bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrafractionated radiation therapy (3x per day) for glioblastoma: Preliminary results of a phase II study
Authors: Beauchesne P. D. , Taillandier L. , Bernier V. , Djabri M. , Michel X. , Maire J. , Martin L. , Verrelle P. , Verrelle P. , Pedeux R.
Published: March 2020

1570

Background: Ultrafractionation radiation therapy consists in irradiating cells or tumors several times daily, delivering low doses at which hyperradiosensitivity occur. We recently reported the high efficiency of ultrafractionation radiotherapy in glioma cell lines and xenografts, and are now conducting a phase II clinical trial to determine the effect of an ultrafractionation regimen for glioblastoma patients. Methods: A prospective, multicenter, phase II study has opened for accrual in September 2003. Patients over 18 years of age who are able to give informed consent and have histologically proven, newly diagnosed and unresectable, supratentorial glioblastoma (WHO grade IV) are eligible. Three doses of 0.75 Gy spaced by at least four hours are delivered daily, five days a week for six consecutive weeks for a total of 67.5 Gy. Conformal irradiation includes the tumor bulk including a margin of 2.5 cm. Tolerance and toxicity are the primary endpoints; survival and progression-free survival are secondary endpoints. Results: To date 25 patients have been enrolled in this study, 19 currently evalualbe: 11 men and 8 women, median age 58 (range 37 to 76), median Karnofsky performance status (80 range from 70 to 100). The median time between histological diagnosis and the start of treatment is 7 weeks. The ultrafractionated radiation therapy has been well tolerated; no acute grade 3 and/or 4 CNS toxicity has been observed. Minor responses at the end of irradiation were seen in 5 patients. Median survival from initial diagnosis was 13.5 months, nine patients remain alive. Conclusions: Ultrafractionated radiation therapy is safe and well tolerated. No acute CNS toxicitiy has been observed. Overall survival of over 13 months for patients without prior debulking surgery compares favorably with other reports. Updated definitive results will be presented.

No significant financial relationships to disclose.
A phase I trial of imatinib, hydroxyurea and RAD001 for patients with recurrent malignant glioma
Authors: Reardon D. , Quinn J. A. , Rich J. N. , Vredenburgh J. J. , Desjardins A. , Sathornsumetee S. , Gururangan S. , Egorin M. J. , Salvado A. , Friedman H. S.
Published: March 2020

1580

Background: This study attempts to extend the anti-glioma activity of imatinib mesylate (Gleevec, IM) plus hydroxyurea (H), by adding RAD001 (R), an orally bioavailable inhibitor of mTOR, a critical intracellular mediator of signal transduction and metabolism. Methods: We employ a “3+3” dose escalation design to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of IM + H + R administered daily among adult recurrent malignant glioma patients s with ≤ 3 prior recurrences, KPS > 60% and adequate organ function. Patients are stratified based on concurrent enzyme-inducing anticonvulsant use (EIAC), and both strata are independently escalated. Initial dose level for each stratum: IM - 400 mg/day; H - 500 mg bid; R - 2.5 mg/day. Each treatment cycle is 28 days. Response is evaluated every other cycle. Pharmacokinetic (PK) studies are performed on days 1 and 28 of cycle 1. Results: Twenty-two recurrent GBM patients have enrolled. The median age is 53 (range 37 to 75), 41% are male, and 45% are on EIAC. Two DLTs (grade 4 hypercholesterolemia and thrombocytopenia) occurred among 5 patients on dose level one (non-EIAC stratum). No other DLTs have occurred. The dose escalation schema has been amended to include alternate day R dosing. IM PK were consistent with those previously reported for patients on IM and HU. IM clearance on day 1 was 492 ± 247 ml/min in the EIAC stratum and 231 ± 100 ml/min in the non-EIAC stratum. On day 28, IM clearance was decreased in both strata (243 ± 93 ml/min in the EIAC stratum and 116 ± 47 ml/min in the non-EIAC stratum) PK results for HU and R are pending. Nine patients continue on study having received 2–8 cycles of therapy. Four partial responses have been observed and accrual is ongoing. Conclusions: Further accrual is warranted. An update of outcome, toxicity and pharmacokinetic analyses will be presented.

[Table: see text]
Imatinib plus hydroxyurea in pretreated non-progressive glioblastoma (GBM)—A single center phase II study
Authors: Dresemann G. , Hosius C. , Nikolova Z. , Letvak L.
Published: March 2020

