bluuebunny/crossref_metadata_2025 huggingface dataset:
Retrospective assessment of adherence to ASCO Surveillance Guidelines following treatment for stage II and III colorectal cancer (CRC)
Authors: Davies J. M. , Lupichuk S. , Batuyong E. , Hilsden R. J. , Easaw J.
Published: August 2020

e17517

Background: The 2005 ASCO guidelines for surveillance following adjuvant therapy for CRC outlined recommended surveillance tests and their frequencies including history and physical examination, CEA testing, CT scan and colonoscopy. The purpose of this study was to assess the impact of these guidelines post treatment of stage II and III CRC in the Calgary Health Region (CHR) before and after implementation of a computer generated, personalized discharge letter (DL). Methods: Cohort 1 patients completed adjuvant chemotherapy or radiotherapy for stage II and III CRC between September 1, 2006, and November 30, 2007, prior to implementation of the DL. Cohort 1 was retrospectively identified from the Alberta Cancer Registry. Registry data was collated with laboratory data and diagnostic imaging data is forthcoming. Adherence to the guidelines at 1-year follow-up in cohort 1 was measured. Prospective data collection on patients who completed adjuvant treatment after implementation of the DL (cohort 2) is ongoing. Comparison of adherence rates to surveillance testing between the two cohorts will be reported upon study completion. Results: For cohort 1, 209 of 238 patients referred to the cancer centre were from the CHR and hence included in the analysis. The average age was 65 and 53% were male. Most patients (136/209) had stage III CRC. 1/209 had a local recurrence only. 27/209 progressed to metastatic disease during the 1-year follow-up period, of which 23 of these patients were initially diagnosed with stage III CRC. CEA adherence (≥4 tests taken within 1-year follow-up period) was 38.3% (95% CI 31.7–44.9). CT scan adherence and use of “inappropriate” surveillance testing for cohort 1 will be available at the meeting. Conclusions: This study assesses compliance with the 2005 ASCO CRC surveillance guidelines at 1-year follow-up post adjuvant treatment at a tertiary cancer centre. Analysis of cohort 1 reveals that adherence to CEA testing is suboptimal. The next phase of this study will assess the impact of a DL, sent to patients and primary care providers outlining recommended surveillance tests and dates, on adherence rates.

No significant financial relationships to disclose.
Breast cancer testing strategies and the utilization of targeted therapies: Data from the real world
Authors: Haas J. , Phillips K. A. , Hassett M. J. , Liang S. , Keohane C. , Armstrong J. , Toscano M.
Published: August 2020

e17518

Background: HER2 testing and the use of trastuzumab is considered a prototype for the translation of a genomic therapy, yet almost nothing is known about use in practice. Uncertainties about the performance of the two types of HER2 tests, immunohistochemistry (IHC) and fluorescence-in-situ-hybridization (FISH) have led to debate about how best to identify women who are most likely to benefit from this costly treatment. Similarly, little is known about the use of gene expression profiling (GEP - e.g., OncotypeDx), which offers the possibility of better recurrence estimation to tailor the use of adjuvant chemotherapy. Methods: Cross-sectional record review of women, 36–64 years, with a new diagnosis of breast cancer in 2006–2007, identified using claims from a large, national health plan (n = 392 to date). Results: Almost all women had a HER2 test (97.7%): 56.2% had IHC alone, 17.4% had FISH alone, and 24.0% had both (2.4% had documentation of a test but not test type). Data for women with both IHC and FISH is shown below. Using the maximum of all available results, 24.9% were HER2-positive, 11.1% intermediate, and 63.9% HER2-negative. Only 55.2% of HER2-positive women received trastuzumab, compared to 16.7% of women with an intermediate score, and no HER2-negative women. The majority of women (85.7%) did not have GEP. Among women with GEP, 58.9% indicated low recurrence risk, 21.4% medium risk, and 5.4% high risk. Adjuvant chemotherapy was received by 27.3%, 91.7%, and 100% respectively (p < 0.001). Conclusions: HER2 tests, primarily IHC, are widely used. There are discrepancies in classification of HER2 status based on IHC vs. FISH. We did not find evidence of overuse of trastuzumab by women who were HER2-negative. Further work should clarify whether the lack of trastuzumab for HER2-positive women is clinically appropriate. We found modest adoption of GEP, and GEP score was associated with the use of adjuvant chemotherapy.

[Table: see text]

No significant financial relationships to disclose.
Incidence, annualized cost, and utilization burden in patients with metastatic renal cell carcinoma
Authors: Burke J. P. , Liu Z. , Zheng J. , Johnson J.
Published: August 2020

e17529

Background: Data on burden of metastatic renal cell carcinoma (MRCC) is scarce. The objectives of this study are to examine the incidence of MRCC and the cost and utilization burden of MRCC over time. Methods: Administrative claims data from a large, US managed care plan were used to identify commercially insured and Medicare enrollees with newly diagnosed MRCC during 01/01/03–12/31/07 and continuous enrollment 12 months prior to and at least 90 days after MRCC diagnosis. Mean (median) costs and utilization during the follow-up period were annualized. Costs were 2007 CPI-adjusted. Results: 1,427 patients were identified with newly diagnosed MRCC (average age: 62.4 years 62.6% male). The annual incidence of MRCC in the managed care plan population was 3.4, 3.8, 2.9, 3.3, and 4.4 per 100,000 enrollees in 2003 through 2007, respectively. The mean (median) annual number of ambulatory visits per patient increased among patients diagnosed in 2003 to those diagnosed in 2007, from 44.9 (33.2) to 63.7 (54.8). Mean (median) annual medical costs per patient increased by year of diagnosis from $70,797 ($33,031) in 2003 to $92,521 ($48,117) in 2007. Pharmacy costs (excluding costs for medications delivered in medical settings) increased from $5,651 ($2,004) to $13,290 ($3,609), and were approximately 7.4%-14.3% of total costs during the time period. Conclusions: This study showed an apparent slight increase in MRCC incidence rates and revealed that treatment costs and health care utilization per patient increased substantially from 2003–2007 among members of this US managed care plan. The increases in health care utilization and cost suggest the evolution in treatment options over time as more therapies become available.

