bluuebunny/crossref_metadata_2025 huggingface dataset:
A reasonable methodology to estimate the relationship between workload and human resources demand in a cancer unit
Authors: Fasola G. , Aita M. , Bin A. , Follador A. , Mansutti M. , Pella N. , Puglisi F. , Sacco C. , Troiero G. , Aprile G.
Published: August 2020

e17555

Background: Costs of cancer care account for a growing proportion of European health care spending. Despite the rising price of new cancer drugs draws the attention of medical oncologists and decision makers, personnel spending takes the largest share of health care costs. Nonetheless, few data exist about the relationship between workload and human resources demand in a cancer unit. Here we describe an empirical model to determine staffing requirements according to the annual number of patients. Methods: The Department of Oncology at the University Hospital of Udine, Italy, is a computerized Unit within the regional cancer network taking care of about 1,500 pts/year. Each clinical episode is recorded on a centralized database. Standard time limits are set for different types of consultation. We queried the database to obtain the total number of consultations for every pt taken charge of by the Unit during 2006. Considering both the time scheduled for each type of visit and the number of yearly working hours per employee, we could reach a reasonable estimate of the annual physician and nurse hours per pt and of the number of needed personnel. Results: In 2006, each case generated an average of 16 clinical evaluations, with small differences among breast, lung and colorectal cancer. Corresponding physician- and nurse-time per pt was of 8 and 16 hours, respectively. For the first year - in Units with a mean number of 1,500 pts/year - this translates into a global amount of about 12,000 physician- and 24,000 nurse-hours and a needed number of 7 physicians and 13 nurses, respectively. In the second year, the same cases induced a mean of 4.5 consultations; using a similar approach, the demand for additional time and resources could be estimated as well. Conclusions: A preliminary assessment of the time required for different types of consultation, together with a centralized recording of each clinical episode, allows a reasoned estimate of needed time and personnel resources, thus providing a simple tool to determine the total staff expenditure of a cancer unit.

No significant financial relationships to disclose.
Perception and knowledge of clinical trials and factors affecting participation of regional and rural cancer patients of North Queensland
Authors: Sabesan S. S. , Burgher B. , Varma S. , Piliouras P.
Published: August 2020

e17558

Background: The best treatment option for most cancers is participation in clinical trials. Participation in trials is generally low and among rural patients it is likely to be even lower. The aim of this study was to assess knowledge about and attitudes towards clinical trials among rural and regional cancer patients of North Queensland. Methods: A questionnaire-based survey was conducted in outpatient clinics at the Townsville Cancer Centre on all types of cancer patients. Results: The mean age of the 178 participants was 56 years and 45.4% lived in rural or remote areas. Median distance to the trial centre (Townsville) for rural participants was 180 km (range 80 - 1300 km). Being asked whether they would take part in a RCT, 13.2% of participants said no, 56.3% said yes, and 30.5% were unsure. There were no significant relationships between willingness to participate and rurality (p = 0.896) or education level (p = 0.943). For the majority of patients, the number of clinic visits and blood tests required did not matter. Cost of travel (41.1% rural/remote; 23.5% regional; p < 0.001) and the need for family or friends to accompany (38.9% rural/remote; 24.1% regional; p = 0.021) were more important for rural/remote than regional patients as factors affecting participation. Only 16.4% of participants were aware of early studies. After education, percentage of patients willing to participate in phase I and II studies were 57% and 84%, respectively. Rural patients were less willing to participate in phase I studies than regional patients (33.9% vs 52.6%, p = 0.029). Conclusions: Rural patients are as interested in participating in clinical trials as urban patients except for phase 1 trials and should not be excluded because of rurality. Knowledge of trials is poor and there is a need for education early. Cost of travel seems more important for rural patients and as such budgets should include cost of travel to encourage participation of rural patients.

No significant financial relationships to disclose.
Distribution and determinants of patient satisfaction in oncology with a focus on health-related quality of life
Authors: Lis C. G. , Rodeghier M. , Gupta D.
Published: August 2020

e17578

Background: Cancer patients usually undergo extensive and debilitating treatments, which makes patient satisfaction with care in oncology an important health care assessment measure. We conducted a study to examine patients’ experiences with the care they receive and to investigate the clinical, demographic and quality of life (QoL) factors that can predict satisfaction in a large heterogeneous sample of cancer patients. Methods: A case series of 538 cancer patients treated at Cancer Treatment Centers of America (CTCA) at Midwestern and Southwestern Regional Medical Centers between August 2006-December 2007. A patient satisfaction questionnaire developed in-house by CTCA was used. The questionnaire covered the following dimensions of patient satisfaction: hospital operations and services, physicians and staff, and patient endorsements for themselves and others. QoL was assessed using EORTC QLQ-C30. The available clinical, demographic and QoL factors were evaluated for predictive significance using univariate (t-test or chi-square test) and multivariate logistic regression. Results: The response rate for this study was 24.4%. The mean age of our patient population was 54.1 years (SD = 10.5, range 17–86), with a slight preponderance of females (57.2 %). Breast cancer (n = 124, 23.0 %) and lung cancer (n = 101, 18.8%) were the most frequent cancer types. 481 (89.4%) patients were “very satisfied” with their overall experience with CTCA. Age and several QoL function and symptom scales were predictive of satisfaction upon univariate analysis. However, in the multivariate modeling, only those with a score above the median on the fatigue measure (i.e., worse fatigue) had reduced odds of 0.28 of being “very satisfied” with CTCA (p = 0.03). Conclusions: We found that fatigue was an independent significant predictor of patient satisfaction. This finding argues for special attention and programs for cancer patients who report higher levels of fatigue. Such efforts will help lessen the effect of fatigue on their daily functioning, and may increase their satisfaction with treatment.