1583

Background: GBM is a highly malignant tumor with a median survival of less than 15 months. Dysregulated signalling of platelet derived growth factor receptors (PDGF-Rs) is implicated in pathogenesis. Imatinib (I) plus Hydroxyurea (HU) is effective in patients (pts) with recurrent progressing GBM. In a pilot series of 30 pts with recurrent GBM progression free survival (PFS) at 6 and 24 months was 32 % and 16 % respectively. 37 % of pts achieved disease stabilisation (SD). Despite the aggressive course of GBM, short periods without progression after primary treatment or effective treatment of relapse is common. The current Phase II study is designed to analyse the efficacy of I plus HU treatment in GBM pts with SD as sequential treatment. Methods: From Dec 2003 up to June 2005 30 pts were included. No enzyme-inducing anticonvulsive drugs were allowed. I at the dose of 600 mg and 1000 mg of HU were given as a continuous daily treatment, follow up included blood cell count weekly and magnetic resonance imaging (MRI) every 6 weeks. The primary endpoint is 12 months PFS. Results: All pts are eligible for safety and 28 pts of them for 6 months PFS and 6 months overall survival (OS) so far; 25 pts were male, 5 pts female, median age was 44 years (32 to 71). All 30 pts had prior irradiation, 21 pts had temozolomid containing and 9 pts non-temozolomid containing regimens. Eight pts were free from relapse, 17 pts after first and 5 pts after second relapse. 25 pts had measurable disease in MRI scan, 5 pts had no evidance of disease. The median follow up was 14 months. The best response was partial remission in 4 pts. SD for more than 3 months in 20 pts. 6 months PFS was 64% (18/28) and 6 months OS was 93 % (26/28). Hematotoxicity grade 2 and 3 occurred in 11 out of 30 pts (anemia grade 3: 2 pt; anemia grade 2: 4 pts; leucopenia grade 3:2 pts; grade 2: 7 pts; thrombopenia grade 2: 4 pts) and required dose reduction of HU in 8 pts, dose reduction of I in 1 patient and G-CSF subcutaniously in 8 pts. Conclusions: I (600 mg/d) and HU (1000 mg/d) showed significant efficacy as sequential treatment. Hematotoxicity was higher compared to I (400 mg/d) and HU (1000mg/d). Six months PFS and OS data are promising so far. Complete analysis according to the primary endpoint will be presented at the 2006 ASCO meeting.

[Table: see text]
The effect of changes in the treatment paradigm for chronic lymphocytic leukemia: A tumor registry study
Authors: Waheed S. , McClune B. , Buadi F. , Wright K. , Przepiorka D.
Published: March 2020

16000

Background: In the early 1990s, several new agents became available for treatment of chronic lymphocytic leukemia (CLL), leading to a shift in the treatment paradigm with the hope of improving long-term survival. To determine if that outcome has been achieved, we performed a retrospective analysis of survival of patients in our community. Methods: The hospital tumor registry was queried to identify patients with CLL diagnosed 1980 to 2004. Zip code at diagnosis was used to assign a median household income based on census data. Survival was estimated by the method of Kaplan and Meier. Comparisons between the two groups were made by chi square. Hazard ratios for mortality were calculated in a Cox proportional hazard model using a backward stepping procedure retaining factors having a p-value < 0.1. Results: There were 192 patients with a diagnosis of CLL for analysis. The study cohort was comprised of 58% males and 42% females of median age 67 years (range, 39–96 years) at diagnosis. Fifty-three (28%) were <60 years of age, 29% were 60–69 years old, 26% were 70–79 years old, and 18% were >79 years at diagnosis. The group was 71% caucasian and 29% African American. Seventy-five (39%) patients had a household income greater than the median for the state, and the remainder had lesser incomes. There was a significant increase in the proportion of African Americans diagnosed >1990 compared to those diagnosed ≤1990 (40% vs 19%, p = 0.002), but there were no differences between time periods in gender, age, age category or income category. On multivariate analysis, factors predicting mortality differed between time periods as shown in the table. Median survival was 4.0 years for all patients, 3.9 years for the early group and 4.1 years for the later group (p = NS). Conclusion: We conclude that with changes in the treatment paradigm for CLL, gender and race are no longer prognostic for mortality, and the relative hazard for death is less amongst those 60–69 years and >79 years old, but there is no difference in survival for patients overall.

[Table: see text]

No significant financial relationships to disclose.
Survey of the sociodemographic and motivational profile of volunteers in oncology
Authors: Nanni O. , Serra P. , Tison C. , De Castro M. , Ridolfi R. , Falcini F. , Amadori D. , Erroi V. , Meggiolaro E.
Published: March 2020

16011

Background: The volunteer sector developed rapidly in Italy throughout the 1980s, especially in the areas of cancer and palliative care. Istituto Oncologico Romagnolo (IOR), a non profit organization based in Forlì, actively supports the public health sector in the fight against cancer by funding scientific research, organizing voluntary work, promoting education campaigns, and setting up prevention and screening programs. The aim of the present work is to trace a sociodemographic and motivational profile of IOR volunteers. Methods: In May 2005, all IOR volunteers were invited to complete an anonymous questionnaire composed of 12 structured questions designed to collect sociodemographic data, information on type of voluntary work done and the reasoning behind such a choice. Results: Of IOR’s 1043 volunteers, 471 completed the questionnaire, of whom 70% were female and about one-third over 65 years of age. The majority of professions were represented, even though about two-thirds of men and half of the female volunteers were retired. About 40% of the group had been doing voluntary work for more than 10 years. Although fund-raising proved to be the most frequent activity (80%), there is a growing number of volunteers, especially those of a younger age group, involved in home- and hospital-based care. Various reasons were given for becoming a IOR volunteer: ethical considerations (35 % males and 28% females), personal experiences (24% and 38%, respectively), high regard held for IOR and its work (31 and 26%, respectively), and involvement directly through other volunteers (29 and 36%, respectively). Conclusions: The major involvement in fund-raising and perseverance over time of volunteers indicate a favorable social perception of medical research. It also emerged that the decision to start voluntary work was often closely linked to a previous personal experience of loss or disease, especially in female volunteers, who tend to react more constructively and develop a more active and concrete solidarity than men. We can therefore conclude that volunteers in the area of cancer act out of a sense of responsibility and awareness rather than out of pity or a desire for self-gratification.

