had geriatric syndromes. 23% were “frail” (at least one of the following items): ADL < 80; ≥ 3 comorbidities, performance status < 60, ≥ 1 geriatric syndrome. Conclusions: Our results are better than reports from other geriatric teams using CGA, in terms on functional status and frailty. A high prevalence of comorbidity in our study, similar to other reports. A selection bias cannot be excluded, as the fitter patients are those that usually keep on with the follow-up. While those frail patients that do not due to their functional impairment are usually lost. Older patients with early breast cancer on follow-up have a high prevalence of comorbidity. However, in our serie, function and independence is maintained.

No significant financial relationships to disclose.
BCIRG 006: Docetaxel and trastuzumab-based regimens improve DFS and OS over AC-T in node positive and high risk node negative HER2 positive early breast cancer patients: Quality of life (QOL) at 36 months follow-up
Authors: Robert N. J. , Eiermann W. , Pienkowski T. , Crown J. , Martin M. , Pawlicki M. , Chan A. , Bee V. , Slamon D. , Au H.
Published: March 2020

19647

Background: The primary objective of the BCIRG 006 trial was to determine if the use of trastuzumab in early high-risk HER2-positive breast cancer significantly improved clinical outcomes. A secondary objective was to evaluate the QOL of patients receiving the 2 treatments. Methods: The BCIRG 006 trial compared adjuvant standard AC (doxorubicin/cyclophosphamide x 4 cycles) followed by docetaxel x 4 [AC-T] or 2 trastuzumab-containing regimens, AC followed by T with trastuzumab x 1 year [AC-TH] or TCarbo x 6 with trastuzumab x 1 year [TCH] in patients with node positive or high-risk node negative HER2-positive early breast cancer (n=3222). Results: The 2nd planned interim analysis, median follow-up at 36 months, showed that both AC-TH and TCH significantly improved the DFS and OS over the control (relative reduction risk of relapse 39% (P<0.0001) and 33% (P=0.0003) respectively, for AC-TH and TCH vs control). Relative reduction in the risk of death was 41% (P=0.0041) and 34% (P =0.017) respectively, for AC-TH and TCH vs control. Congestive heart failure occurred in 0.4% of patients in AC-T and TCH vs 1.9% of patients in AC-TH. Global safety profile was acceptable in all 3 arms and more favourable in TCH than AC-TH. QOL, a secondary endpoint of this trial, was assessed using the EORTC QLQC-30, BR-23, and EQ5D. We will present the primary QOL endpoints comparing Physical Function, Global Health Status, Future Perspectives, and Systemic Treatment Effects change scores from baseline to mid-chemotherapy, end of chemotherapy, and 12 months follow-up (with a 10% change considered clinically important). The proportion of patients with improved/stable/worsened QOL scores will be compared with chi-square tests. Other QOL exploratory analyses will be presented.

[Table: see text]
Quality of life and survival in patients receiving chemotherapy for advanced non-small cell lung cancer (NSCLC)
Authors: St-Pierre D. M. , Kreisman H. , Kasymjanova G. , Agulnik J. S. , Swanson T. , Pepe C. , Lajeunesse L. , Gagne S. , Dajczman E. , Pereira L. , Small D.
Published: March 2020

19649

Background: Quality of life (QoL) is an important endpoint measure in clinical cancer trials. We evaluated prospectively the effects of two cycles of chemotherapy (CT) on QoL and the relationship between QoL and survival in advanced NSCLC patients (pts). Methods: The short-form of the SF36 was completed prior to and after 2 cycles of chemotherapy. An ITT analysis was used; a score of 0 was assigned to those who died and the last observation was carried forward for those with missing data. Results: Fifty-nine pts consented to participate and pre-chemo evaluation was available for 58 pts. Of these 58, only 40 pts completed the study (4 died, 14 did not complete the post evaluation). There were 26M: 32F with a median age of 61±11 years. Fifty pts (86%) were stage 3B (pl. eff)/4 and 50pts (86%) were PS 0–1. Overall QoL decreased significantly from 100±19 to 91±36 after two cycles of chemotherapy (p=0.03). This decline was attributed to a significant decrease in the physical health subscale (p=0.001), with 36% of pts reporting a clinically significant decline of =2. No change in the mental health subscale was observed. The symptoms that had the most profound negative impact on the physical health subscale were: ‘easily get sick’ (54%), ‘increased pain’ (30%) and ‘decreased activities’ (27%). SD+PR occurred in 36 (62%) pts, whereas 22 (38%) pts had PD after two cycles of chemotherapy. No correlation was found between response to chemo and change in QoL. The median survival (15±6.8mo), of pts whose QoL score remained stable or improved (n=36) was significantly better than those (n=22) whose QoL decreased (9±3.2 mo) (p=0.01). Conclusions: QoL decreased following chemotherapy due to a decrease in the physical health subscale. Further studies are required to determine if training can improve physical health and thus QoL and survival.

