bluuebunny/crossref_metadata_2025 huggingface dataset:
Best supportive care in combination with polychemotherapy versus best supportive care alone as second-line therapy in stage IV metastatic melanoma (DeCOG MM-PAL 8)
Authors: Ulrich J. , Trefzer U. , Tilgen W. , Schadendorf D. , Kaatz M. , Mohr P. , Garbe C. , Hauschild A.
Published: March 2020

8567

Background: To date, there is no evidence of survival benefit from randomized trials in stage IV metastatic melanoma (MM) after disease progression to first-line therapy. Therefore, we initiated a phase III trial to evaluate the impact on survival of polychemotherapy in patients (pts.) receiving best supportive care (BSC) as second-line therapy. Methods: This prospective multicenter controlled study was conducted by the Dermatologic Cooperative Oncology Group (DeCOG) with 13 participating centers. Pts. with stage IV MM disease between 18 and 75 yrs. and a Karnofsky performance status (KPS) > 60 with progression after first-line chemotherapy or chemo-immunotherapy were offered to choose between polychemotherapy + BSC or BSC alone. Pts. were required to have adequate renal, liver and bone marrow function. The regimen consisted of cisplatin (50 mg/m2), vindesine (3 mg/m2) and dacarbacin (450 mg/m2) given on day 1 and 8 every 28 days (CVD). Reevaluation according to WHO response criteria were performed every 2 cycles. Primary endpoint was the median overall survival (OS). Secondary endpoints were overall response rate (OR) (only CVD arm) and quality of life (QOL). Results: Between 1/02 and 8/06 120 pts. were recruited, a minority of 35 pts. (29%) chose the BSC arm (A) and 85 (71%) the CVD + BSC arm (B). Five pts. were ineligible, and thus 115 pts. treated per protocol. There was a significant lower KPS in arm A at study entry. At the time of data analysis, 85% of the pts. had died from melanoma. There was no siginificant difference (p=0.093) in median OS between the two arms, 9.0 [95% CI: 3,9–14,1] months in arm A and 8.0 [95% CI: 6,5–9,5] months in arm B. The OR in arm B was 7.5% (2 CR, 3 PR). Conclusions: Polychemotherapy (CVD) + BSC as second-line therapy in stage IV MM does not improve overall survival as compared to BSC alone.

No significant financial relationships to disclose.
Serum YKL-40 is elevated in a subgroup of patients after surgery for stage IIb-III melanoma
Authors: Jensen M. , Johansen J. S. , Christensen I. J. , Schmidt H. , Nørgaard P. H. , Bastholt L.
Published: March 2020

8574

Background: High serum YKL-40 is associated with poor prognosis in patients with adeno- and squamous cell carcinoma, glioblastoma, and stage I-II and IV melanoma. YKL-40 is secreted by cancer cells, macrophages and neutrophils. YKL-40 is a growth and differentiation factor, and plays a role in tissue remodelling and angiogenesis. The aim of our study was to compare serum YKL-40 in patients after surgery for stage IIb-III melanoma with healthy individuals and with clinical and histological prognostic parameters. Methods: YKL-40 was determined by ELISA (Quidel, CA) in serum samples from 231 patients, with stage IIb-III melanoma. The 74 women and 157 men had a median age of 50 (range 22–76 years), and they were enrolled in a Nordic adjuvant protocol, randomizing to observation or interferon therapy (1 or 2 years). Baseline samples were drawn <70 days after primary biopsy, but prior to start of therapy. Results: Serum YKL-40 was increased (p=0.003) in the 231 patients (median 47 μg/l, range 20–1,416 μg/l) compared to healthy individuals (43 μg/l, range: 20–184 μg/l, n=245). Serum YKL-40 was higher than the age-corrected 95th percentile of s-YKL-40 in healthy individuals in 19% of the patients with melanoma thickness >4 mm and no lymph node metastasis (n=27), in 8% with sentinel lymph node metastasis (n=89) and in 14% with clinical lymph node metastasis at time of surgery or as recurrence in the follow-up period (n=111). Comparison of serum YKL-40 in the 3 groups showed no significant differences (p=0.22). No difference was found comparing serum YKL-40 between the three groups of Breslow thickness (< 1 mm, 1–2 mm, > 2 mm)(p=0.66), and the two groups of Clark′s level (II-III, IV-V)(p=0.88) was found. A weak association (p=0.045) was found between s-YKL-40 and localization of primary tumor, with trunc having the highest median concentration of s-YKL-40. No association between an elevated s-YKL-40 with number of positive lymph nodes (0.36), ulceration (p=0.81), extranodal growth (p=0.56), or histologic subtype of primary tumor (p=0.48) was observed. Conclusion: Serum YKL-40 is elevated in a subgroup of melanoma patients with stage IIb-III and not associated with classical clinical and histological parameters. It is not known if the increased YKL-40 reflects the biological behaviour of the disease.