No significant financial relationships to disclose.
Regional differences in the use of trastuzumab in Sweden
Authors: Wilking U. , Bergh J. , Wilking N. , Jönsson B.
Published: March 2020

16019

Background: The number of deaths due to metastatic breast cancer (MBC) in Sweden is around 1.500 patients/year. It is important that patients have access to new drugs that may delay disease progression and potentially improve survival. HER2 over expression (H+) is used to identify patients eligible for trastuzumab treatment (T). Between 15–30% of patients with MBC have H+ disease. Methods: This study uses sales data from the retail supplier in Sweden, as well as breast cancer mortality data from the National Board of Health and Welfare. Date of marketing approval for trastuzumab in Sweden is Oct 2000. The median treatment time used in this study, as reflected in the pivotal trials, has been set to 38 weeks. This study examines the variation of use in the six health care regions of Sweden (total population 9 millions). Results: The per capita use of T in patients with H+ MBC varies significantly across Sweden. In 2000 minor regional differences in usage were observed. These differences increased and in Q4 2004 usage (measured in sales) varied between 12.500 USD and 37000 USD per 100,000 inhabitants (regions with the lowest/highest sales). Only half (approx. 1100 patients) based on the estiamted prevalent 2200 patients (based on 25% H+ MBC patients) have received T. The first year after marketing authorization 9% of the prevalent population received T. Four years later 93% of the incident population received T. Conclusions: Access of T to patients with H+ MBC in Sweden varies significantly across the 6 Health Regions. Uptake has been slow and not all eligeble patients receive T, even 5 years after marketing authorization.

[Table: see text]
The use of innovative oncology drugs in Europe
Authors: Wilking N. E. , Svedman C. , Jönsson B. , Zethraeus N.
Published: March 2020

16020

Background: A number of new innovative cancer drugs have recently been approved or are in the process of being approved. Rapid patient access to new innovative drugs is important as it may lead to improved survival. Methods: We have analysed the access and uptake of new oncology drugs in 19 European countries over a 15 year period based on sales data provided by IMS Health. In the study we focus on select, “targeted” drugs that have been introduced over the last 10 years: rituximab, trastuzumab and imatinib. We have also analysed data to assess the composition of the drug “arsenal” used in the selected countries based on % of total sales for cancer drugs introduced before 1993; between1993–1998 and after 1999. Results: We see different patterns of uptake in countries studied, both with respect to speed and level of usage, in relation to use per person dying of the specific cancers.. Fast uptake is seen in Austria, Switzerland and Spain, and slow uptake as well as low usage is seen in Poland, Hungary, Norway and the UK. For example, trastuzumab uptake indicates that countries with the fastest uptake treat the majority of HER2 over expressing metastatic breast cancer patients within 2–3 years after introduction while countries with slow uptake still after 5 years seem to have a large proportion of patients not receiving trastuzumab treatment. On the other hand, for a drug like imatinib the uptake has been more rapid and uniform in most countries. The composition of the cancer drug “arsenal” used also differs significantly in between countries. Conclusions: Patient access to innovative cancer drugs varies significantly between European countries.

[Table: see text]
Age as a factor influencing patterns of care for women with breast cancer receiving chemotherapy
Authors: Bule W. , Quigley J. M. , Runyon J.
Published: March 2020

16026

Background: Older patients with breast cancer are underrepresented in clinical trials evaluating chemotherapy agents. Articles recently in JAMA and JCO have stated that older patients with cancer are being under treated. We investigated chemotherapy usage in patients with breast cancer who were greater then 70 years old and under 70 years old. Methods: Physicians capture de-identified data on up to 20 patients per week using a clinically validated, software driven algorithm from a randomized sample of oncologists in the US. Using this validated database with physician entered, de-identified patient data we evaluated all female patient records with breast cancer that were receiving chemotherapy for their disease, from January 2005 through November 2005. All data elements are required fields, allowing for a complete patient record with each entry, including race, age, stage of disease, nodal status, hormone status, her 2 status and chemotherapy treatments. Results: During this 11 month period, 8717 breast cancer records were received for patients receiving chemotherapy. All were included in this analysis. Of the 8717 patient records, age ranges were: 70+ years n = 1332, under 70 years n = 7385. These patients had the following characteristics, the 70+ patients had an avg. age of 76, 23% were her 2+, 66% were ER+, and 25% were node+. The under 70 patients had an avg. age of 53, 32% were her 2+, 59% were ER+ and 36% were node +. The top 3 regimens overall in the 70+ patients were: AC, Xeloda, and CMF. Top 3 regimens overall for the under 70 patients were: AC followed by Taxol (dose dense), AC followed by TH and Herceptin. Segmenting the 70+ patient by adjuvant therapy, the top 3 regimens were AC, AC followed by Taxol (dose dense) and CMF. The adjuvant 70 and under patients top 3 regimens were AC followed by Taxol (dose dense), AC followed by TH, and TAC. Conclusions: The use of anthracyclines, and taxanes is less in the 70+ patients, in the overall population (metastatic and adjuvant) as well as the adjuvant patient population. Further investigation into co-morbid conditions, performance status and segmentation by pathologic grade are warranted.