No significant financial relationships to disclose.
Does race affect outcomes in triple negative breast cancer (TNBC)?
Authors: Ahmed S. , Mirza M. M. , Farooq A. , Kronish L. , Jahanzeb M. , Sachdev J. C.
Published: August 2020

e17543

Background: TNBC is associated with a worse prognosis than luminal subtypes. There is discordance among studies assessing the impact of race on outcomes of TNBC. Our objective was to assess whether African American (AA) vs. Caucasian (CA) race predicted survival outcomes for women with TNBC treated at a single institution in Memphis, TN. Secondary objectives were to examine the association of race with patient and tumor characteristics. Methods: Patients with stage I-III TNBC were identified from our breast cancer database and confirmed by review of pathology reports. Event free survival (EFS) was measured from the date of surgery to the date of first recurrence (locoregional, distant, or contralateral), death from breast cancer or last follow-up. Breast cancer specific survival (BCSS) was measured from the date of surgery to the date of death from breast cancer or last follow-up. Fisher's exact test was used for association between variables, Kaplan Meier method for survival estimates, and log rank test for survival comparison between groups (p < 0.05: significant). Cox proportional hazards models with patient, tumor and treatment variables were fitted for EFS and BCSS. Results: Of the 105 patients with TNBC, 71% were AA. There was no significant association between race and stage at diagnosis (p = 0.68). 71% of AA women were < 55 years old and 43% were pre-menopausal vs. 50% and 23% of CA women respectively. There was a trend towards association of race with age and menopausal status (p = 0.08). Ninety three percent of the patients received neo/adjuvant chemotherapy. With a median follow up of 26 months, 26% of AA vs. 20% of CA women had an event (p = 0.62). Overall 3 year EFS and BCSS estimates were 69% and 82% respectively. Racial differences in EFS and BCSS for AA vs. CA (65% vs. 80% and 78% vs. 89%, respectively) did not achieve statistical significance (log rank p = 0.22 for EFS and 0.26 for BCSS). Race was not a significant predictor of EFS or BCSS on uni-variable or multi-variable analysis. Stage at diagnosis retained significance for EFS and BCSS on uni-variable and multi-variable testing. Conclusions: Race did not affect outcomes in our cohort of TNBC patients treated similarly. The high event rate underscores the poor prognosis of TNBC and the need for more effective therapies.

No significant financial relationships to disclose.
Longitudinal analysis of quality of life (QoL) within a randomized phase III trial in patients (pts) with metastatic pancreatic adenocarcinoma (MPA)
Authors: Bonnetain F. , Maillard E. , Seitz J. , Mitry E. , Ychou M. , Gasmi M. , Raoul J. , Mariette C. , Bedenne L. , Dahan L.
Published: August 2020

e17544

Background: The FFCD phase III trial in pts with MPA comparing LV5FU2-P followed by gemcitabine (arm A) versus the opposite sequence (arm B) had failed to demonstrate a significant difference in median OS. To longitudinally compare QoL according to treatment sequence we have explore definitions of time until definitive deterioration (TUDD) of QoL scores according to minimal clinically important difference (MCID) cut off. Methods: From August 2003 to May 2006, 202 pts with measurable MPA, PS 0–2, non prior CT were included in 33 centers, 102 in arm A and 100 in arm B. QoL was evaluated using EORTC QLQ-C30 every 8 wks up to death. We focused analyses on the following scores: global health (GH), emotional functioning (EF), physical functioning (PF), fatigue (FA), and pain (PA). TUDD were estimated using Kaplan Meier, and compared using log-rank tests. They were defined as the time interval between randomization and the first occurrence of a decrease in QLQ-C30 score ≥ 5 points without any further improvement in QoL score ≥ 5 points or any further available QoL data. These analyses were repeated using a 10 points MCID, and by including deaths as event. Results: Amongst the 202 pts, 179 had completed at least one QoL questionnaire (89%) and the mean number of available QoL data was 3 (SD: 2.14). Using a 5 points MCID as well as 10 points, TUDD of the 5 scores did not differ according to treatment arm. About 25% of patients reported definitive score deteriorations≥ 5 points and 15%≥ 10 points. Including death as event for a 5 points MCID, median TUDD of GH score was 5.2 months (4.3–6.2) in Arm A and 6.1 months (5.1–6.1) in Arm B (log rank p = 0.50). Median TUDD of FA score was 4.8 months (3.5–6.3) in Arm A and 5.6 months (4.2–7.7) in Arm B (log rank p = 0.76). Median TUDD of scores was reached after median PFS and at median time of second-line PFS. While treatment had no impact, multivariate Cox model showed that tumor localization and progression were independently associated with TTDU (p < 0.05). Conclusions: We have investigated QoL analyses modalities using survival techniques dealing with binding drop out missing data and with an easier clinical interpretation of results. Progression seems to negatively impact QoL.

