bluuebunny/crossref_metadata_2025 huggingface dataset:
Dose increases in patients with chronic myeloid leukemia (CML) treated with imatinib mesylate (IM): Estimated using administrative claims data in a US managed care population
Authors: Davis C. C. , Hines P. , Devercelli G. , Ray S. , Cheng S. , Cortes J. E.
Published: March 2020

16014

Background: Dose increase is often the first step when resistance is encountered in CML patients treated with IM. The primary objective of this study is to determine the proportion of CML patients who experienced a dose increase from their starting dose within one year after initiation of IM therapy. Methods: Patients ≥18 years of age diagnosed with CML (ICD-9-CM code = 205.1) between 2001 and 2003 and treated with IM were identified in the Pharmetrics Integrated Claims Database which covers a US managed care population. Eligible patients had at least two claims for IM and were continuously enrolled for at least six months following their first IM prescription. Follow-up was one year after their first IM prescription. Results: A total of 113 CML patients using IM were identified. Eighty-four percent of these patients started IM at 400 mg/day; eight percent started at doses ≥ 600 mg/day; remaining started at doses < 400 mg/day The mean daily dose of IM used by the study group was 419 mg (SD = 91). Nineteen percent of users required at least one dose increase from their starting dose within one year. The first dose increase was most frequently 200 mg/day (mean daily dose = 574 mg (SD = 199). The median maximum daily dose reached by patients experiencing dose increases was 600 mg/day (25th– 75th percentile: 500, 750 mg). The median ending dose in these patients was 600 mg/day (25th–75th percentile: 400, 600 mg). Median time to first dose increase was 5.8 (25th–75th percentile: 2.0, 7.4 months). Median time to maximum dose from initial IM dose was 6.5 (25th–75th percentile: 2.7, 7.4 months). Conclusions: Nearly 20% of all IM-treated CML patients required a dose increase of approximately 200 mg/day within one year. Of those dose increases, 50% occurred within the first 6 months.

No significant financial relationships to disclose.
End-of-life care resource utilization: A single provider perspective
Authors: Stewart J. A. , Runde D. , Rovick K. , Cleary J. , Grossman J.
Published: March 2020

16022

Background: Most cancer physicians are aware that significant resources are spent in the last year of life but they are provided little feedback on cost or yield of care. Awareness of resource allocation for patients near the end of life may influence physician conversation with patients and families, treatment recommendations, and hospice referral. Methods: UWHealth cancer registry data were used to identify 90 patients who had died in a recent three year period and were cared for at least in part by the medical oncologist being evaluated. Health services utilization within UWHealth (hospital and hospital based clinic sites) was assessed for the last 6 months of life in 66 patients where a clear date of death could be identified. Data included in- and out-patient, pharmacy, laboratory, radiation and imaging services. Hospice charges are not included. Results: In the last 6 months of life, radiology, radiation therapy and pharmacy charges made up 52% of the total. Use of CT, MRI and palliative radiation increased near the end of life. In the last two months of life, 47% of the entire pharmacy charges were spent. In-patient services were greatly increased in the last month of life. Overall charges and more expensive services were highest in the last month of life. Conclusions: Care near the end of life is expensive. This review targeting patients affiliated with one medical oncologist at a large academic health center showed that radiology, radiotherapy, and pharmacy charges involved more than half the total accrued in the last 6 months of life. Feedback such as this if routinely provided to individual oncologists and disease oriented teams may generate strategies for improving end of life care. Even if expensive, some services may be helpful and necessary, others may not. Discussion regarding accountability for resource allocation within the multidisciplinary setting of cancer care may aid in developing improved end of life approaches for patients.

No significant financial relationships to disclose.
Improving quality of care: Challenges to implementing quality indicators
Authors: Owen J. B. , Wilson J. F.
Published: March 2020

16030

Background: To assess the overall quality of cancer care, efforts seek consensus quality indicators that crosscut health services. Although pilot programs have collected and analyzed relevant clinical data, they have been unable to collect radiation oncology (RO) data detailed enough to assess the quality of services or to inform key decision makers. Quality Research in Radiation Oncology (QRRO) conducted retrospective surveys of national practice since 1973 with major positive impact on the quality of practice through recursive processes. Methods: From Donabedian’s model of quality assessment, QRRO analyzes crucial quality components by conducting Facilities, Process, and Outcomes Surveys. Survey design allows calculation of national averages for patients treated with RO and comparisons by key factors. Evolving data collection methods allow assessment of modern technologies. Methods start with definition and measurement of evidence-based quality indicators but allow greater detail and specification than most other quality measurement efforts. Results: QRRO showed that radiation dose affected outcomes for prostate cancer patients. Higher radiation doses were associated with improved local tumor control rates and treatment techniques affected toxicity rates. These results, presented widely in numerous venues, stimulated dose escalation clinical trials. Trials conducted in the USA all used QRRO results as critical data, providing the major impetus to test new directions in dose escalation and new methods to target delivery more precisely. National practice shifted to higher doses and use of conformal techniques. The dataset is unique in providing cross-sectional information on practice patterns with a wide variety of treatment approaches from many institutions and sufficient details of treatment delivery to allow examination of questions about quality and effects of techniques. Conclusions: Mounting societal demands for improvement in the quality of care, ever increasing complexity of radiation therapy, and escalating use of multi-modality treatment make continuing to measure, report, and improve quality of care in RO crucial to patients and the profession. Methods must keep pace with new technologies and techniques in radiation therapy. [Supported by NCI grant CA 65435].

