bluuebunny/crossref_metadata_2025 huggingface dataset:
EXTRA Trial-Evaluation of capecitabine treatment with radiotherapy (RT) in anal cancer: Preliminary results on toxicity and outcome
Authors: Glynne-Jones R. , Meadows H. , Wan S.
Published: March 2020

14085

Background: Phase III trials have shown RT + 5-Fluorouracil (5-FU) + mitomycinC (MMC) as the standard treatment for patients with epidermoid anal carcinoma. The objective of this trial is to determine if capecitabine in combination with MMC has a similar outcome in terms of complete response (CR) rate and toxicity to a 5-day infusion of 5-FU. Capecitabine is a rational alternative to 5-FU as these cancers express high levels of thymidine phosphoralase. Methods: Main eligibility criteria are histologically proven anal carcinoma (epidermoid, squamous, basaloid), fit to receive capecitabine and MMC and ineligible for the ongoing phase III UK trial, ACT II. Exclusion criteria include complete local excision, prior chemoradiation, uncontrolled cardiovascular disease and known HIV+ve. All patients receive: 50.4Gy in 28F(RT) and capecitabine 1650mg/m2/day on each RT treatment day (M-F) over 6 weeks. In addition patients receive MMC 12mg/m2, day 1 only. Assessment of response is by CT scan at 4 wks post chemoradiation. Results: To date 18/30 patients have been registered. Pre-treatment characteristics are: median age 59 yrs (44–85); 7 male, 11 female; 13 Canal, 5 Margin; 5T1, 4T2, 6T3, 2T4, 1Tx; 4N+ve, 13N-ve, 1Nx. Data on 14 evaluable pts are presented here. RT compliance: 12 pts completed planned treatment, treatment was interrupted in 2 cases (chest pain 1; machine breakdown 1). Chemotherapy compliance: 10 pts completed protocol treatment, in 3 pts chemotherapy was affected due to toxicity (1 dose reduced, 2 stopped early 1 due to chest pain and 1 due to grade 3 skin and diarrhoea). One patient decided to stop treatment. Grade 3 toxicity was reported in 2 pts during treatment: dyspnoea 1, diarrhoea 1. Four weeks post chemoradition, 10 had CR, 3 had partial response and 1 pt was not assessable. Thirteen pts are alive and disease free at a median follow-up of 6 months (range 1 -13). One pt has relapsed in an inguinal node 9 months after the end of treatment following a previous CR. Conclusions: This early information suggests that this regimen can be given without interruption and with acceptable toxicity. The early response data is encouraging and the trial aims to reach target accrual by Summer 2006. Educational grant provided by Roche pharmaceuticals.

[Table: see text]
Fixed dose-rate gemcitabine infusion as first-line treatment for advanced-stage carcinoma of the pancreas and biliary tree: series of 106 consecutive patients
Authors: Malaguti P. , Milella M. , Gelibter A. J. , Bossone G. , Sperduti I. , Ruggeri E. , Bria E. , Terzoli E. , Marolla P. , Cognetti F.
Published: March 2020

14099

Background: Our group recently published a phase II trial of GEM infused at fixed dose-rate of 10 mg/m2/min over 100 min in patients with advanced PDAC and BTC. (Cancer September 15,2005). Given the promising results obtained in the first 40 pts, we expanded the cohort under an observational protocol and this is the report of such experience. Methods: From April 2002 to September 2005, 106 advanced PDAC (n = 75) or BTC (n = 31) pts (median age: 63 yrs, range 28–82; M/F: 48/58; PDAC/BTC: 75/31; LA/Met: 36/70; PS 0/1/2/3: 31/53/17/5) were treated with GEM 1000 mg/m2 at the fixed dose-rate of 10 mg/m2/min for 7 consecutive wks and weekly × 3 q4 wks thereafter (FDR-GEM). All patients and 1154 treatment weeks were evaluable for toxicity, 100 were evaluable for response, 87 patients were evaluable for clinical benefit response (CBR) according to Burris criteria, and 56 patients had elevated CA19.9 serum levels at entry. Results: From April 2002 to September 2005, 106 advanced PDAC (n = 75) or BTC (n = 31) pts (median age: 63 yrs, range 28–82; M/F: 48/58; PDAC/BTC: 75/31; LA/Met: 36/70; PS 0/1/2/3: 31/53/17/5) were treated with GEM 1000 mg/m2 at the fixed dose-rate of 10 mg/m2/min for 7 consecutive wks and weekly × 3 q4 wks thereafter (FDR-GEM). All patients and 1154 treatment weeks were evaluable for toxicity, 100 were evaluable for response, 87 patients were evaluable for clinical benefit response (CBR) according to Burris criteria, and 56 patients had elevated CA19.9 serum levels at entry. Conclusions: The results obtained with FDR-GEM in a series of 106 consecutive pts confirm previous results obtained in smaller series and suggest that pharmacokinetically rationale GEM scheduling may improve its therapeutic index. FDR-Gem may constitute a viable alternative to standard Gem infusion as first-line treatment in advanced PDAC and BTC.