No significant financial relationships to disclose.
Economic guidelines for oncology products: Adaptation of the Canadian Agency for Drugs and Technologies in Health (CADTH) technology assessment guidance document
Authors: Mittmann N. , Evans W. K. , Rocchi A. , Longo C. J. , Au H. J. , Husereau D. , Isogai P. K. , Krahn M. , Coyle D. ,   Working Group on Standardized Pharmacoeconomic Guidelines in Oncology
Published: August 2020

e17572

Background: Economic evaluations (EE) are routinely used by decision-makers in Canada. CADTH's “Guidelines for the Economic Evaluation of Health Technologies: Canada” Third edition, 2006, provide guidance on the conduct of EEs for all therapeutic products. The consistency and quality of oncology EEs are variable and therapeutics in the cancer care environment presented unique challenges in decision making. Several chapters of the CADTH document adequately defined methods for the conduct of an oncology EE. However, some chapters required more specific guidance to improve the quality of oncology EEs. The goal was to provide direction on methods for the conduct of high quality EEs in oncology. Methods: The Working Group on Economic Analysis, NCIC CTG and CADTH jointly initiated this project and formed a working group (WG) of oncologists, health economists, decision makers and economic analysts. The WG identified CADTH chapters where oncology-specific guidance would be required. In-person and teleconference meetings provided content and structure for the document. Formal reviews by external academic experts, cancer agencies, patient groups and the pharmaceutical industry were conducted. Feedback was reviewed by the WG and incorporated as appropriate. Results: Chapters requiring guidance included: target population, comparators, perspective, effectiveness, modeling, type of evaluation, valuing health, time horizon, costs and resources, sensitivity analysis and equity. Guidance included clarity around CADTH methodology and recommendations for oncology products. For example for the effectiveness chapter, there was guidance around the use of intermediate outcomes (progression free survival vs. overall survival) and type of evidence (phase II vs. phase III). Overall recommendations for chapters will be presented. Conclusions: The oncology adapted economic guidelines provide specific guidance on the conduct of EEs for oncology products and will be published as an addendum to CADTH's third edition document. Their use should lead to more consistent application of EE methodologies for anti-cancer drugs and higher quality information for decision-makers at a national and perhaps international level.

No significant financial relationships to disclose.
Neutrophil dynamics and death in postchemotherapy septic neutropenia
Authors: Othieno-Abinya N. A. , Kiarie G. W. , Mlombe Y. , Wanzala P.
Published: August 2020

e17579

Background: Mortality rates from septic neutropenia vary between studies, ranging from 7% to 30%. We observed the mortality rate for patients hospitalized for postchemotherapy septic neutropenia was 28.6% in one of our studies. Many deaths appeared to have occurred at the time of neutrophil recovery. We attributed this to immune reconstitution inflammatory syndrome akin to what is seen in HIV/AIDS. Methods: Records of patients who died during hospitalization with septic neutropenia. Results: Twenty one patients, 14 males (67%) and 7 females (33%) were included, age range 14–67 years. Six (28.6%) had World Health Organization (WHO) grade 0 neutropenia at the time of death, none had grade 1, one (4.8%) had grade 2, one (4.8%) grade 3, and 14 (67%) had grade 4. The last absolute neutrophil count (ANC) at death ranged between 0.005 and 6.3 x 109/litre. Ten patients (47.6%) died during neutrophil upswing and 11 (52.4%) during neutrophil decline. Thirteen patients (61.9%) also had grade 4 thrombocytopenia but no death was attributed to bleeding. Five of 18 (27.8%) had WHO grade 3 renal function impairment, and six (33.3%) had grade 2 impairment. The main cause for renal function disturbance was hypotension that was usually sudden and unexplained. There was no correlation between ANC and renal function impairment (p > 0.5). Conclusions: Death from septic neutropenia could not be attributed to neutrophil dynamics and by extension immune reconstitution from this study. Neutropenia grade 4 still stood out as a major predictor of death. Larger prospective studies are required to address this issue.

No significant financial relationships to disclose.
A comparative study of single-dose pegfilgrastim versus daily filgrastim in patients with acute myeloid leukemia
Authors: Kunivayalil S. , Jain A. , Satheesh C. , Tejinder S. , Lakshmaiah K. , Suresh T. M. , Lokanatha D. , Babu G.
Published: August 2020

e18005

Background: Prophylactic treatment with recombinant human granulocyte colony stimulating factor (rhGCSF) is used to decrease the severity and duration of neutropenia in patients receiving myelosupressive chemotherapy. It can be used during induction and consolidation chemotherapy in acute myeloid leukemia (AML). Mechanism of action of pegylated GCSF is the same as filgrastim except for delayed clearance. Few studies addressed the use of pegylated filgrasim in AML. Methods: After 24 hours of consolidation chemotherapy, 8 patients in the study arm received single dose of subcutaneous 6 mg pegfilgrastim. The control group received daily filgrastim at a dose of 5 microgram per kg.until absolute neutroophil count of 2 ×109 cells/μL for 2 consecutive days. The neutrophil recovery time, febrile neutropenia and its duration, duration of hospitalization and safety profiles were compared. Results: There were 20 episodes of pegfilgrastim administration. The median age was 41 years in pegfilgrastim arm and 39 years in filgrastim arm. Medium time to neutrophil recovery was 14 days for pegfilgrastim arm and 17 days for filgrastim arm. In the pegfilgrastim arm 12 (60%) episodes of febrile neutropenia occurred compared to 11 (55%) in filgrastim arm. The median duration of febrile neutropenia was 3 days in pegfilgrastim arm versus 4 days in filgrastim arm. The median duration of hospitalization was 15 days in pegfilgrastim arm and 18 days in filgrastim arm. Safety profile and complete remission status did not differ between the two groups. Conclusions: The present study showed favorable profile of pegfilgrastim for netrophil recovery, duration of neutropenia and hospital stay. There was no difference with regard to safety or response to treatment.