No significant financial relationships to disclose.
Atypical variant of hypereosinophilic syndrome responsive to imatinib mesylate: A case report
Authors: Kuruvilla J. N.
Published: March 2020

16530

Background: Idiopathic hypereosinophilic syndrome (HES) was first described by Chusid et al in 1975. The diagnosis of HES rests on three features: A persistent eosinophil count of greater than >1500 cells/μL for more than 6 months, no other etiologies for eosinophilia, and symptoms of organ involvement. The requirement of end organ damage differentiates HES from benign eosinophilia, in which there is no organ damage, in spite of years of eosinophilia. Methods: We present a case of a 28-year-old African American male, admitted for shortness of breath and leg swelling. Past medical history was significant only for asthma. Results: Laboratory investigation demonstrated an average white blood cell count of 15,900 U/L and eosinophilia of 29.6% over a 6-month period. Stool studies for ova and parasite, Rheumatoid factor, antinuclear antibody, pANCA, cANCA and complements were within normal limits. Thyroid stimulating hormone, liver function studies, and erythrocyte sedimentation rate were within normal limits. IgE level was 158 (mildly high). Peripheral smear showed only mature eosinophils. A bone marrow biopsy showed a hypercellular marrow consistent with an atypical variant of HES. Cytogenetic studies did not reveal any clonal abnormalities. Trans-esophageal echocardiogram showed severe mitral regurgitation. During the hospital course the patient had a mitral valve replacement with a St. Jude’s mechanical valve and mitral valve pathology showed post inflammatory changes and ventricular myocardial biopsy staining for eosinophilic major basic protein confirmed eosinophilic changes. The patient remained refractory to aggressive steroid therapy, and was started on imatinib mesylate, which lead to a complete remission. Conclusions: HES is a very rare and often fatal condition. A 1989 French study showed a 5-year survival of 80%, and a 15-year survival of 42%. HES has three known variants: The atypical myeloproliferative variant of HES is often refractory to glucocorticosteroid therapy, but responds to treatment with the tyrosine kinase inhibitor, imatinib mesylate.

No significant financial relationships to disclose.
A phase II study of the safety and efficacy of the MDR inhibitor VX-710 combined with doxorubicin and vincristine in small cell lung cancer
Authors: Gandhi L. , Harding M. , Neubauer M. , Langer C. J. , Crawford J. , Moore M. , Rooney J. , Ross H. , Einhorn L. H. , Johnson B. E. , Lynch T. J.
Published: March 2020

17001

Background: Tumors with multidrug resistance (MDR) frequently show upregulation of efflux proteins MDR protein (MRP-1) and P-glycoprotein (Pgp). MDR represents a major obstacle to successful chemotherapy treatment and can be reversed in Pgp or MRP1-expressing cells by the MDR inhibitor VX-710. A phase II study was designed to evaluate the safety/tolerability and efficacy of VX-710 combined with doxorubicin (D) and vincristine (V) in patients (pts) with relapsed SCLC. Methods: Eligible pts had progressive, measurable disease and a PS <2 after response to 1st-line chemotherapy. Stage I safety evaluation was done with planned expansion to a second stage if 9 responses were confirmed in the first 35 pts. Pts were treated with VX-710 (120 mg/m2/h) for 72 hours with D (45 mg/m2) and V (1.4 mg/m2) given 4 hours after the start of VX-710. Pts were treated q 21 days until progression or intolerable adverse events (AEs). Severe neutropenia was noted in the first 15 pts, so the protocol was amended to include prophylactic G-CSF or ciprofloxacin. Interim analysis was performed after 36 pts were treated. Results: 36 pts were enrolled from 12/98 to 12/00. Neutropenia was the major toxicity, occurring in 25/36 (69%) pts. This was more severe (30% vs. 20% grade 4) and occurred earlier (58% vs. 38% in cycle 1) among the 15 pts enrolled prior to an amendment requiring neutropenia prophylaxis vs. those enrolled afterward. Other common treatment-related AE’s: asthenia (53%), nausea (50%), constipation (44%), alopecia (42%), dyspnea (42%), anemia (42%). 67% were grade 1 or 2 in severity. Four pts died on study or within 30 days of termination: 2 from infections likely related to therapy and 2 from disease progression. Among 32 evaluable pts, 7 (22%) had partial responses; 6 of these sustained responses through 6 cycles (with one response lasting 3 years). Three additional pts had unconfirmed responses. Median survival was 6 months (95% CI 4–7 months). Conclusions: The addition of VX-710 to D and V therapy did not improve anti-tumor activity or survival. Hematologic toxicity was severe, causing 2 pt deaths from neutopenic fever. Although there were some durable responses, response criteria were not met to proceed with stage 2. Further development with VX-710 has since stopped.

[Table: see text]
Phase II trial of oxaliplatin and gemcitabine with bevacizumab in first-line advanced non-small cell lung cancer (NSCLC)
Authors: Davila E. , Lilenbaum R. , Raez L. , Seigel L. , Tseng J. , Graham P.
Published: March 2020