No significant financial relationships to disclose.
The retrospective analysis of single agent gemcitabine for biliary tract cancers
Authors: Kiba T. , Matsumoto S. , Hatano E. , Mori A. , Yasumi S. , Doi R. , Kitano T. , Ishiguro H. , Yanagihara K. , Teramukai S. , Fukushima M.
Published: March 2020

14122

Background: At present, outcomes of advanced biliary tract cancers are dismal despite the prognosis of other many cancers are improving. Methods: We retrospectively analyzed survivals of 46 advanced biliary tract cancer patients, who were diagnosed between January 2001 and June 2005, and treated with gemcitabine 600–1,000 mg/m2 as an intravenous 30-min infusion on days 1, 8, and 15 for every 28 days, thereafter. Results: The median age was 63 (range 41–76) with 28 males and 18 females. Twenty-nine (63.0%) had no prior chemotherapy and 18 (30.4%) patients were inoperable cases. One (2.2%) achieved complete response; 5 (10.9%) achieved partial responses; 25 (54.3%) had stable diseases; 9 (19.6%) had progressive disease; and 6 (13.0%) were not evaluated for response. The median survival time and the 1 year-survival of all advanced biliary cancer patients were 8.6 months and 43.9%, respectively, those of the patients, who had the recurrence or residual cancer lesions after surgical resection were 13.5 months and 68.8%, and those of the inoperable patients were 5.4 months and 8.3%. Patients reported grade 3/4 neutropenia/leucopenia (4.3%) and grade 3 thrombocytopenia (2.2%). Grade 3 non-hematologic toxicities were general fatigue (4.3%) and renal failure (2.2%). Multivariate analysis demonstrated that history of surgical resection with tumor recurrence or with residual tumor was the independent predictors for survival. Moreover, except the features of the history of surgical resection, the prognosis of patients with low levels of serum albumin (< 3.7 g/dl) or ≥ 70 ages was worse than that of high levels of serum albumin (≥ 3.7 g/dl) or < 70 ages. Conclusions: In the treatment of biliary tract cancer, it seems that surgical resection even with possible residual tumor is beneficial for patients with good surgical candidate. The present study also suggests the possibility that the prognosis of patients with low levels of serum albumin (< 3.7 g/dl) or ≥ 70 ages might be worse than that of high levels of serum albumin (≥ 3.7 g/dl) or < 70 ages.

No significant financial relationships to disclose.
Comparative proteome analysis of gonadal and extragonadal germ cell tumors
Authors: Honecker F. , Glaesener S. , Rohlfing T. , Brummendorf T. H. , Bokemeyer C. , Balabanov S.
Published: March 2020

14530

Background: Germ cell tumors (GCTs) are the most common malignancy in young Caucasian males aged 20–40. Even though highly effective treatment strategies have been developed for the majority of patients (pts) with GCT, long term survival rate in pts with primary mediastinal non-seminomas nowadays remains below 50%. The molecular mechanism underlying the increased resistance to treatment remains elusive. Therefore, a systematic approach of global proteome analysis was used as a screening tool to compare GCT cell lines of gonadal and extragonadal origin. Methods: Comparative protein expression analysis of two GCT cell lines, NTERA2 (of gonadal origin) and NCCIT (of mediastinal origin) was performed using 2-dimensional gelelectrophoresis. Differentially expressed proteins were analyzed using matrix-assisted laser desorption/ionization - time of flight mass spectrometry (MALDI-TOF). Identification of proteins was performed using peptide mass-fingerprinting and NCBI/SwissProt database search. Results: On average, 761 spots on each gel were detected. Of these, 66 proteins were found to be differentially expressed in an at least in 2-fold manner. Expression of 47 proteins was found to be higher in NCCIT than in NTERA2, 19 proteins showed lower expression in NCCIT than in NTERA2. All 66 spots were analyzed, and 35 (51%) proteins were positively identified by peptid mass fingerprinting and database search. These proteins could be grouped into different categories: 9 are involved in metabolism, 5 each in protein folding and DNA-binding/transcription, 4 in cytoskeleton/cell movement, 3 in cell signaling/differentiation, and 1 each in ion transport and membrane/vesicle trafficking. Of 7 proteins, the function is currently unknown. Conclusions: This analysis demonstrates that proteomic tools are valuable in studying similarities and differences between gonadal and primary extragonadal GCTs. Further characterization and functional analysis of selected proteins is ongoing, with special emphasis on factors potentially involved in treatment resistance and sensitivity. Furthermore, the acquired proteome map of untreated cells will help to identify cellular changes occuring under different experimental conditions in vitro like induction of differentiation and response to cytotoxic treatment.

No significant financial relationships to disclose.
High frequency of human leucocyte antigen (HLA) A2 and HLA-B7, -B44, -B15 and -DRB1–4 haplotypes in Swedish prostate cancer patients
Authors: Masucci G. V. , Andersson E. , Egevad L. , Kälkner K. , Harmenberg U. , Ryberg M. , Nilsson S. , Pisa P.
Published: March 2020

14543

Background: Immune escape mechanisms depend on alterations in the expression of major histocompatibility complex (MHC) molecules and are known to play a crucial part in tumour development. We have previously presented high prevalence of the A2 allele in Scandinavia, which decreases with latitude in Europe and we noticed that prostate cancer mortality decreases among European countries in a similar way. We have furthermore characterized a group of prostate cancer patients with high frequency of HLA-A2 phenotype. Here we present prospectively the incidence of HLA-A2, homozygotes and haplotypes related to clinical parameters. Methods: Unbiased selected patients (n = 35) with localized prostate cancer, stage T1–3, NX-0, M0, eligible for curative full-dose radiotherapy, were analyzed for the genotypes HLA-A, -B, -C, and -DRB1 loci, by PCR/sequence-specific oligonucleotide hybridisation. Furthermore they have been compared to the frequencies of HLA alleles of healthy bone marrow donors in Sweden (based on 43 000 individuals). Results: The HLA-A2* phenotype frequency was 69% compared to the healthy Swedish population 58% (genotype frequency 39% vs. 35%). We also observed an increase in haplotypes compared to A2-B7 (14% vs 6%), A2-B44 (13% vs 6%), A2-B15 (14% vs 6%), A2-DRB1*04 (24% vs 8%). The ancestral haplotype HLA-A2, -B44, -DRB1*04 and HLA-A2, -B15, -DRB1*04 were expressed in 6% and 13% respectively in the patients group compared to the healthy Swedish population (2% and 3%). Conclusions: Our findings indicate that there is an unusual overrepresentation of the HLA-A2 allele and related haplotypes in prostate cancer patients. Further investigations are mandatory to establish if the negative prognostic correlation with HLA-A2 and the high frequent haplotypes is related to histological and clinical parameters as a result of disfunction of the immune system.