No significant financial relationships to disclose.
Final report of a randomized phase II study of docetaxel/oxaliplatin (DO) and docetaxel (D) in previously treated non-small cell lung cancer (NSCLC) patients (pts). A novel design, Alpe-Adria Thoracic Oncology Multidisciplinary group study (ATOM 019)
Authors: Belvedere O. , Follador A. , Rossetto C. , Sibau A. M. , Defferrari C. , Aita M. , Meduri S. , Fasola G. , Ceschia T. , Grossi F.
Published: August 2020

e19010

Background: No combination regimen has proven superior to single agent chemotherapy as 2nd-line treatment for NSCLC. The absence of cross-resistance with cisplatin/carboplatin, favorable toxicity profile, along with both pre-clinical and clinical evidence of activity make O a good candidate for combination with D as 2nd-line therapy of NSCLC. We evaluated the activity of DO in this setting using a novel phase II trial design. Methods: This multicenter, non-comparative randomized phase II trial evaluated the activity of D (75 mg/m2 d1) and O (70 mg/m2 d2) every 3 weeks in previously treated NSCLC pts; the comparator arm was D (75 mg/m2 d1 every 3 weeks). This one-stage, three-outcome phase II trial design (Sargent, Control Clin Trials 2001) had 21 evaluable pts/arm. All had histologically confirmed NSCLC that progressed during/after platinum-based chemotherapy. Primary endpoint was response rate; secondary endpoints were toxicity, time to progression (TTP), 1-yr survival. Results: Fifty pts were enrolled. Pts characteristics: M/F, 76/24%; median age 62 yrs (range 43–69); ECOG PS 0/1, 36/64%; adenocarcinoma/other, 36/64%. With 48 pts evaluable, partial response was seen in 20% and 8% of pts; stable disease in 52% and 32% and progressive disease in 24% and 56% for DO and D, respectively; 1 pt was inevaluable due to early death (D arm). Main grade 3–4 toxicities were: neutropenia 56% and 64%; febrile neutropenia 4% and 8%; diarrhea 12% and 4% for DO and D, respectively. Median TTP was 4.9 and 1.8 months, median survival 10.9 and 6.9 months, and 1-yr survival 41% and 16% for DO and D, respectively. Conclusions: This study shows how novel phase II trial designs enrolling a limited number of pts may help identify promising regimens for subsequent study in phase III trials. The level of activity for DO we observed satisfied the pre-defined study primary endpoint and warrants further evaluation of this combination as 2nd-line therapy for NSCLC. Protocol developed at the 6th FECS/AACR/ASCO Workshop on Methods in Clinical Cancer Research, Flims 2004, with Professors Marc Buyse and Chris Twelves.

[Table: see text]
Lung cancer symptoms with cetuximab/taxane/carboplatin in first-line advanced NSCLC: Analysis of the BMS099 trial
Authors: Patel T. , Dreisbach L. , McCleod M. , Heim W. J. , Hermann R. C. , Woytowitz D. , Lu H. , Weber M. R. , Lynch T. J.
Published: August 2020

e19011

Background: The phase III BMS099 trial investigated cetuximab (C) added to taxane/carboplatin (TC) for 1st line treatment of advanced NSCLC. Progression-free survival (PFS) was not significantly different with C; response rate (RR) was significantly higher. Median overall survival (OS) was longer, with a difference not statistically significant, but similar in magnitude to the significant OS improvement from the FLEX trial (cisplat/vinorelb±C). A secondary objective of the BMS099 study was to assess the effect of C on Lung Cancer Symptoms (LCS). Methods: Chemonaïve patients (pts) with stage IIIB/IV NSCLC (any histology or EGFR expression status) were randomized to TC±C. LCS were measured using the functional assessment of cancer treatment-lung cancer subscale questionnaire (FACT-LCS), given at baseline and before each therapy cycle until disease progression (scoring 7 symptoms: breath loss, weight loss, clear thinking, coughing, appetite, chest tightness, breath ease, on a 0–4 scale). The main endpoints were rates of symptom response/progression (≥ 2 point improvement/decrease from baseline in 2 consecutive assessments), compared between arms with a stratified Cochran-Mantel-Haenszel (CMH) test; a stratified log-rank test was used to compare time to symptomatic progression. A Wei-Lachin test was used to compare between arms the changes from baseline in LCS score, and a longitudinal model was constructed to measure treatment effect on those score changes. Results: With 676 patients randomized, the baseline compliance rates for the FACT-LCS questionnaire were 99.4% and 99.1% for CTC and TC respectively, decreasing by week 18 to 74.0% and 66.4%. Baseline FACT-LCS scores were similar across treatment arms (median, 19.0). Symptom response rates were similar with CTC vs TC (32.6% vs 28.5%, CMH P=0.26), and time to symptomatic progression was not significantly different (log-rank P=0.58). Changes from baseline in FACT-LCS scores did not differ significantly between arms (Wei Lachin P=0.912; longitudinal model P=0.81). Conclusions: The addition of C to TC for the 1st treatment of advanced NSCLC resulted in similar symptom response/progression rates and did not affect trends in LCS score changes throughout treatment.