No significant financial relationships to disclose.
Phase II single institution study of sequential biochemotherapy (BCT) for patients (pts) with stage IV melanoma (M)
Authors: Bojanapally P. R. , Alexandrescu D. T. , Rusciano V. , Wiernik P. H. , Dutcher J. P.
Published: March 2020

8580

Background: The utility of BCT for M remains controversial. A prospective phase II study was conducted to assess the clinical benefit of BCT in patients with stage IV M. Methods: Between March 2005 and March 2006 11 pts (6 Male and 5 Female with a median age of 54 (range 36 - 82)) with metastatic M were treated with paclitaxel 225 mg/m2 via continuous 24 hour IV infusion every 3 wks for 4 cycles or maximum benefit followed by HD IL2, 1.33 mg/m2 every 8 hours for 5 days of wk1 and wk3 based on pts tolerance to a maximum of 12 doses per wk. 2 Male pts received IL2 followed by paclitaxel. Pts had a ECOG performance status of 0 - 2, with a median time of 60 months since diagnosis of disease (range 7 to 240 months). 11 pts (92%) had multiple metastatic sites (50% had lung mets, 58% had liver mets) and 4 pts (33%) had prior chemotherapy or immunotherapy. Results: Of the 13 assessable pts one achieved a PR after paclitaxel and CR after IL2 continuing at 20+ months. One had SD for 1 year after receiving HD IL2 and SD for 6 months while on paclitaxel independently, One had PR for 6 months on paclitaxel and one had MR with paclitaxel for 3 months. 9 pts (69%) had PD on paclitaxel and again on IL2, with a median survival from treatment of 7 months, 2 of these got no IL2 due to rapid PD. An overall response rate of 30% (1 CR on paclitaxel + IL2 , 1 PR on paclitaxel, 2 SD (including MR) on paclitaxel) was seen with a median survival from treatment of 15 months. Conclusions: In this study there may be prolonged survival among responders, which may be due to synergy of sequential BCT, or may reflect single agent activity of each drug. BCT should still be considered as an experimental therapy and further evaluated.

No significant financial relationships to disclose.
Financial burden from wage losses after early breast cancer: Extent and determinants among Canadian women
Authors: Lauzier S. , Maunsell E. , Drolet M. , Hébert-Croteau N. , Brisson J. , Coyle D. , Masse B. , Abdous B. , Robidoux A. , Robert J.
Published: March 2020

9000

Background: Wage losses after breast cancer may result in considerable financial burden. More women now participate in the workforce and breast cancer is managed using multiple treatment modalities that could lead to long work absences. We evaluated the burden from wage losses and determinants among Canadian women in the first 12 months after newly diagnosed non-metastatic breast cancer. Methods: This prospective cohort study was conducted among 800 women from 8 hospitals (participation 83%) of whom 459 were working at diagnosis. For these latter women, information on potential determinants of wage losses, work absences, compensation received and perception of financial situation was collected by 3 telephone interviews over the year. Information on medical characteristics came from medical files. The main outcome was the relative loss, namely wages lost divided by annual wages the woman would have earned had she not been absent from work. ANOVA was used to identify determinants. Results: The median relative loss in the first year after diagnosis for the 403 women reporting an absence or reduced work hours was 19% or $5,502 (Can dollars). Multivariate analysis showed that the mean relative loss was 13% for women who reported that breast cancer was not at all costly compared to 22%, 33% and 38% among women who said that breast cancer was a bit, quite or very costly, respectively (ptrend<0.0001). A higher relative loss was significantly associated with a lower level of education (difference between lowest and highest levels = 8 %, ptrend=0.0016), living =50 km from the surgery hospital (diff = 6%, p=0.0697), lower social support (diff = 8%, p=0.0119), invasive disease (diff = 6%, p=0.0861), chemotherapy (diff = 17%, p<0.0001), self-employment (diff= 17%, p<0.0001), shorter tenure in the job (diff between lowest and highest levels = 12%, ptrend<0.0001) and part-time work (diff = 10%, p=0.0003). Conclusions: Financial effects of wage losses could add to the overall burden of breast cancer. Clinicians and policy makers should be sensitized further to the fact that financial burden may be important for working women having more aggressive treatment and precarious work situations.

No significant financial relationships to disclose.
Pyridoxine is not effective for the prevention of hand foot syndrome (HFS) associated with capecitabine therapy: Results of a randomized double-blind placebo-controlled study
Authors: Lee S. , Lee S. , Chun Y. , Kim M. , Chang H. , Kim T. , Ryu M. , Lee J. , Lee J. , Kang Y.
Published: March 2020

9007

Introduction: Although pyridoxine has been used empirically for the prevention of HFS associated with capecitabine, its efficacy has not been proven yet. We performed a prospective randomized double-blind study to determine whether pyridoxine can prevent the development of HFS when given concurrently with capecitabine. Method: Chemotherapy-naive patients (pts) with gastrointestinal tract cancers who were going to have capecitabine-containing chemotherapy were randomized to receive either oral pyridoxine (200 mg/day) or placebo daily during chemotherapy after stratified by chemotherapy regimen: 1) capecitabine alone, 2) capecitabine and cisplatin, or 3) docetaxel, capecitabine, and cisplatin. The patients were observed until grade 2 or 3 HFS (by NCI CTC version 2.0) developed or capecitabine containing chemotherapy ended. When grade 2 or 3 HFS developed in pts in placebo group, the pts were randomized again to receive either pyridoxine or placebo for next cycle of chemotherapy in order to determine whether pyridoxine could improve the HFS. Result: From Jun 2004 to Oct 2005, total 389 pts were entered onto the study. But, 29 pts (15 in placebo group and 14 in pyridoxine group) were excluded from the study because of ineligibility or pts’ refusal. Pts’ characteristics were well balanced between the 2 groups. Grade 2 or 3 HFS developed in 55 of 180 (30.6%) pts in placebo group and in 57 of 180 (31.7%) pts in pyridoxine group. (p=0.788) The median cycles of chemotherapy to grade 2 or 3 HFS was 3 in both groups. The mean cumulative dose of capecitabine until occurrence of grade 2 or 3 HFS was not different statistically between the two groups. (221,157.5 mg/m2 vs. 259,808.5 mg/m2, p=0.788). Total 44 of 55 pts in placebo group who had grade 2 or 3 HFS were randomized to receive either placebo or pyridoxine at next cycle. There was no significant difference between the two groups in the proportion of pts with improvement of HFS (43% vs 48%, p=0.94). Conclusion: These results indicated that pyridoxine is not effective for the prevention of HFS associated with capecitabine therapy.