No significant financial relationships to disclose.
Quality-of-life index: Implications for prognosis in colorectal cancer
Authors: Neelam R. , Lis C. G. , Citrin D. L. , Williams S. , Vashi P. G. , Lammersfeld C. A. , Wodek T. , Grutsch J. F. , Granick J. , Gupta D.
Published: March 2020

16032

Background: Quality of Life (QoL) assessment is important to evaluate the impact of disease and treatment in patients with advanced cancer. Recently, it has been hypothesized that patient satisfaction with their QoL may have a prognostic role in cancer, however, there is little evidence in the literature to support this view. The Ferrans and Powers Quality of Life Index (QLI) is one such instrument. QLI defines QoL as a person’s sense of well-being that stems from satisfaction or dissatisfaction with the areas of life that are important to him/her. The purpose of this study was to determine whether baseline QLI would predict length of survival in patients with colorectal cancer undergoing care in a non-clinical trial setting. Methods: We examined a case series of 177 colorectal cancer patients treated at Cancer Treatment Centers of America between 04/01 and 11/04. QLI measures global QoL and QoL in four major subscales: health and physical, social and economic, psychological and spiritual, and family. All scores range from 0 to 30 with higher scores indicating better QoL. QLI subscales were dichotomized at the median to split the patient population into 2 distinct groups. Kaplan Meier method with Log Rank test was used to calculate survival. Results: Of 177 patients, 46 were newly diagnosed and 131 had prior treatment history. The median age was 53 years (range 25– 85 years). 8 patients had stage I disease, 16 stage II, 51 stage III, and 77 stage IV. Table 1 describes the median survival for all QLI subscales. Conclusions: Baseline levels of patient satisfaction with their health and physical functioning provided useful prognostic information in colorectal cancer. Interestingly, the other subscales that evaluate various existential and economic issues did not provide statistically significant differences in survival. These findings need to be evaluated further to ascertain which subscales of QLI have a role in predicting patients’ prognosis.

[Table: see text]

No significant financial relationships to disclose.
Quality indicators for end-of-life breast cancer care: Is there agreement between stakeholder groups?
Authors: McIntyre P. , Grunfeld E. , Mykhalovskiy E. , Cicchelli L. , Dent S. F. , Zitzelsberger L. , Paszat L. , Earle C.
Published: March 2020

16034

Background: Quality indicators (QIs) are tools designed to measure quality of care and help enhance quality through identifying areas needing improvement. Breast cancer offers a disease model to examine QIs for end-of-life (EOL) care. The objective of this study was to assess agreement among stakeholder groups in two Canadian provinces on QIs for EOL breast cancer. Methods: A qualitative study design using a modified Delphi method and focus groups at each study site. After a literature review, an expert panel identified 19 QIs that were potentially measurable using administrative data. The Delphi panels and focus group sessions incorporated the 19 QIs as discussion topics in Halifax, NS and Ottawa, Ont. The Delphi panels involved a multidisciplinary group of oncology health care professionals. Separate focus groups were conducted with women with metastatic breast cancer and bereaved caregivers. All group sessions were audio-taped, transcribed verbatim, audited and a thematic analysis was conducted. Results: A total of 23 health care professionals, 16 patients, 7 bereaved caregivers participated in the study. Participants attended only one group discussion, depending on group assigned. There was good agreement on QIs among patient and caregiver groups in both cities. The need for effective communication was identified as a major theme. The Delphi process yielded overall moderate agreement with QIs among health care professionals. Conclusion: Aspects of quality EOL care important to stakeholders may not be measurable from administrative data. Results from the Delphi panels indicate that patient preferences and differences in health care delivery between different jurisdictions modulated extent of agreement with QIs.

No significant financial relationships to disclose.
Medical decision making under uncertainty in adult patients (pts) with multiple primary cancer (MPC)
Authors: Gil Deza E. , Loviscek L. F. , Negro F. , Calarame J. C. , Garcia Gerardi C. , Morgenfeld E. L. , Cascallar D. , Carnaval S. , Rivarola E. G. , Gercovich F. G.
Published: March 2020

16037

Background: Evidence-based Oncology (EBO) is founded in clinical trials, medical expertise and patient’s quality of life. Pts with MPC are excluded from clinical trials and there is a lack of clinical expertise as regards to these cases. With the aim to analyze the clinical reasoning for treatment recommendation on those pts, we interviewed oncologists in charge (doc’s) at Instituto Oncológico Henry Moore (IOHM) and Universidad del Salvador (USAL). Methods: The medical records of 8,500 pts from IOHM’s database over last eight years (1997–2005) were reviewed in order to measure the incidence and characteristics of MPC pts. A total of 35 oncologists in charge were identified and participated on a survey which had ten points. The 10 items should be ranked in order of importance: 1 = the most important one and 10 = the least one. Results: One hundred and seventy eight MPC pts (2.09%) were detected, and the oncologist in charge was asked to complete the survey. All doc’s completed the survey. The following table shows the rank and the scoring for each item. (See table below) Conclusions: Four domains ( I to IV) in medical decision making for the treatment of MPC pts were identified: I = PS; II = Characteristics of the tumor; III = Morbidity from therapy and IV = Pt preferences. The pt and family preferences were ranked in the last place and it could reflect a paternalistic approach. To our understanding, this is a good model to test clinical skills and biases in medical treatment selection.