17009

Background: Oxaliplatin-Gemcitabine (GemOx) is an active and well tolerated. Bevacizumab (BV) prolongs survival when combined with carboplatin-paclitaxel. This phase II trial evaluates the efficacy of GemOx + BV as 1st line therapy for advanced NSCLC patients. Methods: Pts with stage IIIB (effusion) and IV non-squamous NSCLC, ECOG PS 0 or 1, no CNS metastasis, and no other contraindications to BV, are eligible. Prior therapy for earlier-stage disease allowed if completed at least 12 months before enrollment. Treatment consists of Gem 1000 mg/m2 on d1 and 8, Ox 130 mg/m2 on d1, and BV 15 mg/kg on d1, repeated every 3 wks for a total 4 cycles. Pts who respond or have stable disease receive BV maintenance until progression. Main endpoints are response rate (RR), grade (Gr) 3–4 toxicities, time to progression (TTP), and overall survival (OS). Results: As of 12/05, 26 out of 50 projected pts have been enrolled from 4 institutions. M/F 17/9; median age 65y (45,81); IIIB/IV 3/23; PS 0/1 8/18. Median F/U time is 3.7 months. 24 pts are evaluable for toxicity: 1Gr3 ANC; 1Gr3 and 4 PLT; no FN.3 Gr3 diarrhea and 2 Gr3 N/V; 1Gr3 and 4 hypophosphatemia; 1 pt had ischemic bowel after the 1st cycle, recovered fully and was removed from study; 1 pt died of liver failure in the 1st cycle. No bleeding complications have occurred. 22 pts are evaluable for RR (ITT): 7 PR (31%); 8 SD (36%). TTP and OS data not yet available. Conclusions: This is the first report of GemOx in combination with BV in advanced NSCLC. This regimen has minimal hematologic toxicity but selected non-hematologic toxicities are noted. Activity appears promising and merits further investigation. Accrual is ongoing.

[Table: see text]
Phase II study of docetaxel and carboplatin in elderly patients with advanced non-small cell lung cancer
Authors: Yoshimura N. , Kudoh S. , Kimura T. , Mitsuoka S. , Hirata K.
Published: March 2020

17013

Background: Single-agent chemotherapy has been considered as standard treatment for elderly patients with non-small cell lung cancer (NSCLC). However recent subset analyses suggest that platinum-based combination chemotherapy may be safely administered to the elderly with good performance status (PS). We evaluated the efficacy and safety of carboplatin and docetaxel in a phase II study of elderly patients aged 70 years or older. Methods: Chemotherapy-naive patients aged ≥70 years with advanced NSCLC (IIIB-IV), ECOG performance status (PS) of 0 or 1, a measurable lesion, and adequate organ functions were enrolled. Patients received carboplatin (AUC 5) and docetaxel (60 mg/m2) administered on day 1 every 3 weeks. The primary endpoint was response rate (RR). This study, with a planned sample size of 25, had 80% power to support the hypothesis that the true RR was >30%, and 5% significance to deny the hypothesis that the true RR was <10%. Results: Between October 2003 and September 2005, 26 elderly patients with NSCLC were enrolled in the study and all patients were treated. Demographics: M/F 17/9; PS 0/1 2/24; median age 75 (range 70–84). Median number of treatment cycles was 4. Responses in the 26 evaluable patients included 1CR; 12PR; 7SD; for an objective RR of 50% (95% CI 31–69%) and a disease control rate of 77%. Median survival period and 1-year survival rate have not yet been reached. Grade 3/4 hematologic toxicities included leukopenia (82%), neutropenia (86%), thrombocytopenia (5%) and anemia (5%). Non-hematologic toxicities were mild with no grade 4 toxicities; grade 3 nausea (9%), anorexia (23%), diarrhea (14%), fatigue (9%), allergic reaction (9%) and infection (18%) were observed. Conclusions: The combination of carboplatin and docetaxel was safe and promising for the treatment of chemotherapy-naive elderly patients with advanced NSCLC. This regimen warrants further evaluation in a phase III trial.

No significant financial relationships to disclose.
Role of chemotherapy (CT) in performance status 3 and 4 small cell lung cancer (SCLC) patients
Authors: Cronenberger E. , Rodrigues A. , Small I. , De Biase P. , Zamboni M. , Zukin M. , Ferreira C.
Published: March 2020

17026

Background: SCLC is an aggressive malignancy, but has shown high response rate to CT. Performance status (PS) has been recognized as one of the main prognostic factors in SCLC. Sudden and toxic deaths after CT were found to correlate with poor PS. There are few data about risk-benefit ratio of CT in PS 3 and 4 patients, although it has been often used. This study was performed to assess the clinical and laboratorial factors and the outcome of poor PS SCLC patients that received CT in our institution. Methods: A retrospective review was performed at INCA’s tumor registry for SCLC cases diagnosed between January 2001 and December 2004. Patients with pre-treatment ECOG PS 3 and 4 that received CT were selected for analysis. Results: Thirty of 107 SCLC patients (28%) were eligible (73.3% PS 3/ 26.7% PS 4). The median patient age was 64 years and 73.3% were male. Extensive- disease was observed in 83% of these patients. At the first cycle, 21 patients (70%) had to be hospitalized to receive CT and 5 of them (24%) required respiratory support. There were 10 deaths (33.3%) after the first cycle of CT. The median response rate was 77.8% and median overall survival was 2.8 months (138 days for PS 3 and 5 days for PS 4). In this series, there was a statistically significant correlation of PS 4, high serum LDH, hospitalization to start treatment and respiratory support with worse survival. Conclusions: Despite good response rate, poor PS patients, especially PS 4, had high risk of early CT related mortality and had dismal survival. Further studies are required to determine how to best treat these high-risk patients, in particular PS 4 patients, to minimize the early treatment related mortality and to give them the best form of palliation and prolongation of life.

