bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality of life (QOL) in patients (Pts) with hormone resistant prostate cancer (HRPC) treated with docetaxel (D) and celecoxib (C)
Authors: Chang V. T. , Sambamoorthi N. , Yan H. , Gonzalez M. , Cogswell J. , Srinivas S. , Zhong F. , Crump B. , Blumenfrucht M. , Kasimis B. S.
Published: April 2020

18598

Background: The impact of chemotherapy on QOL for pts with HRPC is not well described. Thirty patients(30) participated in a trial of D and C(Kasimis et al, submitted ASCO 2006). The objectives for this companion study were to study QOL outcomes with the FACT instrument including the Prostate subscale(FP) and utility from the EQ5D. Methods: In a phase II trial, 30 pts with progressive HRPC were treated with D and C for 4 wks in each cycle. Response evaluation was made by RECIST criteria and PSA reduction by >50% for biochemical response every 2 cycles. Patients completed the FACT and EQ5D instruments at the beginning of every cycle. We analyzed the FACT subscales with different statistical approaches, and compared FACT and utility for responders and non responders. Results: All 30 pts accrued were evaluable for toxicity and response. Thirty (30) pts received a minimum of 2 cycles, median (M) 4.5 (range 2–8). The M age was 74 yr (55–94), ECOG PS 1 (0–2). For 19 pts, the baseline mean score for the FACT P was 29, Standard Deviation 10. The Cronbach’s Coefficient was 0.83. The FACT Physical Well Being (PWB) correlated with the EQ5D utility score 0.76 (p < .0003), as did the Functional Well Being (FWB) 0.67 (p < .003) and FACT P 0.62 (p < .006). The FACT PWB, EWB, FP, Treatment Outcome Index, and EQ5D Utility differed significantly between responders and non responders by radiographic parameters, alpha = 0.1. The results for PSA reduction >50% are similar. Conclusions: The FACT Prostate subscale has good psychometric properties, correlates with EQ5D utility measure, and also with responder status by radiography and PSA.

[Table: see text]
Microanatomic characteristics of melanoma metastases in the sentinel node(s) (SN) predict survival and question the need for complete lymph node dissection (cLND)
Authors: Van Akkooi A. C. , De Wilt J. H. , Verhoef C. , Schmitz P. I. , Van Geel A. N. , Kliffen M. , Eggermont A. M.
Published: April 2020

8005

Introduction: The SN procedure has become a widely used staging procedure for stage I/II melanoma patients. We previously reported on the high SN+ identification rate with the use of the EORTC MG group pathology protocol (van Akkooi et al., Eur J Cancer: 2006, in press). Because only approximately 20% of SN positive patients have additional non-SN lymph node involvement in the cLND specimen, we have proposed to identify a SN+ patient group, which can be spared a cLND. Therefore further microanatomic analyses of the metastatic SNs has been performed to identify patient/tumor or SN factors which predict DFS and OS as well as additional non-SN nodal positivity. Methods: 262 stage I/II pts were included into the SN database between 10/97 and 5/04. 77 were SN+ (29%). 74 pts had SN material for re-evaluation in this study. Microanatomic analysis categorized a.o. the location of tumor cells; subcapsular, parenchymal (or combined), multifocal or extensive; the Starz classification and the measurement of the amount of tumor load (in mm). Tumor load was quantified by size: <0.1mm (single melanoma cells), 0.1 - 1.0mm, >1.0mm. DFS, OS and additional non-SN positivity was calculated for all the microanatomic analyses. Results: Mean/Median Breslow was 3.5/3.0 (0.8 - 12.0) mm, mean/median FU was 35/30 (6 - 81) months. There were no signif. differences in OS or additional non-SN positivity for the different loc. of involvement. The estimated 5yr OS rates were 100%, 63% and 35% for the different groups of tumor load, <0.1mm, 0.1 - 1.0mm, >1.0mm respectively (Figure)(P=0.03). There were no patients with add. non-SN positivity in the group with involvement <0.1mm. On multivariate analysis the tumor load was the most important prognostic factor for DFS (P=0.005) and OS (P=0.03). DFS, OS and add. non-SN positivity of all other analyses will be presented at the meeting. Conclusions: It is questionable whether SN with onlysingle cells involvement (<0.1mm) should be considered positive. Dist. mets are exceedingly rare (1/16 = 6.3%) and was identical to the SN- patient pop., and non-sentinel node involvement was not observed at all. These patients should probably not undergo add. LND and may not be considered stage III patients.

No significant financial relationships to disclose.
Preliminary results of a randomized phase II study comparing two schedules of temozolomide in combination with sorafenib in patients with advanced melanoma
Authors: Amaravadi R. K. , Schuchter L. M. , Kramer A. , Barth S. F. , Villanueva J. , Troxel A. B. , Tuveson D. A. , Nathanson K. L. , O’Dwyer P. J. , Flaherty K. T.
Published: April 2020

