bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II pilot study of neoadjuvant cetuximab in combination with cisplatin and gemcitabine in patients with resectable IB-IIIA non small cell lung cancer
Authors: Coate L. E. , Gately K. , Barr M. P. , Meaney J. , O’Connell F. , Nicholson S. , McGovern E. , Young V. , O’Byrne K. 
Published: March 2020

17107 Background: Adjuvant and neoadjuvant chemotherapy play a role in optimising long term outcome of patients with resectable non small cell lung cancer (NSCLC). The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase which is overexpressed NSCLC. Cetuximab is a monoclonal antibody which attaches to the extracellular domain of the EGFR preventing ligand binding. Preclinical data and phase II evidence in advanced NSCLC suggest cetuximab potentiates the effect of conventional cytotoxic agents. Methods: Patients with histologically confirmed resectable stage IB-IIIA NSCLC and adequate end-organ function, giving informed written consent are eligible. Three weekly cycles of cisplatin 80 mg/m2 D1, gemcitabine 1250 mg/m2 D1,D8 and cetuximab loading dose of 400 mg/m2 on first infusion, thereafter weekly 250 mg/m2 are used. The primary endpoint is response rate (radiological and pathological). Secondary endpoints are safety and tolerability of the combination, resection rate following therapy, overall survival and relapse free survival. In addition, molecular prognostic and predictive biomarkers of response are being assessed. Sequential samples of tissue, plasma, serum and white blood cells are being collected before, during and after therapy on all patients. Results: 16 patients have been recruited to date. (10 men, 6 women). Median age 66 (range 29–76). 3 patients stage I, 4 patients, stage II, 9 patients stage III. 11 have completed treatment. Response (RECIST guidelines); PR - 6 patients, SD - 4 patients, PD - 1 patient. The most common toxicity was skin rash (100%). Grade 3/4 toxicities were neutropenia (73%), thrombocytopenia (45%). There were 2 grade 3 and 2 grade 4 cardiovascular toxicities in patients with significant co-morbid cardiovascular histories. Conclusion: The response rate is consistent with that established for neoadjuvant chemotherapy. Ongoing biomarker studies may identify those patients most likely to benefit from induction treatment. No significant financial relationships to disclose.
PDGFR-β expression in small cell lung cancer patients
Authors: Lu B. 
Published: March 2020

17128 Background: Small cell lung cancer (SCLC) carries an extremely poor prognosis and treatment options for this disease remain poor. PDGF and PDGFR-β are expressed and have been found to have prognostic value in several human cancers. Data in non-small cell cancer cell lines have suggested that PDGFR is a therapeutic target for drug development. In the current study PDGFR-β expression and prognostic value in SCLC was investigated. Methods: Paraffin embedded tissue blocks from 53 patients with limited and extensive stage SCLC were obtained for immunohistochemical staining. Tumors from each patient were sampled three times and stained with PDGFR-β specific antibody. Patients were divided into low and high staining groups based on intensity. Results: There was high intensity PDGFR-β staining in 20 patients with SCLC. Another 29 expressed low intensity PDGFR- β staining, with only 4 patients showing no PDGFR- β staining. There was no statistically significant difference in five year overall survival between patients with low levels of PDGFR-β staining versus those with high level staining SCLC tumors (P = 0.538). Conclusions: Though expression of PDGFR-β may not be a predictor of prognosis, due to its high expression in SCLC it may represent an important target for improved tumor control, however, further studies are required to confirm this. No significant financial relationships to disclose.
The rationale for the NEOCOR study: A new paradigm in locally advanced non-small cell lung cancer
Authors: Mitra S. S. 
Published: March 2020