No significant financial relationships to disclose.
The significance of SUV of 18-FDG PET for the diagnosis and treatment of lung cancer
Authors: Guo H. , Hu X. , Li Z.
Published: March 2020

17032

Background: To explore the possibility that the standardized uptake value(SUV) of positron emission tomography(PET) could be a prognostic factor for lung cancer and whether it holds more significance than clinical stage,the current predominant prognostic factor for NSCLC patients. To assess the possible connection between the SUV and clinical and histopathologic characteristics of lung cancer patients(especially the histology), in order to build a comprehensive picture for the potential application of SUV. Methods: Eighty-two patients taking PET examination before receiving any treatment were analysed, the majority of which(fifty) consisted of patients treated with multiple modality treatment where surgery played a central role. 1-year and 3-year survival(OS) Rate, Progress Free Survival(PFS) Rate were calculated by Kaplan-Meier method and evaluated with the log-rank test.The prognostic significance was assessed by univariate and multivariate analyses.Nonparametric tests were performed to determine whether there was valuable difference amid each SUV group classified by certain clinical or histopathologic characteristic. Results: A SUV cutoff of 5.0 for the primary tumor showed the greatest discriminative value for overall survival.As for the PFS,the cufoff is 4.0. The SUV for the primary tumor was a significant predictor for both overall survival and PFS, based on the result that the relative risk was 7.075 and 2.719 respectively. As a result of multivariate analyse,the prognostic value of SUV and Clinical Staging was independent of each other, and the value of the SUV was considerably higher than the latter. The SUV for the small-cell lung cancer group was statistically higher than the non-small-cell lung cancer group. And there was significant overall discrepancy across the groups sorted by the degree of differentiation. Conclusions: The SUV of the primary tumor has the potential to be the leading prognostic factor for patients treated by multiple modality treatment, leading to substantially improved management for lung cancer patients. And there could be close connection between SUV and histopathologic or differentiation feature of lung cancer tissue, although it is still open to discussion. Analysis for larger number of cases could settle the issue.

No significant financial relationships to disclose.
Infusional topotecan with concurrent radiation followed by consolidation etoposide platinum and docetaxel for patients with high risk unresectable stage III non-small cell lung cancer (NSCLC)
Authors: Seung S. , Fisher B. K. , Ross H. J.
Published: March 2020

17042

Background: Good PS patients (pts) with locally advanced NSCLC treated with concurrent chemoradiotherapy have a 20–40% 3 year survival. Treatment is arduous and poor PS or high risk pts often cannot complete a full course of treatment. The optimal combination of chemotherapy and radiation and the role of consolidation chemotherapy are unknown. Despite response rates exceeding 50%, most pts eventually progress with brain as the first site of relapse in up to 30%. Continuous infusion chemotherapy is better tolerated than intermittent chemotherapy combined with radiation and may improve outcome in other locally advanced aerodigestive malignancies, however it has not been studied extensively in NSCLC. Topotecan is active in NSCLC, can safely be combined with radiation, can be given by continuous infusion and penetrates the CNS making it an attractive study agent in locally advanced NSCLC. Methods: In this pilot study, 20 pts were treated with infusional topotecan 0.4 mg/m2/d with 3D conformal radiation to 63 Gy both delivered M-F for 7 weeks. Pts without progressive disease underwent consolidation chemotherapy with etoposide and platinum for one cycle to take advantage of upregulation of topoisomerase II by topotecan. Two cycles of docetaxel consolidation followed. Study endpoints include response, time to progression, survival, toxicity and development of CNS metastases. Results: All pts have completed induction chemoradiotherapy. 12/20 have completed consolidation. 17/20 pts had a PR and 1/20 SD after induction chemoradiation. 1 pt developed CNS metastases 228 days after study entry and is alive with disease at 541 days. 3 pts had pulmonary emboli. Therapy has been well tolerated with 1/20 grade 4 lymphopenia. Grade 3 hematologic toxicity was seen in 17/20 pts. Other grade 3 toxicities include esophagitis (3/20), esophageal stricture (2/20), pneumonitis (6/20), fatigue (6/20), weight loss (1/20). Conclusion: Continuous infusion topotecan with radiation is well tolerated and shows evidence of activity in the management of poor risk patients with unresectable stage III NSCLC. Survival data will be presented at the meeting.

No significant financial relationships to disclose.
Elderly advanced non-small-cell lung cancer (NSCLC) patients (p) treated with vinorelbine (vrb) plus gemcitabine (gem): Molecular correlates
Authors: Maestu I. , Isla D. , Diz P. , Muñoz J. , Oramas S. , García R. , Provencio M. , Jaen A. , Taron M. , Rosell R.
Published: March 2020

17043

Background: The clinical benefit of non-cisplatin doublets (vrb/gem) vs a single agent (vrb or gem) in elderly p is still controversial. The present study focuses on clinical outcome with vrb/gem in the elderly and the role of functional status. Genetic predictive markers of response to vrb/gem will also be examined in genomic and cDNA from tumor and circulating tumor DNA. Methods: NSCLC p with stage IIIB (pleural effusion or supraclavicular lymph nodes)-IV or recurrent disease and age ≥ 70 years were treated with vrb (25 mg/m2 iv or 60–80 mg/m2 oral) plus gem 1200 mg/m2, days 1,8 every 21 days. Activities of daily living (ADL), instrumental activities of dalily living (IADL) and comorbidities were evaluated. Primary tumor and baseline serum DNA were collected for assessment of microtubule associated protein 4 (MAP4) in tumor and checkpoint with forkhead-associated and ring finger (CHFR) methylation in serum. A preliminary analysis of response and toxicity was performed on 51 p. Results: From April 2004 to December 2005, 145 p were included. Data on 68 p is available: median age 74.5 years (70–83); stage IIIB: 21.2%, IV: 78.7%; PS 0: 23.4%, 1: 54.6%, 2: 21.8%. Self-sufficiency in ADL and IADL was 56.2% and 25% of the p analyzed. All p but 8 had comorbidities. Response rate for 51 p: partial response, 12% (95% CI, 8.9–20%); stable disease, 32% (95% CI, 19.2–44.8%). Main hematological toxicities: grade 3/4 neutropenia, 8.3/4.1%; grade 3 thrombocytopenia, 4.1%; grade 3 anemia, 4.1% of the p respectively. Conclusions: Preliminary findings indicate that vrb/gem is feasible in elderly p with acceptable toxicity. Complete data on response, survival and genetic markers will be presented.