8009

Background: Sorafenib (SO) is an oral Raf kinase/VEGFR-2 inhibitor that has anti-melanoma activity when given with carboplatin/paclitaxel. The primary objective of this study is to estimate the duration of progression-free survival (PFS) for patients with metastatic melanoma (MM) taking SO + temozolomide (TEM). Secondary objectives are to determine the optimal dosing of TEM when given with SO, response, and toxicity rates. Correlative studies include BRAF genotyping and assessment of intratumoral Raf inhibition. Methods: Patients with MM and ECOG PS<2 are eligible. Prior therapy is allowed. Accrual is designed for 167 patients in one stage. All patients receive SO 400 mg po bid continuously. After one week of SO alone, patients without brain metastasis and no prior TEM are randomized to receive either extended daily dosing (EDD): TEM 75 mg/m2 po qd for 6 /8 weeks (Arm A), or standard dosing (STD): TEM 150 mg/m2 po qd for days1–5/28 (Arm B). Patients with prior TEM use are treated with EDD (Arm C) and patients with brain metastasis without prior TEM are treated with STD (Arm D). Responses are assessed using RECIST criteria. Results: 65 patients were evaluated for toxicity. Of these, 58 received SO + TEM and were evaluable for response (Table). SO + TEM resulted in a 24% overall response rate (ORR) [95% CI 11–41%] in patients without brain metastasis or prior TEM and 20% ORR [95% CI 3–56%] in patients with brain metastasis and no prior TEM. Observed grade 3 toxicities attributable to study medication were: hand-foot syndrome (12%), rash (8%), nausea (5%), anorexia (8%), and hypertension (3%). Nausea and anorexia were more prevalent with STD. Tumor blocks and 8 paired biopsy samples have been collected for correlative studies. Conclusions: Initial phase II results demonstrate encouraging antitumor activity and safety profile for SO + TEM in MM. Updated PFS data, response and toxicity rates, and correlative results will be presented.

[Table: see text]

[Table: see text]
Mismatch repair (MMR) and base excision repair (BER) protein expression correlates with clinical response to dacarbazine (DTIC)/temozolomide (TMZ) therapy of patients with metastatic melanoma
Authors: Sobol R. W. , Tawbi H. , Jukic D. M. , Mule K. , Mascari R. , Kirkwood J. M.
Published: April 2020

8015

Background: The non-classical alkylators DTIC and TMZ exert their cytotoxic effect through methylation of DNA bases. DNA damage is repaired by direct reversal of the O6-MeG lesion by the protein O6-methylguanine-DNA methyltransferase (MGMT/AGT); recognition of alkylation-damage-induced replication errors by the MMR pathway and excision repair of alkylated bases (N7-MeG and N3-MeA) conducted by the BER pathway. We report the results of a study evaluating the correlation between MGMT, MMR and BER protein expression in tumor tissue of patients (pts) with metastatic melanoma and documented clinical response to chemotherapy. Methods: Frozen tumor tissue was obtained from 17 pts with metastatic melanoma treated with DTIC/TMZ. Tumors were classified as sensitive (S) if pts showed stable disease (SD), partial response (PR) or complete response (CR) by RECIST criteria; and resistant (R) if progressive disease (PD) was observed after 2 cycles of treatment with DTIC/TMZ. Immunohistochemical staining for MGMT, MLH1 (MMR), and DNA polymerase-ß (pol-ß, BER) was performed. Levels of expression were assessed by a pathologist blinded to response data. Fisher’s Exact and Wilcoxon Rank Sum statistical tests were used to assess correlations. Results: 9 tumors were considered to be sensitive (S) and 7 resistant (R). Clinical response was found to significantly correlate with functional MMR (increased MLH1 expression): 7 of 9 S tumors had high MLH1 expression as compared to 1 of 7 R (p-value=0.015). Clinical response was also found to be inversely correlated with pol-ß expression: 6 of 9 S tumors expressed low levels of pol-ß as compared to 1 of 7 R tumors (p-value=0.08). MGMT expression did not seem to correlate with response. Conclusions: The presence of a functional MMR pathway is a requirement for the cytotoxic effect of alkylating agents and was significantly correlated with clinical response. Decreased BER potential (pol-ß expression) was correlated with increased sensitivity to alkylator-based chemotherapy. These findings lend additional support to the view that DNA repair status correlates with response to alkylator-based chemotherapy for melanoma.

No significant financial relationships to disclose.
Surgical resection for stage IV melanoma: A Southwest Oncology Group trial (S9430)
Authors: Sondak V. K. , Liu P. Y. , Warneke J. , Vetto J. , Tuthill R. , Redman B. , Sosman J. A.
Published: April 2020

8019

Background: Surgery is the treatment of choice for isolated distant metastases of melanoma. Based on a number of retrospective reports, patients (pts) who have undergone complete resection of metastatic disease can have an excellent survival. Methods: In SWOG, we prospectively evaluated surgical resection for stage IV melanoma. Pts enrolled prior to surgery; treatment following resection was at the discretion of the treating physician. Resected specimens were collected, whenever possible, for future molecular analyses. Results: Over a 9 year period from 1996 to 2005, 77 pts were enrolled from 18 centers, with 7 centers accruing ≥4 pts. Of 77 pts, 10 were incompletely resected and 5 had no evidence of stage IV disease. Therefore, 62 pts (81%) felt to have resectable stage IV actually did, and were included in the analysis. Pts characteristics were: median age 54 yrs (range 23–81); M:F 69%:31%; PS 0–1 100%; prior adjuvant IFN 45%. Resected sites included skin/soft tissue 40%; distant LN 21%; lung 13%; liver 8%; CNS 5%; bone 2%; other visceral sites 27%. Post-surgical complications included 1 grade IV pulmonary embolus and 1 grade III liver toxicity. Following surgery but prior to any further recurrence, 18 pts received adjuvant treatment including 8 with IFN and 7 with radiotherapy. After surgery, median progression-free survival (PFS) was 6 mos (95% CI 3–7 mos) with 9 patients (15%) remaining progression-free. Median overall survival (OS) was 21 mos (95% CI 15–28 mos); 3- and 4-yr OS was 33% and 29%, respectively. Conclusions: These results provide an estimate of prognosis for resected stage IV disease from a diverse patient base. They illustrate the potential for prolonged OS even with a short PFS. In some cases, pts can be repeatedly resected for long-term control of their disease. Pts with resectable stage IV melanoma are appropriate candidates for inclusion in adjuvant therapy trials.

