bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary chemotherapy, stereotactic radiosurgery, or whole brain radiotherapy in non-small cell lung cancer (NSCLC) patients with asymptomatic brain metastases
Authors: Kim K. , Lee J. , Chang M. , Uhm J. , Yun J. A. , Yi S. , Park Y. , Ahn J. , Park K. , Ahn M.
Published: August 2020

e19063

Background: Approximately 25 to 30% of patients with lung cancer develop brain metastases at some stage and 12∼18% at the time of initial presentation. Whole brain radiotherapy (WBRT) has long been a mainstay of treatment of brain metastases. Another treatment approach, Stereotactic radiosurgery (SRS) is a method of delivering high doses of focal irradiation to a tumor while minimizing the irradiation to the adjacent normal tissue. However, the prognosis of NSCLC patients with asymptomatic brain metastases, who are not treated with SRS or WBRT, has not been fully investigated yet. This study aimed to analyze the outcome for various treatment modalities in NSCLC patients with asymptomatic brain metastases. Methods: We reviewed the medical records of 129 patients with a histopathologically proven NSCLC and a synchronous brain metastases between January 2003 and December 2007. The patients were categorized as primary chemotherapy, primary SRS, and primary WBRT group: primary chemotherapy (78 patients), primary SRS (24 patients), and primary WBRT (27 patients). Results: With median follow-up of 30.0 months (7.2 -70.7), the median overall survival (OS) for the entire patients was 15.6 months (0.5–50.7) and the progression free survival (PFS) was 6.1 months (0.3- 53.0). The OS was 22.4m for primary SRS group, 13.9m for primary chemotherapy group, and 17.7m for primary WBRT group; p=0.86). However, patients treated with primary SRS showed trend toward prolonged survival compared to those of primary WBRT p=0.06). Subset analysis of 110 adenocarcinoma patients showed that the median OS for patients treated with primary SRS was longer than those of primary WRBT (29.3m vs 17.7m p=0.01) or primary chemotherapy (29.3m vs 14.6m p=0.04). Conclusions: These results suggest that for NSCLC patients with asymptomatic brain metastases at first diagnosis, SRS rather than primary chemotherapy or WBRT might be considered as initial treatment, especially for patients with adenocarcinoma.

No significant financial relationships to disclose.
Phase II study of combination chemotherapy with docetaxel and carboplatin for elderly patients with advanced non-small cell lung cancer
Authors: Kim B. , Kim H. , Kim T. , Lee H. , Lee B. , Kim J. , Nam S.
Published: August 2020

e19073

Background: More than 50% of advanced non-small cell lung cancer (NSCLC) are diagnosed in patients older than age 65 years. Cisplatin-based chemotherapy has been used in patients with advanced NSCLC as standard treatment, and we investigated the efficacy and safety of combination chemotherapy with docetaxel and carboplatin for elderly patients with advanced non- small cell lung cancer. Methods: Chemotherapy-naïve patients (age ≥ 65 years) with stage IIIB or IV NSCLC were enrolled. Patients received docetaxel (75 mg/m2 on D1) and carboplatin (AUC of 5 mg/ml/min on D1) every 3 weeks. End points included response, time to progression, overall survival, and toxicity. Results: Total 37 patients were enrolled between March 2005 and August 2008. Median age was 75 years old (range, 65 to 84 years), and 33 patients (89.2%) had ECOG PS 0 or 1. Twenty two patients (59.5%) had increased Charlson comorbidity index score (CCI ≥1). The median number of treatment cycles was five (range, 1–8), and relative dose intensity was 95.6% in docetaxel and 95.8% in carboplatin. Overall response rate was 51.3% (95% CI 34.9–67.1) with one complete response, and 18 partial responses. The median time to progression was 6.7 months and median overall survival was 12.3 months. In 164 cycles, grade 3 or 4 hematologic toxicities included neutropenia (10.4%), anemia (1.8%), and thrombocytopenia (1.2%). Non-hematologic toxicities were tolerable. Conclusions: The combination chemotherapy with docetaxel and carboplatin was effective with tolerable toxicities in elderly patients with advanced non-small cell lung cancer.

No significant financial relationships to disclose.
Treatment of advanced non-small cell lung cancer (NSCLC) with a biweekly schedule of irinotecan (I), paclitaxel, and cisplatinum (P): A phase II study
Authors: Gonzalez M. , Rebollo J. , Rami R. , Belda J. , Farré J. , Azinovic I. , Crespo A. , Brugarolas A.
Published: August 2020

e19076

Background: Irinotecan, paclitaxel (taxol, T), and cisplatinum are among the most active agents in the treatment of NSCLC, given alone as single agents or in combination. Based in previous data (Proc ASCO 2003 # 2816), we performed a confirmatory phase II study of the activity of a bi-weekly combination of I (120 mg/m2), T(60 mg/m2) and P (40 mg/m2) in advanced NSCLC. Methods: Forty-three patients (pts) (37 male, 6 female) with histologically proven IIIA-IV NSCLC were treated at our institution. Median age was 61 years (33–79). All pts were ECOG 0–2. 14 pts had locally advanced disease (8 IIIA, 6 IIIB) and 29 metastatic disease. Previous treatments included surgery (5 pts), radiotherapy (4 pts), chemotherapy (5 pts), surgery + radiotherapy (3 pts) and surgery + chemotherapy (2 pt). In three cases, treatment was administered as adjuvant after resection of a primary (2 cases) or a metastatic tumor (1 case). Results: A total of 299 courses were administered (median 6, range 2–14). Toxic episodes grade III-IV were neutropenic fever (10/299; 3.3%), anemia (1/299; 0.3%), asthenia (3/299; 1%), diarrhea (5/299; 17%), hemorrhagic colitis (1/299; 0.3%), mucositis (2/299, 0.6%), vomiting (4/299; 1.3%) and peripheral neuropathy (1/299; 0.3%). With a median follow-up of 72 months (9–97), 2 pts (4.6%) presented pathological complete response, 26 (60%) partial response, 11 (25%) stable disease and 1 pt progressed. Four partial responders were rendered free of disease after rescue surgery. Median time to progression was 6 months. Median survival was 10 months. The actuarial 2 and 5-year overall survival are 26% and 13% respectively. Conclusions: I, T and P at the referred doses can be safely administered in a bi-weekly basis, with a good tolerance and response rate in advanced NSCLC pts.