No significant financial relationships to disclose.
Objective improvement in lung cancer patient care by the development of a multidisciplinary clinic (MDC) in the community
Authors: Mayfield W. , Bordoni R. , Holder R. , Waldman M. , Muster A. , McLaughlin M. , Hermann R.
Published: March 2020

17086

Background: Medical resources allocated to lung cancer management are limited, scattered and uncoordinated, resulting in sub-optimal care. The MDC offers patients access to multi-disciplinary care (Pulmonary Medicine, Thoracic Surgery, Medical and Radiation Oncology) to operate in an efficient, cost effective way. Methods: 2004 Cancer Registry data on time to treatment (TTT) for lung cancer was 53 days. A project with the primary endpoint of reducing the TTT from 53 to 30 days was designed. Secondary endpoints were improvement in treatment planning; enhancement in clinical trials referral, and patient satisfaction. On 9/15/05 the MDC open its doors. The project was assigned to this clinic including patients with solitary lung nodules, lung, esophageal, and mediastinal cancers, mesothelioma, and other thoracic malignancies. Results: 54 pts were seen in the first 90 days; median age 60 (range 41–82), 29 males; 32 (59%) lung cancer (94% NSCLC), 8 (15%) esophageal cancer, 6 other diagnosis, and 6 abnormal radiological findings without diagnosis. The TTT of 30 evaluable patients is 26.36 days. Of the 30 NSCLC the TNM stage was: 4 IA, 5 IB, 2 each IIA/IIB, 8 (27%) IIIA, 3 (10%) IIIB, and 6 (20%) IV. Fifteen of the cases had pathologic staging. Out of 9 pts with cstage I, 7 (78%) had definitive surgery; 4 pts confirmed to have pstage IB, were evaluated for adjuvant chemo. Four pts with cstage II had surgery, 2 of them adjuvant chemo. Of the 11 pts with cstage III, 5 (46%) received concurrent CHRT, 1 (stage IIIA) underwent surgery f/b chemo, 2 received chemo alone and 2 refused therapy. Out of 6 pts with stage IV, 5 (83%) received systemic therapy. Conclusions: The TTT of 26.36 days represents a 50.26% improvement from our institutional benchmark of 53 days. Updated and expanded data on our project primary and secondary endpoints will be presented at the meeting.

No significant financial relationships to disclose.
Phase II trial of imatinib maintenance therapy after irinotecan and cisplatin in patients with c-kit positive extensive-stage small cell lung cancer (ES SCLC)
Authors: Schneider B. J. , Gadgeel S. , Ramnath N. , Worden F. P. , Wozniak A. , Ruckdeschel J. , Kalemkerian G. P.
Published: March 2020

17089

Background: The prognosis for patients (pts) with ES SCLC is poor, with a median survival of 9 mo. This trial was designed to evaluate the efficacy and toxicity of cisplatin plus irinotecan followed by maintenance imatinib (Gleevec) in pts with c-kit positive ES SCLC. Methods: Immunohistochemistry for c-kit was performed on paraffin-embedded tissue prior to enrollment. Treatment consisted of irinotecan 65 mg/m2 IV on days 1 and 8 plus cisplatin 60 mg/m2 IV on day 1 repeated every 21 days for 4 cycles. If no evidence of disease progression was identified, Gleevec was given at 400 mg orally BID until disease progression or unacceptable toxicity. Results: 14 pts have been enrolled: median age 61 yrs (range 47–73); 9 men: 5 women; PS 0/1/2 = 3/10/1. 6 pts did not begin Gleevec due to disease progression (4), persistent grade 3 emesis (1), and referral for radiation therapy (1). 8 pts had a PR with cisplatin/irinotecan and received Gleevec. Median number of wks on Gleevec was 6.1 (range 4.6–25.1). Reasons for discontinuation of Gleevec were disease progression (7) and persistent neutropenia (1). Median progression-free survival was 4.7 mo. (range 0.7–16.3) for all pts and 5.5 mo. (range 4.7–16.3) for pts receiving Gleevec. There were no objective responses to Gleevec, but 3 pts (21%) had stable disease for 12, 15 and 25 wks. Median survival was 8.1 mo. (range 3.7–19.6) for all pts and 10.0 mo. (range 7.1–19.6) for those receiving Gleevec. Myelosuppression was mild (grade 1–2 ANC 13%, anemia 76%, platelets 13%) with one pt with grade 3 neutropenia. Non-heme toxicity included grade 1–2 nausea 76%, diarrhea 51% and peripheral edema 75%. Conclusions: Gleevec did not appear to maintain disease stability after response to chemotherapy in the majority of pts despite c-kit tumor positivity. Although disease stability with Gleevec was noted in 3 pts (12–25 wks) and therapy was well tolerated, this approach does not appear to warrant further clinical study. Supported by Novartis Pharmaceuticals.