No significant financial relationships to disclose.
Phase I/II trial of a PrimeBoost therapeutic vaccine in stage III/IV metastatic melanoma
Authors: Hawkins R. E. , Dangoor A. , Keilholz U. , Schadendorf D. , Harris A. , Ottensmeier C. , Smyth J. , Hoffmnan K. , Anderson R. , Pearce G.
Published: April 2020

8030

Background: This trialevaluated the safety, immunogenicity and tumour response of increasing doses of DNA plasmid (DNA.Mel3) and MVA viral vector (MVA.Mel3), containing 7 melanoma epitopes. Methods: 41 HLA-A2 positive stage III/IV melanoma patients with unresectable measurable disease were enrolled. Immunisations were administered three weeks apart with continued MVA.Mel3 boosting in patients with tumour control. Epitope-specific CD8+ T cell responses were evaluated using ex vivo tetramer staining and interferon gamma (IFN-γ) ELISPOT assay. Results: DNA.Mel3 was well tolerated at all doses. Dose-related grade 3 local skin reactions and systemic immune-associated reactions were observed following MVA.Mel3, no reactions led to early study discontinuation. Melan-A tetramer responses were observed in 23/36 (64%) evaluable patients, of which 9/36 showed an IFNγ response to at least one epitope in ELISPOT assay. Seven patients (17%) showed tumour control (PR, MR, or SD >6 months), of which 3/7 patients had associated immune responses, including one with PR > 21 months who underwent extended MVA.Mel3 boosting. Overall median progression free survival was 9 weeks (16 weeks for immune responders). Median overall survival for the intention-to-treat population is 11.7 months with follow up of 16 patients continuing. Conclusions: High dose heterologous PrimeBoost immunisation was safe and stimulated immune responses in >50% of late stage metastatic melanoma patients treated. Tumour control was observed with some evidence of association with immune response.

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[Table: see text]
A phase I/II study of telomerase peptide vaccination in combination with chemotherapy in patients with stage IV malignant melanoma
Authors: Aamdal S. , Dueland S. , Engebraaten O. , Owre K. , Dyrhaug M. , Trachsel S. , Gaudernack G.
Published: April 2020

8031

Background: A phase I/II feasibility study was conducted to investigate the safety, tolerability and immunological response to vaccination with the telomerase peptide GV1001 (hTERT: 611–626) in combination with temozolomide (T). Methods: Twenty-five patients with malignant melanoma (15 stage M1c,10 stage M1b) received T day 1–5 every four weeks for 1–9 cycles. During the first cycle (4 weeks) they received i.d. injections of 560 μg GV1001 with local GM-CSF in week 2,3 and 4, followed by injections in week 6 and 7 in the second cycle and week 11 in the third cycle. The treatment period was 12 weeks (3 cycles). Booster vaccinations with 560 μg GV1001 were offered every third month. Monitoring of blood samples, clinical examination were performed regularly with radiological staging every 12th week. Immune responses were measured as DTH and in vitro T-cell proliferation. Results: The treatment was generally well tolerated with only grade 1–2 toxicity in most patients. Of 14 patients, 4 developed grade 3 toxicity and one grade 4 toxicity (neutropenia). Immune responses against GV1001 were detected in 17/21 patients (81%) at 12 weeks. Patients receiving up to 9 cycles of T exhibited stable proliferative responses to GV1001 throughout the treatment period. None of the patients had DTH response at trial entry and no DTH responses were observed in patients receiving T. This was not due to a shift in the cytokine profile since cloned GV1001-specific CD4+ T cells displayed a Th1 cytokine profile. Upon evaluation in week 12, 6 patients had SD, 10 PD. One patient had a PR with shrinkage or disappearance of multiple lung metastases. A patient continuing on vaccine alone developed significant DTH response when T therapy was stopped. Conclusions: Telomerase vaccination of patients receiving concomitant T treatment is feasible. The unexpected high proportion of patients showing an immune response indicates that regulatory T-cells may have been removed by T treatment. The chemotherapy may also have influenced effector cells required for development of skin reactions. In spite of lacking DTH response however, the majority of the patients demonstrated significant immune response indicating different regulation of DTH and T-cell response.

No significant financial relationships to disclose.
Randomized phase II study of low (100mg) versus intermediate (400mg) doses of thalidomide (Thal) plus DTIC in metastatic melanoma (MM)
Authors: Von Moos R. , Dummer R. , Inauen R. , Ruhstaller T. , Meier S. , Skalsky J. , Hitz F. , Korte W. , Cerny T. , Gillessen S.
Published: April 2020