No significant financial relationships to disclose.
Measurement of DKK1 and FRP in breast and prostate cancer patients with bone metastases: Impact of zoledronic acid (ZA)
Authors: Helsten T. , Corr M. , Mortimer J. E.
Published: March 2020

19659

Background: Bone metastases produce an imbalance in osteoblast and osteoclast activity. While metastases from prostate cancer are osteoblastic, metastases from breast cancer may be osteolytic, osteoblastic or mixed. The wnt/frizzled pathway is involved in maturation of osteoblasts and in adult bone homeostasis. We explored the wnt antagonists dickkopf (DKK1) and frizzled related protein (FRP) as potential biomarkers in bone metastasis after ZA treatment. Methods: This is a pilot cohort study in bisphosphonate naive breast and prostate cancer patients with bone metastases. Cancer therapy was not specified. Patients received 2 monthly doses of ZA 4 mg IV. Pre- and post-treatment (day 60) sera were collected for measurement of FRP and DKK1, along with IL-6, calcium, creatinine and bone-specific alkaline phosphatase (BAP, a marker of osteoblast activity). Primary endpoint: mean change in FRP and DKK1; Secondary endpoints: correlation of biomarkers with each other and comparison of breast vs. prostate cancer patients. Biomarkers were measured using standard ELISA assays. Statistics: comparison of means = student t-test, correlation coefficients = Pearson. Results: Mature data from 14 patients are reported here, 9 with breast and 5 with prostate cancer. Mean age = 61 years (range 42–89). Two breast cancer patients were premenopausal. One prostate and 3 breast cancer patients received chemotherapy; all others were treated hormonally. After ZA, calcium decreased in all patients (p = 0.09). BAP decreased in all but 1 breast and 1 prostate cancer patient (mean decrease 20.0, p = 0.16). IL-6 was undetectable in most patients. FRP decreased in all but 4 patients (mean decrease 6.2, p = 0.13). There was no discernable pattern for DKK1. Pre-treatment DKK1 correlated with FRP (p = 0.01, r2 = 0.39), but there was no correlation post-treatment. Post-treatment DKK1 correlated with both serum calcium (p = 0.04, r2 = 0.49) and BAP (p = 0.005, r2 = 0.65). There was no difference between breast and prostate cancer patients. Conclusions: It is feasible to measure DKK1 and FRP in patients with malignant bone disease. Treatment with ZA has measurable effects upon these and other serum markers. Further studies with more patients are needed to evaluate their potential as biomarkers.

No significant financial relationships to disclose.
Osteonecrosis of the jaw and bisphosphonate therapy: Experience from a single Italian institution
Authors: Collovà E. , Paulli S. , Morabito M. , Frattini D. , Martelli O. , Fava S.
Published: March 2020

19661

Background: Osteonecrosis of the jaw (ONJ) is reported as serious side-effect after bisphosphonate (B) therapy. Although the number of patients (pts) presenting with ONJ seems to be increasing, the exact prevalence and etiology of osteonecrosis are not well established because of heterogeneous of clinical reports. Methods: From May 2005 and October 2006, 12 cases of ONJ were diagnoses at our Institution. Results: Characteristics of patients: the median age at presentation of ONJ was 64.2 years (range 43–79); 9 pts were female and 3 pts were male. All pts were treated with Zoledronic acid, none of pts were pretreated with other B. Location of necrosis was mandible and maxilla. Presenting symptoms were: parondotosis disease, bone exposure and ulceration. Osteonecrosis was preceded by dental extraction in 5 pts (45%). The diagnosis of ONJ was: clinical (exposed bone) and radiological in all pts; the biopsy was performed in 3 pts, none of wich showed the presence of neoplastic disease. The treatments of ONJ were: antibiotic in 3 pts, partial maxillectomiy in 2 pts, curettage in 8 pts. Only 1 pts was documented residual sites of necrosis after surgical malignancies. All pts are alive at the time of this report, with except of one. Characteristics of malignancies: breast cancer 7 pts, prostate cancer 2 pts, multiple myeloma 1 pts, carcinoma of unknown primary 1 pts. Concomitant or previous therapies for malignancies were: chemotherapy and/or radiotherapy in all pts. None of pts received radiotherapy to the involved region. B therapy has been continued in about half pts, irrespective previously ONJ, without worsening clinical condition. Conclusions: In our experience the number of pts with previous history of dental extraction and subsequent ONJ during B therapy is consistent as described in many reports. This condition may represent an important risk factor for developing osteonecrosis correlated with prolonged infusion of B. In order to reduce incidence and serious side effects of B therapy, we adopted alternative schedule treatment with bi or tri - monthly infusion.