No significant financial relationships to disclose.
A phase II trial to assess the activity of MVA5T4 plus interleukin-2 in patients (Pts) with metastatic renal cell carcinoma (MRCC)
Authors: Gary A. , Marsh L. , McDonald M. , Naylor S. , Harrop R. , Bernard D. , Amato R. J.
Published: March 2020

14642

Background: MVA 5T4 consists of a highly attenuated vaccinia virus (modified Vaccinia Ankara, MVA) containing the human tumor associated antigen (TAA) 5T4. Greater than 90% of renal cell cancers are overexpressed by the 5T4 antigen. The primary purpose of this trial is to validate the hypothesis that, in this group of pts, it is possible to induce immune responses either humoral and/or cellular to 5T4 and to break tolerance to the antigen. The immune response will be correlated to clinical outcome. Methods: Eligibility included: pathologic diagnosis of confirmed clear cell or papillary cancer, progressive measurable MRCC, adequate organ/marrow function, Karnofsky Performance Status (KPS) ≥ 80%, any prior therapy, and no active CNS involvement. The dosage schedule of subcutaneous low dose IL-2 will be an initial dose 250,000 U/kg/dose for 5 days in week 1 followed by 125,000 U/kg/dose for 5 days each of weeks 2–6 inclusive. There will then be a 2 week recovery period before the next cycle commences. The dosage regimen of MVA 5T4 will be intramuscular injections given 14 days prior to the first cycle, day 0 and 1 injection given at the beginning of week 4 of the first cycle. In subsequent cycles, booster injections of MVA 5T4 will be given at week 1 only, prior to the commencement of subcutaneous IL-2 therapy. Results: 10 pts have been treated with MVA 5T4 and the LD IL2 regimen. The combination has been extremely well tolerated with no MVA 5T4 related events thus far. Although the study is still continuing to accrue, there are early signs of clinical responses in a number of patients receiving the combination. The immunological analysis is in progress. Conclusion: MVA 5T4 is well tolerated in this group of patients. The immune response will be presented along with clinical outcome.

[Table: see text]
A multicentre, prospective phase 2 study of weekly schedule of carboplatin (C) plus paclitaxel (P) in first-line treatment of elderly patients (pts) with ovarian cancer (OC). The MITO (Multicentre Italian Trials in Ovarian cancer)-5 study
Authors: Zagonel V. , Ferrandina G. , De Vivo R. , De Matteis A. , Fabbrocini A. , Natale D. , Cavazzini G. , Scollo P. , Di Maio M. , Pignata S.
Published: March 2020

15012

Background: CP every 3 weeks is the standard for pts with OC, but elderly pts frequently receive modified schedules or single agent chemotherapy to avoid toxicity. A prospective phase 2 study was conducted to describe tolerability and activity of a weekly schedule of CP in elderly pts with OC. Methods: Pts aged ≥70 years with chemo-naive OC, stage IC-IV, ECOG PS≤2 were eligible. Treatment was C (AUC 2) + P (60 mg/m2) on days 1, 8, 15 every 4 weeks, up to 6 cycles. A 2-stage minimax design was applied. With rate of pts without unacceptable toxicity in the first 3 cycles (UT) as primary endpoint, alpha 0.05 and beta 0.10, p0=0.75, p1=0.95, ≥23/26 pts without UT were required at the final stage. Toxicity was coded with NCI-CTC and response by RECIST. Geriatric assessment was performed by ADL (Activities of Daily Living) and IADL (Instrumental ADL). Results: 26 pts were enrolled. Median age was 77 (range 70–84). PS0: 10 pts, PS1: 16 pts. 14 pts (53.8%) had ≥2 comorbidities. 32%/72% had some ADL/ IADL dependency, respectively. 23 pts (88.5%) did not suffer UT. The 3 UT recorded were g3 heart rhythm (1 pt), g3 liver (1 pt), prolonged haematological toxicity (1 pt). Other main toxicities: g3 thrombocytopenia 1 pt, g2 constipation 2 pts (8%), g1 neuropathy 4 pts (15%). Out of 13 pts with at least one measurable lesion, 4 partial responses were observed (response rate 30.8%, 95% exact CI: 9.1–61.4). Out of 6 pts with non-measurable disease and 2 pts evaluable only for Ca125, 4 complete responses were observed (50%). Conclusions: In this series of elderly OC pts, characterized by a high incidence of comorbidities and functional impairment, weekly CP has a favourable toxicity profile. In this setting, a comparison of weekly vs 3-weekly CP is advisable to compare efficacy.

No significant financial relationships to disclose.
Phase II trial of concomitant low dose temozolomide with external beam radiation (EBRT) followed by 12 months of temozolomide and irinotecan for newly diagnosed glioblastoma (GBM): Preliminary results of RTOG 04–20
Authors: Lieberman F. S. , Tsien C. , Berkey B. , Curran W. , Werner-Wasik M. , Smith R. , Grossheim L. , Hug E. , Mehta M.
Published: March 2020