No significant financial relationships to disclose.
A phase II trial of paclitaxel plus carboplatin in patients with non-small cell lung cancer previously treated with chemotherapy
Authors: Yoh K. , Kubota K. , Kakinuma R. , Ohmatsu H. , Goto K. , Niho S. , Nishiwaki Y. , Saijo N.
Published: March 2020

17103

Background: The purpose of this phase II trial was to evaluate the efficacy and toxicity of paclitaxel plus carboplatin in the treatment of advanced non-small cell lung cancer (NSCLC) previously treated with chemotherapy. Methods: Eligible patients were aged 20 to 75 years with a performance status (PS) 0 to 1, previous treatment with one or two prior chemotherapy regimen for advanced NSCLC, and adequate organ function. Paclitaxel 200 mg/m2 was infused over 3 hours, before carboplatin (area under the curve 6; Calvert formula) infused over 1 hour, once every 3 weeks for six cycles maximum. The primary endpoint of this study was response rate. Simon’s two-stage design was used to determine the sample size and the planned accrual was 30 patients. Results: Thirty patients were enrolled. Complete response was observed in one patient and partial response in eleven patients for an overall response rate of 40% (95% confidence interval: 23–59%). The median time to progression was 5 months. The median survival was 9.9 months (range, 2.5–33.8 months), and the 1-year survival rate was 46%. The hematologic toxicities were 7% for grade 4 neutropenia, 3% for grade 3 febrile neutropenia, 17% for grade 3 and 4 anemia, and 7% for grade 3 thrombocytopenia. Grade 3 non-hematologic toxicities included rash (7%), myalgia/arthralgia (3%), arrhythmia (3%), and infection (3%). There were no toxic deaths. Conclusions: The combination of paclitaxel plus carboplatin is an active and well-tolerated regimen in the treatment of patients with NSCLC previously treated with chemotherapy who have a good PS.

No significant financial relationships to disclose.
Artificial intelligence, complex system analysis and simulation modeling in recognition of N1–2 lymph node metastases of non-small cell lung cancer
Authors: Kshivets O.
Published: March 2020

17123

Background: Precise recognition of N1–2 lymph node metastases (RLN) of non-small cell lung cancer (LC) means great importance in prediction LC patients (LCP) survival after surgery. We examined the immunologic factors associated with LCP with N0 and N1–2. Methods: In trial (1987–2005) the data of consecutive 289 LCP after complete pneumonectomies/lobectomies and mediastinal lymph node dissection (age = 58.1 ± 0.5 years; tumor size = 4.4 ± 0.1 cm; m = 260, f = 29) with pathologic stage I-III (T1–4N0–2M0) (squamous = 169, adenocarcinoma = 102, large cell = 18; G1 = 67, G2 = 110, G3 = 112; T1 = 100, T2 = 114, T3 = 54, T4 = 21; N0 = 147, N1 = 70, N2 = 72; pneumonectomies = 135, bi/lobectomies = 154) was reviewed. Variables selected for ED study were input levels of 64 immunity blood parameters, sex, age. Representativeness of samplings was reached by means of randomisation based on unrepeated random selection. Logistic regression, clustering, discriminant analysis, neural networks computing, structural equation modeling, Monte Carlo and bootstrap simulation were used to determine any significant regularity. Results: Logistic regression modeling displayed that RLN of LC significantly depended on: CDw26, CD16, phagocytic number, ratio of lymphocytes, T-lymphocytes, CD4+2H to LC cells (P = 0.003–0.043). Neural networks computing, genetic algorithm selection and bootstrap simulation revealed relationships between N1–2 and blood IgM (rank = 1), eosinophils (2), T-lymphocytes (3), CD8 (4), phagocytic number (5), CD8+VV (6), CDw26 (7), B-lymphocytes (8), IS2 (9), CD4 (10), CD4+2H (11), NST-A2 (12), monocytes (13), index of thymus function (14), IgA (15). Conclusions: Correct RLN of LC was 79.2% by logistic regression (odds ratio = 15.65), 82.0% by discriminant analysis and 99.6% by neural networks computing (area under ROC curve = 0.99; error = 0.059).

No significant financial relationships to disclose.
Efficacy of erlotinib in the treatment of patients with brain metastasis from non small cell lung cancer
Authors: Abigerges D. , Khater R. , Mokadem W. , Chammas S.
Published: March 2020

17149

Background: Erlotinib has shown good activity in lung cancer.Brain metastases remain a major problem in lung cancer treatment because of the blood brain barrier.We report three cases of adenocarcinoma of the lung metastatic to the brain treated with erlotinib100 mg daily. Methods: Two males (age 54 and 57 years) and one female (age 50 years). The two male patients received combination chemotherapy for stage IV disease (carboplatine, gemcitabine, docetaxel) and recurred after initial response. Both have been irradiated to brain with relapse. The female patient received adjuvant chemotherapy (carboplatine and gemcitabine) and adjuvant radiation to the mediastinum and presented one month after the end of radiation with right upper limb paralysis and clonic crisis. Results: The three patients presented very rapid response to erlotinib, with almost disappearance of neurological signs within the first two weeks. MRI of the brain showed partial response after 15 days in two patients and after one month in the third. The female patient is still responding and well doing after four months on erlotinib without radiation nor corticosteroids or antiepileptics, the later treatments being refused by the patient. One male patient died from pulmonary embolism 40 days after the initiation of erlotinib while he was still presenting tumor response. The other two patients are still alive with partial response and no neurological symptoms, four months after the initiation of erlotinib. Conclusions: We believe that erlotinib deserves further evaluation in non small cell lung cancer metastatic to the brain. The very quick response to treatment can select responders very early because of the cost of the drug.