No significant financial relationships to disclose.
Participative design of a support questionnaire for the process of diagnosing anorexia-caquexia syndorme (ACS) in cancer patients
Authors: Valentín V. , Casas A. , Carulla J. , Camps C. , Baron M. Gonzalez , Lizón J. , Sanz J. , Iglesias L. , Covas A. , Pisa S.
Published: March 2020

19662

Background: Early treatment of the anorexia-cachexia syndrome (ACS) provides a significant benefit for cancer patients, hence the need for early diagnosis. Currently available tools are complex, hampering their systematic application in clinical practice and treatment does not begin until moderate-to-severe states of malnutrition are reached. After holding 20 workshops between 2003–2005 involving about 150 Spanish oncologists, it was concluded that the ACS diagnosis should be based on questionnaires, anthropometric assessment and analytical determination, hence the need for design a brief and efficient questionnaire to support the process of diagnosing ACS in cancer patients. Methods: Between February and June 2006, 9 working sessions were held and 123 oncologists consulted to assess the symptoms and diagnostic tests required for the evaluation of ACS. In all sessions a preliminary presentation was given on the conclusions of the workshops held over the previous two years, followed by a structured discussion that was facilitated by a moderator using the Metaplan work method. Results: Questions achieving a consensus of over 75% were deemed as essential. Included among the questions to be answered by the patients are: anorexia (79.7%), dysphagia (78.9%) and vomiting/nausea (79.7%). The physician’s set of questions include: evolution of body weight determined by weight loss >10% (94.3%); stage of the disease (80.5%), considering stage IV to be an alert sign of ACS; the location of the neoplasia (78.9%), with head and neck, esophagus, pancreas, biliary ducts and stomach being the most prevalent neoplasia locations among these patients and albumin level (77.2%), being suspected ACS diagnosis on 2.1 mg/dl or less. It was agreed that the questionnaire should be a simple tool, phrased in easy-to- understand language and formulated with short (92%) and few (85%)questions and to keep the format simple, making it easier to fill in (36.5%). The inclusion of closed “Yes/No” type answers was regarded positively. Conclusions: The proposed ACS diagnosis questionnaire meets the expectations set at the start of the project. We are currently carrying out a validation process in order to ensure its reproducibility.

No significant financial relationships to disclose.
The utility of assessing physical activity in ovarian cancer patients following chemotherapy
Authors: Zakashansky K. , Higgins S. , Montgomery G. , Dottino P. , Bovbjerg D.
Published: March 2020

19666

Objective: The purpose of this preliminary study was to explore the utility of objective assessments of physical activity for investigating the patterns and predictors of reduced physical activity levels in patients receiving standard chemotherapy for ovarian cancer. Methods: Ovarian cancer patients receiving standard regimens of Taxol/Carboplatin chemotherapy (n=9) were recruited prior to their treatment infusion. After signing informed consent, they completed the 20-item Center for Epidemiologic Studies Depression Scale (CESD); post treatment daily activity levels were assessed with a wrist watch-sized, water proof, omnidirectional, actigraphy monitor (Actiwatch-64, Mini Mitter, Bend, OR) worn on the nondominant wrist for the three weeks between treatment cycles. Identical actigraphy data were collected on a sample of healthy female staff (n=9) over a 1 week interval to provide a benchmark for comparison. Results: As expected, waking activity levels in the control sample showed no significant changes across days (p=0.41), so mean levels (343.45 counts) and 95% confidence intervals were calculated for comparison purposes. Chemotherapy patients had significantly lower levels of activity, as well as evidence of recovering physical activity over the 21 days following treatment (p=0.01). Interestingly, the subset (n=4) of patients with higher levels of pretreatment depression (Hi-CESD) did not show significant recovery in physical activity while the Lo-CESD subgroup showed substantial recovery (p=0.001). Conclusions: Objective assessment of physical activity in ovarian cancer patients following chemotherapy treatment reveals significant reduction in activity levels, and a failure to recover in patients with higher levels of pretreatment depression. Actigraphy of daily activity levels may provide a sensitive means of quantifying reductions in physical activity and recovery patterns following chemotherapy treatment for gynecologic cancer.