[Table: see text]
Optimal duration of chemotherapy (CT) for advanced non-small cell lung cancer (NSCLC) in the first- and second-line settings
Authors: Grossi F. , Belvedere O. , Defferrari C. , Brianti A. , Follador A. , Rijavec E. , Ceschia T. , Pronzato P. , Fasola G. , Aita M.
Published: August 2020

e19037

Background: No difference in efficacy has been observed between 3 or 4 vs 6 cycles of 1st line CT in patients (pts) with advanced NSCLC. Although longer treatment may improve progression-free survival, this must be weighed against increased toxicity and potential for worse quality of life. There are no prospective, randomized data on the optimal duration of 2nd line CT. The aims of this retrospective study were to (i) confirm the lack of impact of treatment duration on response rate in 1st line NSCLC and (ii) investigate the impact of treatment duration in the 2nd line setting. Methods: Eligible pts had received at least 4 cycles of 1st line (n=95) or 2nd line (n=55) CT for stage IIIB/IV NSCLC in clinical trials of the ATOM group, Udine, Italy, or the National Cancer Institute, Genoa, Italy and achieved stable disease or responded to treatment; trials included one in the elderly, and the addition of biological agents to CT. Response was assessed according to RECIST after alternate CT cycles and tumor dimensions recorded. The proportion of pts achieving a complete or partial response, as well as its timing and any subsequent tumor shrinkage, were analyzed by treatment line. Results: In the 1st line setting, 48 of 95 pts responded; they did so after 2 (29 pts, 61%), 4 (15 pts, 31%) and 6 cycles (4 pts, 8%). In these pts, 16 (55%) and 9 (41%) pts who had responded by the 2nd and 4th cycle respectively and continued on treatment showed further tumor shrinkage; the median further reduction in tumor size was 16% (range 1–52%) and 6% (range 1–11%), respectively. In the 2nd line setting, 12 of 55 pts responded; they did so after 2 (3 pts, 25%), 4 (7 pts, 58%), and 6 cycles (2 pts, 17%). One and two pts who had responded by the 2nd and 4th cycle respectively and continued on treatment showed further tumor shrinkage of 25%, 5% and 24%, respectively. Conclusions: Approximately 90% of CT-naive pts who responded did so by the 4th cycle; most such pts achieved only minor tumor reduction with further CT and did so at the likely expense of increased toxicity. In the 2nd line setting the achievement of response appeared slower. These results support the discontinuation of 1st CT after 4 cycles and suggest the same is true for 2nd line CT.

No significant financial relationships to disclose.
The palliative effect of EGFR inhibitors in platinum-resistant NSCLC
Authors: Tassinari D. , Tamburini E. , Scarpi E. , Santelmo C. , Carloni F. , Castellani C. , Lazzari Agli L.
Published: August 2020

e19053

Background: To assess the clinical benefit of EGFR-inhibitors (erlotinib or gefitinib) in terms of quality of life and symptoms control in platinum-resistant NSCLC. Methods: A systematic review of literature in the MEDLINE and EMBASE data bases from 2000 to 2007 was independently performed by two authors (DT and ET) The 2 randomized phase III trials comparing erlotinib or gefitinib (the BR21 and ISEL trials respectively) with placebo were considered eligible and included into the pooled analysis. Overall quality of life was the primary outcome of the pooled analysis; symptoms control the secondary one. Heterogeneity between the trials was analysed using the I2 test; the outcome analysis was performed using a random effects model and an alpha error lower than 5%. Results: The outcomes of 2423 patients enrolled into the BR21 and ISEL trials were compared in the pooled analysis. 1129 patients were treated with gefitinib, 488 with erlotinib and 806 with placebo. A methodological heterogeneity was detected in the preliminary qualitative analysis of the trials (the 2 trials assessed quality of life and symptoms control with different tools), while a relative homogeneity was documented from a statistical point of view, using the I2 test (I2=0, p=0.733). An absolute improve of quality of life was documented in favour of the treatment with EGFR-inhibitors (+8%, p<0.001) and symptoms control (+4%, p=0.034). Nevertheless, as quality of life and symptoms control were assessed with different tools in the 2 trials, the comparisons of the 2 main outcomes have uniquely a descriptive aim. Conclusions: Although a comparison of the outcomes of quality of life and symptoms control in a pooled analysis of the BR21 and ISEL trials is quite difficult for the intrinsic heterogeneity between the trials, our preliminary analysis seems to suggest a benefit in favour of patients treated with EGFR-inhibitors when compared with placebo. Further trials comparing EGFR-inhibitors with chemotherapy (mainly docetaxel and pemetrexed) are probably needed to identify the gold standard of second line chemotherapy for NSCLC, whose main aims are quality of life and symptoms control.

No significant financial relationships to disclose.
Phase I trial of vorinostat in combination with erlotinib in advanced non-small cell lung cancer (NSCLC) patients with EGFR mutations after erlotinib progression
Authors: Reguart N. , Cardona A. F. , Isla D. , Cardenal F. , Palmero R. , Carrasco-Chaumel E. , Rolfo C. , Massuti B. , Moran T. , Rosell R.
Published: August 2020