1510

Background: Irinotecan and temozolomide compare favorably to regimens tested in recurrent GBM. RTOG 04–20 intensifies the Stupp R, et al. (N Engl J Med. 2005 Mar 10;352(10):987–96) adjuvant regimen, using irinotecan and temozolomide in place of temozolomide alone. Methods: Adult patients with newly diagnosed histologically confirmed, supratentorial GBM were eligible. Subjects began temozolomide 75mg/m2 daily the night before initiation of EBRT, and continued until the final day of RT. Pneumocystis prophylaxis was begun prior to RT and for 2 weeks following RT. Within 6 wks after EBRT, subjects with stable or improved MRI were scheduled to receive temozolomide 150mg/m2 on days 1–5, and irinotecan 200mg/m2 on days 1 and 15 of 28 day cycles × 12. Clinical assessments and post contrast MRI are required prior to EBRT, after RT, and after every 2 treatment cycles. Only nonenzyme inducing anticonvulsants were allowed. Results: Accrual of 170 patients was completed in September 2005 with 140 patients currently evaluable. Median age is 57yr, 80% were RPA class III or IV. Prior to cycle 1 of adjuvant therapy, 32 subjects withdrew (20 progressed, 4 toxicity). Of the first 25 subjects receiving irinotecan, 10 suffered grade 3–4 hematologic toxicities in the initial 3 cycles. The protocol was modified by dose reducing irinotecan to 100mg/m2 in cycle 1, escalating to 150 and 200mg/2 in subsequent cycles only if no dose limiting hematologic toxicity occured. No data is yet available on patients who started adjuvant therapy at the lower dose of irinotecan. Diarrhea and constitutional symptoms are the most common nonhematologic toxicies Conclusions: Irinotecan 200mg/m2 days 1 and 15 with temozolomide 150mg/m2 days 1–5 of 28 day cycles was well tolerated treating recurrent GBM, but this regimen was too myelosuppressive when given after concomitant low dose temozolomide and EBRT. Primary outcome data should be available in late 2006.

[Table: see text]
Assessment of the functional diffusion map (fDM) as an imaging biomarker for early stratification of glioma clinical response
Authors: Ross B. D. , Hamstra D. A. , Chenevert T. L. , Moffat B. A. , Johnson T. D. , Tsein C. , Meyer C. R. , Mukherji S. , Junck L. , Rehemtulla A. , Lawrence T. S.
Published: March 2020

1518

Background: Current assessment of glioma treatment response relies on changes in the product of the maximal perpendicular tumor diameters at 2 months following treatment. Due to the fact that patients with malignant glioma have high mortality rates and a short median survival (about 41 weeks), the ability to stratify these tumors into responsive and non-responsive categories prior to treatment completion would allow for individualization of treatment. Changes in glioma water diffusion values were quantified using diffusion MRI as a biomarker for therapeutic-induced changes in tumor cellularity. Methods: A total of 37 patients with Grade III/IV supratentorial malignant gliomas (restricted to anaplastic astrocytomas (Grade III) and glioblastomas/sarcomas (Grade IV)) into a clinical imaging study. Standard and diffusion MRI scans pre-treatment and at 3 weeks post-initiation of chemo- and/or radio-therapy were acquired. Images were co-registered to pretreatment scans, and changes in tumor water diffusion values were calculated and displayed as a functional diffusion map (fDM) for correlation with clinical response. Results: Analysis of the patient data revealed that the fDM volumes of total detected diffusion change (VT) was able to statistically discriminate (P<0.001) between the stable disease (SD) and progressive disease (PD) patient populations 3 weeks into therapy. Patients classified as PD by fDM analysis at 3 weeks were found to have a shorter OS in the PD group compared with SD patients (median survival, 8.0 versus 18.2 months; p<0.01). The fDM measurements provided an early biomarker for response, TTP and OS in malignant glioma patients. Conclusions: This novel imaging biomarker (fDM) was found to be a viable and early predictor of WHO clinical outcome. This clinical study strongly supports the hypothesis that fDM analysis provides a sensitive measure of therapeutic-induced changes in tumor cellularity, which can thereby serve as a predictive clinical surrogate marker for treatment response. Further evaluation of this imaging biomarker is ongoing.

[Table: see text]
Prospective analysis of expression of circulating levels of matrix metalloproteinase-9 (MMP-9) in the serum of patients with primary central nervous system lymphoma (PCNSL)
Authors: Hottinger A. F. , Gu B. , Fleisher M. , Abrey L. E. , Holland E. , Deangelis L. M. , Hormigo A.
Published: March 2020

1532

Background: Matrix metalloproteinases have been associated with angiogenesis, tumor infiltration and metastases formation in systemic lymphoma. Disease status in PCNSL is determined by brain MRI; however it may be inconclusive and non-invasive tests to evaluate disease status would be useful. This study was designed to determine whether circulating levels of MMP-9 could be related to disease status in PCNSL. Methods: Circulating levels of MMP-9 were determined by ELISA and correlated with disease status assessed by MRI in a prospective longitudinal study. The disease status was classified as no evidence of disease (CR) versus active disease (AD). Results: We enrolled 18 PCNSL patients and obtained 93 blood samples (median 6 per patient, range 1–10) from August 2002 to December 2005. When in CR (12 patients, 59 samples), the mean MMP-9 level was 205.5 ± 19.1 ng/ml (median 162.3 ng/ml, range: 35.9–649.1 ng/ml). MMP-9 levels were significantly higher in AD (16 patients, 34 samples), with a mean MMP-9 of 638.2 ± 140.7 ng/ml (median 287.5 ng/ml, range 24.7–3340.6 ng/ml) (p = 0.0001). Paired samples obtained before and after therapy were obtained in 10 patients. Patients in AD had a mean of 1223.9 ± 336.5 ng/ml (median 770.1 ng/ml, range 284.1–3340.6 ng/ml) before treatment and levels fell to a mean of 143.5 ± 38.4 ng/ml (median 86.7 ng/ml, range 28.1–356.5 ng/ml) (p = 0.005) when CR was reached. During follow-up, 4 of the 18 patients developed recurrent disease (total 5 recurrences). MMP-9 levels increased from 154.22 ± 34.9 ng/ml (median 162.4 ng/ml, range 64.5–260.3 ng/ml) to 324.4 ± 98.5 ng/ml (median 251.5 ng/ml, range: 159.5–709.7 ng/ml) (p = 0.14) at relapse. Conclusions: PCNSL patients in CR have circulating MMP-9 levels that are significantly lower than in patients with AD. A significant drop in MMP-9 was seen after treatment compared to baseline. MMP-9 levels increased with disease recurrence but did not reach statistical significance in this small population. MMP-9 has the potential to complement neuroimaging to confirm remission or progression.