No significant financial relationships to disclose.
Metronomic antiangiogenetic biochemotherapy of non-small cell lung cancer patients with fractionated cisplatimum, oral etoposide, and bevacizumab
Authors: Remondo C. , Migali C. , Martellucci I. , Carbone F. , Ricci V. , Addeo R. , Del Prete S. , Fulfaro F. , Francini G. , Correale P.
Published: August 2020

e19083

Background: Chemotherapy efficacy in advanced non small cell lung cancer (NSCLC) patients may be augmented if combined with bevacizumab, a monoclonal antibody to vascular endothelial growth factor (VEGF) with anti-angiogenetic activity. Metronomic chemotherapy is a newest approach which employs cytotoxic drugs at lower doses with very close and regular administrations, which has shown anti-angiogenetic effects, epigenetic attenuation of cancer phenotype and immune-modulation. Metronomic chemotherapy with cisplatinum and oral etoposide (mPE) has been tested in NSCLC patients with promising results. We have thus investigated a newest biochemotherapy regimen with mPE + bevacizumab (mPEBev regimen) in advanced NSCLC patients. Methods: This is a phase IB/II trial designed to evaluate toxicity, anti-tumor and biological activity of bevacizumab given at escalating doses in combination with mPE chemotherapy. Twenty-six patients with inoperable NSCLC and an ECOG≤2 were enrolled in the study and received every 21 days, iv. cisplatinum (30 mg/sqm, days 1–3), oral etoposide (50 mg/sqm, days 1–15) and bevacizumab (day 3) at different dose levels (no antibody/control group; 2.5; 5; 7.5; and 10 mg/kg). Results: The treatment resulted very active in those patients who received bevacizumab with a 95% objective response rate (19/20), with a median time to progression of 7.55 months. There were two early deaths at higher bevacizumab dosages: one due to a cardiovascular accident (7.5 mg/kg) and another to lung hemorrhage (10mg/kg). We reported also 4 cases of psychic depression and 4 cases of pneumonia which evolved into lung cavitation. A magnetic resonance monitoring showed a significant treatment-related blood perfusion reduction in the tumor site. It was also observed a progressive decrease in VEGF, thrombospondin-1 levels which were not dependent upon bevacizumab dose and were not observed in the controls. Conclusions: mPEBev regimen resulted very active in advanced NSCLC patients. Our metronomic biochemotherapy regimen with lower bevacizumab doses (2.5–5 mg/Kg) deserves to be investigated in further phase II-III trials.

No significant financial relationships to disclose.
A phase II trial of first-line bevacizumab in combination with pemetrexed and carboplatin in advanced nonsquamous non-small cell lung cancer (NSCLC)
Authors: Skaff Z. G. , Hageboutros A. , Krieger K. , Coakley S. , Somer R. , Stevenson J.
Published: August 2020

e19091

Background: Combining bevacizumab (Bev) with platinum doublet yields a survival benefit in previously untreated patients with advanced nonsquamous non-small cell lung cancer. Carboplatin with pemetrexed is an efficient combination that is potentially less toxic. This phase II trial evaluates the efficacy and the safety of adding bevacizumab to carboplatin and pemetrexed in advanced non-small cell lung cancer. Methods: This is a single arm, open-label phase II trial. Eligibility stipulated enrollment of patients with stage IIIB/IV non-squamous non-small cell lung cancer with an ECOG PS 0–1 and no other contraindications to Bev. Treatment consisted of pemetrexed 500 mg/m2, carbo AUC 6 and Bev 15mg/kg on day 1, repeated every 3 weeks. If clinical benefit was proven, patients received Bev maintenance until progression. The response was evaluated every two cycles. The primary endpoint was time to progression (TTP); secondary endpoints included overall survival, response rate (RR) and grade 3–4 toxicities. Results: As of September 2008, 27 out of 42 projected patients were enrolled of which, 14 were males and 13 females; median age 68 (72% older than 60); IIIB/IV 5/22; median number of cycles 9 (range 2–33). At the time of analysis, 25 patients were evaluable. Preliminary results show a median time to progression of 7.25 months (95% CI, 6.4 to 8.2). 23 patients (92%) had disease control (95%, CI 82–96%) with an overall response rate of 36% (95%, CI 25–47%).14 patients had stable disease (56%), 8 had partial response (32%) and one achieved a complete response (4 %). Median survival has not yet been reached. Grade 3/4 adverse events include: Cerebral ischemic event (N=1), Anorexia (Gr 3: N= 5/ Gr 4: N= 4), gastrointestinal fistula (N=1), hypertension (Gr3: N=3), epistaxis (Gr 3 N=1), vomiting (Gr 3; N= 3), fever (Gr 4: N=1) and neuropathy (Gr 3: N=2). Conclusion: The addition of bevacizumab to carboplatin and pemetrexed appears to be an active first line treatment with a high disease control rate and an acceptable toxicity profile in the setting of advanced non-small cell lung cancer.