[Table: see text]

No significant financial relationships to disclose.
Advanced colorectal cancer treatment and outcome in the community oncology setting
Authors: Koeller J. M. , Kwan P. , McKibbin T. , Simon J.
Published: March 2020

16040

Background: The treatment of advanced (adv) colorectal cancer (CRC) is currently a moving target due to the availability of new agents and a multitude of clinical trials. It is of interest to see how community oncologists have responded to these changes, and what effect they have had on outcome (survival). We report the chemotherapy treatment (tx) of adv CRC in the community oncology setting. Methods: This is an IRB-approved retrospective study. All available patient (pt) records with adv CRC, treated with chemotherapy, and having expired between 2003 and 2005, or who were still alive at data capture were included. Results: Two hundred and seven pts (60% newly diagnosed; 40% recurred), from 4 clinics (FL, OH, NV, ME) receiving 2444 cycles (3% in 2002; 18% in 03; 40% in 04, 39% in 05) were identified. Fifty percent of pts were male, the mean age was 65 yo, and the ECOG P.S. were 21%-0; 49%-1; 25%-2; 5%-3. Pts received a mean of 12 cycles of tx. A large variation in regimen usage was seen. Forty-three percent of pts received only 1 line of tx including 20+ regimens (top 10: Folfox4; IFL; 5FU/leuc; CapeOx; Folfox6; Xeloda; Folfiri2; Folfox7; CPT-11, Folfiri1), 24% received 2 lines of tx including 18+ regimens 2nd line (top 10: Folfox4; CPT-11; CapeOx; IFL; Xeloda; 5FU/leuc; Folfiri2; Folfox6; Cetuximab; Folfiri1), 15% received 3 lines of tx including 16+ regimens 3rd line (top 10: Folfox4; CapeOx; CPT-11; Xeloda; 5FU/leuc; IFL; Cetuximab; Xeliri; Folfiri1; Bevacizumab). In addition, 9% of pts received 4 lines of tx and 5% received 5 or more lines of tx. Of interest, looking at 1st line tx, IFL decreased and Folfox4 increased over the study period. Biologics were found in 48% of cycles (bevacizumab 35%; cetuximab 13%). Seventy-seven percent of pts had significant toxicity. Toxicity defined as a dose or regimen change, toxic delay or a return visit was seen in 23% of cycles (combined endpoint). Survival was available for 74 pts (81% of deaths were reported in 2004/05). Overall median survival was 17 months (<66 yo - 20.3 mo; >65 yo - 11.5 mo; newly diagnosed - 19.0 mo; recurred - 14.3 mo). Conclusions: Community oncologists utilized a multitude of agents/regimens in the tx of adv CRC. This may be appropriate in light of all the recent changes in disease tx strategy. Although, survival rates are near those published in the literature.

[Table: see text]
Autologous peripheral blood stem cell transplantation in first remission in adult patients with Burkitt and lymphoblastic lymphoma: A single center phase-II study
Authors: Ataergin S. , Arpaci F. , Pektas M. , Beyzadeoglu M. , Ozet A. , Komurcu S. , Ozturk B. , Kuzhan O. , Ozturk M.
Published: March 2020

16517

Background: Optimal therapeutic modality and duration of adult Burkitt and lymphoblastic lymphoma (LL) are still unknown. Despite long-lasting and intensive chemotherapy administration, post-therapy relapses are common. Methods: In this single center phase-II prospective study, high-dose therapy (HDC) and autologous peripheral blood stem cell transplantation (APSCT) was done during the first remission following induction and consolidation therapy for 18 patients with Burkitt (n: 5) and LL (n: 13) without bone marrow and central nervous system involvement at presentation. Cyclophosphamide, vincristine, prednisolone, adriamycin with or without L-asparaginase induction regimen was followed by dexamethasone, cytarabine, and cisplatin consolidation therapy with total body irradiation and cyclophoshamide conditioning. Results: Mean patient age was 24.6 (range: 21–55) years and male to female ratio was 5 to1. 44% (8/18) of the patients were in the intermediate and high-risk groups of International Prognostic Index. Median treatment duration until APSCT was 104 days (range: 87–128). 83% and 17% of the patients were in complete and partial remission before transplantation. One patient with Burkitt lymphoma out of 5 (20%) and 6 patients with LL out of 13 (46%) have died of progression. Overall survival (OS) at 113-month follow-up for all patients was 59.03% with 59.26% of disease-free survival (DFS). However, LL cases revealed OS and DFS rates of 50.35% and 50.77%, respectively. Only one early death (5.5%) was noted due to liver toxicity following HDC and APSCT. Conclusions: In conclusion, this single center phase-II study reveals an acceptable toxicity, short treatment period and high survival rate in adult Burkitt and LL cases, suggesting APSCT to be a good treatment option in the first remission.

No significant financial relationships to disclose.
Complete remission after induction therapy of donor cell derived secondary AML in a CML transplant patient
Authors: Fauser A. A. , Kraut L. , Trebeljahr G. , Thiele B. , Gulzad N. , Roemer E.
Published: March 2020

16523

Background: Malignant diseases arising from donor derived cells are an exceptionally rare condition with approximately 20 cases only reported in the literature. We report on diagnosis and salvage chemotherapy of a CML transplant patient relapsing with donor cell derived secondary MDS resp. AML. Methods: Chimerism analysis were performed by quantitative short tandem repeat (STR) DNA detection in bone marrow as well as in peripheral blood, detection limit 0.5%. Standard procedures were used for all other methods. Results: In a female patient transplanted with a HLA-DRB1 mismatched female unrelated donor in July 1998 for Ph+ CML, secondary MDS was diagnosed in March 2005 transforming into secondary AML in June 2005. The results from chimerism analysis after diagnosis of sMDS resp. sAML in this transplant patient, i.e. no detection of the STR pattern of the recipient, clearly confirmed a donor cell derived sMDS resp. sAML almost 7 years after allogeneic BMT. Cytogenetics showed a normal female karyotype, and no molecular aberrations were detected by FISH resp. PCR. After diagnosis of sAML the patient received 2 induction courses consisting of FLAG-Ida and MTC regimen, respectively. Bone marrow analysis after the first and second course revealed no evidence of blasts whereas the MDS continued to be detectable. Cytogenetics during and after reinduction therapy were normal. Repeated chimerism analysis showed complete donor chimerism (> 99.5%). Thus, a complete remission of donor cell derived sAML using conventional induction chemotherapy was achieved. This remission is now lasting 6 months without intensification. Medical evaluation of the donor did not reveal any disturbed or malignant hematological disorder. Conclusions: This is an interesting case of rare donor cell derived leukemia and its successful treatment. The question arises with regard to altered stromal factors in the bone marrow of the patient as potential cause of the disease.