e19057

Background: Vorinostat (SAHA) is a histone deacetylase inhibitor that induces differentiation, growth arrest and apoptosis of malignant cells. In vitro, there is a synergistic interaction of vorinostat in combination with gefitinib in NSCLC cell lines. Moreover, vorinostat increases levels of E-cadherin, p21, and downregulates expression of phospho-AKT and phospho-ERK1/2. These molecular findings could reverse resistance to erlotinib in mutant patients. Methods: We conducted a standard 3+3 Phase I trial of oral erlotinib 150 mg QD in combination with oral vorinostat (dose level 1 [DL1], 300 mg QD on days 1–7 every 21 days; DL2, 400 mg QD on days 1–7 every every 21 days, and; DL3, 400 mg QD on days 1–7 and 15–21 in a 28-day cycle). Cycles were repeated for a maximum of 6 cycles until progressive disease (PD) or intolerable toxicity. Pts with advanced NSCLC with EGFR mutations (Exon 19 and 21) after erlotinib progression and ECOG ≤2 were eligible. The main objectives were to determine the maximum tolerated dose (MTD), drug activity and safety of the combination regimen. Results: Thirteen patients have been enrolled up to date, with 9 patients available for this interim analysis (median age, 59 years; range 41–77). One patient (DL3 cohort) experienced a dose limiting toxicity (Grade 3 diarrhoea). The MTD has not been reached. The most common drug-related toxicities of any grade in the first cycle of treatment were anemia (77.8%), skin alterations (66.7%), diarrhoea (66.7%), xerostomy (55.6%), asymptomatic changes in liver function tests (55.6%), and asthenia (55.6%). There were no Grade ≥3 drug-related adverse events during first cycle of treatment and the global analysis of cycles showed asthenia (11.1%), somnolence (11.1%) and hyporexia (11.1%). Four pts discontinued treatment, all due to PD. Of 9 evaluable pts for efficacy, 6 had stable disease as best response (median duration of treatment 6.0 months, range 4–12). Final data will be presented at ASCO meeting. Conclusions: Although accrual continues to determine the MTD, the combination of vorinostat and erlotinib appears to be well tolerated and effective in this group of advanced NSCLC pts with EGFR mutations after erlotinib progression.

No significant financial relationships to disclose.
Safety and efficacy of gefitinib monotherapy for patients (pts) ≥80 years (yrs) with advanced non-small cell lung cancer (NSCLC): A phase II subset analysis
Authors: Ebi N. , Semba H. , Tokunaga S. , Takayama K. , Wataya H. , Kuraki T. , Yamamoto H. , Akamine S. , Okamoto I. , Nakanishi Y. ,   Lung Oncology Group in Kyushu (LOGIK)
Published: August 2020

e19059

Background: Lung cancer is a disease of the elderly with median age at diagnosis of 70 yrs. The very elderly pts (age ≥80 yrs) with advanced NSCLC have not been well studied, even though this proportion is increasing over coming years. There are no data to evaluate the safety and efficacy of gefitinib treatment for pts ≥80 yrs with advanced NSCLC. Methods: We reported the phase II trial of gefitinib monotherapy in chemotherapy-naïve pts of 75 yrs or older with advanced NSCLC (J Thorac Oncol. 2008;3: 1166–1171). We analyzed data for pts ≥80 yrs, comparing with those <80 yrs in our trial. Results: A total of 28 pts were 80 yrs old and over in our trial. Patient characteristics: male/female = 12/16, median age = 82 (range 80–90), ECOG PS 0/1/2=7/13/8, stage IB/IIIA/IV=1/3/24, and adenocarcinoma (Ad)/non-Ad= 22/6. Five pts achieved partial response. The response rate was 18% (CI 95%, 6–39). The disease control rate was 50%. Median survival time was 9 months and 1-year survival rate was 39%. The most frequent adverse events were skin disorders (86%). Nine pts (32%) experienced toxicities ≥grade 3. There were two pts with possible interstitial lung disease including one treatment-related death. Tumor samples from 10 pts were analyzed for EGFR mutation status. EGFR mutations were detected in tumor tissues from 5 pts, of which 3 had partial responses (60%). Table shows the difference between the pts ≥80 yrs and those <80 yrs. Conclusions: Gefitinib monotherapy is effective and relatively well tolerated for pts ≥80 yrs with advanced NSCLC. Gefitinib has potential as a first-line therapeutic option even if elderly pts are more than 80 yrs old.

[Table: see text]

No significant financial relationships to disclose.
Use of an Internet-based protocol to collect clinical information and blood from patients with lung cancer who never smoked cigarettes
Authors: Girard N. , Klein R. , Riely G. J. , Reddy R. , Kris M. G. , Pao W.
Published: August 2020

e19064

Background: At least 10% of patients develop lung cancer despite smoking <100 cigarettes in a lifetime. These “never smokers” with lung cancer have a unique clinical course and likely represent a subgroup genetically distinct from lung cancer patients with a history of cigarette smoking. Few genes associated with the development of lung cancer in this population have been found. To identify genetic risk factors, we plan to perform genome-wide association studies (GWAS) but need to study a large group of cases - more than that seen at a single institution in a reasonable timeframe. To speed accrual, we hypothesized that we could use the internet to collect clinical information and blood from never smokers with lung cancer. Methods: We established an IRB- approved protocol to collect prospectively clinical information and blood samples from patients recruited via the internet. Interested patients enroll via the website ( www.mskcc.org/neversmokerswithlungcancer ), or by email ( neversmokerswithlungcancer@mskcc.org ). Eligibility criteria: age ≥18 yo, pathologic diagnosis of lung cancer, smoking history <100 cigarettes in a lifetime, resident of the U.S. Study materials (information packet, screening questionnaire, consent form, and tissue sample collection kit) are directly sent to patients. Bloods are drawn at routine local doctor visits and returned to study investigators by free overnight shipping. All data are kept confidential. Results: The website went online on 14 Sept 2008. As of 5 Jan 2009, 70 patients from 25 states contacted us via the internet. 33 patients signed the consent form, 27 were eligible, and 19 sent blood samples. For those who sent blood, the median time between first email contact and receipt of blood was 29 days. Conclusions: Collection of clinical information and blood samples from cancer patients is feasible over the internet. We are expanding efforts to connect with individuals appropriate to this study, with a target of 2000 patients. The identification of risk variants associated with lung cancer through GWAS can facilitate the development of new strategies for prevention, diagnosis, and treatment.