No significant financial relationships to disclose.
A phase I trial of S-1 plus vinorelbine in patients with unresectable advanced or metastatic non-small cell lung cancer
Authors: Suyama H. , Shigeoka Y. , Igishi T. , Matsumoto S. , Kodani M. , Takeda K. , Sumikawa T. , Morita M. , Ueda Y. , Shimizu E.
Published: August 2020

e19098

Background: We reported the efficacy of the combination treatment of tegafur-uracil (UFT) and vinorelbine (VNR) for the elderly patients (pts) (>70) with advanced non-small cell lung cancer (NSCLC) in ASCO 2007 (Abstract - No. 18075). Although the cisplatin-based doublets are still milestone for the pts with advanced NSCLC, non-platinum based doublet regimens remain as a matter of development judging from recent meta-analysis. Tegafur-5-chloro-2,4-dihydroxypyridine-potassium oxonate (S-1), a new oral fluoropyrimidine, has been studied extensively, and appears promising for various kinds of cancers including NSCLC. Thus, we conducted this phase I trial using VNR and new oral fluoropyrimidine, S-1. Methods: Pts with advanced NSCLC, who had received at least one prior platinum-containing regimen, were eligible. In this phase I study, VNR was infused on days 1 and 8, and S-1 was administered from day 2 to day 6 and from day 9 to day 13 of a 3-week cycle. The starting dose of S-1 was 80 mg/m2/day and, if necessary, the dose was decreased to 65 mg/m2/day; VNR was increased from 20 to 25 mg/m2 in this trial. Results: From August 14, 2007 to April 1, 2008, 8 pts enrolled in this study. Median age was 61 (range 49–75). Dose limiting toxicity (DLT) was evaluated during the first 6 weeks of the treatment. No DLT was observed at dose level I (80 mg/m2/day S-1, 20 mg/m2 VNR). At dose level II (80 mg/m2/day S-1, 25 mg/m2 VNR), DLT in the form of neutropenia, hyperglycemia and hyponatremia was observed in 3 of 5 pts. The maximum tolerated dose (MTD) for the present treatment was 80 mg/m2/day S-1 and 25 mg/m2 VNR; the recommended tolerable dose for future phase II trials is therefore 80 mg/m2/day S-1 and 20 mg/m2 VNR. Conclusions: Three-week cycle of VNR (20 mg/m2), infused on days 1 and 8; S-1 (80 mg/m2/day), administered from day 2 to day 6 and from day 9 to day 13, is being examined in our phase II trial for first-or second-line treatment of NSCLC.

No significant financial relationships to disclose.
Colloidal cDNA encoding recombinant multimodular proteins rMDVA comprising disintegrin/cysteine rich disulfide bond 2RGD, and C-terminal domain (ammodystatin), metalloprotease-domain (ammodylysin), and dimeric disintegrin/MLD-VGD domain (VADD) isolated from vipera ammodytes, exerted synergistic action with vinorelbine against metastatic NSCLC, circumventing chemotherapy-mediated systemic toxicity
Authors: Dritsas J. , Giannios J. , Michailakis E. , Alexandropoulos N.
Published: August 2020

e19100

Background: We investigate if venom proteome of vipera ammodytes can induce apoptosis in NSCLC. Methods: We developed a large scale expression system with lung cell line (LCL), which we modified genetically by cloning. We expressed cDNA encoding multimodular disintegrin (rMDVA) comprising 3 domains from the venom of vipera ammodytes. The cDNA of rMDVA was cloned into the plasmid vector pcDNA III, which was transferred into LCL. The multimodular peptide rMDVA was encapsulated in the hydrophilic phase of liposomes termed as LIP-rMDVA. The in-vivo studies with human metastatic NSCLC were performed in an orthotopic xenograft model. Results: The venom proteome contained 140 proteins. We isolated the multimodular disintegrin displaying cysteine rich disulfide bond 2RGD, and C-terminal motif (ammodystatin), the dimeric MLD/VGD motif (VADD) and metalloprotease-domain (ammodylysin). Ammodystatin with the 2 (ARG-GLY-ASP) RGD motifs interacts with integrins avb5, a5b1 inhibiting invasion, angiogenesis/vasculogenesis and blocked the bFGF-induced avb3 integrin, and avb5 downregulating VEGF, and Ras. It also disrupts the actin cytoskeleton inducing G1 DNA replicative phase arrest, and blocks endothelial cell (EC) secretion of MMP-2, MMP-9, and urokinase type plasminogen activator with its receptor inhibiting proteolysis, and dissolution of ECM blocking invasion. Ammodystatin and ammodylysin lead to type I PCD/apoptosis of tumor cells in masses up to 2 mm, and EC. Beyond that size, ammodystatin inhibits the development of the required vascular network according to HUVEC, MVD, and IHC. VADD causes burring and blocked adhesion of a4b1 integrin to VCAM1. LDH, BrdU and MTT exhibited inhibition of tumor and EC proliferation. TEM exhibited apoptotic signs of irreversible D2 stage in tumor and ECs. Conclusions: Novel liposomal formulation LIP-rMDVA is an effective angiostatic, and cytostatic agent against metastatic NSCLC minimizing ST.

No significant financial relationships to disclose.
Role of gefitinib (G) in heavily pretreated non-small cell lung cancer (NSCLC)
Authors: Tamburini E. , Tassinari D. , Pasquini E. , Papi M. , Possenti C. , Drudi F. , Castellani C. , Santelmo C. , Carloni F. , Ravaioli A.
Published: August 2020

e19102

Background: To assess the role of a palliative treatment with gefitinib in advanced and heavily pre-treated NSCLC. Methods: The records of all the consecutive patients treated with G in our department were reviewed; all the patients pre-treated with at least one courses of a platinum-containing regimen were considered eligible and enrolled into the trial. All the patients were treated with G 250 mg/die until progression of the disease or intractable toxicity. All the patients were evaluated every 21 days for toxicity and every 2 months for survival. Primary end point was time to progression (TTP); secondary ones were overall survival (OS) and safety. A sub-analysis comparing TTP and OS on the basis of sex (male/female), smoker status (smoker/never-smoker) and histology (adenocarcinoma/non-adenocarcinoma) was performed using the Log-Rank test. Results: Till today 63 patients were considered eligible and enrolled into the trial; the results are summarised in the table . Toxicity was mild with no haematological side effects, and no grade III-IV non-haematological toxicity. Conclusions: G seems to represent an interesting options in patients with NSCLC heavily pre-treated with chemotherapy. Our data seems to confirm that G is active mainly in female, no-smoker patients with adenocarcinoma, suggesting the need of reintroducing the molecule in the treatment of such a subset of patients.