No significant financial relationships to disclose.
The evidence base for the risk and management of thrombosis in hematological malignancies patients
Authors: Hassan F. M.
Published: March 2020

16526

Background: To evaluate of hypercoagulable state and tumor procoagulant activity in hematological malignancies patients.To address the Primary thromboprophylaxis managed. Methods: Paper-based reply-paid questionnaire was distributed between patients, included the information about the duration, treatment used, sex, age, and type of malignant. We respectively analyzed 96 Patients male and female in all age groups treated for the prevention of recurrent venous thromboembolism in patients with hematological malignancies patients, against 33 (19–75 years, 15 male, 18 female) apparently healthy adults individual setting as control groups. The clinical analysis included thrombotic markers (protein S, protein C, PF1.2, TAT, PAI-1and fibrin D-dimer) were done to all patients and control. Low-molecular weight heparin (LMWH) versus Oral anticoagulant frequency distribution were compared between cases and controls using statistical analysis. Results: In total, 93 completed questionnaires were returned, respondents were reported the routine treatment of more than 10 types of haemopatopoietic and lymphoid tissues tumours. Of these, CML and CLL were most commonly treated (by 45%-62% of respondents), with lymphoma, plasma cell myeloma, AML, polythycythemia vera, and mast cell sarcoma the next most common (treated by 26%-38% of respondents). Most of patients (76%) showed a markedly elevation of PAI-1 and D-dimer and significantly elevated in whose treated Surgically, while the other thrombotic markers (protein S, protein C, PF1.2, TAT were normal compared to control groups. Conclusions: Thrombosis is a common complication in patients with haemopatopoietic and lymphoid tissues tumours that adversely affects their survival. There are several problems associated with the treatment of VTE in patients, especially with the use of oral anticoagulants.

No significant financial relationships to disclose.
Response and tolerability of a 5-day azacytidine schedule in pateints with myelodysplastic syndromes
Authors: Haq B. , Rossetti J. M. , Kramer W. , Latsko J. M. , Jasthy S. , Lister J. , Shadduck R. K.
Published: March 2020

16532

Background: Azacitidine (AZA) is a DNA methyltransferase inhibitor with activity in patients with myelodysplastic syndrome (MDS). The current approved schedule of AZA is 75 mg/m2/d for 7 days every 28 days. This schedule is inconvenient for patients and providers because of the need for weekend administration. Methods: The records of 9 patients who received AZA 100 mg/m2/d for 5 days with an anticipated 28 day cycle between 10/04 to 1/06 were reviewed to determine response, duration of response and tolerability. A minimum of two cycles were required for response evaluation (n = 8). All patients were assessed for tolerability. The International Working Group response criteria for MDS was utilized for evaluation. Results: Patients had secondary MDS (n = 4), chronic myelomonocytic leukemia (n = 2), refractory anemia (n = 2) and refractory anemia with ringed sideroblasts (n = 1). Of the 8 patients who received at least 2 cycles of therapy, 5 responded: 1 achieved partial response, 3 achieved hematologic improvement in at least one cell line and 1 remained in a stable disease state. The overall response rate was 63%. Average response duration was 6.2 months. The longest response duration was 10 months. Myelosuppression was seen in 2 of the 9 patients treated, one of whom continued treatment with growth factor support; therapy is currently on hold for the other patient. Injection site reaction was seen in 2 patients, resulting in discontinuation of treatment in one. One patient experienced severe malaise after 2 cycles and was given the standard dose for further therapy with a major hematologic improvement. Other isolated events included mouth ulcers, mild nausea and flare of erythema nodosum. Of the 5 responders, 1 later died of disease progression (after 7 cycles), 1 died of a complication of comorbidity (after 5 cycles), 1 is alive with disease progression (after 10 cycles) and 2 are continuing therapy with AZA (after 4 and 5 cycles, respectively). Conclusions: AZA 100 mg/m2/day for 5 days every 28 days seems to be tolerated as well as the 7-day treatment schedule. It also appears to have efficacy similar to the standard dose and schedule. If larger studies are confirmatory, this 5-day schedule may be more convenient for patients and providers.