No significant financial relationships to disclose.
Does health-related quality of life (HRQL) improve for patients who respond to chemotherapy? Analysis of patients with advanced pancreas cancer (APC) receiving gemcitabine on Cancer and Leukemia Group B (CALGB) study #80303
Authors: Romanus D. , Archer L. , Wang X. , Goldberg R. , Mulcahy M. , Kindler H. , Schrag D.
Published: March 2020

9008

Background: Gemcitabine chemotherapy for APC is palliative and confers only modest survival advantage. Therefore HRQL concerns are of paramount importance. Methods: We compared HRQL scores based on response to chemotherapy at the first interval restaging (8 weeks). We evaluated HRQL at baseline on paper, and then q8 weeks by phone using the EQ5D instrument in patients with APC participating in a double-blind, randomized trial comparing overall survival for gemcitabine with bevacizumab (GB) or placebo (GP). The EQ5D is a HRQL measure whose composite (C) and visual analog scale (VAS) scores respectively reflect societal and patient valuations. Results: Among 552 patients starting protocol treatment, characteristics did not differ between 359 who did and 193 who didn’t complete baseline assessments. Patients who didn’t complete 8 week assessments were more likely to have died, progressed or discontinued protocol therapy. Changes in EQ5D scores from baseline to 8 weeks did not differ by treatment arm (p-values=0.84, 0.79 for C and VAS scales, Wilcoxon rank sum test). At 8 weeks, all patients and those with progressive disease had a modest decline in VAS scores (p-values≤0.02, Wilcoxon signed rank test). Comparisons of changes from baseline in C scores at 8 week follow-up revealed no differences within other response group strata (all p-values > 0.05). Conclusions: Based on this preliminary analysis, gemcitabine therapy was not associated with higher HRQL scores, nor was there any strong association between tumor response and HRQL. To increase data representativeness, future APC trials should assess HRQL more often than every 8 weeks. HRQL Scores Based on Gemcitabine Response Strata. Values are Mean (SD)

[Table: see text] [Table: see text]
Angiotensin-converting enzyme gene polymorphism (ACEGP) and cancer cachexia (CC): Is there a link?
Authors: Vigano A. A. , Hamel N. , Morais J. , Foulkes W. , Kilgour R. , Bond R. , Trutschnigg B. , Brar S. , Theberge J. , Tremblay M.
Published: March 2020

9011

Background: ACEGP greatly influences functional status and is currently the gene most involved in human fitness. The insertion allele (II) (a 287 bp fragment) rather than the deletion allele (DD) for the angiotensin-converting enzyme (ACE) gene is associated with low ACE levels in tissues and enhanced metabolic efficiency, as demonstrated by an improved response to vigorous training in healthy individuals. In addition, lower tissue ACE activity in mice was associated with decreased insulin resistance, greater glucose uptake in the skeletal muscle, and higher glycogen and fat stores. The aim of the study was to gather preliminary data on the potential association between muscle mass and ACEGP in advanced cancer patients (ACP). Methods: Buffy coat serum and plasma was obtained from 55 patients 18 years or older, newly diagnosed with Stage III (inoperable)-IV non-small cell lung cancer and unresectable/ metastatic gastrointestinal cancers seen within the McGill University Health Center. Muscle surface area (MSA-cm2) was calculated from computerized tomography slices at the L3 vertebrae using TOMOVISION SliceOmatic software version 4.3. Muscularity (M-cm2/m2) and lean body mass (LBM-kg) were calculated by extrapolation of image analysis used to quantify lean tissue. Results: ANOVA confirmed significant difference (p<0.001) among MSA (II: 134.04±35.23; ID: 122.37±29.74; DD: 115.22±27.55), M (47.72±8.67; 41.65±9.26; 41.80±9.26), and LBM (43.00±11.21; 39.29±9.46; 37.01±8.77). In a multiple linear regression model, the II allele was associated with higher M (p=0.042) and a trend for higher MSA and LBM (p=0.059) independent of age, gender, diagnosis, and treatment received. Conclusions: Our data suggest ACEGP influences muscle mass in ACP. Further investigations in a larger sample of ACP are underway to determine whether ACEGP is an important predisposing factor to CC-associated muscle wasting.

No significant financial relationships to disclose.
Cytokine gene polymorphisms and cancer-related symptoms in lung cancer patients
Authors: Reyes-Gibby C. C. , Spitz M. , Wu X. , Shete S.
Published: March 2020

9012

Background: Cytokines, aberrantly produced by cancer cells, have recently been implicated in the severity of cancer-related symptoms. We hypothesize that functional variations in cytokine genes could explain variability in self-reported pain and depressed mood in lung cancer patients of all stages. Methods: Pain, depressed mood, clinical and demographic variables were assessed at presentation, and prior to initiating any cancer treatment in 514 white patients with non-small cell lung cancer (NSCLC). Using the TaqMan method, we genotyped single nucleotide polymorphisms in interleukin (IL) −6 (−174 G>C), IL-8 (−251 T> A), and tumor necrosis factor-alpha (TNF-; −308 G> A), and determined their associations with pain and depressed mood. Results: Sixteen and 7% of respondents reported severe levels of pain (≥ 7, on a 0–10 scale) and depressed mood most/all of the time, respectively. The severity of pain and depressed mood predictably varied by clinical, sociodemographic, and genotype variables in the univariate analyses. Multivariable logistic regression analyses showed that variant allele in IL8 (OR=2.05;95%CI=1.04–4.06), early age of onset (≤ 50 years) (OR=1.80;95%CI=1.02–3.14), and depressed mood (OR=4.55;95%CI=2.105–9.81) were significant predictors for severe pain. For depressed mood, results showed that variant allele in IL6 (OR=0.49;95%CI=0.24–0.49), severe pain (OR= 3.77;95%CI=1.79–7.95) and a history of stroke (OR=3.50;95%CI=1.03–11.82) as significant predictors. Classification and Regression Tree analyses revealed potential higher order gene-gene interaction for pain (IL1 and IL6) and depressed mood (IL8 and IL6). Conclusions: Variations in individual inflammatory responses could partly explain variability in pain and depressed mood in patients with lung cancer.