[Table: see text]

No significant financial relationships to disclose.
Amplification and overexpression of the PSMB5 gene contributes to bortezomib resistance in retreatment of patients with multiple myeloma
Authors: Altavilla G. , Arrigo C. , Marabello G. , Galletti G. , Santarpia M. , Sauta M. , Pitini V.
Published: August 2020

e19500

Background: The proteasome inhibitor Bortezomib is a novel anticancer drug that targets primarily the beta5 subunit (PSMB5) of the 26 S proteasome which has also demonstrated efficacy in re-treatment of almost half of relapsed Multiple Myeloma (MM) pts. Recent studies have identified qualitative and quantitative alterations at the level of PSMB5 subunit, which is located at 14q11, and cells that carry these alterations displayed a marked resistance to proteasome inhibition. We investigated the relevance of amplification and PSMB5 overexpression in the clinical outcome of pts with MM during retreatment with bortezomib. Methods: Between January and June 2008 pts with secretory MM on relapse were elegible for bortezomib re-treatment (1.3 or 1.0 mg/mq on days 1,4,8 and 11 of a 21 day cycle) if they had at least a partial remission to a bortezomib based on most recent treatment and a free interval of at least 6 months since the last dose. Bone marrow samples for morphologic analysis, mRNA expression levels of PSMB5, classical cytogenetics, FISH and in situ hybridization using a fluorescein-labeled probe to detect the amplification of PSMB5 gene, were obtained from 26 pts (16 male, 10 female mean age 64 years) before and during re-treatment with Bortezomib. Results: At the time of analyses all pts who received at least two cycles were evaluable. We identified 12 pts refractory to retreatment and five of these pts (3 males, 2 females, mean age 65 years) had a detectable amplification and overexpression of PSMB5 which interestingly appears rapidly following exposure to bortezomib and wanes with time off-therapy, even if it curiously reappeared rapidly after re-exposure to bortezomib. Conclusions: Amplification and overexpression of PSMB5 contributes to bortezomib resistance in clinical practice. These findings do highlight the susceptibility of proteasome units to genetic modifications under constant selective pressure which occur with continued treatment, furthermore, the drug resistance remains dormant but it rapidly revives upon re-exposure to bortezomib.

No significant financial relationships to disclose.
Efficacy and safety of lenalidomide oral monotherapy in patients with relapsed or refractory diffuse large B-cell lymphoma: Results from an international study (NHL-003)
Authors: Czuczman M. S. , Vose J. , Zinzani P. , Reeder C. , Buckstein R. , Haioun C. , Bouabdallah R. , Polikoff J. , Ervin-Haynes A. , Witzig T.
Published: August 2020

e19504

Background: Patients with diffuse large-B-cell lymphoma (DLBCL) who are not cured with R-CHOP or high-dose chemotherapy with autologous stem cell rescue have a dismal prognosis. A recent phase II trial (NHL-002) of lenalidomide in patients with relapsed or refractory aggressive non-Hodgkin's lymphoma (NHL) demonstrated a 19% overall response rate (ORR) with a 7-month median duration of response (DR) in the subset of patients with DLBCL. A supporting international phase II trial (NHL-003) of single-agent lenalidomide was initiated for patients with relapsed or refractory aggressive NHL that had received at least one prior treatment and had measurable disease. Herein, we report the data from the DLBCL patients enrolled in this trial. Methods: Patients received 25 mg oral lenalidomide once daily on days 1–21 of every 28-day cycle and continued therapy until disease progression or toxicity. The 1999 IWLRC methodology was used to assess response and progression. Results: One hundred-three DLBCL patients were enrolled and were evaluable for response assessment. The median age was 66 years (21–87) and 70 patients (68%) were male. Median time from diagnosis was 2 years (0.4–18.6), patients had received a median of 3 prior treatment regimens (1–10) and 46 of the patients (45%) had received a prior stem cell transplant (DLBCL-stem cell). Response rates are shown in the Table . Grade 3 or 4 adverse events occurring in more than 5% of patients were neutropenia (34%), thrombocytopenia (18%), asthenia (9%), anemia (8%), leucopenia (7%), back pain (6%) and dyspnea (6%). Conclusions: This international study demonstrates that lenalidomide is active in heavily pre-treated patients with relapsed or refractory DLBCL and has manageable side effects.