17146 Background: Most patients with locally advanced NSCLC die of systemic disease. (Chevalier et al JNCI 1991). Concurrent chemoRT + adjuvant chemotherapy is the standard of care based on a metaanalysis comparing sequential chemoRT and Concurrent chemoRT, with median survival increased by 3 months. (Hak Choy ASCO 2003) The aim is to critically review all the sequential trials and the metaanalysis against a scientifically valid criteria. Methods: A scientifically valid trial comparing the two approaches: sequential chemoRT versus Concurrent chemoRT needs to have equivalent chemotherapy in both arms. It also needs to have equivalent chemoRT in both arms. There needs to be an adequate course of neoadjuvant chemotherapy (at least 4 cycles) in the sequential chemoRT arm. All the relevant sequential chemoRT versus concurrent chemoRT trials are critically reviewed. Results: The sequential chemoRT trials had an average of 2 cycles of chemotherapy before radiation. (Dillman et al CALGB B 8433, Sause et al ECOG 4588, Schaakee - Koning et al NEJM 1992). The Hak Choy metaanalysis is not a comparison of the two approaches: sequential chemoRT versus concurrent chemoRT. The WJLCG Furuse trial had more intensive chemotherapy in the concurrent arm. The GLOT-GFPC study had Etoposide chemotherapy on the concurrent arm. The LAMP study, Zatloukal - Zemanova study & RTOG 9410 all had 2 cycles of chemotherapy followed by radiotherapy or concurrent chemoRT. SWOG 9504 using Cisplatin + Etoposide concurrent with Radiotherapy and adjuvant Docetaxel suggests that systemic treatment is important along with concurrent chemoRT. Betticher et al ( JCO 2003) showed that neoadjuvant chemotherapy with Docetaxel + Cisplatin achieves a 19% complete pathological response & overall 66% response rate. Conclusions: Most patients with locally advanced NSCLC still die of systemic disease. Sequential chemoRT trials did not have adequately intensive chemotherapy regimens.Concurrent ChemoRT is a better form of RT. The author proposes a phase II trial of Neoadjuvant Chemotherapy with 4 cycles of Docetaxel 85 mg/m2 D1+ Cisplatin 50 mg/m2 D1 & 2 followed by 2 cycles of Concurrrent Chemoradiotherapy with Cisplatin 50 mg/m2 D1 & D8 + Etoposide 50 mg/m2 D1–5 concurrent with 61 Gy of Radiotherapy as a new paradigm in Locally advanced NSCLC. No significant financial relationships to disclose.
ECOG 1503: A phase II trial of triapine (NSC#663249) with gemcitabine (T/G) as 2nd line treatment of non-small cell lung cancer (NSCLC)
Authors: Traynor A. M. , Levy D. E. , Bayer G. K. , Tate J. M. , Thomas S. P. , Mazurczak M. A. , Graham D. L. , Kolesar J. M. , Schiller J. H. 
Published: March 2020

17151 Background: Triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone) is a novel chelator of the ribonucleotide reductase (RR) subunit M2. Triapine was shown to enhance cellular uptake and DNA incorporation of gemcitabine in tumor cell lines. Preclinical evidence suggested that cells with the wild-type (wT) MDR1 gene may have lower intratumoral concentrations of Triapine. Objectives: Primary objective was response rate (RR). Secondary objectives included rate of stable disease (SD), progression free survival (PFS), overall survival (OS), and safety of T/G in the 2nd line treatment of advanced NSCLC. Correlative objectives were to examine the effects of MDR1 polymorphisms, RRM1, RRM2, and p53R2 protein and gene expression, and germline and tumor mutations of p53 on clinical outcomes. Methods: Pts with relapsed NSCLC who failed one prior cytotoxic regimen were eligible; prior gemcitabine was excluded. Treatment: Triapine 105 mg/m2 IV on days 1, 8, and 15 and gemcitabine 1000 mg/m2 on days 1, 8, and 15, of a 28 day cycle. Results: 18 pts enrolled from 11/04–1/05. Stage: IIIB (1 pt); IV (17 pts). PS: 0 (4 pts); 1 (14 pts). Median number of cycles administered: 2. No objective antitumor responses were seen. 5 pts experienced SD (range 7–135 days). Median OS: 5.4 mo (95%CI 3.98, not yet reached); median PFS: 3.2 mo (95%CI 1.7, 6.4); estimated 1 yr OS: 39% (SE 13%). Worst Gr 3/4 toxicities: leucopenia (Gr 3–8 pts; Gr 4–1 pt), neutropenia (Gr 3–8 pts; Gr 4–2 pts), hypoxia (Gr 3–4 pts), vomiting (Gr 3–2 pts). Genotyping for MDR1 polymorphisms C1236T, G2677T, and C3435T was performed on all pts. None of the 5 pts with SD were wTs. Pts with wT MDR1 had increased GI and pulmonary toxicity. Additional correlative data will be available for the meeting. Conclusions: T/G did not demonstrate clinically relevant activity in relapsed NSCLC. Genotyping for MDR1 polymorphisms may predict both efficacy and toxicity. [Table: see text]
Expression of telomerase enzyme as predictive factor of response to first line chemotherapy with gemcitabine/carboplatin in advanced non-small cell lung cancer (IIIB and IV)
Authors: Pluma-Jimenez M. , Castillo-Medina S. , Murillo-Ortiz B. , Labastida S. , Alvarado I. , Olivares-Beltran G. , Silva J. A. , Astudillo-De La Vega H. 
Published: March 2020