No significant financial relationships to disclose.
Dose-ranging study of the combination of paclitaxel poliglumex and pemetrexed in advanced non-small cell lung cancer (NSCLC)
Authors: Slagle B. M. , Rigas J. R. , Dragnev K. H. , Williams I. , DiSalvo W. , Engman C. , Lipe B. , Simeone S.
Published: August 2020

e19090

Background: Taxanes continue to play an important role in the treatment of advanced NSCLC. Paclitaxel poliglumex (XyotaxTM) is an ester α-poly-L-glutamic acid conjugate of paclitaxel allowing for solubility in aqueous solution, not requiring Cremophor or ethanol for intravenous administration or premedications. This is a non-randomized single-arm, single-institution open label dose-ranging study was designed to evaluate the combination of pemetrexed and paclitaxel poliglumex. Methods: The primary objective of this study was to evaluate the safety of this combination. Patients (pts) were enrolled in 2 different dosing levels. The first 6 received 135 mg/m2 paclitaxel poliglumex and 500 mg/m2 pemetrexed intravenously every 3 wks. None of the 6 pts experienced an initial dose limiting toxicity (IDLT) following 2 cycles of therapy and the paclitaxel poliglumex was then escalated to 175 mg/m2 with 500 mg/m2 pemetrexed. Eligibility included advanced NSCLC, one or more measurable lesions (RECIST), ECOG = 0–2, prior chemotherapy and radiation allowed, no grade 2+ peripheral neuropathy, no untreated brain metastases, and no active cardiac disease. Results: Twelve pts were enrolled, 6 pts to each dose level. Four of the pts were female, the median age was 65 years (48- 74), 11 had a performance status of 0–1, and only 1 pt received prior chemotherapy. There were no IDLTs at the first dose level, and there was one IDLT of infection with neutropenia at the second dose level. The median number of cycles completed was 5 (range 1–12 cycles). Aside from grade 3 fatigue in 2 pts there were no grade 3 or greater non-hematologic toxicities. Common non-hematologic toxicities included peripheral neuropathy, constipation, fatigue, and alopecia. Of the 12 pts, the best response was stable disease in 9 pts, 2 are without disease progression, and 6 pts are alive to date. The median progression free survival was 3.3 months (range 0.7–10.7 months). Conclusions: The combination of paclitaxel poliglumex and pemetrexed was well tolerated at the proposed phase II dose of 175 mg/m2 and 500 mg/m2. The PFS is encouraging and future studies of this combination are recommended.

No significant financial relationships to disclose.
A phase II trial of pemetrexed (P), gemcitabine (G), and bevacizumab (BV) in untreated patients (pts) with advanced non-small cell lung cancer (NSCLC)
Authors: Wozniak A. J. , Kalemkerian G. P. , Gadgeel S. M. , Schneider B. J. , Valdivieso M. , Venkatramanamoorthy R. , Hackstock D. M. , Chen W. , Heilbrun L. K. , Ruckdeschel J. D.
Published: August 2020

e19099

Background: P and G are active agents with acceptable toxicity profiles in the treatment of NSCLC. The addition of BV to chemotherapy has resulted in a significant improvement in survival for pts with non-squamous NSCLC. We are currently conducting a phase II trial of P, G and BV on a novel every two week schedule in untreated pts with advanced NSCLC. Methods: Advanced, non-squamous NSCLC pts with measurable/evaluable disease, no prior treatment for advanced disease, PS 0–1, adequate hepatic, renal and bone marrow function, treated brain metastases were eligible. No unstable hypertension/cardiac disease/vascular disease, hemoptysis, anti-coagulation, recent major surgery, no cavitation or close proximity of primary cancer to a major vessel were allowed. Pts received P 500 mg/m2, G 1,500 mg/m2, and BV 10 mg/kg every 2 weeks for 12 cycles. Doses were reduced to P 400 mg/m2 and G 1,200 mg/m2 when grade 4 neutropenia occurred in the first 2 patients. BV was continued until disease progression or toxicity. Planned accrual is 42 patients. Primary endpoint is progression-free survival. Secondary endpoints are response rate (RR), toxicity, time to progression and overall survival. Results: 20 pts have been accrued. Median age 57.5 yrs, males-55%, stage IV 90%, adenocarcinoma 75%. 18 pts are response evaluable (2 were too early to assess). 11/18 (61%) pts had a response (1 CR, 7 PR, 3 unconfirmed PR) (90% CI for RR is 0.42 - 0.77), and 3 had SD ( 17%) for a disease control rate of 78%. Currently the median treatment cycles for all pts are 6 (range 1–12). All pts are evaluable for toxicity. Grade 3- 4 toxicities: neutropenia 4, anemia 1, thrombocytopenia 2, lymphopenia 1, febrile neutropenia 1, fatigue 4, hypertension 1, GI 2, ALT/AST 3, pneumonitis 1, muscular weakness 1, metabolic 2, otitis media 1. Conclusions: The combination of P, G, and BV is a very active and tolerable treatment for NSCLC despite the preliminary nature of these results. Updated information will be presented at the meeting. This research is supported by Lilly Oncology and Genentech.

[Table: see text]
Interest, attitudes, and participation in clinical trials among lymphoma patients with online access
Authors: Schwartz K. ,   Advisors to Patients Against Lymphoma
Published: August 2020

e19514

Background: There is an increasing number of investigational agents for lymphomas and a limited patient pool, approximately 5% of available patients. Thus, identifying and addressing obstacles to study enrollment is vital to making progress. Methods: This analysis was made from a non-random population of 251 lymphoma patients with online access to our survey. Results: In this cohort, 43% reported High Interest in clinical trials, 50% have Considered Trials, and 27% Have Participated. Patients who considered studies (126) ranked the following reasons for declining as significant: Randomization (70), Insurance (49), Study Risks / Toxicities (42), Travel and Lodging (30), Eligibility (28), Tests and Procedures (12), and a perception that Regular Treatment is superior (6). See Table 1 for associations with consideration of clinical trials and participation. Conclusions: In this cohort, interest in clinical trials and participation rates were much higher than generally cited. As expected, the discussion of clinical trials with the patient's oncologist was associated with the highest consideration (85%) and participation (53%) rates, suggesting a need to increase awareness of study protocols among treating physicians so that this discussion can become more routine. Patient issues and perceptions regarding randomization, study risk, eligibility, and tests and procedures suggest an opportunity to improve enrollment in clinical trials by focusing on these aspects of study design, specifically, attending to the rationale of the protocol as a treatment decision.