No significant financial relationships to disclose.
Assessment of safety with abbreviated, weight-based bevacizumab infusions in a variety of solid tumors
Authors: Hart J. W. , Murillo J. R. , Oholendt M. S. , Preti H. A.
Published: March 2020

19674

Background: Bevacizumab (BEV), a humanized monoclonal antibody that neutralizes vascular endothelial growth factor, has shown improved responses in patients with colorectal cancer (CRC) and non-small cell lung cancer (NSCLC) while displaying activity in a variety of other solid tumors. Phase I clinical trials with BEV utilized standard 90- 60-, and 30-minute infusions for 1st, 2nd, and subsequent infusions, as tolerated; initial doses reported less than 3% incidence of infusion-related adverse events (AEs), with 0.2% grade III/IV reactions. Recommended infusion rates for BEV remain unchanged despite the minimal risk of infusion-related AEs. Saltz and colleagues recently reported novel data supporting the safety and tolerability of abbreviated BEV infusions in CRC patients within a single institution. Our objective was to replicate previously reported safety profiles while utilizing abbreviated infusions of BEV in multiple tumor types. Methods: An internal retrospective analysis revealing minimal infusion AEs with standard infusions facilitated this current study. BEV- naïve and previously-treated patients were consented for the study utilizing the following weight-based infusion times: 5, 10, and 15 mg/kg doses over 10, 20, or 30 minutes, respectively, for all doses. Patients were assessed throughout and immediately following the infusion for any infusion-related AE. Results: A variety of tumor types are represented in 26 enrolled patients including CRC, NSCLC, breast, ovarian, pancreatic, and brain. Central nervous system involvement accounted for 35% of patients [primary brain (23%) and metastatic disease (12%)]. A considerable number of patients (19%) were treated with single-agent BEV. Nine BEV-naïve patients were initiated on abbreviated infusions, while 16 were converted from the standard infusion schedule. Seventy-seven total doses utilizing the abbreviated infusions failed to produce infusion-related AEs. Conclusion: These results support previous data affirming the safety and tolerability of abbreviated BEV infusions in CRC patients, while also reporting promising safety of abbreviated infusions in a variety of additionally unreported solid tumors types.

No significant financial relationships to disclose.
Promoting evidence-based management of anemia in cancer patients: Background and scientific validation of RESPOND, a web-based clinical decision support system
Authors: Van Erps J. , Aapro M. , MacDonald K. , Soubeyran P. , Muenzberg M. , Dunlop R. , Eeckhout C. , Warrinnier H. , van Well M. , Abraham I.
Published: March 2020

19676

Background: The 2006 European Organisation for Research and Treatment of Cancer (EORTC) guidelines for erythropoietic proteins in cancer-related anemia provide the most up-to-date assessment of the evidence base. To promote clinicians’ adoption of evidence- based (EB) practice guidelines (EBPGs), it is critical to bring guidelines to the point of care. RESPOND is an EB clinical decision support system (CDSS) based on the EORTC guidelines. CDSSs are seldom validated. We describe the methodologies of two studies being conducted to validate RESPOND. Methods. Study 1: descriptive design - accuracy and content validity. Five experts are asked to rate the accuracy of algorithms derived from the guidelines; the objective being an intraclass correlation coefficient =0.90 for each of 27 algorithmic sets. Study 2: hybrid matched pre-post design - concurrent and discriminant validity. Two patient cohorts (n=33 each) matched by type of cancer and similarity of chemotherapy regimen ie, sample 1 (4 months prospective data after RESPOND [post]) and sample 2 (4 months retrospective data prior to RESPOND [pre]) were used to test concurrent validity (congruence scores [CS] of sample 1) and discriminant validity (difference between sample 2 and sample 1 CS). A score is calculated for each patient to quantify the extent to which treatment and outcomes are congruent with the EORTC EBPG. Table 1 . Calculation of the congruence score ESA, erythropoiesis-stimulating agent; Hb, hemoglobin, Q1W, once weekly, Q3W, once every three weeks Conclusions. These studies will provide the necessary validation for RESPOND as an evidence-based clinical support tool.