No significant financial relationships to disclose.
A phase I study of tumor treating fields (TTFields) in combination with pemetrexed for pretreated advanced non-small cell lung cancer
Authors: Kirson E. D. , Weinberg U. , Betticher D. , Von Moos R. , Fischer N. , Studt J. , Buess M. , Burger N. , Palti Y. , Pless M.
Published: August 2020

e18500

Background: TTFields (tumor treating fields) are low intensity, intermediate frequency, alternating electric fields which slow the growth of solid tumors in-vivo, and have shown promise in pilot clinical trials in patients with advanced solid tumors. TTFields are a regional treatment which acts both by interfering with microtubules polymerization and by physical disruption of the cell structure during cytokinesis. It has been shown previously that TTFields sensitize non-small cell lung cultures to Pemetrexed. In-Vivo, TTFields did not increase pemetrexed related toxicity. Methods: A prospective trial was performed in 14, pretreated, stage IIIb-IV, NSCLC patients. Patients with brain metastases were excluded, as were patients with abnormal marrow, kidney, liver or cardiac functions. Patients with history of clinically significant arrhythmias or those having pacemakers were excluded as well. Patients received Pemetrexed 500mg/m2 IV q3w together with daily TTFields (12 h/day) using a portable medical device (NovoTTF-100L). The device generated 2 direction (AP and Lat), 150 kHz TTFields. Patients were followed every three weeks and had a lung CT every 9 weeks. The primary endpoint was the safety and tolerability of the NovoTTF-100L device in combination with pemetrexed. Results: The 14 patients received an average of 4 courses of pemetrexed (Range 1–9) and a cumulative TTFields treatment time of 182 weeks. The device was well tolerated as indicated in the device log files which showed an average daily use of 11±1 hours. There were no device-related, nor pemetrexed-related SAEs. In addition, no unexpected abnormalities were evident in the lab tests or EKGs, done every 3 weeks for all patients. There were no reports of arrhythmias. The only device related AE seen in all patients was dermatitis under the electrodes. This improved with meticulous skin care, topical steroid use and in extreme cases oral steroids. One patient (7.6%) had a CR, 1 a PR (7.6%), 9 SD (69.2%) and 3 PD (23%). 77% of patients were progression free at 12 weeks and the 6 month survival was 89%. Conclusions: TTFields are well tolerated when given together with pemetrexed. The excellent safety profile and initial efficacy results reported here justify further clinical testing.

[Table: see text]
Influence of smoking dose on the outcome of Japanse patients with non-small cell lung cancer who had gefitinib treatment
Authors: Asami K. , Kawahara M. , Atagi S. , Kawaguchi T. , Kubo A. , Okishio K. , Yagi Y. , Matsuda Y. , Kagawa T. , Kitaichi M.
Published: August 2020

e19004

Background: Non-smoking history and epidermal growth factor receptor (EGFR) mutation are associated with increased sensitivity to gefitinib in non-small cell lung cancer (NSCLC). However, it is still unclear how much smoking dose is associated with survival and response to gefitinib among smokers. Methods: NSCLC patients (pts) with detailed smoking history who received gefitinib at our institution between 9/02 and 9/04 were reviewed. An analysis was conducted to the pts for association between smoking dose, EGFR mutations, performance status (PS), response and overall survival using multivariate analysis. Results: Data were available for 100 pts including 30 females and 70males. We expressed smoking dose as pack year (Py).The median dose of smoking was 32 Py (0.1–100 Py). We defined the group of <10 Py as light smokers(17 pts) and the other group of 10 Py or more as heavy smokers(83 pts). We detected 31(31%) EGFR mutation (median 14 Py 0.1–75 Py) with exon 18 / 19 /21 mutation;3/17/11 pts .Cox survival analysis showed that overall survival was preferably associated with small dose of smoking(<10 Py)(HR=0.505; [95% CI 0.277–0.921; P=0.013]), EGFR mutation(HR=0.452[95% CI 0.235–0.87;P=0.035])and PS;0–1(HR=0.347 [95% CI 0.207–0.583 P<0.001]). EGFR mutations were significantly more frequently observed in light (12/17:71%) than heavy smokers(19/83:23%) (p<0.001). Disease control rate(DCR) was significantly higher in light (13/17;76%;PR 6, SD 7) than heavy smokers(29/83;35%;PR 15, SD 14)(P=0.002), but there was not significant difference between those groups in terms of response rate (RR)(P=0.187). There were significant differences between pts with EGFR mutations (PR 13 SD 14; RR 42%,DCR 87%) and pts without EGFR mutations (PR 8 SD 15; RR 12%, DCR 33%) in terms of RR(P<0.001) and DCR(P<0.001). In pts with EGFR mutation, there was no significant difference between light and heavy smokers in terms of RR (light smokers 5/10, heavy smokers 8/21; P=0.701) and DCR (light smokers 10/10, heavy smokers17/21; P= 0.277). Conclusions: EGFR mutations were predictive factor and prognostic factor. Small dose of smoking (< 10 Py) was prognostic factor, however it was not a predictive factor of smokers with NSCLC.