17156 Background: Non-small cell lung cancer (NSCLC) is the most frequent neoplasia in the world and the main cause of death for cancer. The palliative chemotherapy is the elected treatment for patients in stage III and IV. The telomerase enzyme is expressed in 82% of neoplasias and its activity is implied in the genomic instability, apoptosis inhibition and cell immortalization. Objective: To determine the predictive value of the expression of the telomerase enzyme with the first line regimen gemcitabine (1 gr/m2 SC, days 1 and 8) and carboplatino (AUC of 5 in day 1) every 28 days in patients with NSCLC clinical stages IIIB and IV. The response and toxicity rate was also determined. Methods: Patients were recruited in a period between 04/01/2004 and 11/30/2004, ages between 18 and 80, ECOG ≤ 2, measured disease (RECIST), virgin to treatment, permissible hematic biometry for chemotherapy and optimal kidney function. A total of 17 patients with an average age of 61 (range 44 to 77 years old) 9/17 (53%) males and 8/17 (47%) females, 4/17 with clinical stage IV (23%) and 13/17 with clinical stage IIIB (77%) from which: 8/13 (61%) presented pleural effusion. From the total number of patients, 1/17 presented ECOG 0 (6%), 14/17 ECOG 1 (82%) and 2/17 ECOG 2 (12%). The histopathologic diagnosis was adenocarcinoma in 12/17 (70%) and epidermoid carcinoma in 5/17 (30%). A rabbit polyclonal antibody was used to asses the expression of the telomerase enzyme by the immunohistochemical method. Results and Conclusions: It was demonstrated in 11/17 patients that the high expression of telomerase enzyme is directly correlated to the lack of response to treatment (3/11 patients stable disease and 4/11 with progressive disease); and a low or absent expression (4/11 patients) was correlated to a response higher than 30% (p = 0.045). The obtained response rate was lower that the previous ones reported with the regimen gemcitabine (days 1, 8 every 21 days and 1, 8 and 15 every 28 days) presenting a minimum hematologic toxicity. This analysis suggests that the telomerase enzyme could be a response predictive marker in the NSCLC with this therapeutic regimen. No significant financial relationships to disclose.
A dose dense low toxicity salvage regimen for histologically aggressive non-Hodgkin’s lymphoma (NHL): Gemcitabine, rituximab, oxaliplatin combination (GROC) plus pegfilgrastim
Authors: Cabanillas F. , Liboy I. , Rodriguez-Monge E. , Pavia O. , Robles N. , Maldonado N. , Rivera E. , Suau L. 
Published: March 2020

17513 High dose chemo/autologous stem cell transplant (ASCT) is standard treatment for relapsed aggressive NHL. However many are unable to receive ASCT because they are refractory to salvage therapy, too old or too sick. More effective, less toxic salvage regimens are needed prior to ASCT. Gemcitabine (G) and Oxaliplatin (O) are active agents in NHL and exhibit synergism so their combination is attractive to explore together with Rituximab (R). We hereby report the results of a phase I-II trial designed to explore the GROC regimen administered every 14 days with Pegfilgrastim support. After the first 6 pts were entered, the phase I portion was completed; recommended dose: R = 375 mg/m2 on day 1, G = 1,250 mg/M2 on day 2, O = 100 mg/m2 on day 2 and Neulasta 6 mg day 3. So far we have entered 21 pts of which 19 are currently evaluable. Median age = 58 (range = 27–88); 9 were refractory to 1st line therapy, 5 were on 1st relapse, 3 on 2nd and 2 >2 relapses, 12 had high LDH, 10 high Beta-2-M. Using IWG/PET criteria ORR = 79%, CR = 42%, PR = 37%. There was a correlation between response to preceding chemo regimen and response to GROC ( table ). In 6 the response to GROC was better than to preceding regimen while only in 2 was the response worse. At 1 year the projected OS is 49% and PFS 34%. So far, only 5 of 15 responders have relapsed. An intriguing finding is that in 6 of 15 responders, PFS has been longer with GROC than with preceding regimen and shorter in only 1. Grade 4 hematologic toxicity occurred only once. No neutropenic fevers seen. Most common toxicity was reversible transaminitis in 13 (grade 1–2 in 10, grade 3 in 3), neuropathy in 9 (grade 1–2 in 8, grade 3 in 1), diarrhea in 3 (grade 4 in 1). We could deliver courses at a median interval of 14 days. Conclusions: 1- GROC is an effective dose dense salvage regimen. 2- It appears effective even in pts with poor prognostic features including primary refractory disease. 3-Hematologic toxicity is very low and non-hematologic toxicity acceptable. [Table: see text] [Table: see text]
A phase II study of R-CHOP in treatment of diffuse large B-cell lymphoma (DLBCL) subgroups
Authors: Cao Y. , Lin T. , Wang S. , Fu X. , Xiao J. , Yi J. , Lin H. , Guan Z. 
Published: March 2020