[Table: see text]
Phase II study of weekly irinotecan and cisplatin for refractory or recurrent non-small cell lung cancer (NSCLC)
Authors: Takiguchi Y. , Asaka-Amano Y. , Moriya T. , Kawashima T. , Mizoo A. , Kurosu K. , Nagao K. , Kuriyama T.
Published: March 2020

17002

Background: A current option for recurrent NSCLC is monotherapy with docetaxel. However, cisplatin, if tolerable, may still have power for this condition. Irinotecan is also a key drug for NSCLC. The objectives of this study were to evaluate the clinical relevance of weekly chemotherapy consisting of irinotecan and cisplatin as a 2nd-line therapy for NSCLC. Methods: Patients meeting all following criteria were eligible: proven NSCLC refractory or recurrent after previous single-regimen chemotherapy, PS (0–2), age > 15 years, adequate organ functions, measurable lesions by RECIST, life expectancy exceeding 8 weeks, and written informed consent. Patients with any of the following conditions were ineligible: previous treatment with irinotecan and/or surgery, requirement of thoracic irradiation, interstitial lung disease, pleural effusion or ascites requiring treatment, pericardial effusion, symptomatic brain metastasis, concomitant malignancy or other inadequate condition. Irinotecan (60 mg/m2 in 500 ml electrolyte soln, day 1) and cisplatin (25 mg/m2 in 500 ml saline, day 1, without further hydration) were administered every week for at least 6 courses unless encountering defined skip criteria. Calculated minimum sample size was 43 based on Simon two-stage optimal design with p0=0.10, p1=0.25, α error=0.05 and β error=0.20; planned sample size was 48. The primary endpoint was response rate, and the secondary ones were toxicity and survival time. Results: Since February 2002, 48 patients (consisting of 29 with adeno-, 14 with squamous cell, 3 with large cell carcinoma and 2 with NSCLC not further specified) with a median age of 62-years were enrolled, with 1 death before treatment. Therefore, 47 patients were eligible for evaluation of response rate and toxicity, whereas all 48 were analyzed for survival. Chemotherapy was administered for a median 6 courses (range, 0–15). Response rate was 25.5% (95% CI: 12.9–38.1%). Toxicity of grade 3 or 4 consisted of neutropenia (29.8%), thrombocytopenia (6.4%), anemia (29.8%), diarrhea (10.6%) and nausea (21.3%). MST was 10.6 months, and 1-year survival rate was 43%. Conclusions: This 2nd-line chemotherapy for NSCLC showed promising efficacy with tolerable toxicity.

No significant financial relationships to disclose.
Daily set up variation in patients receiving radiation with tomotherapy for lung tumors
Authors: Mohammed N. , Mehta M. P. , Bentzen S. M. , Khuntia D. , Tome W. A.
Published: March 2020

17005

Background: The on-board megavoltage (MV) computed tomography (CT) capabilities of a Tomotherapy unit were used to obtain the daily MVCT images of lung cancer patients. For daily patient alignment, differences between the MVCT scan and planning CT were resolved by calculating the necessary couch shifts in the X = mediolateral, Y = craniocaudal, and Z = anteriorposterior directions. Daily shifts were analyzed. Methods: 583 alignments from 36 patients with lung cancer were available for analysis. The systematic (Σ) and random (σ) errors were calculated and a covariate analysis was performed with tumor size, Karnofsky Performance Score (KPS), and presence of atelectasis. Two error minimization strategies were applied to the data - 1) shifts from fraction 1 were subtracted from subsequent shifts, and 2) the average of shifts 1–3 were subtracted from shifts 4 onward. Σ and σ were calculated for each of the 3 data sets and applied to van Herk’s margin recipe 2.5 Σ + 0.7σ. The mean, standard deviation, and standard error of the magnitude shifts for 13 patients who each received 23 fractions were analyzed by Spearman’s rank correlation test for the relationship between shift magnitude and fraction number. Results: The presence of atelectasis was significantly related to a smaller σ in millimeters, 2.8 ± 0.08 vs. 3.5 ± 0.09 (p = 1.1 × 10−8). The other covariates were not significantly related to set-up error. The 2nd error minimization strategy decreased Σ in the X, Y, and Z directions from 4.7 ± 0.6, 5.8 ± 0.9, 4.9 ± 0.6 to 2.1 ± 0.1, 4.2 ± 0.5, 3.4 ± 0.3 (p = 2.0 × 10−5, 0.13, 0.02) respectively. Calculated margins from van Herk’s equation for all data reported as (x, y, z) in mm were (13.8, 19.6, and 15.9). For strategies 1 and 2 respectively, calculated margins were reduced by (27.2%, 11.5%, 10.6%) and (46.7%, 21.5%, 23.2%). The mean magnitude of isocenter shift and the standard deviation were found to increase with fraction number (p = 1.0 × 10−6 and 5.0 × 10−5 respectively). Conclusion: The error correction strategies significantly reduced Σ but did not reduce the margins dramatically. Drift in accuracy during a long treatment course and an inability to identify subgroups of patients based on our covariates who may not need daily imaging suggests that daily image verification + correction will help reduce error and margins.

No significant financial relationships to disclose.
Impact of hemoglobin level on the outcome of advanced non-small-cell lung cancer (NSCLC) treated with cisplatin and gemcitabine
Authors: Juan Vidal O. , Alberola V. , Muñoz J. , De Las Peñas R. , Camps C. , Massutí B. , Garcia Gómez R. , Provencio M. , Isla D. , Sánchez J.
Published: March 2020