8048

Background: Single agent DTIC is the standard therapy for MM. In an effort to improve the response rate (DTIC 7–13%), Thal, a molecule with antiangiogenic effect was added in two different dosages to DTIC. Methods: Eligibility: Stage IV MM, ECOG performance status 0–2, no prior treatment with DTIC or Thal. Design: Randomized multicenter phase II Bryant and Day 2-stage optimal design with 20 patients (pats) per arm. Treatment regimens: DTIC 200mg/m2 d1–5 q3w plus Thal (100 versus 400mg per day). Responses were assessed every two cycles. Endpoints: Toxicity, feasibility, response rate (RR) and time to treatment failure (TTF). Results: 26 pats (12 male/ 14 female) at a median age of 58 years (range 24–82) with stage IV melanoma (M1a-2, M1b-2, M1c-22) were enrolled between 2001–2005 and received a median of 4 cycles (1–6). All the pats were evaluated for toxicity, 25 (96%) were assessable for objective response (WHO criteria). The overall response rate of the evaluable patients was 27% (100mg, RR 25%; 400mg, RR 33%), one patient (4%) had a complete response, 6 pats (23%) had a partial response, 11 pats had stable disease (42%), and 7 pats (27%) progressed. The median TTF was 5.2 months. Using NCI 2.0 Common Toxicity Criteria, grade 3 haematological toxicity was 12% (anemia-1, leucopenia-1, thrombocytopenia-1). Cumulative non-haematological toxicity grade 3/4 was 35% including fatigue in 5 pats (all on 400mg Thal arm), thromboembolic events in 2 (1 each treatment arm) and bleeding in 2 (1 cerebral). Polyneuropathy and constipation were a minor problem (no grade 3/4). The 400mg Thal arm was stopped according to the protocol because of intolerable fatigue in 5 out of 6 patients. Two of the first 14 pats suffered from pulmonary embolism. Thromboprophylaxis with low molecular weight heparin (LMWH) was mandatory after an amendment . Thereafter no thromboembolic events were seen but one fatal cerebral bleeding occurred in one patient. Conclusions: 400mg Thal in combination with DTIC was not feasible due to toxicity. 100mg Thal was well tolerated and showed significant clinical activity. Using our low dose Thal regimen prophylactic LMWH is necessary to prevent severe thromboembolic events.

No significant financial relationships to disclose.
Effects of depression on quality of life in Medicare beneficiaries with prostate cancer
Authors: Chang C. , Knight S. J. , Bennett C. L.
Published: April 2020

8510

Background: Depression is very common in the elderly and is particularly costly because of associated mortality, excess disability, and interactions with other physical health problems. We aimed to examine the impact of depression on quality of life in the older prostate cancer patients receiving Medicare benefits. Methods: Data came from the 2003 Cohort VI Baseline Medicare Health Outcomes Survey. Among the 109,115 individuals, only those who were under treatment for prostate cancer and completed the survey themselves were included in this study (n=2,191). Quality of life was assessed using the SF-36 questionnaire and the physical and mental health component scores (higher scores indicating better health) were analyzed. Results: Eighty-eight percent were whites, 75% were married, 76% had at least high school education, 45% were aged 65 to 74, and 55% were aged 75 and older. Those who reported having been depressed in the past two weeks (n=453; 21%) had significantly lower physical health (34.06 vs. 40.24; p < .001) and mental health (41.14 vs. 54.41; p < .001) than those who did not. Similar patterns were observed for those who endorsed questions indicating “depression much of the time in the past year” and “depression most of the time in the past 2 years”. Conclusions: Depression is prevalent among older men diagnosed with prostate cancer, and those who acknowledge being depressed in the past 2 weeks to 2 years have significantly worse mental and physical health. Attention to depression, in addition to prostate cancer specific issues, should be considered among prostate cancer patients who report mental or physical health problems. Early detection and treatment of depression in this population could potentially alleviate their suffering and improve their quality of life.

No significant financial relationships to disclose.
Patients’ characteristics and outcomes of palliative care inpatient consults at a comprehensive cancer center
Authors: El Osta B. , Braiteh F. S. , Reddy S. , El Osta H. , Bruera E.
Published: April 2020

8524

Background: There is limited information about the characteristics and outcomes of inpatient palliative care consults in cancer centers. Two mobile teams (MT) each with a physician, fellow, and a nurse, provide consultation to hospitalized patients (pts) with complex symptoms. Methods: We analyzed the pts characteristics and outcomes during a two-month period. The charts were reviewed for demographics, cancer data, reason for consultation, symptoms, interventions, and outcomes. Results: Sixty-one pts were analyzed. Pain was the main reason for a consult request in 46 pts (75%), delirium in 10 (16%), anxiety in 4 (7%) and constipation in 5 (8 %). Some pts had more than one reason. 56(92%) pts had metastatic disease, diagnosis for ≤1 year in 26 (42%) and ≤2 years in 44 (72%) (Median =17 months). The Edmonton Symptom Assessment Scale (ESAS), 0–10, is summarized in the table. We uncovered new issues at consultation, such as 20 pts (38%) screened positive for alcoholism with CAGE questionnaire and the 34 pts (56%) had clinical delirium. Features of opioids toxicity such as constipation (N=43;70%), confusion (N=35;57%) (Mean MMSE = 23 ± 5), hallucinations (N=21;34%), myoclonus (N=16;26%) and miosis (N=18;29%) were frequently identified. The MT interventions included imaging studies (23%), enema (43%), laxatives (49%), neuroleptics (54%), metoclopramide (39%), corticosteroids (25%). Half (N=30;50%) of the pts had opioid rotation and/or had counseling (N=27;46%). One out of two pts (N=30;49%) required transfer to the palliative care unit. Conclusions: Most pts had previously undiagnosed opioid toxicity, delirium, and other symptoms. Opioid toxicity occurred secondary to rapid opioid escalation, possibly linked to chemical coping, and psychosocial distress. The outcome of these pts improved by opioid rotation, adding laxatives, metoclopramide, neuroleptics, and steroids.