[Table: see text]

[Table: see text]
Age at diagnosis does not adversely affect outcome in patients with Hodgkin's Disease (HD) after autologous transplantation
Authors: Popat U. R. , Saliba R. , Hosing C. , Khouri I. , Alousi A. M. , Giralt S. A. , de Lima M. J. , Qazilbash M. H. , Champlin R. , Anderlini P.
Published: August 2020

e19507

Background: Age at diagnosis is a poor prognostic factor for overall survival after standard therapy for HD. Whether older age is a prognostic factor for outcome after autologous transplantation is not known. We sought to evaluate the effect of older age at diagnosis on transplant outcome. Patients and Methods: All patients with HD undergoing autologous transplantation with BEAM conditioning (BCNU, Etoposide, Cytarabine, and Melphalan) between January 1996 and December 2007 were included in this study. During these 12 years, 248 patients (103 males) underwent autologous transplantation. Seventy two patients (29%) were older than 40 years of age at the time of initial diagnosis. Median age at transplantation was 31 years (range 11–74). At transplantation, 63 (25%) were in complete remission (CR); 148 (60%) were in partial remission (PR); and 37 (15%) had stable (SD) or progressive disease (PD). Forty-six patients (19%) had received more than 3 courses of chemotherapy prior to transplantation. LDH was elevated in 131 (53%). Peripheral blood stem cells were used as stem cell source in 241 (97%) patients. Results: With a median follow up of 48 months (range, 1–143 months), the 48-month overall (OS) and event-free survival (EFS) were 72% (95% CI; 65%-77%) and 57% (95% CI; 50%-63%), respectively. The cumulative incidence of non-relapse mortality at 1 year was 1.6%. The cumulative incidence of secondary MDS or AML was 8%. In univariate analysis, disease status (p<0.001) and number of prior chemotherapy regimens (p=0.007) were the only factors significantly predicting OS. Disease status was the only factor significant (p<0.01) in a multivariate analysis with a hazard ratio of 2.7 (1.1–6.9) and 9.2 (3.4–25) for patients in PR, and SD/PD respectively (CR reference group). Age at diagnosis was not a significant factor (see table ). Conclusions: High-dose chemotherapy and autologous transplantation abrogate the adverse impact of age at diagnosis in patients with HD.

[Table: see text]

No significant financial relationships to disclose.
Survival benefit of post induction consolidation therapy in MCL (mantle cell lymphoma): A Polish Lymphoma Research Group (PLRG) retrospective multicenter analysis
Authors: Jurczak W. , Giza A. , Krochmalczyk D. , Sobocinski M. , Zimowska-Curylo D. , Stella-Holowiecka B. , Boguradzki P. , Kisiel E. , Wróbel T. , Knopinska-Posluszny W. , Skotnicki A. B.
Published: August 2020

e19510

Background: In MCL, early intensification and consolidation of the first line therapy by ASCT is the treatment of choice. Elderly age and co-existing co-morbidities makes it however feasible for less than a third of patients. Methods: All MCL cases consulted in 8 PLRG centers within the last 5 years (n=140) were included in a retrospective analysis. Only 23% (n=32) were consolidated with ASCT, further 28% (n=40) by radioimmunotherapy (Ibritumomab), while in 49% (n=68) neither consolidation was performed. Rituximab was used in 36/72 patients subjected to consolidation and 25/68 treated without consolidation. There were no statistically significant differences in IPI, CS (clinical stage), frequency of extranodal manifestations and B symptoms between analyzed subgroups ( Table ) although patients subjected to ASCT were younger (median age 54 vs 62) and tend to have higher LDH (556 IU vs 473), while those who were not consolidated more frequently had a large tumor burden (defined as a mass > 7 cm, 24 vs 15%). Results: There was a clear impact of consolidation on overall and progression-free survival (OS,PFS): at 5 years OS 65 vs 20 % (p= 0.0003 in Gehan Wilcoxon test); and PFS 40 vs 0 % (p= 0.0003 in Gehan Wilcoxon test). Rituximab used in the first line therapy further increased it's efficiency in terms of PFS, prolonging median time to progression from 15 to 26 months, however the OS benefit was seen only in consolidated patients (at 5 years 75% OS in those with Rituximab including induction followed by consolidation). Conclusions: With all limitations of retrospective analysis, it strongly supports the necessity of post induction therapy in MCL patients. The role of ASCT is established in younger patients, radioimmunotherapy may prove to be a feasible approach for the elderly and unfit ones.

[Table: see text]

No significant financial relationships to disclose.
Factors that determine survival among patients with multiple myeloma (MM) treated with zoledronic acid (ZOL)
Authors: Yellin O. , Crowley J. , Swift R. A. , Makary A. , Gravenor D. S. , Yang H. H. , Upadhyaya G. H. , Flinn I. W. , Staszewski H. , Tiffany N. M. , Berenson J. R.
Published: August 2020

e19519

Background: Although the overall survival of MM patients has improved with new treatment options, few studies have evaluated prognostic factors since these new therapies have become available. Monthly ZOL has been incorporated into many of these regimens to reduce skeletal complications. Side effects from ZOL have been reported but their frequency and outcomes have not been well-defined. This retrospective study aimed to identify key baseline and on-treatment prognostic factors among MM patients treated with ZOL. Methods: Three hundred patient charts were consecutively reviewed. Data was collected from the date of MM diagnosis to the date of chart review. Patient chart inclusion criteria required a diagnosis of MM and having received at least one dose of ZOL. Results: The median survival of among patients in this study was 131 months. Significant early risk factors for overall survival included skeletal-related events (SRE), increased serum creatinine, elevated serum calcium, and ISS Stage II or III at diagnosis. Fourteen patients (4.7%) developed osteonecrosis of the jaw (ONJ) after 9–96 months of ZOL treatment. Notably, there was a trend toward an increased risk of ONJ among diabetic patients. Thirteen patients with ONJ remain alive and currently are in remission or with stable disease. One patient with ONJ died while in remission from a myocardial infarction. Among the patients with a follow up of 4–49 months from the diagnosis of ONJ, 2 showed some worsening of this complication, 5 remained stable, while 7 improved or resolved. Patients with ONJ showed an improved overall survival using both landmark and time-dependent analysis. In addition, the overall skeletal morbidity rate (SMR; SREs/year) was 0.16. Notably, patients who developed ONJ had a lower SMR than among patients who did not develop ONJ. Conclusions: These results suggest that skeletal complications are an important prognostic factor for MM. Although ONJ occurs in MM patients, most patients show improvement with proper management and this complication appears to be associated with a reduced risk of SREs and improved overall survival.