No significant financial relationships to disclose.
Radiation treatment of spinal tumors using Cyberknife radiosurgery
Authors: Liao J. J. , Nasr N. M. , Gagnon G. J. , Henderson F. C. , Collins B. T. , McRae D. , Harter K. W.
Published: March 2020

1545

Background: Morbidity associated with spinal tumors can leave patients with functional limitations, pain, and poor quality of life. Since the integrity of the spinal column and the spinal cord must be preserved, treatments are limited especially in the setting of previous radiotherapy. We describe our experience using Cyberknife fractionated stereotactic radiosurgery in the initial treatment and retreatment of spinal tumors and its impact on patient quality of life. Methods: 152 patients with primary or metastatic spinal tumors were treated to 228 spinal sites at Georgetown University Hospital from 2002 to 2005. Neurologic examination, pain assessment by visual analog scale (0–100), and quality of life evaluations by SF-12 survey (mental and physical health scores) were performed initially and at 1, 3, 6, 9, 12, 18, and 24 months following treatment. The primary endpoints were pain and quality of life. 44 patients (109 sites) received Cyberknife radiosurgery as a component of their initial management. The median dose delivered was 2400 cGy (range 1400–8000) in 1–5 fractions (median 3). Median tumor volume was 56 mm3 (range 0.65–457.26). 108 patients (119 sites) with recurrent/persistent disease and a history of prior conventional radiation to the spine received Cyberknife radiosurgery as retreatment. Previous radiation doses ranged from 2000–5940 cGy. The median retreatment dose delivered was 2100 cGy (range 750–3500) in 1–5 fractions (median 3). Median tumor volume was 107.2 mm3 (range 0.94–838.9). Results: Optimized treatment plans were designed with the goal of limiting spinal cord doses. Median follow up is 13 months. No complications have been observed, including treatment related myelitis. Across all patients, the mean initial pain score was 73. Mean pain scores decreased significantly after the first month to 49 and remained significantly lower (40–44) for over one year. SF-12 PCS (initial mean 33) and MCS scores (initial mean 47) remained stable during the duration of the study. Conclusions: Fractionated stereotactic radiosurgery using the CyberKnife is a safe and effective treatment capable of delivering high-dose radiation to primary and recurrent spinal tumors. Follow-up data demonstrates durable pain relief and stable quality of life.

No significant financial relationships to disclose.
Induction chemotherapy with S-1 plus cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN)
Authors: Chung J. , Choi Y. , Shin H. , Choi G. , Lee W. , Joo Y. , Shon C.
Published: March 2020

15501

Background: This study was to assess the efficacy and safety profiles of the combination treatment with S-1 and Cisplatin in patients with locally advanced SCCHN. Methods: Eligible patients were defined as histologically confirmed SCCHN, stage III or IV with no evidence of distant metastasis, evaluable lesions, adequate organ function, age of 20–80 years, and performance status 0,1 or 2. Cisplatin was infused over 1 hour on day 1 (75 mg/m2) and S-1 was administered orally for 14 consecutive days (day 2–15). The dosages of S-1 were assigned according to the patients’ body surface area (BSA): 50 mg twice a day (BSA < 1.5m2), 60 mg twice a day (BSA > 1.5m2). Each course was repeated every 3 weeks. After 2 course, tumor response were evaluated by CT scan and laryngoscopy. If the patients achieved a response (complete response: CR, or partial response: PR), they received one more course of chemotherapy before undergoing the radiotherapy or operation as a definitive local treatment. Results: All 22 patients were assessable for response and toxicity. The overall response was 80.9% (CR: 3, PR: 14). The adverse reactions occurred 120 times in 54 courses of 22 cases. The most common grade 3/4 adverse events were neutropenia, which occurred in 8 patients. Non-hematological toxicity of grade 3 and 4 included nausea and vomiting in 4 patients, fever in one patient and, fatigue in one patient. Since the observation period is short, the analysis about survival rate is not obtained so far. Conclusions: S-1 plus Cisplatin combination chemotherapy is effective against locally advanced SCCHN with mild toxicity.

No significant financial relationships to disclose.
Rituximab and yttrium-90 ibritumomab tiuxetan radioimmunotherapy as treatment options in patients with indolent lymphoma of the orbit
Authors: Esmaeli B. , Pro B. , Saville M. , Mc Laughlin P.
Published: March 2020

15532

Objective: To report a cohort of patients with lymphoid tumors of the orbit whose disease responded to immunotherapy with rituximab alone or rituximab followed by Zevalin (yttrium-90 ibritumomab tiuxetan). Methods: Between October 2002 and June 2005, 9 patients with indolent non-Hodgkin’s lymphoma and 1 with orbital benign lymphoid hyperplasia were treated with monoclonal antibodies against CD20. 6 patients with orbital lymphoma (3 follicular B-cell, 2 MALT, and 1 mantle cell lymphoma) received rituximab followed by Zevalin. 2 patients with indolent orbital lymphoma (one with follicular B cell and the other with small lymphocytic lymphoma) and 1 patient with benign lymphoid hyperplasia received rituximab alone. 3 out of the 6 patients who received Zevalin were part of a prospective trial evaluating the efficacy of Zevalin for indolent B-cell lymphoma of the orbit; the rest were treated in other trials at M. D. Anderson. Clinical records and imaging studies were reviewed to document response. Results: 4 men and 5 women were between23 and 83 years old (median age, 63 years). Of the 8 patients with orbital lymphoma, 4 had stage IE, 4 had stage IV, and 6 had previously untreated disease. All 9 patients experienced resolution of the orbital tumor in response to monoclonal antibodies against CD20. Follow-up time ranged from 6 to 32 months (mean, 12 months) after completion of immunotherapy. There were no serious systemic or ocular side effects during the study period. The most common side effect was mild fatigue. All 6 patients treated with Zevalin had transient pancytopenia which normalized within 3 months. Conclusions: Rituximab and Zevalin may be considered as alternative treatment modalities to radiotherapy for indolent B-cell lymphoma or MALT of the orbit. Systemic targeted immunotherapy may potentially have the advantage of lower rate of distant (out-of-field) relapse and less ocular toxicity compared with radiotherapy; these potential advantages would have to be verified in long-term studies and in larger number of patients.