No significant financial relationships to disclose.
Primary pulmonary adenocarcinoma in a 13-year-old girl with absence of EGFR gene mutation
Authors: Lim Y. , Ghim T. T. , Park B. , Park H. , Lee J. , Hah J. , Jung E.
Published: March 2020

17150

Non-small cell carcinoma of lung frequently associated with cigarette smoking is extremely rare in children. We, here, describe a 13-year-old female diagnosed with stage IV pulmonary adenocarcinoma. She had never started smoking. Yet, she had environmental tobacco smoking exposure in the household as her father had been a long-time heavy smoker. The patient presented with 6-month history of chronic recurring cough. A CT of chest showed a mass obstructing the left upper lung bronchus with a collapse of the lung in the left upper segment. A bronchoscopic biopsy revealed a poorly differentiated adenocarcinoma. There were bilateral pleural and pericardial effusions along with multiple nodular lesions in the brain, liver and bones suggesting of wide dissemination of the lung cancer. In her past, there was no history of radiation exposure or immune deficiency. She had never had any other childhood cancer treated previously. Interestingly, there was no evidence of EGFR gene mutation in the genomic DNA analysis of the tumor specimen. In the hospital, she was treated with palliative chemotherapy initially starting with gefitinib and later with regimen of navelbine, gemcitabine and cisplatin combination with no response. A palliative radiation therapy to mediastinum was added mainly to relieve her airway obstruction. Currently, after 6 months from initial diagnosis, she remains clinically stable and ambulatory without tumor progression on docetaxel monthly chemotherapy cycle. Our report here suggests that a primary pulmonary adnenocarcinoma without previous radiation exposure to chest in a child who never had smoking may occur. It might be that environmental tobacco smoking exposure may have had a deleterious impact.

No significant financial relationships to disclose.
Phase I trial of chir-258 in multiple myeloma
Authors: Lonial S. , Alsina M. , Anderson K. C. , Richardson P. , Stewart K. , Fonseca R. , Heise C. , Fox J. , Allen A. , Michelson G.
Published: March 2020

17502

Background: CHIR-258 is an orally active small molecule receptor tyrosine kinase (RTK) inhibitor which has potent activity against multiple RTKs involved in tumor growth and angiogenesis (IC50 ≤13 nM for FGFR, VEGFR, PDGFR, C-KIT, and FLT3). Approximately 15% of newly diagnosed MM patients harbor a t(4;14) translocation, which results in ectopic expression of FGFR3 and MMSET and is associated with poor treatment outcome [0]and reduced survival. CHIR-258 inhibits proliferation and induces apoptosis in FGFR3-expressing MM tumor xenografts as well as FGFR3-expressing primary MM cells (Trudel et al, Blood 2005). CHIR-258 was synergistic with dexamethasone (dex) in vitro. Methods: CHIR-258 was administered once daily in a dose-escalating phase 1 study to patients with relapsed/refractory MM. Drug tolerability and safety, pharmacokinetics (PK) and pharmacodynamics (PD) were assessed. Results: as of December 2005, 9 total pts have been treated (50, 100, and 200mg qd cohorts) [6M, 3F; median age: 58 (range: 44–68), median of 3 prior therapies(range:1–7)]. Prior tx: 9/9 pts-thalidomide; 8/9 -Velcade; 8/9-transplant; 8/9- had progressed through dex. 4 of 9 pts treated were FGFR3+ and 4 pts remain on study (3 are FGFR3+). No CR or PR have been observed; stable disease has been noted. CHIR-258 has been generally well tolerated, and most drug related AEs were CTC grade 1 or 2, including: headache, dysgeusia, fatigue and anorexia. No neuropathy. One DLT has been observed to date: neutropenia (200mg cohort). Five pts had dex added to CHIR-258 of which 3 are ongoing (all FGFR3+). FGFR3+ pts receiving dex and CHIR-258 have a greater decline in urine and serum paraproteins (pp) vs CHIR-258 alone. Plasma exposure and Cmax increased proportionally across the doses. Conclusions: CHIR-258 is a novel inhibitor of RTKs involved in MM growth and proliferation. FGFR3+ pts have a more marked reduction in pp than FGFR3- pts. CHIR-258 has generally been well tolerated and further accrual continues.

[Table: see text]
Antiviral treatment in Hepatitis C Virus (HCV)- related low grade non-Hodgkin lymphoma: An update of a multicenter study
Authors: Vallisa D. , Bernuzzi P. , Lazzaro A. , Trabacchi E. , Arcari A. , Moroni C. F. , Bertè R. , Mordenti P. , Cavanna L.
Published: March 2020

17526

Background: HCV is largely diffuse in North-western Europe and U.S.A. It has been shown to play a role both in hepatocellular carcinoma and in B-cell non-Hodgkin lymphoma (B-NHL). Up to now the exact biological mechanisms that could explain the lymphomagenic role of the virus are under study. Methods: We have previously published a series of 13 patients, affected by low grade B-cell NHL and characterized by an indolent course (i.e. doubling time less than 1 year, no bulky disease), who underwent antiviral treatment only with peghilated interferon and ribavirin (peghilated interferon 50–70 microgram weekly, ribavirin 1000–1200 mg daily). Now we report the second update of this study. Up to now 17 patients are evaluable with a mean follow up of 12.1 ± 8 months (range 2–31 months). Results: Eight patients experienced complete or good partial haematological response that has lasted up to now with a mean follow up of 19,5 months, among them 3 splenic marginal lymphomas, 2 nodal marginal, 1 follicular lymphoma, 1 plasmocytoid and 1 marginal extranodal lymphoma. Three other patients achieved a long lasting partial response. The only one relapse (marginal nodal lymphoma) occurred about one year after the end of treatment, hematological relapse happened together with viral relapse, the lymphoma reappeared as highly chemo resistant high grade lymphoma, and two months later the patient died. Interestingly complete and good partial responses were more likely to be seen in viral genotype 2 (p = 0.04) and were strictly related to the decrease of viral load under treatment (p = 0.005). Toxicity causes the stop of the treatment in 3 patients; however one of them was able to achieve complete hematological response. Time to achieve hematological response was quite long (mean 8 ± 4.5 months). Conclusions: This kind of experience strongly provides a role for antiviral treatment in patients affected by HCV related low grade B-cell NHL. Especially viral genotype 2 infection may be considered a good prognostic marker for hematological response as well as decrease of viral load under treatment. Toxicity in our hands was however significant and further experiences are warranted in order to better modulate antiviral therapy doses.