No significant financial relationships to disclose.
Normalization of bone markers and improved survival during zoledronic acid therapy
Authors: Lipton A. , Cook R. , Coleman R. E. , Major P. , Terpos E. , Body J. , Smith M. R. , Brown J. , Garnero P.
Published: March 2020

9013

Background: In patients (pts) with bone metastases, elevated N-telopeptide of type I collagen (NTX) levels correlate with increased relative risks (RR) of skeletal-related events (SREs), disease progression, and death (Brown et al. J Natl Cancer Inst. 2005;97:59–69; Coleman et al. J Clin Oncol. 2005;23:4925–4935). Therefore, we conducted an exploratory analysis of 3 large, randomized, controlled trials to investigate whether reductions in NTX levels by treatment with zoledronic acid (ZOL) correspond with decreased risks of SREs and death. Methods: Urinary NTX was measured at baseline and at 3 months in pts with bone metastases from breast (BC; n = 379), prostate (PC; n = 314), or lung cancer and other solid tumors (LC/OST; n = 204) who received ZOL for up to 24 months. Pts were stratified by baseline NTX levels (normal, < 64 nmol/mmol creatinine; elevated, = 64 nmol/mmol creatinine). Results: Approximately 50% of pts had elevated baseline NTX, and NTX normalization occurred within 3 months of ZOL treatment in 81% of pts with BC or LC/OST and in 70% of PC pts. For all tumor types, NTX normalization in response to ZOL correlated with reduced risk of first SRE and death compared with pts whose NTX did not normalize ( Table ). Further analyses using NTX level as a continuous variable revealed that, for all tumor types, any reduction in NTX levels correlated with lower risk of first SRE and death regardless of baseline NTX level. Conclusions: Pts whose NTX normalized on ZOL at 3 months had a lower risk of first SRE and death compared with pts whose elevated baseline NTX did not normalize. Regardless of baseline NTX level, a reduction in NTX over 3 months (absolute and % change) provided a continuum of SRE risk reduction and survival benefit.

No significant financial relationships to disclose.

[Table: see text]
Impact of pre-operative chemotherapy on the quality of life (QL) of patients with resectable non-small cell lung cancer (NSCLC): Experience from the MRC LU22/NVALT/EORTC 08012 multicentre randomised trial
Authors: Hopwood P. , Nankivell M. , Pugh C. , Gilligan D. , Nicolson M. , Stephens R. J.
Published: March 2020

9020

Aim: To evaluate QL during the first 2 years follow-up in patients randomised to receive 3 cycles of platinum-based chemotherapy (CT-S) prior to surgical resection of NSCLC compared to those receiving surgery alone (S). Methods: A total of 519 patients were entered into the LU22 trial from 70 centres in the UK, The Netherlands, Germany and Belgium. All patients were asked to complete the SF-36 QL questionnaire prior to randomisation and at 6 and 12 months then annually to 5 years. The scores from the SF-36 questionnaire were combined into 8 domains and also summarised as physical component summary (PCS) and mental component summary (MCS). The 6,12 and 24 month PCS and MCS scores were analysed using multivariable regression to identify prognostic factors and investigate the difference between the regimens. Results: 82% patients completed QL at baseline, and compliance at 6, 12 and 24 months was 59%, 60% and 67% respectively. Median age was 63 (range 25 to 79 years) and 72% were male. At 6 months patients in the S group reported somewhat better functioning in all domains except general health and mental health, but no differences were seen at 12 or 24 months. The regression analyses indicated that better physical health outcomes (PCS) were predicted by baseline PCS and MCS at all follow-up points (all p<0.05), whereas longer time since surgery predicted better PCS at 6 months (p<0.05), and younger age predicted better PCS at 24 months (p=0.07). For mental health, better MCS was predicted at all time points by baseline MCS (p<0.05). In addition, female gender (p=0.07), and PCS (p<0.05), were predictors at 6 months, and younger age predicted better MCS at 24 months (p<0.01). Treatment regimen had no effect on QL at any time point. At 1 and 2 years more than 50% patients considered their health comparable to others, and 45% were generally optimistic about their future health. Conclusions: Over 2 years follow-up, QL was not adversely affected by pre-operative chemotherapy and there were no significant differences between the regimens. Many patients saw themselves as fit as their contemporaries.

[Table: see text]
Prognostic significance of patient-physician disagreement about performance status in patients with advanced cancer
Authors: Schnadig I. D. , Fromme E. K. , Loprinzi C. L. , Sloan J. A. , Mori M. , Li H. , Beer T. M. , Perrin N.
Published: March 2020