[Table: see text]
Evaluating cancer treatment access in two community cancer centers in Brazil: When managerial tools turns into bad medicine
Authors: Pinto C. F. , Deboer G. B. , Marotta E. S. , Taborda M. , Mendes A. D. , Albino G. R. , Santos G. L. , Altoe L. , Mandolesi A. , Turci C. F.
Published: March 2020

16036

Background: Despite great developments in cancer treatment, access to treatment is still an important variable that can affect individual prognosis. Phase II or III adjuvant treatment protocols require inclusion to treatment between four to eighth weeks (28 to 56 days) after the initial procedure. The “lead-time” outside clinical trials can be longer than usually recommended and the meaning of this bias over outcome cannot be measured effectively, but reduce this “gap” is considered appropriate. Methods: Two different public community cancer centers (CCC) were evaluated regarding access to a medical oncologist. Referred patients were included and different referral routines were used. Data was collected only for breast cancer patients submitted to adjuvant (or neoadjuvant) systemic therapy. Data included the date the attending physician referred the patient to the CCC and the date patient effectively went on a consultation with an oncologist. Center A referrals depends on “in Hospital” referral center, where all patients are referred and then scheduled to the “needed” specialist. Center B patients are referred promptly to a medical oncologist, regardless of indication, if, i.e., a surgical evaluation or intervention is needed, the oncologist will reschedule it. Results: 76 breast cancer patients were referred to center A and 60 to center B in 2003. Most patients received an adequate surgical intervention, more than 80% of patients were stage I or II. Median time from referral report to a medical oncologist consultation was ten (10) days in Center B and twenty eight (28) days in Center A. Table 1 show treatment variables. Conclusions: Reasons to an almost three times increase in lead-time to access a medical oncologist can be attributed to bureaucratic and managerial policies developed to grant and regulate access to public practice that, in effect, reduced access, created bottlenecks, increased patient expenditures and, potentially, can reduce the overall outcome.

[Table: see text]

[Table: see text]
National multi-center epidemiological study on prevalence and treatment of cancer-related symptoms in Russia
Authors: Novik A. A. , Ionova T. I. , Kalyadina S. A. , Kishtovich A. V. , Wang S. , Cleeland C. S.
Published: March 2020

16039

To have a better understanding of the current status of symptom management the national multi-center epidemiological study among patients with advanced cancer was initiated in Russia in 2005. Specific aims of this study are to describe the prevalence of pain, fatigue, and other cancer-related symptoms among cancer patients being treated in multiple sites across Russia and to assess current symptom treatment and response to it across different centers. The expected sample size is 500 patients with advanced cancer from 10 cancer centers across Russia. Symptom status was assessed using M.D. Anderson Symptom Inventory and Brief Pain Inventory at two time points. The analysis of data from 252 patients: male/female ratio - 111/141, mean age 44.3 (SD 30.1), included in the study from all participating centers is presented. As a result, the most severe symptom was fatigue (4.3) with its prevalence of 83.7%. Other pronounced symptoms were pain (3.4), distress (3.4), and sadness (3.1) with the prevalence of 66.7%, 67.7%, and 68.7% respectively. Out of the total sample, 70 patients (27.7%) had only mild symptoms and 179 patients (71%) reported at least one symptom as moderate-to-severe. Among them there were 72 patients (40.2%) who had 5 or more moderate-to-severe symptoms and 10 patients (5.6%) who had 10 or more such symptoms. Fatigue was treated only in 66 (26.9%) patients; the decrease in fatigue level was achieved in 15 (22.7%) patients. Inadequate pain management (as confirmed by the negative value of the Pain Management Index) was provided for 38.5% of patients. In conclusion, fatigue was prevalent in the vast majority of advanced cancer patients, but the attending oncologists offered the treatment of this symptom to less than 30% of patients. In addition, two thirds of patients reported at least one moderate-to-severe symptom. The results of this symptom outcome study will provide the initial data on symptom control in Russia and will establish the framework for identifying the populations who experience poor symptom assessment and management.

No significant financial relationships to disclose.
Changes in Internet utilization by cancer patients in the Veteran’s Administration (VA) hospital setting
Authors: Vachani C. , Hampshire M. K. , Whittington R. W. , Vachani A. , Metz J. M.
Published: March 2020

16042

Background: A previous study (2002) showed only 5% of VA cancer patients access the Internet to investigate information related to their cancer or cancer treatment. Since this study was published, access to the Internet and computers has changed over the interval. This study was designed to evaluate Internet usage patterns and factors that may promote Internet usage among cancer patients at a Veteran’s Administration (VA) hospital. Methods: From 09/2005 to 12/2005 a 15-item questionnaire was administered to 44 radiation oncology patients presenting for consultation and/or daily radiation treatments. The questionnaire evaluated basic demographics, Internet access and utilization, and interest in educational programs to promote utilization. Results were compared to a questionnaire study of 201 patients performed at the same institution in 2002. Results: The population is predominantly male (98%), with a racial distribution of 39% African American and 61% Caucasians. Two-thirds of the population are between the ages of 50 and 70. The most common primary tumor sites were prostate (65%), lung (11%), and head and neck (7%). Overall, 28% reported using the Internet to find information about their cancer, compared to only 5% in 2002 (p < .0001). An additional 42% reported a friend or family member searched the Internet on behalf of the patient. Seventy-four percent of subjects knew where to gain access to the Internet, which included public library (36%), personal computer (34%), friend/family’s home (13%). Of the 44 patients 18 (42%) were interested in free classes to learn how to access information on the Internet. African-American patients were somewhat more interested in taking educational classes on Internet utilization (OR 2.6, 95% CI 0.6–11.1). Conclusions: Internet use among VA cancer patients has increased over the last 3 years. A majority of VA patients know where to access Internet resources. Many patients are interested in educational programs to teach them how to utilize cancer based Internet resources. Future studies will assess the impact of this educational intervention in the VA population.