[Table: see text]
A multivariate analysis for the survival of nodal peripheral T-cell lymphoma (PTCL)
Authors: Oki M. , Isozaki M. , Nakamura N. , Kikuchi A. , Tsuchiya T. , Arbogast P. , Ogawa Y. , Ando K.
Published: August 2020

e19521

Background: Nodal peripheral T-cell lymphoma (PTCL) is uncommon lymphoma with various subtypes and poor prognosis. There is no definitive therapeutic improvement by conventional chemotherapy (CT) for decades. However, the superiority of high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has remained inconclusive. The infrequency of PTCL is an obstacle to perform a large prospective study. We conducted a retrospective study of fifty six patients with three major nodal PTCL, histologically classified as PTCL-not specified (NOS, n=29), angioimmunoblastic T-cell lymphoma (AITL, n=19), and ALK-negative anaplastic large cell lymphoma (ALCL, n=8) who underwent ASCT (n=14) or not (n=42) after CT in Tokai University Hospital, Ebina General Hospital, and Hadano Red Cross Hospital, Kanagawa, Japan between 1997 and 2008. We determined whether international prognostic index (IPI), serum soluble IL-2 receptor level (sIL-2R) and ASCT were correlated with the survival. Methods: Retrospective, multicenter cohort study by time-dependent or non-time-dependent multivariate survival analysis with Cox proportional hazard regression. Results: Median age was 61 (18–81). The percentage of IPI more than 3 was 50. Median sIL-2R was 4120 ng/ml. (311–96,800). In non-time-dependent analysis, both ASCT and sIL-R were significant prognostic factors for overall survival (OS). Hazard ratio (HR) of ASCT, IPI, and sIL-2R were 0.24 (95%CI: 0.08–0.76, p=0.02), 0.77 (95%CI: 0.34–1.77, p=0.54), and 1.45 (95%CI: 1.129–1.857, p=0.035), respectively. But in time-dependent manner, the significant effect of ASCT was offset for OS. HR of ASCT was 0.82 (95%CI: 0.25–2.71, p=0.75). Only sIL-2R was still statistically significant, which HR was 1.31 (95%CI: 1.04–1.66, p=0.03). On the other hand, ASCT was only important effect on progression-free survival (PFS) by non-time-dependent analysis, which HR was 0.20 (95%CI: 0.07–0.55, p=0.02). After time-dependent analysis, no variates influenced PFS. Conclusions: The OS advantage of high-dose chemotherapy followed by ASCT is offset by time-dependent Cox proportional hazard analysis. The level of sIL-2R has impact on OS. Prospective multicenter randomized trial will be needed to show or not to show an advantage for ASCT.

No significant financial relationships to disclose.
Clinical activity of rituximab with either CHOP or CVP in MALT lymphoma
Authors: Aguiar Bujanda D. , Bohn Sarmiento U. , Saura Grau S. , Rodriguez Franco C. , Aguiar Morales J.
Published: August 2020

e19530

Background: Optimal management of MALT lymphoma remains undeffined. Rituximab has been proven to be an active agent in the treatment of MALT lymphoma. Several reports suggest that the activity of rituximab can be improved when added to chemotherapy. We aimed to evaluate safety and activity of rituximab combined with chemotherapy (CHOP or CVP) in first-line therapy for MALT lymphoma. Methods: Retrospective review of patients with MALT lymphoma treated in first-line with R-CHOP or R-CVP. Patients with gastric MALT lymphoma were included if resistant to or not eligible for anti-Helicobacter pylori therapy. Results: There were 22 patients (8 male, 14 female) with a median age 60 years (range 34 to 77 years). Primary origin: 14 stomach (64%), 3 skin, and 5 others (nodal, parotid gland, orbital, colon, and lung). Stage of disease wa I in 13 patients (59%), II in 2 patients (9%), and IV in 7 patients (32%). Bone marrow infiltration was present in 5 patients (23%). Chemo-immunotherapy was R-CVP in 13 patients and R-CHOP in 9 patients. The median number of cycles for patient was 6. The treatment was well tolerated with mild toxicity. Patients with gastric lymphoma did not have bleeding or perforation during therapy. One patient had to stop rituximab after second cycle because severe infusion reaction. In three patients the vincristine was reduced or removed because sensitive neuropathy. The overall response rate (ORR) in 21 evaluable patients was 95% (CR 81%, PR 14%). None of the patients progressed during therapy. Patients with gastric lymphoma (n=14) showed an ORR of 93% (CR 86%, PR 7%, SD 7%). Radiation therapy was given as consolidation after chemotherapy to 3 patients with extra-gastric origin. With a median follow-up of 28 months, two patients (gastric lymphoma) have relapsed at 4 and 12 months respectively. All patients are alive and 19 (86%) in complete response. Conclusions: Combination of rituximab with either CHOP or CVP is very active with acceptable toxicity in the treatment of MALT lymphoma. Further studies are needed to elucidate the optimal combination of rituximab and chemotherapy in this patient population.