17010

Background: Negative impact of anemia on survival has been described in NSCLC patients (pts) treated with radiotherapy (RT) or concurrent radiochemotherapy, but scarcely data exist in NSCLC treated with chemotherapy (CT). PURPOUSE: To evaluate the prognosis value of baseline hemoglobin (Hb) among pts with advanced NSCLC treated with cisplatin and gemcitabine. Methods: 433 pts included in two trials conducted by the Spanish Lung Cancer Group (176 pts from the arm A of a randomized phase III trial comparing 3 regimens of CT and 257 pts from a phase II trial) were included in this analysis. No significant differences in baseline characteristics, response and survival (median 8.73 and 9.87 months, p=0.46) were observed between pts of the two trials. The baseline Hb and other potential risk factors for survival were analyzed with Cox Proportional Hazards model in an univariate an multivariate analysis. Results: Stage IIIB with positive pleural effusion (25%), stage IV (75%). 85% had ECOG PS 0–1. Median age: 60 years (range 31–82). 89% male. Histology: 41% adenocarcinoma, 39% squamous cell, 6.5% large cell, 14.5% NSCLC not otherwise specified. Median number of cycles received was 4 (range 1–8). Mean Hb level prior CT was 13.2 g/dl (range 8 to 19.6 g/dl). Response rate was 41% and median survival was 9.57 months (95% CI: 8.57–11–57). No statistically differences in survival were observed by stage (IIIB vs IV), age and gender. In the univariate analysis, number of cycles received (≤3 vs. >3 cycles), ECOG (2 vs 0–1), response (SD+PD vs CR+PR), baseline Hb (≤11 vs >11 gr/dl); minimum Hb during the CT (<10 vs ≥10) and second line CT (No vs Yes) emerged as prognostic factors for survival and were introduced in the multivariate model (see Table ). Conclusions: Hb level at the initiation of CT is an independent prognostic factor of survival this homogenous group of advanced NSCLC treated with cisplatin and gemcitabine. Baseline Hb should be considered as prognosis factor for survival in addition to ECOG.

[Table: see text]

No significant financial relationships to disclose.
Diagnostic strategy based on preoperative serum CEA levels in clinical stage IA NSCLC
Authors: Sawabata N. , Okada M. , Higashiyama M. , Nakagawa K. , Miyake M. , Maeda H. , Matsumura A. , Matsumura A. , Okumura M. , Taki T. , Kodama K.
Published: March 2020

17011

Background: Following surgery, clinical stage IA NSCLC diagnosed using non-interventional examinations is occasionally pathological stage III or IV. The level of carcinoembryonic antigen (CEA) in serum has been reported to be a predictor of up-staging to advanced stages, however, there are few multi-center studies of serum CEA that utilized a short accrual period. Methods: A multi-center retrospective study was performed to assess serum CEA level as a predictor of advanced stage in 862 consecutive patients with clinical stage IA NSCLC from 2002 to 2004. The subjects were 493 males with a mean age of 65.2 years old, 460 of whom were smokers, who had a total of 689 adenocarcinomas with a mean tumor size of 19.5 cm. They were divided into 4 groups by smoking status and adenocarcinoma histology, after which AUC was calculated using an ROC curve, which provided an estimate of the probability efficiency of pathological diagnosis of stage III or stage IV. When AUC was greater than 0.7, sensitivity, specificity, and positive predictive values were calculated, and multivariate Cox regression analysis was performed to confirm independence. Results: There were 72 cases (8.1%) in an advanced stage. AUC was greater than 0.7 in the group of non-smokers with an adenocarcinoma (n = 413), in which the sensitivity, specificity, and positive predictive values were 0.14, 0.97, and 0.64, respectively, with a CEA cut-off level of 20 ng/ml. Thus, serum CEA level was shown to be an independent predictive factor. Conclusions: In smokers with an adenocarcinoma, a high level of CEA in serum was frequently found in those with pathologically advanced disease, thus intervention should be mandated in such cases.

[Table: see text]

No significant financial relationships to disclose.
Biweekly docetaxel and carboplatin as first line chemotherapy in advanced non small cell lung cancer (NSCLC)
Authors: Fírvida J. L. , Esquerdo G. , Amenedo M. , Salgado M. , Llorca C. , González A. , Pérez E. , Cervera J. M. , Ramos M.
Published: March 2020

17016

Background: Platinum therapy has been the backbone treatment in NSCLC. The concomitant use of platinum derivatives and taxanes has shown high antitumoral activity with moderate toxicity. To improve the therapeutic index of this combination, we performed a study with biweekly carboplatin and docetaxel. Primary objective was determination of objective response rate (ORR). Secondary objectives were time to progression, tolerability and overall survival. Methods: Patients histologically confirmed of non-small cell lung cancer, aged ≥ 18, ECOG PS 0–2, measurable lesion according RECIST criteria, adequate bone marrow, renal and hepatic function were included. Prior chemotherapy was not allowed. Patients received treatment with a combination of Docetaxel 50 mg/m2 and Carboplatin AUC-4 each 15 days for a maximum of 8 cycles. Results: Fifty patients were included between March 2004 and July 2005, 84% were male, median age was 63 years old (range 48–77), 78% had ECOG PS 0–1 and 64% of patients had stage IV. Histology was squamous cell carcinoma (54%) adenocarcinoma (36%) and large cell carcinoma (10%). A total 316 cycles were administrated (median 7, Range 1–12). Over 46 evaluable patients for response, one achieved CR, 13 PR, 21 SD and 11 PD, with an overall response rate of 30.5% (95% CI: 17.2–43.8). Median follow up of patients is 8.3 months, with a median TTP of 6.3 months and median overall survival of 11.1 months. Grade 3–4 toxicity per patient was: neutropenia (22.0%), asthenia (16.0%), anaemia (10.0%), thrombocytopenia (2%), mucositis (2%) and nauseas (2%). Conclusions: These results suggest that biweekly schedule of carboplatin / docetaxel is a safe and active regimen in first line advanced NSCLC patients.

No significant financial relationships to disclose.