No significant financial relationships to disclose.
Phase I study utilizing an intravenous busulfan test dose to prospectively target and determine the maximum tolerated systemic exposure (MTSE) of a continuous intravenous infusion
Authors: Walko C. M. , Shea T. C. , Rao K. , Gabriel D. , Serody J. , Comeau T. , Gilman A. , Krasnov C. , Lindley C. M.
Published: March 2020

16502

Background: Busulfan systemic concentration has correlated with toxicity and efficacy. We previously demonstrated that administration of intravenous high-dose busulfan (HD-Bu) as a 90 hour continuous infusion (CIV) has efficacy, safety, and mean daily area under the concentration curves (AUC) comparable to intermittent dosing regimens and that it is possible to use a test dose of busulfan to predict the systemic exposure with less than 10% variability. The objective of this study is to identify the MTSE of CIV HD-Bu utilizing a test dose for AUC targeting. Methods: Prior to HD-Bu, patients received a single test dose of Bu (0.8 mg/kg) by two hour infusion with blood concentrations obtained at 0, 2.5, 4, 5, and 6 hours. Serum concentrations were analyzed using GC-MS. Non-compartmental PK analysis was used to determine clearance using WIN-NONLIN software. The systemic clearance (dose/AUC) of the test dose was used to predict the 90 hour CIV dose of Bu needed to achieve the desired AUC. On days -7 to -3, the treatment dose was administered and blood samples were collected at 0, 12, 16, 18, 48, 60, 72, and 89.5 hours to verify that the desired AUC was reached. Dose adjustments were made after 18 hours if necessary. A blood sample was obtained for evaluation of polymorphisms in genes associated with busulfan metabolism and transport. Results: Five patients (4 MUD, 1 matched-sibling donor) were enrolled at the 24 hour Bu target AUC of 4800 uM*min ± 15%. One patient was not able to be evaluated due to errors in PK acquisition. 3 of the 4 patients required CIV doses different than that based on weight alone (i.e. 12.8 mg/kg). All 4 patients had AUCs within the desired range (mean 24 hour busulfan AUC of 4708 uM*min) with a mean bias and precision of −1.9% and 8.7%, respectively. No adjustments were required after 18 hours. No grade 3 or greater chemotherapy related toxicity has been identified. Conclusions: The systemic clearance determined by a busulfan test dose may be used to prospectively target the desired AUC of a 90 hour CIV. Enrollment on this Phase I study will continue beyond the first dose level which is at the upper limit of the normal range (4800 uM*min).

No significant financial relationships to disclose.
Inhibition of WT1 and bcl2 in leukemic cell lines by small interfering RNA (siRNA)
Authors: Glienke W. , Milz E. , Bauer N. , Bergmann L.
Published: March 2020

16504

The expression of Wilm‘s tumor gene-1 (wt1) and bcl-2 is considered to have a proliferating and survival supporting effect in leukemia blast cells. The downregulation of wt1 by means of antisense-oligonucleotides and ribozymes revealed an inhibition of cell proliferation and induction of cell death. Here we describe the effect of siRNA against wt1 and bcl-2 in leukemic cell lines. RT-PCR and western blot analyses were performed to examine wt1 and bcl-2 gene expression in transfected leukemia cell lines. Apoptosis was detected with FACS analysis. K562 and HL-60 cell lines transfected with wt1 siRNA showed decreasing levels of wt1 mRNA and protein expression after 24 and 48 hours. The cell proliferation was reduced between 45% and 76% 48 hours after transfection, and apoptosis increased from 6.6 % in control cells to 12.2 % 24 hours after transfection in transfected cells. 48 hours after transfection the amount of apoptotic cells increased up to 45 % in transfected cells. Bcl-2 siRNA only induced apoptosis in about 15% of the cells. The combination of wt1 and bcl-2 siRNA had no additive effect on the induction of apoptosis. The expression of wt1 seems to be more important for cell survival than expression of the anti-apoptotic gene bcl-2. We therefore consider siRNA targeting human wt1 as possible tool against leukemic cells overexpressing wt1.

No significant financial relationships to disclose.
Allogeneic stem cell transplantation improves cerebro-vascular disease in two sickle cell anemia patients
Authors: Kraut L. , Al-Momen A. , Nürnberger W. , Boguth L. , Erken E. , Fauser A. A.
Published: March 2020