[Table: see text]

No significant financial relationships to disclose.
Effect of the number of bone lesions on efficacy of zoledronic acid for prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors
Authors: Shirina N. , Coleman R. E. , Chen Y. M.
Published: April 2020

8529

Background: It has been postulated that greater numbers of bone metastases and thus greater tumor burden may lead to increased skeletal morbidity. To assess the effect that the number of baseline bone metastases may have on the efficacy of zoledronic acid in patients with solid tumors, we conducted a retrospective analysis of 3 large, randomized, controlled trials. Methods: Data were evaluated from the intent-to-treat population with breast cancer (n = 739), prostate cancer (n = 397), or lung cancer and other solid tumors (n = 480) who were treated with zoledronic acid 4 mg, pamidronate 90 mg, or placebo and had information available on number of baseline bone lesions. Patients were stratified into 2 groups: those with ≤ 3 bone lesions or > 3 lesions. Results: In general, patients with > 3 lesions had a higher skeletal morbidity rate (SMR) compared with patients with ≤ 3 lesions (Table 1), and zoledronic acid reduced SREs regardless of the number of bone lesions, but the benefit of zoledronic acid appeared greater in patients with > 3 lesions. In patients with lung cancer and other solid tumors who had > 3 bone lesions, zoledronic acid significantly reduced the mean SMR (P = .008) and significantly prolonged time to first SRE (median, 171 vs 84 day; P = .005) compared with placebo. In prostate cancer patients with > 3 bone lesions, zoledronic acid also significantly reduced the mean SMR compared with placebo (Table 1). In breast cancer patients with > 3 bone lesions, the mean SMRs were similar for zoledronic acid and pamidronate groups (Table 1). Conclusions: Patients with a greater number of bone lesions are at higher risk for skeletal complications and receive greater clinical benefit from treatment with zoledronic acid.

[Table: see text]

[Table: see text]
Activity limitation and clustering of symptoms in breast cancer patients
Authors: Sawhney R. , Sehl M. E. , Sanati H. , Satariano W. A. , Naeim A.
Published: April 2020

8540

Background: While previous cancer symptom research has been focused on individual symptoms, more recent studies have attempted to identify symptom clusters in breast cancer patients. However, there has been no large study that has examined both clustering of symptoms and activity limitation in breast cancer patients. Methods: Data were taken from a survey study of 1,011 patients found to have histologically confirmed breast cancer, identified by the Metropolitan Detroit Cancer Surveillance System. Patients were surveyed at both 3 and 12 months after diagnosis. Survey data on 1,054 control participants were also obtained for matching variables. Participants were asked whether or not they had each of 21 symptoms, and whether or not they attributed any activity limitation to each symptom. Results: Of 21 symptoms examined, prevalence of symptoms listed in Table 1 was significantly higher in cancer patients than in controls (p<0.05) at baseline. Though the prevalence of each symptom decreased significantly at follow up, each symptom remained significantly more prevalent than in the control group, with the exception of depression. Activity limitation attributed to 4 of the 5 symptoms listed in Table 1 was significantly higher than that of controls, and this difference persisted at follow up. Symptoms tended to cluster together amongst breast cancer patients. For example, at baseline, 73% of patients with depression also reported fatigue, and 30% of patients with pains in chest area also reported both fatigue and depression. These associations persisted at follow up. Symptoms were significantly correlated with each other at baseline (p<0.00005), with correlation coefficients ranging from 0.13 to 0.26, with most correlations remaining significant at follow up. Conclusion: In a large survey of breast cancer patients, symptoms were found to be associated with significant activity limitation, and tended to cluster together. This correlation persists at 12 months after diagnosis, even after treatment is complete.

[Table: see text]

No significant financial relationships to disclose.
Comorbidity and choice of adjuvant endocrine therapy in breast cancer patients (pts) older than 70 years
Authors: Monfardini S. , Brunello A. , Molino A. , Sacco C. , Simoncini E. , Gasparini G. , Bella M. A. , Crivellari D. , Vamvakas L. , Basso U.
Published: April 2020

8546

Background: Tamoxifen (Tam) and aromatase inhibitors (AI) have different profiles of toxicity which may influence the therapeutic choice in the presence of associated diseases, but few data are available concerning the prevalence of such comorbidities. Methods: A retrospective analysis on 434 consecutive pts (≥70 years) radically operated for breast cancer was conducted in 26 italian centers to determine how comorbidity influenced the choice of endocrine therapy during the year 2004. Results: Out of 434 pts, 367 with estrogen receptor positivity (median age 75, range 70–93) were treated with endocrine therapy alone (330 pts) or combined with chemotherapy (37 pts). The mean number of comorbidities was 1.8; 99 pts (26.2%) had ≥3 associated diseases. Tam was given to 194 pts (52,8%), AI to 173 pts (47,2%): Anastrozole (149 pts) Letrozole (22 pts) or Exemestane (2 pts). In 126/367 pts (34%) AI were prescribed instead of Tam because of the contraindications listed in the table below. AI were the preferred choice in 46/367 (12,5 %) pts in the absence of contraindications to Tam. Whereas the prevalence of osteoporosis is more than 30% in women after 70 years in Italy, a reduction of bone density had been instrumentally documented only in 10 pts (2.7%) of this survey, and AI were prescribed in 6 of them. Conclusions: Tam was still the preferred option in elderly women with early breast cancer, but was contraindicated in more than one third of pts. These data suggest that osteoporosis is being probably underdiagnosed in patients over 70 years. In view of a possible treatment with bisphosphonates, screening bone mineralometry should become standard before starting therapy with AI.

[Table: see text]

No significant financial relationships to disclose.
Randomized pharmacokinetic evaluation of subcutaneous versus intravenous administration of granisetron in cancer patients treated with platinum-based chemotherapy
Authors: Perez-Gracia J. , Sadaba B. , Lopez-Picazo J. , Azanza Perea J. , Cabello J. , Campanero Martinez M. , Martin Algarra S. , Gil-Aldea I. , Garcia-Foncillas J. , Gurpide A.
Published: April 2020