[Table: see text]

No significant financial relationships to disclose.
High-dose intense doxorubicin-based regimens in aggressive non-Hodgkin's lymphoma: A systematic overview
Authors: Azim H. A. , Malek R. A. , Santoro L. , Gandini S. , Bociek R. G. , Azim H. A.
Published: August 2020

e19528

Background: Aggressive non-Hodgkin's lymphoma represents around 60% of lymphomas in the Western world and even more in Egypt. CHOP has been long been recognized as the standard chemotherapy regimen in this disease. The addition of rituximab (R) to CHOP in the treatment of B-cell subtypes has resulted in a significant improvement in all treatment endpoints. Nevertheless, still a significant fraction of patients in the developing world are not offered R due to economical reasons. Thus CHOP is still offered to these patients as well as those with T-cell subtypes. Data from the early 1990s have suggested that the dose intensity (DI) of doxorubicin may have a prognostic value. Hence we conducted a metaanalysis on chemotherapy regimens incorporating higher DI doxorubicin and compare them to CHOP in terms of complete response (CR) rate, event free survival (EFS) and overall survival (OAS). Methods: A MEDLINE and COCHRANE library search was performed using the search terms ‘CHOP‘, ‘lymphoma‘ and ‘randomized trials‘. Eligible trials were randomized trials, having CHOP as a control arm and any chemotherapy regimen administering doxorubicin at a higher DI than that of CHOP (16mg/m2/week) as the investigational arm. Pooling of data was performed using the mixed effect model. The outcome measure for pooling the CR rate was the odds ratio (OR) while the hazard ratio (HR) was the outcome measure for EFS and OAS. Confidence intervals were estimated according to the method developed by Parmar. Results: Eight trials published until February 2008 met the inclusion criteria. They included 3,668 patients randomly assigned to either CHOP (1,660 patients) or DI doxorubicin-based regimen (2008 patients). Patients receiving DI doxorubicin-based regimen had a significantly better overall survival (HR; 0.79; 95% CI: 0.66–0.94). As for the EFS and CR analyses, there was a trend in favor of patients who received the DI regimens; however the difference was not statistically significant (HR: 0.86; 95% CI: 0.71–1.03 & OR: 0.8; 95% CI: 0.63–1.02 respectively). Conclusions: High DI doxorubicin-based regimens are associated with a better OAS compared to CHOP. Such approach should be considered in patients with aggressive B-cell lymphomas not offered R as well as those with T-cell lymphomas.

No significant financial relationships to disclose.
Value of International Prognostic Score (IPS) in predicting need for bone marrow biopsy (BMB) in Hodgkin's lymphoma (HL)
Authors: Muslimani A. , Spiro T. , Chaudhry A. , Taylor H. , Jaiyesimi I. , Elson P. , Daw H.
Published: August 2020

e19531

Background: BMB is frequently performed during the staging of patients (pts) with HL. Previous data suggested routine use of this procedure may be unnecessary. The Ann Arbor classification is currently used to detect pts requiring BMB. Despite sensitivity (sen) of 100%, specificity (spec) is only 40%. We sought to determine whether IPS [as developed by Hasenclever and Diehl (1998)] would yield greater spec while maintaining good sen. Methods: We retrospectively reviewed charts of 1215 histologically proven HL pts from Jan 2000-Dec 2008 at Cleveland Clinic Taussig and Fairview Moll Cancer Centers. Of 1215 pts, 1089 had BMB (90%). 876 pts were included in our study. 213 were excluded due to un-interpretable BMB or missing data. The IPS is calculated as the number of poor risk features present based on male sex, age ≥45, albumin (alb) <4 g/dL, hemoglobin (hem) <10.5 g/dL, stage IV, white blood cell (WBC) ≥15,000/mm3, lymphocyte (lymph) <600/mm3 and/or <8% of total WBC. Multivariable logistic regression was initially used to assess the association between BMI and each factor in the IPS. All 7 factors were significant (p<.001 for sex, age, albu, hem, stage and lymph; .07 for WBC); and therefore recursive partioning algorithm was used to identify a cutoff for determining bone marrow involvement (BMI). Results: 88 pts (10%) had BMI. Using an IPS of >3 to predict BMI, sen was 97% and spec 87%. BMI by histology was 4% lymphocyte-rich, 5% nodular sclerosis, 20% mixed-cellularity and 21% lymphocyte-depleted. Using the IPS>3 cutoff sen and spec were similar across all types of histologies; ranging from 94–100% and 86–89% respectively. Conclusions: using an IPS of >3 for predicting BMI in HL doubled the spec associated with Ann Arbor classification with little loss of sen. The implementation of IPS is a practical and reliable tool that will allow physicians to predict BMI in HL pts. It may, therefore eliminate painful BMB in many Pts.