No significant financial relationships to disclose.
A phase II first-line study of gemcitabine, carboplatin, and bevacizumab (GCB) in advanced (adv) stage non-squamous non-small cell lung cancer (NSCLC)
Authors: Krupitskaya Y. , Ganjoo K. , Lavori P. W. , Kumar A. , Clement-Duchene C. , Zhao G. , Padda S. , San Pedro- Salcedo M. , Wakelee H. A.
Published: August 2020

e19024

Background: B adds to 1st-line paclitaxel/carboplatin (PC) for pts with adv NSq-NSCLC. Gemcitabine/carboplatin (GC) has equivalent efficacy to PC with a different toxicity profile. This study was designed to evaluate toxicities (AEs) of GCB and to estimate survival. Methods: Patients (pts) with untreated adv NSq-NSCLC, with no evidence of CNS metastases were eligible. Pts received G 1000 mg/m2 on d1, 8; C AUC 5 d1; and B 15 mg/kg d1 q21d for up to 6 cycles. B was then continued q21d until disease progression or unacceptable toxicity. Chemo dose reductions were mandated for significant cytopenias. Imaging was every 2 cycles. Results: From 07/06 to 12/08, 48 pts enrolled (accrual complete): 23(48%) men, 19(40%) never smokers, median age 59yo (35–81). One pt died prior to receiving therapy and is not included in the analysis. Median cycle number is 6(0–37). To date, 35 pts (74%) completed ≥ 4 cycles of 3 drugs. Dose reductions occurred in 29(62%) of pts. G3/4 AEs included: neutropenia (47%/17%), thrombocytopenia (11%/15%), and anemia (6%/0%). No pts were hospitalized for neutropenic fever. G3/G4 non-hematologic AEs included dyspnea (6%/2%), bacterial pneumonia (4%/0) hypertension (4%/2%), 1G3 wound dehiscence, 1G4 MI, 1G3 transaminitis and hyperbilirubinemia, 1G3 proteinuria and 1G3 leucocyturia. 1 pt died from hemoptysis with untreated aspergillosis found post-mortem. Other bleeding included 1 case each with G3 epistaxis, hemorrhoidal bleeding and ecchymosis. Common G1/2 AEs included fatigue, hypertension, anemia, constipation, nausea, headaches, transaminitis and epistaxis. In 42 evaluable pts: we saw 7(17%) PRs, and 31(74%) SDs at 1st f/up. 44/47 pts were followed for a median of 10.5mo (3 recently enrolled pts with f/u < 20d - excluded). Median time to first event (progression/death/toxicity requiring discontinuation) was 6.4mo [95%CI 4.6–8.6mo]. 17/44 (38.6%) pts have died with median overall survival (mOS) not reached but preliminarily estimated at 16.7mo [95%CI 13.4mo-inf]. Estimated OS is 73% at 1yr and 32% at 2yrs. Conclusions: Treatment with GCB has an acceptable toxicity profile with promising mOS despite a low RR and frequent dose reductions in a population with a high proportion of non-smokers and women.

No significant financial relationships to disclose.
Baseline quality of life as a prognostic factor for overall survival in lung cancer patients
Authors: Zhao X. , Sloan J. , Yang P. , Sargent D. , Wampfler J. , Shao Y.
Published: August 2020

e19031

Background: Useful predictors of survival in cancer patients have been found including such as gender, race, age, marital status, state of disease and tumor location. We set to explore the prognostic value of baseline QOL assessments on overall survival in lung cancer patients. Methods: A total of 1,319 lung cancer patients were followed at Mayo Clinic between 1997 and 2007. Overall QOL was assessed by either Lung Cancer Symptom Scale (LCSS) or a single-item Linear Analogue Self Assessment (LASA) with comparable wording. QOL scores were transformed to a 0–100 scale with higher scores representing better status. Patients QOL scores assessed within the first 6 months of follow-up were dichotomized using a priori definition for clinically deficiency score (CDS, ≤50 vs. >50). The Kaplan-Meier method was used to estimate the distribution of survival times by QOL clinical deficient categorization. Cox Proportional Hazards Models were used to evaluate the prognostic importance of QOL on OS alone and in the presence of age, smoking category, gender, treatment, stage of disease, smoking cessation and years of consuming a pack every day. Results: Baseline QOL was significantly associated with OS univariately (HR=0.46 with p<0.0001 based on the CDS categorization). After controlling for all these other factors, the indication of a clinically deficient baseline QOL contributed significantly to the prediction of patient survival (p=0.0002; HR=0.67). Age, treatment, disease stage, smoking cessation and smoking category were also significant predictors of OS multivariately. The median survival for patients that had an overall QOL score less than the CDS (≤50) was 1.6 versus 4.6 years for patients with QOL >50. Conclusions: Baseline overall QOL measured by LCSS or LASA is a significant and independent prognostic factor for OS in lung cancer patients. A meaningful next step in this research is to investigate interventions to improve lung cancer patient QOL and thereby increase their likelihood of survival as well.

No significant financial relationships to disclose.
Prescribing plans (PP) of American Oncologists for first-line therapy (Rx) for patients with stage III (wet)/IV non-small cell lung cancer (NSCLC) and PS 2: Overall selection and impact of gender and smoking status
Authors: Shabbir M. , Daniels L. , Shirai K. , Cole S. , Willey J. , Iovino L. , Labarre K. , Green M. R.
Published: August 2020

e19046

Background: Selection of oral EGFR inhibitors or chemotherapy as 2nd line in patients with NSCLC may be influenced by patients’ performance status (PS), smoking status, gender; tumor histology; tolerance/response to 1st-line Rx; and patient expectations/desires. Methods: Between February ’07 and October ’08, we used a core case scenario of stage IV mucin positive adenocarcinoma (Adeno ca) of lung in a 68-year-old former smoker (FS; stopped 6 years ago) with PS 2, to study patient related variations in PP of almost 800 American medical oncologists during 10 live research events [393 MDs/5 events during 2008]. Impact of gender or/and smoking history on 1st-line Rx selection was assessed. Results: In 2007–08, 97%/97%% MDs planned anti-tumor Rx: 53%/63% combination; 44%/34% single agent. PP for 2008 is shown in the table . [2007 PP data for erlotinb use included]. PP for erlotinib in these 4 scenarios are stable over the 2007 - 08 testing interval. Impact of smoking status dominates over gender. For a female NS with Adeno ca /PS2, ≥2/3 of MDs plan erlotinib 1st-line. In the absence of testing results for EGFR expression by IHC, EGFR gene copy number by FISH, EGFR gene mutation testing, or kras mutation testing, our data show a direct correlation of patient “phenotype” and PP for erlotinib as 1st-line Rx, a setting not specifically an approved indications for this agent. The impact of recently reported progression free survival data from an Asian phase III trial (IPASS: gefitinib or chemotherapy or as 1st-line therapy in non or former light-smoking patients with lung adenoca) on future prescribing plans in this clinical setting will be of great interest. Conclusions: By our observations, smoking status dominates over gender in PP of oncologists when treating wet IIIB/IV Adeno ca of lung. Therefore we plan to continue to assess American oncologists’ PP for this NSCLC setting during 2009.