8557

Background: 5-HT3 antagonists are one of the mainstays of antiemetic treatment and they can be used either intravenously or orally. Nevertheless sometimes neither intravenous (IV) nor oral administration is possible, such as in patients unable to admit oral intake managed in an outpatient setting. Our objective was to assess if pharmacokinetics of subcutaneous (SC) granisetron were comparable to IV delivery, using Area Under the Curve between 0 and 12 hours (AUC 0–12 h) as our main endpoint. Methods: Patients receiving platinum-based chemotherapy were randomized to receive granisetron 3 mg by either SC or IV administration during the first cycle and by the other route during the second one. Blood samples were drawn at 15, 30, 45, 60, 90 minutes and 2, 3, 4, 6, 8 and 12 hours after granisetron. Drug levels were determined by HPLC with fluorescence detection after liquid-liquid extraction of the samples, with a quantitation limit of 1 ng/ml. Clinical assessment of emesis in both cycles was performed. Results were analyzed using Student’s t-test and Wilcoxon test for paired samples. Assuming a 20% difference in AUC 0–12 h between both routes, 25 patients were required to obtain statistical significance (α=0.05, β=0.10). The protocol was approved by the Ethics Committee and all patients signed informed consent. Results: From May to November 2005, 30 patients were included and 25 of them were evaluable. SC granisetron resulted in a 27% increase in AUC 0–12 h (95% CI: 7–74) and higher levels at 12 hours (see table). Cmax was higher and was reached faster by IV route. Emetic symptoms were equivalent with both alternatives. Conclusion: SC administration of granisetron achieves higher AUC 0–12 h than IV administration, resulting in increased exposition to the drug. This is the first study that shows that SC granisetron is a valid alternative to IV or oral use. This new route of administration might be specially relevant for outpatient management of emesis in cancer patients.

[Table: see text]

No significant financial relationships to disclose.
Effects of adjuvant chemotherapy on the protein C anticoagulant pathway in patients with early stage breast cancer
Authors: Mukherjee S. D. , Levine M. , Beaudin S. , Shin L. , Caruso S. , Liaw P.
Published: April 2020

8563

Background: Although chemotherapy treatment is associated with an increased risk of thrombosis, the pathogenic mechanisms are poorly understood. We have previously shown that treatment of endothelial cells with adriamycin and epirubicin impairs the protein C anticoagulant pathway by downregulating EPCR (endothelial protein C receptor), an endothelial receptor required for the conversion of protein C to the anticoagulant enzyme activated protein C (APC). In this study, we examined the effects of adriamycin- and epirubicin-containing chemotherapy on the protein C anticoagulant pathway in early stage breast cancer patients. Methods: We collected blood samples from 20 patients patients with early stage breast cancer undergoing adjuvant CEF (cyclophosphamide, epirubicin and 5-fluorouracil) or CMF (cyclophosphamide, methotrexate and 5-fluorouracil) chemotherapy on days 1, 2 and 8 for the first 2 cycles of treatment. Markers of protein C generation (protein C, thrombin-antithrombin (TAT) complexes, and APC) were measured on these days. Results: Plasma protein C levels were significantly lower at cycle 2 day 8 (0.88 ± 0.14 U/ml) compared to pre-chemotherapy levels (1.07 ± 0.23 U/ml) (p=0.0036). Plasma TAT levels were significantly higher at cycle 2 day 8 (2.87 ± 0.79 μg/L) compared to pre-chemotherapy levels (2.01 ± 1.24 μg/L) (p=0.02). Based on the APC levels, the patients appear to fall into two categories in terms of their ability to generate APC. The first group (n=16) has elevated APC levels that parallel the elevated TAT levels, whereas the second group (n=4) has low APC levels despite elevated TAT levels. Conclusions: Impaired ability to generate APC in a subpopulation of patients may reflect chemotherapy-induced impairment of the protein C pathway through the downregulation of EPCR. This pilot study provides new mechanistic insights into the prothrombotic effects of chemotherapy agents.

No significant financial relationships to disclose.
Prevalence of anemia in cancer patients not receiving antineoplastic treatment (ANT): Data from the European Cancer Anaemia Survey (ECAS)
Authors: Gascon P. , Barrett-Lee P. J.
Published: April 2020

8565

Background: Cancer-associated anemia occurs frequently in patients receiving ANT. Patients not receiving ANT may also have low hemoglobin (Hb) levels that may compromise optimal disease management and patient outcomes. Methods: Patients enrolled in ECAS (Ludwig et al, Eur J Cancer 2004;40:2293–2306) and not receiving ANT (chemotherapy, radiotherapy, or hormonal treatment) at enrollment were evaluated for prevalence of anemia (Hb <12.0 g/dL), effect of anemia on performance according to WHO score (0 to 4), and anemia treatment. Disease status at enrollment was catagorized as newly diagnosed (ND), persistent/recurrent (P/R), or in remission. Results: Of 15,367 enrolled patients, 7947 (53%) were not receiving ANT: 60% ND; 28% P/R disease; 12% in remission. Anemia was present in 32% of patients, with Hb levels 10.0–11.9 g/dL in 24%, and <10.0 g/dL in 8%. Anemia rates were P/R, 38%; ND, 30%; in remission, 25%. Poor performance scores correlated positively with lower Hb levels; for patients with Hb <8.0 g/dL, 8.0–9.9 g/dL, 10.0–11.9 g/dL, and ≥12.0 g/dL, worse WHO scores of 2–4 were recorded for 43%, 41%, 25%, and 15%, respectively. During ECAS 1168 patients with data after enrollment never received ANT, and 40% were anemic at some time (at enrollment and/or at follow-up). Hb nadirs were approximately evenly distributed: 11.0–11.9 g/dL, 37%; 10.0–10.9 g/dL, 29%, and <9.0–9.9 g/dL, 34%. Anemia was infrequently treated with only 31.4% of patients receiving anemia treatment at any time. Anemia treatments administered and mean Hb at initiation were 14% epoetin alone ± transfusion ± iron (9.8 g/dL); 9% transfusion ± iron (8.4 g/dL); 8% iron (11.7 g/dL). Conclusions: Almost one-third of cancer patients who are not actively receiving ANT are anemic, including 25% of patients considered to be in remission. Anemia has a negative effect on performance, with worse WHO scores related to lower Hb levels. Anemia appears to be undertreated, with less than one-third of anemic patients receiving anemia treatment, and then only when Hb nadirs are <10.0 g/dL. To insure optimal management of cancer patients, all should be screened for anemia and receive the most effective anemia treatment.