16524

Background: Sickle cell anemia (SCA) patients are at high risk for vaso-occlusion with cerebral vascular complications like strokes being one of the most devastating clinical events. Prophylactic transfusions might prevent strokes resp. improve cerebro-vascular status in SCA patients. Allogeneic stem cell transplantation (SCT) is considered a therapeutic option with curative intention of SCA, and thus also to improve cerebro-vascular complications by preventing further strokes, as demonstrated by two cases in our center. Methods: Transcranial Doppler sonography (TCD) and cerebral magnetic resonance angiography (MRA) were used to assess cerebro-vascular disease status prior, during and post related SCT of 2 SCA patients. Results: Two sibling SCA patients (male resp. female, aged 13 and 11 years resp.) both suffered from multiple cerebral microinfarcts during the course of their disease, the boy additionally suffered from two strokes. Prior to related SCT in 2004 with unaffected siblings, both patients were assessed by MRA and TCD. The diagnostic data revealed a hypoplastic ACI (right side) in both children as prominent pathological feature, in combination with different grades of stenosises of ACM, AV and ACI (left side), for example. The evaluation of cerebro-vascular status 3–4 months post SCT showed a persisting stenosis of right ACI in both patients, whereas circulation in the cerebrum resp. flow velocity profiles in other intracranial arteries significantly improved or turned to normal. The course of SCT was rather uncomplicated in the immediate post-transplant period except clinically controlled acute GvHD grade III in one patient. Currently, i.e. 18 resp. 21 months after transplant, the children are in good clinical condition. Conclusions: The results of allogeneic SCT in 2 SCA patients suggest that cerebro-vascular disease does not progress after SCT resp. shows major improvement by SCT. Regular follow up is necessary to assess long term results of cerebro-vascular status in these patients.

No significant financial relationships to disclose.
Hematopoietic stem cell transplantation (HSCT) in patients with primary granulocytic sarcoma (GS)
Authors: Hentrich M. , Ledderose G. , Lutz L. , Tischer J. , Gerl A. , Hartenstein R. C. , Kolb H. J.
Published: March 2020

16529

Background: GS preceding acute myeloid leukemia (AML) is extremely rare and the prognosis is poor. Patients usually undergo systemic chemotherapy (CT) but the role of HSCT is not sufficiently defined. Methods: We report on 3 cases of non-leukemic GS, all of those treated with inductive CT followed by either autologous or allogeneic SCT. Furthermore, the literature on the role of HSCT in GS is reviewed. Results: Case 1: A 55-year-old man presented with a mediastinal mass and right pleural effusion. Fluid cytology revealed hematopoietic cells. Mediastinoscopy showed GS but peripheral blood and bone marrow were free of blasts. He underwent 2 cycles of anthracyline-cytarabine (AC) containing induction CT followed by myeloablative conditioning and autologous SCT in 1st remission. Radiotherapy to the mediastinum was applied afterwards. He remained in CR for 6 months when a leukemic relapse was diagnosed. He is currently undergoing reinduction CT and will proceed to receive an unrelated donor (URD) SCT. Case 2: A 51-year old man was diagnosed with GS of the right testicle. After orchiectomy he was followed by observation only. 8 months later a leukemic relapse [karyotype 46 XY, del (9)(q22), der(13) t(8;13)] occurred. The patient received 2 courses of AC-based induction CT followed by myeloablative conditioning and an HLA-matched URD transplant in 1st CR. However, 27 months after HSCT another leukemic relapse was diagnosed. He received a 2nd URD transplant but died of severe graft versus host disease (GvHD) and veno-occlusive disease 10 weeks later. Case 3: A 37 year-old woman was diagnosed with non-leukemic GS located at multiple bone sites. She underwent 4 courses of AC-containing CT resulting in a CR. 6 months later she presented with multiple recurrent GS confined to the skeleton. She received myeloablative conditioning followed by an allogeneic SCT from her HLA-mismatched brother. Another CR was attained. However, she suffered from severe GvHD and died of severe sepsis 3 months after HSCT. Conclusions: The outcome of patients with primary GS appears to be poor even after treatment with HSCT. However, allogeneic SCT has curative potential as indicated by some cases of successful transplants reported in the literature.

No significant financial relationships to disclose.
Prognostic value of baseline inflammatory markers in inoperable non-small cell lung cancer (NSCLC)
Authors: MacDonald N. , Kasymjanova G. , Dobson S. , Kreisman H. , Cohen V. , Agulnik J. S. , Small D.
Published: March 2020

17035

Background: Markers of chronic inflammation are not commonly included in standard NSCLC staging, which remains anatomically based. Several studies have reported that an increased C-reactive protein (CRP), a marker of chronic inflammation, presages short survival for NSCLC patients (pts). A cohort of 68 pts with advanced NSCLC (stages 3A, 3B and 4) was studied in order to evaluate the prognostic value for survival of various pretreatment inflammatory parameters. Methods: The following factors were collected at the time of diagnosis prior to treatment: sex, age, stage, performance status, CRP, LDH, hemoglobin, platelets, albumin, and white blood cells (WBC). Statistical evaluation employed univariate and multivariate analyses. Survival was calculated using the Kaplan-Meier method and compared using the log-rank test. Results: Median survival for the entire cohort was ten months (mo) (95% CI 7, 15). Those with stages 3A, 3B (18 pts) had a survival of 11 mo (95% CI 6,15), whereas those with 3B (effusion)/4 (50 pts) had a survival of 8 mo (95% CI 3,13). Univariate analysis identified CRP and WBC as the only significant prognostic factors for survival (p < 0.01). Multivariate analysis also demonstrated that CRP (p = 0.005), and WBC (p=0.009) displayed independent correlation with prognosis. CRP and WBC were then combined into a prognostic index (PI) ranging from 0–2. The total score demonstrated a better stratification value for survival. Both parameters were normal [WBC ≤ 11, CRP ≤ 10] (PI 0) in 26 (38%) pts; one parameter was elevated (PI 1) in 27 (40%) pts; and both parameters were elevated (PI 2) in 15 (22%) others. Pts with PI 0 had a median survival of 14 mo (95% CI 12, 21); those with PI 1 had a median survival of 7 mo (95% CI 5, 10); and pts with PI 2 had a median survival of 5 mo (95% CI 3, 7). Conclusions: Systemic inflammatory markers predicted survival in our cohort with NSCLC. These data need to be confirmed in a larger validation study. Studies on staging systems that include inflammatory markers are indicated. Clinical trials linking anti-inflammatory therapies with chemotherapy should be prioritized.

No significant financial relationships to disclose.