[Table: see text]

[Table: see text]
A randomised prospective study of prolonged treatment with tocopherol and pentoxifylline, in addition to carbogen in the management of radiation late effects
Authors: Brennan S. M. , O Shea C. , Salib O. , Moriarty M.
Published: March 2020

19682

Background: Pentoxifylline (PTX) and tocopherol (Vitamin E) are antioxidants previously shown to be useful in combination in the treatment of late radiation effects. To our knowledge, this is the first study to examine the clinical benefit of combination therapy with carbogen, tocopherol and pentoxifylline in the mitigation of late radiation effects. The optimal duration of PTX and tocopherol treatment has not been fully established. Therefore, we also studied short versus extended treatment duration. Methods: We conducted a phase II prospective randomised study of inhaled carbogen (95% oxygen + 5% carbon dioxide) over 90 minutes, 5 days per week for 3 weeks in addition to short versus prolonged treatment with pentoxifylline (800 mg) and tocopherol (1,000 IU) orally once daily. All 18 patients received carbogen therapy. Patients with grade 3 toxicity post radical radiotherapy for a variety of cancer primaries were eligible for the trial. The primary endpoint was improvement in maximum Lent-Soma toxicity scores. Ethical approval was obtained. Results: Maximum Lent-Soma scores improved with treatment in six of the eighteen patients giving a 33% response rate. The proportion of patients responding to treatment in the prolonged treatment arm B was more than double than in the shorter arm A (Fisher’s exact test: p = 0.321). Two patients in arm B had complete resolution of their symptoms, which was maintained at 2 and 3 years follow up. Conclusions: As late radiation effects are progressive by nature and have such a negative impact on quality of life in long-term cancer survivors, any treatment, which may ameliorate their symptoms, should be considered of benefit. This study confirms the benefit of prolonged treatment and we would recommend clinical use of these agents with treatment duration of at least 12 months, in the management of late radiation effects.

No significant financial relationships to disclose.
Clinical outcome of chemoradiotherapy in elderly patients with non-small cell lung cancer at G.V Montgomery Veterans Affairs Medical Center
Authors: Choi M. , Chan W. , Jaiwatana J. , Khansur T.
Published: March 2020

19683

Background: More than 2/3 of lung cancer patients are age = 65 and the proportion of elderly patients are expected to rise in the United States. However data on the use of optimal chemoradiotherapy in this group of patients are limited. Methods: All lung cancer patients = 65 years, who received both chemotherapy and radiation therapy at the G. V. Montgomery VAMC between Jan 2000 to Dec 2005, were analyzed from tumor registry and computerized medical records. Patients who only received palliative radiation therapy for bone and brain metastasis were excluded. Results: Among 652 lung cancer patients diagnose, 46 patients = 65 years received both chemotherapy and radiation therapy over the 6 year study period. The median age was 72 (range:65–84) and 70% of the patients were = 70 years. All patients were male with 65% white and 35% black population. The majority of patients were stage III (85%) while there was one stage I and six stage II patients. 41 patients (89%) were able to complete the planned radiation therapy and median dose delivered was 6140 cGy. The chemotherapy regimen was carboplatin and paclitaxel either weekly during radiation therapy and every three weeks in sequential treatment. There was only 1 treatment related mortality and only 15% of patients survived less than 6 months. The 1, 2, 3 year survival rates were 67%, 24%, and 15% respectively and median survival was 15.3 months. 15 patients were treated sequentially(S) with chemotherapy (median cycle-3) followed by radiation therapy and 31 patients concurrently (C) with chemoradiotherapy. (median- 5 weekly treatment) The survival among the two groups did not differ statistically. (median survival-19.1 month (S) vs. 14 month (C) p=0.78) Conclusions: Both sequential and concurrent chemoradiotherapy is feasible and beneficial in elderly patients with lung cancer. Sequential treatments might be as effective as concurrent chemoradiotherapy in elderly VA patient population.

No significant financial relationships to disclose.