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Pegfilgrastim induces elevation of serum CA 15–3 in breast carcinoma patients after receiving dose-dense adjuvant chemotherapy
Authors: Saura C. , Vilar E. , Cortes J. , Bellet M. , Ocaña A. , Gomez P. , Baselga J.
Published: April 2020

8595

Background: CA 15–3, an epytope related with MUC-1 gene products, is a well known tumour marker to predict early recurrent disease breast cancer. MUC-1 expression can be detected in neutrophil membrane and cytoplasm. It is known that patients with breast cancer who receive adjuvant chemotherapy with G-CSF support may show CA 15–3 false positive elevations Methods: We identified by medical records 76 patients who received adjuvant sequential chemotherapy for breast cancer consisted in Doxorubicin/Ciclophosphamide for 4 cycles followed by Paclitaxel for 4 cycles every-2 (with haematopoietic support with Pegfilgrastim (Cohort A, n=29) or Filgrastim (Cohort B, n=10)) and every-3-weeks without haematopoietic support (cohort C, n=37) between October 2003 and November 2005. Mean values of CA 15–3 recorded at the first follow up (FU) visit after treatment and number of patients with levels above the cut-off value of 40 U/mL were compared between the three patients cohorts. Correlation between CA 15–3 with alkaline phosphatase (AP) levels measured at first FU and with absolute neutrophil count (ANC) mean values measured on day 14 of every cycle were performed for each cohort Results: Patients characteristics between cohorts were well balanced except for age. A statistically significantly difference in median CA 15–3 post-treatment values were observed between Cohort A and C (34.01 versus 22.3, p=0.001), but no between Cohort A and B (34.01 versus 30.53). Eight patients in Cohort A, 2 in B and 1 in C had CA 15–3 levels above 40 UI/mL (27.6% versus 20% versus 2.7%, p=0.009). CA 15–3 decreased to normal values at subsequent visits. CA 15–3, mean ANC (r= 0.272, p= 0.020), and AP (r= 0.361, p= 0.002) were found associated each other when the whole database was analyzed Conclusions: These data provide evidence that Pegfilgrastim induces elevation of CA 15–3 level in comparison with patients treated without G-CSF support. This elevation may be related to the increased neutrophil counts. Physicians should be aware of this fact during the follow up to avoid unnecessary diagnostic workup.

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Effect of antithrombotic prophylaxis (AP) on thrombosis-related complications and mortality in cancer patiets (pts) carrying a central venous devices (CVD)
Authors: Cimminiello C. , Isa L. , Vergani C. , Catena L. , Tomirotti M. , Visini M. , Alatri A. , De Paoli A. , Aondio G. , Verga M.
Published: April 2020

8596

Background: Recent guidelines do recommend against antithrombotic prophylaxis in cancer pts having placed a central line to prevent catheter-related thrombosis. Methods: The present study, which was an observational and prospective one, involved 18 centres in Lombardia (Italy) to assess the management of CVD in pts affected by solid or haematological tumors to evaluate in the current practice the attitude to employ the AP and the clinical evolution as regard to the occurrence of catheter-related and systemic venous thromboses and survival. Results: 1,418 pts entered the study and were followed-up during a median period of 6 months for a total of 24,182 patients-months. Subjects receiving a continuous AP, mainly with mini-warfarin according to Levine, were 439 (31.6%): they were significantly older, with a more frequent history of Venous Thromboembolism (VTE), and with a cancer in a more advanced stage. A trend in favour of those not treated with AP was noticed as regard to catheter-related thrombosis, 3.2 % vs 1.5%, (p=0.058). The median time to the first catheter-related complication was 120 days. The frequency of systemic VTE including deep and superficial vein thromboses in sites other than the venous axis where the CVD had been placed and pulmonary embolism was significantly lower in patients not receiving AP: 1.8% vs 12.4%; OR 0.12 (95% CI: 0.07–0.22; p=.001). Mortality of pts avoiding AP was also significantly lower (23.7% vs 38%), OR 0.5 (95% CI: 0.4–0.6; p=.0001) In the multiple logistic regression analysis only advanced cancer and to be given AP were significantly associated with mortality. No major bleeding was recorded among pts assigned to receive continuous AP. Conclusions: The results of the present study do confirm the current drugs and schedules for AP are unable to prevent not only catheter-related thrombosis but also systemic VTE. Mortality does appear lower in those not treated with AP and the difference still exists after adjustment for age, history of previous VTE and to be given chemotherapy. The attitude to give a continuous AP to pts with central lines presenting with more severe disease or at increased thromboembolic risk seems to be ineffective if not dangerous.