9021

Background: Physician-reported performance status (PS) is an important prognostic factor in advanced malignancies and is a commonly used stratification variable in cancer clinical trials. However, the extent, predictors, and prognostic importance of disagreement in PS assessment between physicians and patients have not been examined. Methods: Using NCCTG clinical trials from 1987–1990 (J Clin Oncol 19(15):3539–3546, 2001), we analyzed the difference and agreement of PS (ECOG and Karnofsky [KPS]) and nutritional status assessments reported by physicians and patients individually. The degree of disagreement was analyzed using paired t-test. Overall mortality was estimated by Kaplan-Meier method. The effect of disagreement on overall survival was analyzed by Cox regression. Independent predictors of disagreement were identified by logistic regression. Results: 1,636 patients with advanced lung and colorectal cancer had a median survival of 9.8 months (95% CI, 9.4 to 10.4). Percent agreement between patients and physicians about KPS, ECOG PS, and appetite/nutritional status was 32.9%, 43.4% and 42.0% respectively. Physicians were more likely to rate patients better than individual patients were to rate themselves: ECOG (Mean 0.91 vs 1.30, p<.0001), KPS (Mean 83.3 vs. 81.7, p<0.0001), appetite/nutritional status (Mean 1.6 vs. 2.1, p<0.0001). Inability to work, depression and less than a high school education were independently associated with disagreement. An increased risk of death was observed for patient and physician disagreement on KPS (HR=1.15, 95% CI, 1.03 to 1.27 p=0.01) and appetite/nutritional status (HR=1.39, 95% CI, 1.26 to 1.54 p<0.0001). Conclusions: Patients and physicians frequently disagree about patient PS, with physicians tending to rate patients higher than patients do themselves. Baseline patient demographic factors that independently predict disagreement have been identified. Disagreement confers an increased risk of death in the setting of advanced malignancies. These findings illustrate limitations of physician-only assessed PS.

No significant financial relationships to disclose.
Continuous intravenous lidocaine controls abdominal pain secondary to peritoneal carcinomatosis as a consequence of diffusion into ascites
Authors: Tanaka T. , Tsukui R. , Okano S. , Tsuchiya M. , Obokata K. , Ogawa T. , Abe T. , Ikeya T. , Miyasaki M.
Published: March 2020

9031

Background: Our team reported at the 42nd ASCO meeting that continuous, low-dose intravenous (IV) lidocaine is an effective method for pain relief in terminal patients with peritoneal carcinomatosis. Our aim was to explore the mechanism by which abdominal pain of terminally-ill patients with peritoneal carcinomatosis was improved by continuous IV lidocaine. Methods: 48 patients with peritoneal carcinomatosis due to GI (46) and GYN (2) malignancies were administered lidocaine at low-doses (0.4 and/or 0.8mg/kg- h) for >24 hours, because opiates, NSAIDs, and other adjuvants were ineffective in relieving their abdominal pain. Pain (faces rating scale; 0-no pain, 5-worst pain), oral intake, side effects, and activities of daily life were quantified. Two days after beginning lidocaine, ascites was sampled to measure ascitic concentration of lidocaine, tumor markers and cytology. Results: Mean age (±SE) was 60±2. The volume of ascites was estimated to be 2,700±400ml by the ultrasound 5 points methodology. Abdominal symptoms improved in 1.5±0.2days after beginning lidocaine, and the pain scale decreased from 1.9±0.2 to 0.5±0.1; p<0.001; 75% of patients had improvement in pain of whom 78% had complete relief of pain. Oral intake increased from 18% to 49% of baseline (p<0.001), and 67% in those with improvement in pain had an increased volume of oral intake. There were no obvious differences in response to 0.4 and 0.8 mg/kg-h in patients receiving both doses. Serum concentrations of lidocaine at 0.4 and 0.8 mg/kg-h were 1.7±0.2 and 3.2±0.2 μg/ml, respectively; lidocaine concentrations in the ascites were 1.2±0.2 and 2.1±0.2 μg/ml. No patient complained of pain at the time of peritoneal puncture. Side effects included bradycardia of <60 beats per minutes (3 patients). The duration of lidocaine administration was 23±3 days; 43% of patients were able to be discharged home for end-of-life care, with parenteral nutrition and continuation of lidocaine administration or oral mexiletine (300–450 mg/day) for adjuvant analgesia. Conclusions: Lidocaine diffuses into ascites and almost equilibrates with serum concentrations acting as a peritoneal anesthesia which, as a result, controls abdominal pain in patients with peritoneal carcinomatosis.

No significant financial relationships to disclose.
Aromatase inhibitors (AI) for elderly patients: Efficacy, compliance and safety according to patient age in the BIG 1–98 trial
Authors: Crivellari D. , Sun Z. , Coates A. S. , Price K. N. , Thürlimann B. , Mouridsen H. , Mauriac L. , Forbes J. F. , Castiglione- Gertsch M. , Goldhirsch A.
Published: March 2020

9033

Background: Because elderly patients (pts) are under-represented in clinical trials, care should be taken in extending overall results to that patient group. We compared letrozole (L) with tamoxifen (T) with respect to disease-free survival, treatment compliance, and adverse events (AEs) according to age in the continuous therapy arms of the BIG 1–98 trial. Methods: Between March 1998 and May 2003, 8,028 postmenopausal women with hormone receptor-positive breast cancer were enrolled in the BIG 1–98 trial. This report includes the 4,922 pts allocated to continuous therapy with either T or L for 5 years. Subpopulation Treatment Effect Pattern Plots (STEPP) were used to look at the patterns of differences in disease-free survival and incidences of AEs according to age. In addition, three categorical age groups were defined: “younger postmenopausal” < 65, “older” 65–74, and “elderly” = 75. Cox proportional hazards models were used to compare T and L according to time to first AE, adjusting for relevant pre-existing risk factors. The median follow-up was 40.4 months. Results: STEPP analysis showed the L provided consistent benefit compared with T irrespective of age. Pts 75 and older were less likely to complete trial treatment, but similarly in the two treatment groups. Adjusted treatment comparisons of AEs according to age groups are given below. (T,L: significantly more AEs on T,L; NS: no significant difference) Conclusion: Adjuvant treatment with L had superior efficacy compared with T in all age groups. Physicians should base clinical decisions on the individual patient profile with respect to reduction of risk of recurrence from L as well as existing comorbidities.