No significant financial relationships to disclose.
Soluble CD44 in patients with aggressive non-Hodgkin's lymphoma: Prognostic and clinical value
Authors: Gharib A. F. , Eltarhony S. A. , Elsawy W. H.
Published: August 2020

e19539

Background: CD44 is a cell surface glycoprotein expressed by a large variety of tissues. In addition to their expression on the cell membrane, CD44 proteins are also released from cells, and soluble CD44 proteins are detectable in the normal human circulation. The observation that several human tumors show an overexpression of CD44 and the presence of soluble CD44 in the circulation makes CD44 a potential serum marker for tumor detection. In this prospective study, we investigated the prognostic and clinical value of s-CD44 in patients with aggressive non-Hodgkin's lymphomas. Methods: s-CD44 concentration was measured in the sera of 64 patients with aggressive non-Hodgkin's lymphomas treated with standard CHOP by using chemiluminescence-enzyme immunoassay (EIA). Results: Circulating serum CD44 (s-CD44) levels have been found to change in parallel with response to therapy, but little is known about the predictive or prognostic significance of s-CD44. The median pretreatment s-CD44 level was 510 ng/mL(range, 90 to 2,120 ng/mL). Only 10 (31%) of the 32 patients with an International Prognostic Index (IPI) score 0 or 1 had s-CD44 concentration higher than the median level, whereas 11 (52%) of 21 patients with an IPI score ≥2 had a concentration higher than the median before initiation of treatment (P < .0001). Patients with lower than the median s-CD44 achieved more often a complete response to therapy (P = .0002) and had better survival (P = .007) than those with higher s-CD44 levels. However, in a multivariate analysis, only the IPI score had independent prognostic value (P < .001). Conclusions: Our results showed that a high s-CD44 level before treatment is associated with a high IPI score, poor response to treatment, and unfavorable prognosis in aggressive non-Hodgkin's lymphoma.

No significant financial relationships to disclose.
Are comorbidities present in non-Hodgkin's lymphoma (NHL) patients (pts) enrolled in recent clinical trials different from those observed in previous clinical trials?
Authors: Noga S. J. , Mo M. , Dreiling L. , Ozer H.
Published: August 2020

e19540

Introduction: Co-morbidities are often more prevalent in community practice than in clinical studies due to an increased mortality risk (Kuderer 2006; Noga 2007). As NHL treatments have changed and NHL rates in the US have increased 81% from 1973 to 1997 (Garber 2001), pt characteristics of NHL practice-changing studies may have changed to reflect the general NHL population. Here we summarize major co-morbid conditions present in pts from 4 key NHL trials published from 1976 to 2007. Methods: Intermediate/high-grade NHLs are sensitive to combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP; McKelvey 1974; Fisher 1993), especially when combined with rituximab (RCHOP; Coiffier 2002). Entry criteria and demographics were tabulated from 4 interventional NHL trials published from 1976 to 2007: McKelvey 1976, a randomized study of 420 pts comparing CHOP and HOP; Fisher 1993, a phase 3, randomized study of 899 pts comparing CHOP, m-BACOD, ProMACE-CytaBOM, and MACOP-B; Coiffier 2002, a randomized study of 399 pts comparing CHOP with RCHOP; Noga 2007, an open-label study that included 325 NHL pts in community practice. Results: More recent NHL trials enrolled older pts compared with earlier trials ( Table ). Further, in the community-practice study by Noga et al (2007), nearly 1/3 of treated pts had at least 1 major co-morbidity. Such co-morbidities may have been formally or informally excluded in earlier clinical trials. Conclusions: More recent clinical trials tend to enroll older pts compared with earlier trials and tend to include pts with the major co-morbidities often seen in the general NHL population. Physicians may be more aware that cancer pts often have a significant prevalence of co-morbid conditions and that supportive care may allow these pts to benefit from study treatment. Clinical practice may also be changing to allow more elderly pts with co-morbidities to receive aggressive chemotherapy.

[Table: see text]

[Table: see text]
Outcomes in patients with primary gastric diffuse large B-cell lymphoma after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) chemotherapy
Authors: Sohn B. , Yoon D. , Kim S. , Lee D. , Kim S. , Huh J. , Lee J. , Suh C.
Published: August 2020

e19543

Background: The optimal therapy for primary gastric diffuse large B- cell lymphoma (DLBCL) still needs to be defined. The aim of this study was to investigate the patient's outcomes after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) treatment in primary gastric DLBCL in a single institution. Methods: We searched AMC Registry for Non-Hodgkin's Lymphoma and found 26 patients with primary gastric DLBCL, who received R-CHOP as first-line chemotherapy. Ten of 26 patients had localized disease. Remaining patients had disseminated disease. R-CHOP was repeated every 21 days in all patients. Results: Overall, complete response (CR) was observed in 20 of 26 patients (76.9%). Three-year event free survival (EFS) and overall survival (OS) was 76.5% and 75.0%, respectively. After analyses of 10 patients with localized disease, we found that these patients had received a total 38 cycles, with a median of 3 cycles per patient. Of 10 patients, one patient had 2 cycles of R-CHOP, 4 had 3 cycles, and one had 4 cycles, all 6 patients above followed by consolidation radiotherapy. Remaining one patient and 4 patients had 5 cycles and 6 cycles of R-CHOP, respectively. In patients with localized disease, CR was observed in 10 of 10 patients (100%), and both 3-year EFS and OS was 100% (10 of 10 patients). In analyses with 16 patients with disseminated disease, all patients had received a total 91 cycles, with a median of 6 cycles per patient. In these patients, two patients had radiation therapy after R-CHOP, one patient had CR before consolidation radiation therapy, and another had partial response before radiation therapy. CR after R-CHOP treatment was observed in 10 of 16 patients (62.5%), partial response in 3 patients, stable disease in 1 patient, and progressive disease in 1 patient. Three-year EFS and OS was 61.1% and 57.8% in patients with disseminated disease. Conclusions: R-CHOP regimen showed a promising result in primary gastric DLBCL. Combination with rituximab in CHOP regimen showed excellent prognosis especially in patients with localized disease. In localized disease, CR was 100%, 3-year EFS and OS was 100%. In disseminated disease, CR was 62.5%, 3-year EFS and OS was 61.1% and 57.8%.