No significant financial relationships to disclose.
Statewide survey on the management of psychosocial distress by oncologists
Authors: Pirl W. F. , Muriel A. , Schapia L. , Hwang V. , Moore C. , Temel J. , Kornblith A. , Holland J. C.
Published: April 2020

8601

Background: Although the NCCN has published guidelines for the management of psychosocial distress, no data exists on how oncologists manage it in clinical practice. This study surveyed oncologists in Massachusetts on their estimated rates of distress in their patients, beliefs about distress, and practice patterns. Methods: All Massachusetts oncologists belonging to ASCO were e-mailed an electronic survey up to three times. Survey completion was anonymous and a small incentive was offered for participation. Descriptive statistics and cross-tabulations were compiled. Chi-squared analyses investigated differences in rates. Results: 393 e-mail addresses were identified. 338 surveys were delivered, but the e-mail survey could be blocked by SPAM filters. Ninety-nine responses were obtained yielding a response rate of 29%. Oncologists estimated that 77% (sd=23%) of their patients experience distress, but only 33% (sd=20%) have distress that warrants treatment. Emotional problems unrelated to illness, practical problems, and coping with illness were the three most frequently encountered forms of distress. Sixty-five percent of oncologists reported that they routinely screened for psychosocial distress, but only 3% use a screening instrument. Almost all reported that they would at least consider using a brief screening instrument (93%). Lack of time was identified as the main barrier to screening, but lack of knowledge about treatment of distress was the only variable that predicted lower rates of screening (p=.03). While reported rates of referrals to mental health professionals were high, the majority (85%) reported that they directly address the psychosocial distress in their practice and almost half reported that they initiate psychotropic medications (45%). Conclusions: The majority of oncologists report that they do some screening and management of psychosocial distress in their clinical practices. Although screening appears to mainly be done through the usual clinical encounter, research has shown that this method has a poor rate of detection for psychological disorders. Despite the fact that the NCCN recommends the use of screening instruments and most oncologists report interest in using them, oncologists rarely actually use such measures.

No significant financial relationships to disclose.
A randomized open-label study of darbepoetin alfa administered every 3 weeks with or without parenteral iron in anemic subjects with nonmyeloid malignancies receiving chemotherapy
Authors: Vandebroek A. , Gaede B. , Altintas S. , Smith K. , Yao B. , Schupp M. , Bastit L.
Published: April 2020

8612

Background: Patients (pts) with cancer receiving chemotherapy often have chemotherapy-induced anemia (CIA) and reduced quality of life. Darbepoetin alfa (DA) is an erythropoiesis-stimulating agent (ESA) that can effectively treat CIA when administered once every 3 weeks (Q3W). In patients with CIA, limited data in the literature suggest that administration of intravenous (IV) iron with ESA therapy may increase clinical response. Methods: This randomized, multicenter, open-label, 16-week study evaluated the safety and efficacy of DA 500 mcg administered Q3W using the SureClick injection device in pts with CIA (Hb < 11 g/dL) who received either IV iron or standard practice for iron administration (oral iron or no iron). The dose of IV iron was 200 mcg administered either Q3W with DA Q3W or, if required, as 2 doses (200 mcg total) within a 3-week period. Pts who received ≥ 1 dose of DA and who completed the 16-week study period by October 19, 2005 are included in this interim analysis (planned sample size = 400 pts). Accrual will have finished by conference time. Randomization was stratified by tumor type and baseline (BL) Hb (< 10 or ≥ 10 g/dL). The incidence of adverse events and serious adverse events, in particular embolic/thrombotic events, was summarized. Efficacy endpoints were estimated using the crude % of pts (95% CI). Hb values within 28 days of a transfusion were not included in any efficacy analysis. Results: Of the 114 pts included in this interim analysis, 65% were women, 99% were Caucasian, the mean (SD) age was 60 years (12), and 26% had lung or gynecological tumors; study endpoints are shown in the table. Conclusions: Based on the interim results, the safety profile for pts receiving DA 500 mcg Q3W with IV iron appears to be comparable to pts receiving DA 500 mcg Q3W with oral iron or no iron. The % pts who achieved the target Hb (≥ 11 g/dL) appeared higher, and the % pts who required transfusions appeared lower, in the group receiving IV iron.

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Three-Year Results of a Prospective Statewide Insurance Coverage Pilot for Proton Therapy: Stakeholder Collaboration Improves Patient Access to Care
Authors: Ning Matthew S. , Palmer Matthew B. , Shah Aashish K. , Chambers Laura C. , Garlock Laura B. , Melson Benjamin B. , Frank Steven J.
Published: April 2020

PURPOSE:

Proton therapy is increasingly prescribed, given its potential to improve outcomes; however, prior authorization remains a barrier to access and is associated with frequent denials and treatment delays. We sought to determine whether appropriate access to proton therapy could ensure timely care without overuse or increased costs.

METHODS:

Our large academic cancer center collaborated with a statewide self-funded employer (n = 186,000 enrollees) on an insurance coverage pilot, incorporating a value-based analysis and ensuring preauthorization for appropriate indications. Coverage was ensured for prospective trials and five evidence-supported anatomic sites. Enrollment initiated in 2016 and continued for 3 years. Primary end points were use, authorization time, and cost of care, with case-matched comparison of total charges at 1 month pretreatment through 6 months posttreatment.

RESULTS:

Thirty-two patients were approved over 3 years, with only 22 actually receiving proton therapy, versus a predicted use by 120 patients ( P < .01). Median follow-up was 20.1 months, and average authorization time decreased from 17 days to < 1 day ( P < .01), significantly enhancing patient access. During this time, 25 patients who met pilot eligibility were instead treated with photons; and 17 patients with > 6 months of follow-up were case matched by treatment site to 17 patients receiving proton therapy, with no significant differences in sex, age, performance status, stage, histology, indication, prescribed fractions, or chemotherapy. Total medical costs (including radiation therapy [RT] and non-RT charges) for patients treated with PBT were lower than expected (a cost increase initially was expected), with no significant difference in total average charges ( P = .82), in the context of overall ancillary care use.

CONCLUSION:

This coverage pilot demonstrated that appropriate access to proton therapy does not necessitate overuse or significantly increase comprehensive medical costs. Objective evidence-based coverage polices ensure appropriate patient selection. Stakeholder collaboration can streamline patient access while reducing administrative burden.