[Table: see text]

[Table: see text]
Impact of dose reductions of platinum compounds on survival in stage IIIB/IV non-small cell lung cancer (NSCLC)
Authors: Yumuk P. F. , Teomete M. , Dane F. , Cabuk D. , Basaran G. , Turhal N. S.
Published: August 2020

e19055

Background: Platinum compounds are the main component of the CT in NSCLC. Standard recommended doses of cisplatin/carboplatin is usually couldn’t be administered and dose reductions are necessary because of side effects. We aimed to determine the effect of dose reductions of platinums on outcome of stage IIIB/IV NSCLC. Methods: Data of 420 patients were retrospectively reviewed. A platinum analogue was used in combination with vinorelbine, gemcitabine, paclitaxel, docetaxel or etoposide as first line treatment in 85% patients. Cumulative platinum doses and dose reduction ratios compared to standard doses were calculated. Patients with decreased GFR were excluded from the analysis. Results: Median age was 60 years (range: 28-87), 79% of patients were male, 31% were 65 yearsold/older, 55% had PS of 0, and 27% had stage IIIB disease. Histological subtypes were squamous cell in 32%, adenocarcinoma in 34%, and NSCLC in 31%. Median dose of cisplatin used per cycle was 67mg/m2 and carboplatin was 287mg/m2. 51% of the patients received standard or less than 10% reducted doses of platinum, while dose reductions were 10–20% in 19%, 21–30% in 24% of patients, and more than 31% in 6%. Median overall survival (OS) was 11 months, 1- year and 2-year OS ratios were 56% and 25%, respectively. Median time to progression was 5 months; 1-year progression free survival ratio was 18%. Gender, age, histologic subtype, and treatment with lower dose of platinum didn’t have any statistically significant impact on survival in univariate analysis. Patients with PS of 0, no weight loss, stage IIIB disease, receiving combination CT with docetaxel-cisplatin, and having partial response to treatment lived significantly longer. On multivariate analysis weight loss, stage and type of response to treatment had an impact on OS. Conclusions: Using lower doses of platinum compounds in combination chemotherapy for stage IIIB/IV non-small cell lung cancer might not have a negative impact on survival and definitely have a better toxicity profile.

No significant financial relationships to disclose.
Results from short-term CT assessments in patients (pts) with advanced poor performance status non-small cell lung cancer (NSCLC) receiving pemetrexed in a phase II trial
Authors: Zinner R. , Herbst R. S. , Fossella F. V. , Johnson F. M. , Karp D. D. , Kies M. S. , Heymach J. V. , Price J. S. , Lippman S. M. , Erasmus J.
Published: August 2020

e19069

Background: Early determination of therapeutic failure can potentially spare a pt ineffective and toxic treatment. We previously reported in a retrospective study the use of CT within 4 weeks of initiation of chemotherapy in advanced NSCLC to assess response and progression by RECIST (Bruzzi et al. JTO 2006). Here, we prospectively assess whether CT imaging after the first cycle of pemetrexed in advanced NSCLC has a role in evaluating response and management. Methods: We accrued pts with PS 2 or 3 advanced NSCLC receiving at least one dose of 1st or 2nd line pemetrexed. A repeat CT prior to a 2nd course was required. Pts with progression by RECIST were to come off study. CT scans were done using multislice CT technology (GE Lightspeed Plus), and images were reconstructed with slice thicknesses of 3.75mm or less. All images were reviewed using a PACs workstation (Stentor iSite) and measurements were done with electronic calipers. RECIST criteria: progression, an increase in the tumor's longest dimension by 20%, response, a decrease by 30%. Results: Thirty pts had a median age of 68 years (45 - 81). PS 2/3, 1st/2nd line, and F/M were 16/14, 17/13, and 12/18 respectively. Pts received 1–8 cycles (median 2). Twelve pts received only 1 course of whom 7 pts had f/u CTs at a median of 20 days (12–25) after 1st chemo dose. Of these pts, 5/7 had progression by RECIST and the other 2/7 pts had stable disease with 1 pt who came off due to serial PEs and 1 pt who opted off for reasons of travel. Two of the 5 pts who had progression by CT had no detectable change by CXR. Of 5/12 pts treated with only 1 course without f/u CT, 2 pts died, 2 pts had progression by CXR, and 1 pt stopped after treatment for pneumonia. All 18 pts receiving ≥2 cycles had a repeat CT prior to their 2nd course. Conclusions: The results of this prospective trial support earlier retrospective findings that short-term follow-up using CT in pts with advanced NSCLC can detect tumor progression and impact patient management. We will also present f/u CTs in pts who received ≥ 1course to determine whether early signs of progression predict later RECIST determined progression.