[Table: see text]

No significant financial relationships to disclose.
Omission of radiotherapy after breast conserving surgery among elderly women with favorable prognosis tumors
Authors: Swenson W. T. , Hoffman M. , Hoffman A.
Published: March 2020

9034

Background: Adjuvant radiotherapy after breast-conserving surgery is a standard therapy for invasive breast carcinoma. Controversy exists regarding the benefit of adjuvant radiotherapy for elderly women with favorable prognosis tumors. Methods: Using data from the Surveillance Epidemiology and End Results (SEER) registry, data were analyzed for 28,808 women ages = 65 years, with stage I and II, who underwent breast conservation therapy between 1998 and 2002. Relative survival rates (observed survival/expected survival) were calculated using Kaplan-Meier method for women who underwent radiotherapy and those for whom radiotherapy was omitted. Results: Among women = 65 years with stage I breast cancer who underwent breast conserving surgery (n = 20,400), 71.7% received adjuvant radiotherapy. Among those with stage II breast cancer (n = 8,408), 66.0% received adjuvant radiotherapy. Five-year relative survival rates among stage I patients were 1.000 (95% CI: 0.990, 1.010) for those receiving adjuvant radiotherapy, and 0.959 (95% CI: 0.932, 0.986) for those without adjuvant radiotherapy. Among stage II patients, the 5-year survival rates were 0.998 (95% CI: 0.978, 1.018) for those receiving adjuvant radiotherapy, and 0.832 (95% CI: 0.791, 0.873) for those without adjuvant radiotherapy. Conclusions: Adjuvant radiotherapy following breast conserving surgery may be safely omitted for elderly women with stage I breast carcinoma, especially for women ages 85–94 years.

[Table: see text]

No significant financial relationships to disclose.
Risk factors for hospitalization in elderly cancer patients receiving chemotherapy
Authors: Kleiner J. M. , Culakova E. , Dale D. C. , Crawford J. , Poniewierski M. S. , Wolff D. A. , Lyman H.
Published: March 2020

9035

Background: Chemotherapy-associated hospitalization is a major source of morbidity and cost in cancer care, particularly for elderly (age ≥ 65) cancer patients. Hospitalization in the elderly often leads to an irreversible decline in functional status unrelated to the acute event that prompted hospital admission. Currently, little is known about the risk factors that may lead to increased risk of hospitalization in elderly patients receiving chemotherapy (CTX). Methods: 871 patients with solid tumors or lymphoma initiating a new CTX regimen were prospectively enrolled at 60 randomly selected US community oncology sites between 8/2004 and 10/2005. Of these, 361 elderly patients aged 65–91 were identified and followed. Primary endpoint of this investigation was hematologic toxicity and hospitalization was secondary. Pre- CTX patient data were analyzed for increased risk of hospitalization in univariate analysis using the chi-square test. Results: A total of 155 (18%) patients were hospitalized resulting in 215 hospitalizations. Median time to first hospitalization was the second cycle of CTX. 81/361 (22%) of elderly patients were hospitalized compared to only 74/510 (15%) of younger patients (p=0.003). The rate of hospitalization increased in a linear fashion between ages 65–80. Reasons for hospitalization in the elderly included infection, fever, or febrile neutropenia (36%), cardiopulmonary disease (CPD) (12%), vomiting or dehydration (13%), other gastrointestinal (11%), transfusion (8%), thrombosis (4%), CTX administration (4%), and other (13%). Major independent pre-CTX factors that predicted hospitalization in the elderly included male gender (p=0.0004), hemoglobin <11 g/dL (p=0.02), abnormal platelet count (<150k or >350k) (p=0.05), CPD (p=0.03), creatinine >1.5 mg/dL (p=0.05), and ≥ 2 concomitant medications (p=0.0008). Elderly patients with lung cancer (p=0.001) and lymphoma (p=0.05) had significantly higher rates of hospitalization when compared to other solid tumors. Conclusions: These data suggest that the risk of hospitalization increases in elderly cancer patients with age and that pre-CTX factors may be useful in identifying a subpopulation at increased risk for hospitalization.

No significant financial relationships to disclose.
A validated risk model for early neutropenic events in older cancer patients receiving systemic chemotherapy
Authors: Shayne M. , Culakova E. , Dale D. C. , Poniewierski M. S. , Wolff D. A. , Crawford J. , Lyman H.
Published: March 2020

9036

Background: A prospective, nationwide study was undertaken to develop and validate a risk model for early neutropenic events (NE) in older cancer patients undergoing chemotherapy. Methods: 1,386 patients =65 years of age with lung, breast, colorectal, ovarian cancer or lymphoma were prospectively registered at 117 randomly selected sites. Data on up to 4 cycles were collected upon initiation of chemotherapy. A logistic regression model for cycle 1 NE consisting of febrile neutropenia (FN; fever/infection and absolute neutrophil count nadir <1x109/L) or severe neutropenia (SN; neutrophils <.5x109/L) was derived on 1,378 patients with available data. Validation was performed using a split sample random selection process. Results: No significant differences in distribution of NE or predictive factors were observed between derivation dataset (n=922) and validation dataset (n=464). Major independent baseline clinical risk factors for cycle 1 NE in the derivation model (DM) included: anthracycline based regimens (p<.001), non-chemotherapy immune-modulatory agents (p=.003), elevated bilirubin (p=.016), reduced glomerular filtration rate (p<.001), cancer type (p=.02), planned relative dose intensity =85% (p=.027), and regimens containing cyclophosphamide (p<.001), etoposide (p=.002) or ifosfamide (p=.032). Reduced risk of cycle 1 NE was associated with myeloid growth factor (MGF) prophylaxis (p<.001). DM R2 was 0.478 and c-statistic 0.88 [95% CI 0.86–0.91; p<.001]. At median predicted risk of cycle 1 NE of 7%, model test performance (MTP) showed: sensitivity 90%; specificity 59%; and predictive value positive and negative of 32% and 97%, respectively. Cycle 1–4 FN risk in the DM was 16.6% and 3.3% among high and low risk patients, respectively. The validation model (VM) R2 was 0.508 and c-statistic 0.89 [95% CI: 0.86–0.93; p<.001]. MTP in the VM demonstrated: sensitivity 90%; specificity 65%; predictive value positive and negative of 36% and 97%, respectively. Cycle 1–4 FN risk in the VM was 16.8% and 1.6% in high and low risk patients, respectively. Conclusions: This validated risk model demonstrated good discrimination between older cancer patients at decreased risk for NE, and those at increased risk who may benefit from targeted prophylaxis with MGF.