No significant financial relationships to disclose.
Gemcitabine, ifosfamide, oxaliplatin and rituximab (R-GIFOX), a new effective cytoreductive/mobilizing salvage regimen for relapsed and refractory aggressive non-Hodgkin’s lymphoma: Results of a pilot study
Authors: Corazzelli G. , Capobianco G. , Russo F. , Marcacci G. , Villani O. , Pinto A.
Published: March 2020

17533

Background: We evaluated a new short-course (biweekly), dose intensive, cytoreductive/mobilizing salvage regimen (R-GIFOX) combining the cross-synergistic agents Gemcitabine (G), Ifosfamide (Ifo), Oxaliplatin (Ox) and Rituximab (R), in patients with recurrent CD20+ NHL. Methods: Patients were scheduled to receive three courses of R-GIFOX followed by mobilization and ASCT or three more courses if ineligible for ASCT. Therapy was delivered on a compassionate basis after written informed consent. R-GIFOX consisted of R (375 mg/m2, d 1), G (1000 mg/m2, d 2), Ox (130 mg/m2, d 3), Ifo (5 g/m2, d 3), as a 24-hour single infusion in patients aged ≤ 65 yrs, or fractionated over 3 days (dd 3–5) in those older, G-CSF (5 mcg/kg/d, dd 6–11; 10 mcg/kg/d at the 3rd course). Responses were evaluated after three courses by the integrated FDG-PET/IWC criteria. Results: Twenty patients (median age 62 yrs, r 37–79) with relapsed (n = 15) or refractory (n = 5) aggressive [diffuse large cell (n = 8), mantle cell (MCL) (n = 5), follicular G3 (n = 7)], advanced (stage IV = 75%), poor risk (IPI 3–5 = 60%; previous therapies: median = 2, r 1-4) NHL, were accrued. Eighty-five total courses were given (median 4, r 1–6). Actual dose intensities of the first 3 courses were: G = 82%, Ifo = 83% and Ox = 86.5%. CTCAE v 3.0 toxicity (85 courses) was: G3/G4 thrombocytopenia = 23%; G3/G4 neutropenia = 21%; G3 febrile neutropenia = 5% and G3/G4 infections = 8%. The ORR after three courses was 80%, with 11 complete responses (55%; CR = 8; CRu = 3) and 5 partial; CRu converted to CR at BM biopsy after 6 courses. The ORR was 77 % (6 CR, 4 PR) for patients aged ≤ 65 yrs and 86% (5 CR, 1 PR) for those older. Also, the ORR was 40% (1 CR, 1 PR) for refractory patients and 93% (10 CR, 4 PR) for those relapsed. TTF was 79.4% at a median f.u. of 8 months (r, 2-16). CD34+ cells were harvested in 6 out of 8 eligible patients. Among patients with MCL 3 CRs and 1 PR were obtained, including 2 molecular remissions. Conclusions: R-GIFOX had limited toxicity and good activity in recurrent aggressive NHL. It may offer a less toxic alternative to Cisplatin/ARA-C-based regimens, also for patients aged or unfit for ASCT, and in “difficult” histotypes such as MCL.

No significant financial relationships to disclose.
Low prevalence of Chlamydia psittaci infection in French patients with ocular adnexal lymphomas (OAL)
Authors: Decaudin D. , Subtil A. , Ferreri A. , Vincent-Salomon A. , Ponzoni M. , Lumbroso-Le Rouic L. , Dendale R. , Escande M. , Dolcetti R. , De Cremoux P.
Published: March 2020

17536

Background: A high prevalence of Chlamydia psittaci infection in both tumor tissues and peripheral blood mononuclear cells of Italian patients with OAL has been reported (Ferreri AJ, Guidoboni M, Ponzoni M, De Conciliis C, Dell’Oro S, Fleischhauer K, et al. Evidence for an association between Chlamydia psittaci and ocular adnexal lymphomas. J Natl Cancer Inst 2004;96(8):586–94.) This association has not been confirmed in some regions of the USA, and no data from other European countries are available. We therefore investigated the presence of DNA of C. psittaci, C. trachomatis, and C. pneumoniae DNA in French patients (pts) with OAL. Methods: Tumor samples from ophthalmologic biopsies of 16 OAL pts (10 conjunctiva, 6 orbit) were included in the study. Histologic type were MALT-type (n = 8), lymphoplasmocytic (n = 6), follicular (n = 1), and diffuse large B-cell (n = 1) lymphomas. Two other groups of lymphoproliferative disease were analyzed as controls. First, ten cases of nodal lymphomas (follicular and marginal zone B-cell lymphomas), and ten cases of reactive lymphoid hyperplasia were analyzed. A multiplex touchdown, enzyme time-release PCR designed to simultaneously detect C. psittaci, C. pneumoniae and C. trachomatis DNA sequences was performed. PCR analyses were performed in duplicate in an independent setting either inat the Curie Institut Curie in e, Paris, and in the National Cancer Institute, Aviano. Results: DNA of C. psittaci DNA was detected in the tumoral tissue of only one patient with follicular OAL. No DNA sequences of C. psittaci, C. pneumoniae and C. trachomatis DNA sequences were was detected in all any of the other OALs, or controls. Conclusions: The prevalence of C. psittaci infection in French pts with OAL was sensibly significantly lower than that reported in Italian series. Cross-controls between the two laboratories indicate that this finding is not due to different experimental conditions. Discrepancies may be explained by an heterogeneous epidemiological distribution of the bacterial infection. Large studies aimed to investigate geographical variations in the prevalence of this association are warranted.

No significant financial relationships to disclose.