No significant financial relationships to disclose.
Prognostic value of different B symptoms in upper aerodigestive tract NK/T-cell lymphoma
Authors: Xiao J. , Guo C. , Zhai L. , Li H. , Fu X. , Huang Y. , Huang Y. , Huang J. , Pu X. , Lin T. , Ye S.
Published: August 2020

e19544

Background: Extranodal NK/T-cell lymphoma (ENKL) is a rare disease originated from NK or toxic T cells. ENKL arising from the upper aerodigestive tract (UNKTL) is a newly recognized subtype and commonly presents with B symptoms. This study is to investigate the prognostic value of different B symptoms in UNKTL. Methods: UNKTL cases with detailed clinical, pathological and prognostic data in our center since 2001 to 2007 were retrospectively analyzed with the major study endpoint of overall survival (OS). Central pathological review was performed. Survival curves were estimated by Kaplan-Meier method and tested by Log Rank method. Statistically significant factors in univariate analysis were then included in multivariate analysis. B symptoms were defined as fever, night sweat and weight loss according to the Ann Arbor Cotswolds meeting. The predictive values of survival for each type of B symptoms were studied independently. Results: 172 cases of UNKTL with a median follow-up duration of 27.4 months were included. 45 ladies and 127 gentlemen had a median age of 43 years. 98 cases were Ann Arbor stage I, 54 were stage II and the remaining 20 cases were stage III or IV. About half of the patients present B symptoms: 82 had fever, 5 had night sweat and 6 present weight loss. Totally 18 patients had ECOG PS larger than 1. The 5-year OS rate of the whole group is 41.8%. Patients with persistent fever before treatment indicated a poor outcome in the univariate analysis (p=.033) and its prognostic value was also confirmed by the Cox regression (p=.030) whereas those of night sweat and weight loss were not (p= .960 and .824 respectively). Conclusions: B symptoms were common in UNKTL patients. Our data suggested that only fever among the three types of B symptoms was independent prognostic factor for UNKTL but it still needs further confirmation.

No significant financial relationships to disclose.
Reccurent and prolonged panctopenia with rituximab therapy
Authors: Jajeh A.
Published: August 2020

e19550

Background: Rituximab, a monoclonal antibodies designed against a CD20 glycoprotein expressing lymphocytes. This drug has been implemented in the treatment of B cell lymphoproliferative disorders as well as non-neoplastic disease such as autoimmune thrombocytopenia, immune hemolytic anemia and other disorders related to overexpression of antibodies against the host. Rituximab doccumented side effects such as allergic infusion reaction, tumor lysis syndrome and lymphodepletion are frequently seen. However, transient neutropenia is less common. This abstract reports recurrent and long standing pancytopenia that had adverse deadly sequellae. Methods: This abstract report five cases of recurrent and prolonged pancytopenia not related to concomittant cytotoxic effect of chemotherapy. It is a retrospective analysis of treating three hundred patients in the last six years. Results: Five patient sustained recurrent prolonged pancytopenia post rituximab therapy. Two females (age 33 and 55) and three males (age 40, 50 and sixty). Mean age is 46 years. All developed sever neutropenia as well as pancytopenia. One patient, a female( age 33) had rheumatoid arthritis and the rest had non hodgekin's lymphoma. This female patient died due to sever long standing neutropenia/pancytopenia with pneumonia. All patients had bone marrow biopsy for evaluation. Decreased cellularity below 40% seen. None of the patients with non hodgkin's lymphoma had bone marrow involvement. The four patients are still in remmission. Conclusions: In conclusion the etiology of sustained neutropenia and pancytopenia is not understood. Whether, bone marrow aplasia, dysplasia or other immune mechanism exist need more study.

No significant financial relationships to disclose.
Immunological effects and clinical outcomes in patients with high-risk melanoma given adjuvant therapy with granulocyte-macrophage colony stimulating factor (GM-CSF, sargramostim)
Authors: Spitler L. E. , Weber R. W. , Cruickshank S. , Whiteside T. L.
Published: August 2020

e20004

Background: Our previous study suggested that administration of GM-CSF to high-risk melanoma patients may prolong survival (JCO 18(8):1614–1621, 2000) and led to a prospective randomized trial (E4697). This study has completed accrual and follow-up is now ongoing. Simultaneously, we conducted a follow-on study to gain further information about the immunological effects and clinical outcomes of adjuvant GM-CSF therapy of melanoma. Methods: GM-CSF, 125 μg/m2, was administered subcutaneously in 28-day cycles of 14 days on/14 days off for 1 year. Blood draws were keyed to GM-CSF administration: Days 0 (before), 15 (after 14 days on GM-CSF), 29 (after 14 days off GM-CSF), 155 and 351 (after 14 days on GM-CSF in the 6th and 13th cycle). Forty- nine patients were evaluable for immunologic responses on Day 15. Immunophenotyping of the white cell population was done on a subset consisting of 6 patients. Results: In 42 patients, there was an increase in the WBC counts to above normal after 14 days of GM-CSF therapy in the first cycle. This increase did not occur in 7 patients and these patients had a significantly shorter survival. There was a similar increase in neopterin levels following 14 days of GM-CSF administration, which returned to baseline after 14 days off therapy and did not correlate with clinical outcome. Immunophenotypic analysis showed an increase in activated and regulatory T cells and a decrease in the percent of CD11c+DC (myeloid) cells in the 6 patients evaluated, all returning to baseline on Day 29. Conclusions: GM-CSF therapy was associated an increase in the WBC counts in the majority of patients after 14 days of treatment and patients who did not experience this increase had a significantly shorter life expectancy. The observed increase in neopterin levels is consistent with macrophage activation as the potential mechanism of action of adjuvant GM-CSF administration. Additional immunologic effects which may play a role during GM-CSF therapy include the increase in activated T-cells and decrease in CD11c+DC, which may be moving from the peripheral circulation into the tissues.