No significant financial relationships to disclose.
An analysis of elderly patients (pts) treated on a phase III trial of cisplatin (P) plus etoposide (E) with concurrent radiotherapy (CRT) followed by docetaxel (D) vs observation (O) in pts with stage III non small cell lung cancer (NSCLC)
Authors: Sgroi M. M. , Neubauer M. , Ansari R. , Govindan R. , Bruetman D. , Fisher W. , Johnson C. , Breen T. , Yiannoutsos C. , Hanna N.
Published: March 2020

9037

Background: Concurrent CRT is standard treatment for pts with unresectable stage III NSCLC. HOG LUN01–24 is a phase III trial testing if consolidation D improves survival following EP/XRT. Few data are available on outcomes in elderly pts. We performed a subset analysis to determine the efficacy & tolerability of EP/XRT & consolidation D in elderly pts (≥70 yrs) vs younger (<70) pts. Methods: Patient (n=203), disease characteristics, survival & toxicity were compared for pts age ≥70 (n=52) vs <70 (n=151). Results: Median age for elderly was 73 vs 60 for younger pts. 34% of each group were women. Younger pts had a trend towards PS 0 (61% vs 53% elderly), FEV-1 > 2 L (48% vs 43% elderly), stage IIIB disease (61% vs 53% elderly). Younger pts were more likely to be current smokers (51% vs 15% elderly). 74% of younger pts were randomized vs 67% of elderly. During EP/XRT, elderly pts were more likely to discontinue treatment due to toxicity (12% vs 2%) & require hospitalization (40% vs 28%). Selected G3/4 toxicities during EP/XRT in elderly vs younger pts: neutropenia (42 vs 28%), anemia (9 vs 5%), febrile neutropenia (FN) (6 vs 11%), esophagitis (23 vs 15%), dehydration (15 vs 7%). Elderly pts were less likely to complete 3 cycles of consolidation D (76 vs 84%). Selected G 3/4 toxicities during consolidation D were similar between elderly (n=18) and younger pts (n=55), including FN (11.1 vs 10.9%). There was no difference in MST for older pts vs younger pts (17.2 vs 21.2 mos), p=0.3255. Conclusion: Chemoradiation is associated with higher rates of G 3/4 toxicities in elderly pts, including hospitalization rates. Elderly pts had lower rates of completing D, but similar incidence of D-related toxicity. There was no difference in MST between the age groups.

No significant financial relationships to disclose.
Network analyses to define chemotherapy toxicity clusters in patients with colorectal cancer (CRC)
Authors: Aprile G. , Ramoni PhD M. , Keefe D. , Sonis S.
Published: March 2020

9045

Background: CRC patients undergoing CT are likely to experience multiple concurrent toxicities. Rather than appearing singularly, the hypothesis that certain toxicities occur in clusters may suggest a common pathobiology. We used Markov networks (MN), a probabilistic graphical born at the confluence of statistics and artificial intelligence describing the dependency among set of variables, to identify clusters of CT-induced toxicities, to examine how clusters are connected to each other, and how single toxicities are related to a specific cluster. Methods: Using a standardized data collection tool, we retrospectively reviewed electronic medical charts of 300 consecutive CRC pts receiving FOLFOX, FOLFIRI or 5-FU to record baseline demographic and clinical information. Toxicities were recorded using NCI-CTC criteria during the first cycle of CT. Following the standard Bayesian approach, the MN clustering the CT-induced toxicities was learned from the data as the network with the highest posterior probability given the data. Results: The network, in which associations between toxicities are represented as links, identified five strongly-related symptom clusters: a constitutional cluster involving fatigue, anorexia, and weight loss; a gastrointestinal cluster where dehydration was the connector between diarrhea, constipation and bloating on a side and taste nausea and vomiting, taste alteration, fever and chills on the flipside; a dermatological cluster composed by dry skin, HFS, rash and itching and connected with hemorrhage/bleeding and wound complication toxicity. Furthermore, we noticed strong connections between cough, dyspnea and infection, with palpitation and pain and we detected another cluster where depression and anxiety where connected with cystitis. Conclusions: The application of network analyses to define CT-induced toxicity clusters is new. The technique was effective in defining the relationships between individual toxicities associated with cycle 1 therapy. The lack of randomness between the relationships defined by the network provides a strong suggestion that each cluster shares a common pathobiological basis, which may provide an opportunity for intervention.