No significant financial relationships to disclose.
Impact of the number of cycles on efficacy of denileukin diftitox (Dd) in subjects with cutaneous T-cell lymphoma (CTCL)
Authors: Geskin L. , Sun Y. , Gao J.
Published: August 2020

e19549

Background: Dd, a recombinant fusion protein designed to target interleukin-2 receptor-expressing malignancies, is the most extensively studied agent in patients with CTCL. Dd is approved for 8 cycles in CTCL. Here, we present data from study L4389–11 on the effect of treatment course on the efficacy of Dd. Methods: Subjects received Dd doses of 9 or 18 mcg/kg IV daily for 5 days, repeating every 21 days for up to 8 courses. The majority of subjects had CTCL stage ≤ IIa at baseline. Thirty three percent of subjects had received 2 prior anticancer therapies and 23% had received 3 prior anticancer therapies. For all subjects (n=144), the overall median age was 59 years. Tumor burden in skin, blood and lymph nodes and a physician's global assessment were determined at each study visit relative to baseline. Response confirmation was adjudicated by an independent Data Endpoint Review Committee (DERC) after 3 consecutive courses. The primary endpoint was ORR including CR (no clinical evidence of disease based on tumor burden assessments and photography and histopathology of skin biopsy indicated absence of atypical cells), CCR (no clinical evidence of disease based on tumor burden assessments and photography and either the presence of atypical cells was indicated by histopathology of a skin biopsy or histopathology was unavailable) and PR (≥ 50% reduction in measured tumor burden). Data reflect the first treatment course in which the best response was recorded for Dd-treated subjects who responded (n=44) based on the DERC assessment. All responses counted were confirmed in 2 successive assessments. Results: 45% of best responses occurred in cycles 4 thru 8 and the evolution to CR occurred from 4 cycles and beyond. Conclusions: These data support the approved 8 cycles of Dd therapy in CTCL.

[Table: see text]
HIV-associated peripheral T-cell lymphoma
Authors: Milani C. , Castillo J.
Published: August 2020

e19551

Background: T-cell lymphomas (TCL) constitute 3% of all AIDS-related lymphomas. Over the past 2 decades numerous case reports have documented the emergence of TCL among HIV-infected individuals. These lymphomas comprise a diverse group of disease entities, including peripheral T-cell lymphomas (PTCL), which represent the most common subtype. The aim of this study was to investigate the clinical and pathological features of HIV-associated PTCL. Methods: A MEDLINE search for cases of HIV-associated PTCL was conducted through December 2008. Data regarding patient age, gender, HIV status (CD4 count, viral load, opportunistic infections), use of HAART, lymphoma features (B symptoms, stage, sites of involvement, immunophenotype, molecular studies), EBV coinfection, therapy, and outcome (survival, cause of death) were analyzed and reported descriptively. Results: A total of 34 cases were included. Patients had a median age of 36 years with a male:female ratio of 4:1. Median CD4+ count was 126 cells/mm3. Seventeen patients (50%) had an opportunistic infection, but only 7 patients (26%) were on HAART treatment; 4 patients on HAART (57%) were alive at time of publication. PTCL was extranodal in 75% of cases, affecting predominantly the oral cavity, lung, and GI tract. B symptoms were present in 60% of cases. Stage III and IV disease was found in 17 and 5 cases, respectively, accounting for 76% of the total cases. T-cell receptor gene rearrangement was positive in 10 out of 10 (100%) analyzed cases. EBV was identified in 6 of 12 cases (50%). Median LDH level was 269 IU/L. Therapy for PTCL was administered in 23 cases (68%), while 10 cases (30%) did not receive therapy; 9 of the treated patients (39%) received CHOP with a 33% remission rate. Twenty-two patients (69%) died complicated by infections in 57% and lymphoma progression in 36% of cases. The reported median survival was 12 months. Conclusions: HIV-associated PTCL tends to affect young male individuals with low CD4 counts. Apart from marked immunosuppression, the poor prognosis of HIV-associated PTCL appears to be related to advanced stage at presentation, presence of B symptoms, elevated LDH levels, prominent extranodal disease, and poor response to CHOP chemotherapy. The role of HAART and EBV in the development of PTCL needs further clarification.

No significant financial relationships to disclose.
Primary nasopharyngeal non Hodgkin lymphoma: A retrospective investigation of 26 patients
Authors: Nabil I. N. , Allam W. , Alaoui K. , Errihani H.
Published: August 2020

e19552

Background: Primary nasopharyngeal non-Hodgkin lymphoma (NNHL) was uncommon. In this retrospective study we report our experience dealing with this disease at the National Institute of Oncology. Methods: We retrospectively analyzed various characteristics of Primary NNHL: patient demographics, clinical and histological diagnosis, disease stage, treatment effects and outcome, in 26 patients treated at our institution between January 2001 and December 2007. Results: The average age of our patients was 52.7 years (range: 31 - 87 years). The male/female ratio was equal to 1.5/1. The major symptoms at first diagnosis were: nasal obstruction (88.6%), hypoacousia (88.4%), epistaxis (33.3%) and rhinorrhea (15.3%). Clinical examination founded bilateral cervical lymph nodes in 17 cases (65%). Histological analysis showed follicular lymphoma in 7 cases (26.9%), large B-cell lymphoma in 11 cases (42,3%) and T lymphoma in 4 cases ( 15,3%). Four (15.4%) of the patients were at stage I, 15 (57.6%) were at stage II, and 7 (27%) were at stage III/IV. At early stage, the patients were managed with chemo-radiotherapy and were managed with CHOP based chemotherapy at advanced stage. At the end of total treatment, 18 patients (69.2%) achieved complete response and remained disease free while 4 (15.4%) achieved partial response (>70%) and 4 (15.4%) were progressive (these patients received second line chemotherapy). After 110 months median flow-up, median disease free and overall survival were not reached. Overall, the treatment was well tolerated. Conclusions: From our study and from the literature, we conclude that histological characteristics, principle of treatment and outcome of primary NNHL patients are similar to that of patients with nodal lymphoma.

No significant financial relationships to disclose.