[Table: see text]
Phase II trial of second-line erlotinib and digoxin in patients with non-small cell lung cancer (NSCLC)
Authors: Kayali F. , Janjua M. A. , Laber D. A. , Miller D. M. , Day J. M. , Kloecker G. H.
Published: August 2020

e19077

Background: There is laboratory evidence that digoxin sensitizes cancer cells to the induction of apoptosis by chemotherapy. Inhibition of the Na/K-ATPase enzyme by ouabain disturbs the intracellular ion composition of cancer cells, altering cellular homeostasis. This suggests that inhibition of the Na/K pump results in cellular sensitization of malignant, but not benign cells to induction of apoptosis. Epidemiologic studies also have shown beneficial effects of digitalis in breast cancer incidence. At ASCO 2007 our group presented a phase II study showing encouraging results by adding digoxin to bio-chemotherapy for melanoma. Erlotinib is one of the standard second-line treatments for NSCLC with a response rate (RR) of 10%. This study hypothesized, that adding digoxin to erlotinib may improve the RR and time to progression (TTP) in NSCLC. Methods: This was a phase II trial using daily 150 mg erlotinib and digoxin 0.25 mg. The digoxin dose was adjusted to keep levels between 1–2 ng/ml. Patients with progressive disease (PD) after chemotherapy were enrolled, if they had an ECOG 0–2 and good organ function. CT scans were done every 6 weeks. Treatment continued until PD or significant toxicity occurred. Results: Patient accrual lasted from 3/06–8/08 and was stopped early at time of interim analysis. Twenty eight patients were enrolled and 24, who completed at least 6 weeks of therapy, are presented here. All patients had unresectable stage III/IV at diagnosis. Median age was 61 (34–78), 14 were female, 17 had prior radiation (not involving the target lesions), 23 had one prior chemotherapy and 1 subject had two. Only one patient was a never smoker. Histologies were 50% adenocarcinoma, 30% squamous and 20% unspecified. One patient had a PR, 9 SD, and 14 PD. The median TTP was 61 days (9–366) and median survival 157 days (9–844). Side effects were similar to erlotinib single agent with no treatment related mortality. There were no unexpected or increased adverse events related to digoxin. Conclusions: Digoxin did not increase the response rate of erlotinib in the treatment of progressive NSCLC. TTP and survival seen in this study were similar to the published results with erlotinib alone. This combination does not warrant further clinical studies in NSCLC.

No significant financial relationships to disclose.
The efficacy of chemotherapy in the advanced NSCLC patients who failed with the treatment of EGFR-TKI
Authors: Zhou S. , Ren S. , Zhang L. , Sun H. , Zhou C.
Published: August 2020

e19078

Background: EGFR-TKI such as gefitinib and erlotinib were used as standard 2nd/3rd line therapy in previously treated NSCLC. However, those who benefit from EGFR-TKI will inevitably progress from the disease. We reported the efficacy of chemotherapy(CT) in the advanced NSCLC pts failed with the previously 2nd/3rd line treatment of EGFR-TKIs. Methods: Eligibility criteria included advanced NSCLC pts who got disease control(included CR, PR or SD) initially from TKI therapy and then progressed, PS = 0–2, and normal fatal organ function. Pts received systemic CT (docetaxal, pemetrexed, gemicitabine, novelbine or combined with platinum agent) until disease progression or unacceptable toxicity. Results: 32 pts were enrolled from Oct 15 2007 to Nov 30 2008. Demographics: M 56.3%/F 43.7%; median age 56 y [range 34–72]; stage IV 100%; PS 0/1/2: 3 (9.4%)/22(68.8%)/7(21.8%); adenocarcinoma/non-adenocarcinoma 29(90.6%)/3(9.4%); EGFR-TKI treatment duration >6 m 20(62.5%) /< 6 m 12(37.5%); monotherapy 16 (50%)/ doublets 16 (50%). All pts were evaluable for efficacy; partial response in 5 cases (15.6%), stable disease in 21 cases(37.5%), progressive disease in 15 (46.9%) ( Table ). The response of CT was not related with gender, age, regimens, but these with TKI treatment > 6 m achieved a significantly better response than those < 6 m(p=0.01) and these with PS 0–1 got a marginally significantly better response than PS 2(p=0.095). The toxicity was acceptable. Median progression free survival was 3.4 months and it was not correlated with the gender, age and regimens, but PFS were significant longer in the pts received > 6 m of TKI (median 4.8 vs 1.9, p=0.009) and with PS 0–1 (median 4.7 vs 1.9, p=0.002). Conclusions: Pts benefited from TKI therapy and developed progressive disease could also benefit from CT. The response duration of EGFR-TKI and performance status could be predictive for the better efficacy of CT.

[Table: see text]

No significant financial relationships to disclose.
ERCC1 expression and survival in small cell lung cancer
Authors: Hennemann M. , Sostruznik M. H. , Gaiger A. M. , Barrios C. H.
Published: August 2020