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Survey of arm activity after breast cancer
Authors: Lee T. S. , Kilbreath S. L. , Sullivan G. , Refshauge K. M. , Beith J. M.
Published: March 2020

9054

Background: Post-operative education of women with breast cancer is inconsistent as guidelines provide conflicting advice regarding how vigorously women can use their arm. Current post-operative advice about lymphoedema focuses on the avoidance of strenuous arm activity and exercise, but common physiotherapy practice advocate this to address possible impairments after surgery such as loss of shoulder range and weakness. Methods: A 30-minute survey based on the Protection Motivation Theory was developed to explore the relationship between patients’ perception of what they can do with their affected arm following breast cancer treatment and their intention to use their affected arm. In addition, patients’ cancer and treatment characteristics, demographics, arm and chest symptoms, and arm function were assessed by the survey. The survey was pre-tested, and then distributed to 175 consecutive breast cancer survivors at 6–15 months after breast cancer treatment. Results: Of the women surveyed, 91(52%) had sentinel node biopsies, 67 (38%) had axillary dissection, 14 (8%) had no surgery to the lymph nodes, and 3 (2%) were unknown. There was a high incidence of shoulder restriction and upper limb pain in both women who had sentinel node biopsies and women who had axillary dissections ( Table 1 ). The majority of women who had sentinel node biopsies (51%) and axillary dissections (61%) perceived it was necessary for them to avoid strenuous arm activity. Overall, women who intended to avoid strenuous arm activity were found to have a greater likelihood of reporting upper limb swelling (LR=17.6, p=0.000) and weakness (LR=10.9, p=0.001). Conclusion: Women who had sentinel node biopsies intended to avoid strenuous arm activities even though they have a negligible risk of lymphoedema, placing them at risk of developing secondary musculoskeletal problems.

[Table: see text]

No significant financial relationships to disclose.
A systematic review of the incidence of venous thromboembolism (VTE) and effectiveness of prophylaxis in patients with multiple myeloma (MM) receiving thalidomide
Authors: Wu C. M. , Lee A. Y.
Published: March 2020

9056

Background: Thalidomide (T) is effective for treating MM but is associated with an increased incidence of VTE, especially when combined with other agents. Consequently, prophylaxis in patients receiving T-containing regimens has been recommended. However, the true risk of VTE is uncertain and the effectiveness of prophylaxis has not been established. We performed a systematic review to determine the incidence of VTE and the effect of prophylaxis in MM patients receiving T-containing regimens. Methods: MEDLINE and EMBASE were searched from 1966 to 11/16/2006. Only randomized controlled trials (RCT) and prospective cohort studies (PC) were included. Studies evaluating post-transplant maintenance therapy were excluded. Both authors independently screened and reviewed identified publications, and extracted data of pre-specified variables. Incidence estimates were calculated as proportions along with 95% CI. Results: 363 papers were identified but only 80 were relevant and reviewed. 45 studies (6 RCT and 39 PC) involving 1,886 patients receiving T-containing regimens met inclusion criteria. 9 studies clearly stated objective testing was used to confirm a diagnosis of VTE. The incidence of VTE is summarized in the table . We found 12 trials that used prophylaxis. None included appropriate control groups to allow assessment of effectiveness. Based on limited data, the incidences of VTE with prophylaxis were: ASA 13.9% (95% CI 9.1–19.9%), fixed low- dose warfarin 21.9% (95% CI 16.9–27.5%), therapeutic-dose warfarin 0% (95% CI 0–5.5%), and low molecular weight heparin 13.3% (95% CI 10.5- 16.6%). Conclusions: The incidence of VTE in MM patients receiving T-containing regimens ranges from 3% to 22%, depending on the patient type and agents used. Given the lack of level I/II evidence, recommendation for routine prophylaxis for patients receiving T- containing regimens is premature. A safe and effective antithrombotic regimen has yet to be identified.

[Table: see text]

No significant financial relationships to disclose.
Inpact of a ten week mind-body medicine intervention on peristent fatigue following breast cancer treatment: 6 month follow- up
Authors: Helzlsouer K. J. , Appling S. E. , Scarvalone S. , McBeth M. , Gallicchio L. , Hoffman S.
Published: March 2020

9062

Background: Persistent fatigue following breast cancer treatment, which affects up to 40% of breast cancer patients, is the result of diverse patient and treatment factors. The multi-dimensional underlying etiology of fatigue calls for broad based interventions aimed at managing stress, improving diet and exercise patterns and short term cognitive therapy supporting attitudinal and behavioral changes. A pilot study was conducted to obtain preliminary efficacy information for a ten week group-based mind body intervention to treat persistent fatigue among breast cancer survivors. Methods: The quasi-experimental study design used a before/after evaluation of fatigue scores. Subjects were women who were between six months and five years post-completion of adjuvant chemotherapy and/or radiation therapy for breast cancer and who had a baseline fatigue score of ≤ 50 as measured by the vitality subscale of the SF-36 Health Survey. Twenty- one women entered the study. Three participants dropped out after attending only two of the ten weekly sessions and are excluded from the analysis. Main outcome measures were change in severity of fatigue as measured by the Piper Fatigue Scale and vitality subscale score of the SF-36. Results: At baseline, the mean age of participants was 52.7 years; 66.7% were Caucasian and 23.7% were African-American. Median time since breast cancer diagnosis was 2.9 years. The mean Piper fatigue score improved from 6.0 (SD 1.5) at baseline to 4.0 (SD 2.1) at the end of the ten week intervention (p< 0.001). Fatigue scores at two and six months post-intervention were 3.2 (SD 2.9; p= 0.001) and 4.1 (SD 2.1; p= 0.02), respectively. Similarly the SF-36 vitality subscale score improved following the intervention with persistent improvement at 6 months (p=0.02). Conclusion: A holistic integrated mind body medicine intervention holds promise for long-term impact on reducing fatigue following breast cancer treatment. Sponsored by Susan G. Komen Breast Cancer Foundation

No significant financial relationships to disclose.