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Metronomic schedule of temozolomide with conventional dose of cisplatin in metastatic melanoma
Authors: Simeone E. , Daponte A. , De Feo G. , Montesarchio V. , Chiarion-Sileni V. , De Michele I. , Caracò C. , Palmieri G. , Mozzillo N. , Ascierto P. A.
Published: August 2020

e20009

Background: Dacarbazine (DTIC) is the standard treatment for metastatic melanoma. Temozolomide (TMZ) is a potentially attractive chemotherapeutic agent for this disease because of the oral route of administration and efficacy similar to that of dacarbazine. Cisplatin is active against melanoma and might counteract mechanisms of resistance to TMZ. Metronomic administration of TMZ might be another way to overcome resistance. Patients and Methods: We reviewed data of metastatic melanoma patients treated at our Institutions with cisplatin (75 mg/m2 every 28 days) plus TMZ (75 mg/m2/die from day 2 for 21 days). Our practice included such scheme for patients younger than 75 years, with a performance status not worse than 2, and adequate bone marrow, liver and renal function. Assessment of response was done every 3 cycles. Toxicity was graded according to NCI-CTC. Results: From August 2007 to September 2008, 33 patients were treated with a median age of 44 years (18–74); primary melanoma was ulcerated in 19 cases (58%); most frequent sites of metastases were lung (18 cases), brain and lymph nodes (11 cases each); 29 patients were treated as first-line and 4 as second-line. The median number of delivered cycles was 4 (range 2- 8). Toxicity was mild, with no grade 4 event reported. Nausea and vomiting were the most frequent and severe toxic effects: grade 3 in 2 cases each and grade 2 in 16 and 9 cases, respectively. Other toxicities included thrombocytopenia (2 case grade 3 and 3 cases grade 2), anemia (1 grade 3 and 4 grade 2), neutropenia, and fatigue (1 grade 3 each). Overall, 6 patients had a partial response (18.2%; 95% exact CI: 7.0–35.5) and 8 (24%) had a disease stabilization. With a median follow-up of 20 weeks (95% CI: 19–57), there were 19 progressions and a median progression-free survival of 24 weeks (95% CI:16-nr); 9 patients died with a median survival of 50 weeks (95% CI 43-nr). Conclusions: Results obtained in clinical practice with metronomic temozolomide plus cisplatin in the treatment of patients with metastatic melanoma are encouraging, in light of the negative prognostic features of treated patients. We are now planning a formal phase II study.

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Possible therapeutic reversal of immune suppression in patients with metastatic melanoma by timed delivery of temozolomide chemotherapy: A pilot study
Authors: Quevedo F. , Ashdown M. L. , Suman V. J. , Robinson A. , Kottschade L. A. , Kaur J. S. , Creagan E. T. , McWilliams R. R. , Markovic S. N.
Published: August 2020

e20013

Background: Recent evidence suggests that patients with advanced cancer exhibit an underlying anti-tumor immune response that is continuously attenuated by regulatory T cells (Treg). Depletion of Treg using conventional chemotherapy may be feasible and clinically beneficial. C-reactive protein (CRP) is reported to rise/fall with initiation/termination of the immune response, and may be a surrogate for the periodicity of Treg proliferation that could be utilized for timing of anti-proliferative therapy. Timed delivery of chemotherapy therapy based on CRP cycling may deplete Treg and yield clinical benefit. Methods: We conducted a pilot clinical for 12 patients with metastatic melanoma who underwent serial CRP measurements (every 2–3 days) for 2 weeks. The CRP oscillation cycle was identified and chemotherapy with temozolomide (200mg/m2 for 5 days, every 28 days) was initiated at the estimated peak of plasma CRP. Patients were evaluated for clinical and immune response endpoints every 8 weeks until progression. Results: All 12 patients (median age 61; 4 female; 7 with M1c disease) exhibited oscillating CRP levels with an average periodicity of 7.8 days. Only 11 patients were treated (1 patient had rapid tumor progression). The two patients who remain progression-free for >2 years (1 PR, 1 CR), were treated in the pre-peak section of the CRP cycle, distinctly separate from the other patients treated post CRP-peak (all progressed <5 months). Presented are peripheral blood immunological laboratory correlates (cellular and cytokine) to CRP oscillation. Conclusions: These data suggest that patient clinical outcome may be dependent on the timing of therapy relative to an individual patient's immune response cycle and outline the dynamic equilibrium of systemic immune homeostasis in patients with advanced melanoma. Further investigations of these observations are under way.

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Intra-arterial hepatic bio-chemotherapy for the treatment of melanoma patients with liver metastasis: A phase II clinical study
Authors: Chi Z. , Cui C. , Yuan X. , Si L. , Sheng X. , Shen L. , Guo J.
Published: August 2020

e20014

Background: To investigate the efficacy and safety of hepatic intra-arterial infusion of cisplatin, fotemustine combined with systemic dacarbazine for the treatment of melanoma patients with liver metastasis. Methods: From 2005.7 to 2008.7, thirty-six melanoma patients with liver metastatic were enrolled. Systemic dacarbazine (250mg/m2 d1–5) and intra-arterial hepatic (i.a.h.) of cisplatin (75mg/m2 d6) and fotemustine (100mg/m2 d7) were given repeated for 4-weeks. Response, progress free survival(PFS), and toxicity were analyzed. Results: 27 of the 36 patients were evaluable, with mean cycle 2.16±1.19, one achieved CR, one PR and seven SD. The disease control rate was 33.3% (9/27) with a median PFS of 3.5 months (95% CI 3.45–7.02months), overall survival of 7.5 months (95 CI 6.87–11.06 months, following to 2008.8). The Grade 3/4 toxicity was mainly myelosuppression, with occurrence rates of 40.7% (10/27). Conclusions: Intra-arterial hepatic chemotherapy show its efficacy and may prolong PFS in melanoma patients with liver metastasis.

No significant financial relationships to disclose.