e19080

Background: The excision repair cross-complementation group 1 (ERCC1) protein expression has been suggested as both predictive or prognostic according to the administration or not of cisplatin-based chemotherapy in non-small cell lung cancer. It's role in small cell lung cancer (SCLC) is still uncertain. Methods: Forty four patients (pts) with diagnosis of SCLC were retrospectively analyzed. Paraffin blocks were reviewed to reconfirm a SCLC diagnosis and submitted to semi-quantitative immunohistochemical (ICH) method to detect the ERCC1 protein. The criteria for ERCC1 IHC evaluation was based on the percentage of cells with positive staining. Medical charts were reviewed and findings correlated to the IHC expression. All pts were treated with standard cisplatin-based chemotherapy and concomitant radiotherapy when appropriate according to stage. We report the correlation of ERCC1 expression with the overall survival of the population. Results: The group of pts had 59% (n=26) men with a median age of 60,8 years (±10). Staging revealed limited disease (LD) in 41% (n=18), extensive disease (ED) in 55% (n=24) and was not available from the chart review in 7% (n=3). The median survival time (MST) was 15.84 (±9.73) months (mo) in LD; 8.39 (±8.53) mo in ED. ERCC1 was positive in 50% (n=22) of the pts. From these, 54% (n=12) had ≥50% of the cells with positive staining. The overall median survival of this group was 10.8 (±8.6) mo. The 45% (n=10) of cases presenting with <50% of cells with positive staining had an overall survival of 13 (±10) mo. In the group with positive ERCC1 expression, 45%(n=10) had LD and median survival of 17.1 (±7.8) mo [≥50% staining (n=6): median survival 12.1 (±3.9) mo; <50% staining (n=4): median survival 24.4 (±6.1) mo]. The 11 pts with ERCC1 expression and ED had a median survival of 7.9 (±8.7) mo. [≥50% staining (n=6): median survival 9.4 (±12) mo; <50% staining (n=5): median survival 6.1 (±1.5) mo]. The group with no ERCC1 expression (n=22)] had an overall survival of 9.7 (±10.1) mo. Of these pts 7 had LD and a median survival of 14.03 (±12.4) mo, while 13 pts had ED and a median survival of 8.76 (±8.73) mo. Conclusions: In this group of SCLC pts ERCC1 expression by IHC does not seem to correlate with survival.

No significant financial relationships to disclose.
Activity and tolerability of cisplatin (CDDP) and fotemustine (FTM) in non-small cell lung cancer (NSCLC) patients (PTS) with brain metastases (BM): A multicentric phase II study of the Gruppo Oncologico dell’Italia Meridionale (GOIM)
Authors: Galetta D. , Gebbia V. , Ferraù F. , Carrozza F. , Cigolari S. , Russo P. , Calista F. , Adamo V. , Colucci G.
Published: August 2020

e19085

Background: More than 50% of BM occurs in advanced NSCLC. In most cases BM are multiple and their standard therapy is whole-brain radiation therapy (WBRT) since the role of systemic therapies for is still a matter for investigation due to concerns on the drugs ability cross the blood brain barrier (BBB). FTM is a nitrosourea able to cross BBB and CDDP remains the backbone for medical treatment of NSCLC. Methods: Pts with advanced NSCLC, ECOG PS 0–1 and multiple BM were treated with 2 cycles of FTM 80 mg/m2 d1,8 and CDDP 80 mg/m2 d1 q3 wks followed by WBRT 30 Gy/3 Gy daily; radiological response using Recist Criteria were analysed before WBRT to assess the role of FTM/CDDP both for cranial and extracranial disease. Pts with disease control (DC) received further CT up to 6 cycles. Barthel ADL Index was administered every 2 cycles. The trial has a two step design according to Simon: 29 pts were required to verify if FTM/CDDP was able to achieve a >25% response rate both for cranial and extracranial disease (step 1), and if this was true further pts had to be enrolled up to 81 pts (step 2). Results: At first evaluation 4/29 pts were excluded from the study (2 not treated/ 1 never included/1 not eligible). Therefore patient's demographics were: median age 61 (range 48–73), M/F 16/9, adeno 11, squamous 5, large cell 2, nos 7; PS 0/1: 1/14, Barthel Index median value at the starting point 20 (13–20). Overall 3/25 (12%) partial responses were observed with 9 (36%) stable diseases and 13 (52%) progressions of disease. These data did not satisfy the pre-planned hypothesis and the study was stopped at the first step. Before WBRT after the first 2 CT cycles 13/25 pts (48%) had a systemic DC in contrast with 15/25 pts (60%) with brain tumour DC. WBRT seemed not useful to further modify the results of CT. CT was relatively well tolerated with asthenia as the most relevant specific toxicity while the hematological toxicity was mild. Conclusions: CDDP and FTM combined with WBRT could represent a therapeutic option for patients with NSCLC even if the global therapeutic index was not satisfactory. Further studies evaluating the combination of systemic treatments with WBRT are warranted.

No significant financial relationships to disclose.
First-line treatment of EGFR mutation-positive non-small cell lung cancer (NSCLC) by gefitinib
Authors: Moiseyenko V. , Procenko S. A. , Levchenko E. V. , Barchuk A. S. , Matsko D. E. , Moiseyenko F. V. , Ivantsov A. O. , Iyevleva A. G. , Mitiushkina N. V. , Imyanitov E. N.
Published: August 2020

e19088

Background: Gefitinib shows outstandingly high rates of clinical benefit in NSCLC pts with EGFR mutation and is better tolerable than conventional chemotherapy, therefore its consideration for the upfront treatment is warranted. Methods: 21 chemonaive pts with inoperable NSCLC were selected based on the presence of EGFR mutation in the tumor DNA (16 exon 19 deletions and 5 T858G substitutions). All cases were adenocarcinomas; median age: 60 years (range: 36 - 81 years); males/females: 6/15; ECOG PS 0/1/2/3: 4/10/6/1. Gefitinib was administered at conventional dose 250 mg/d. Results: The overall disease control rate was 95% (CR: 2/21; PR: 11/21; SD: 7/21). Complete responses were observed only in tumors with exon 19 deletion, whereas the only patient with disease progression had codon 858 substitution. Grade III toxicity occurred only in 3 pts (2: skin rash; 1: diarrhea). Time to disease progression ranged from 2+ to 18 months. 3 pts achieved an operable status of the disease upon the treatment, and therefore were subjected to surgical intervention followed by adjuvant gefitinib therapy. Conclusions: Gefitinib may be considered as the treatment of choice for chemonaive EGFR mutation-containing inoperable NSCLC.

No significant financial relationships to disclose.