17540 Background: Recent studies with genes expression profiling and tissue microarray have divided the diffuse large B cell lymphoma (DLBCL) into prognostically important subgroups with germinal center B cell like (GCB) and non-GCB. However, these results are based on the samples of patients who were received standard CHOP regimen. Combination with CHOP and Rituximab (R-CHOP) has been proved to improve the survival of patients with DLBCL. To evaluate the efficacy of R-CHOP in different subgroups of DLBCL, this phase II study has been conducted. Methods: Previously untreated patients with DLBCL were enrolled in this study. No upper age limit was specified. Patients received six cycles of R-CHOP (rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2, and prednisone 40 mg/m2 for 5 days) every 3 weeks. Immunohistochemical stains on paraffin-embedded tissues from diagnostic biopsies from these patients with antibodies against GCB cell (CD10 and Bcl-6) and activation (MUM1). These patients are divided into GCB and non-GCB groups according to the expression of antibodies against CD10, BCL-6 and MUM1. Results: A total of 64 patients were evaluated, 19 in GCB group and 45 in non-GCB group. Complete Remission (CR) rate was achieved 57.9% and 53.3%, in GCB group and in non-GCB group, respectively. (p = 0.737). A median follow-up of 2.2 years, the two-year failure free survival was no different between two groups (p = 0.566). Conclusions: In patients with GCB group or non-GCB group of DLBCL, addition of Rituximab in CHOP regimen, preliminary result was showed in similar response and survival. No significant financial relationships to disclose.
The pre-treatment PET scans SUV inversely correlates with overall survival (OS) of high grade NHL
Authors: Sukari A. , Wong O. , Balasubramaniam M. , Decker D. 
Published: March 2020

17543 Background: Parling-Lynch (Blood 2003; Abs, 102(11):4805). report a high discriminative power of maximum standard uptake value (SUV) in differentiating high and low grade lymphoma. This study examines the relationship between the pre-treatment (18)F-2-deoxy-2-fluoro-D-glucose Positron emission tomography (18-FDG PET) scans, SUV, overall survival (OS) and disease free survival (DFS) in high grade non-Hodgkin’s lymphoma (NHL). Methods: 33 patients with pathological diagnosis of aggressive NHL but without other malignancies were included; the patients had a pre treatment 18-FDG PET scan with calculated SUV. NHL was classified using WHO classification, IPI score was calculated using International Non-Hodgkin’s Lymphoma Prognostic Factors Project criteria. Cox Proportional Hazards Regression analysis was used to assess the effect of SUV and the grouped IPI Score on both overall survival and disease-free survival. Results: 29 patients have diffuse large B-cell lymphoma (DLBCL), 2 have Mantle cell lymphoma (MCL) and 2 have peripheral T-cell lymphoma (PTCL). Over a median follow up of 2.6 years (0.6–4.6), OS and DFS were 76% and 82%, respectively. Median SUV was 18.6 (1.6–55.9). Patients with higher SUV have higher risks of dying after adjusting for their IPI Score (p-value = 0.0038). Specifically, each additional unit of SUV is associated with a 9.8% increase in the hazard of death. Patients with higher IPI Score have higher risks of dying after adjusting for their SUV (p-value = 0.0017). Specifically, each additional level of IPI Score is associated with a 274.9% increase in the hazard of death. SUV is not a significant predictor of disease-free survival once IPI Score is already known/adjusted for (p-value = 0.0731). Patients with higher IPI Score have higher risks of relapse after adjusting for their SUV (p-value = 0.023). Conclusions: Pre-treatment PET scan SUV significantly affects overall survival in high grade NHL. Our data indicate statistically non significant correlation between SUV and DFS. These findings could be secondary to small study sample or short median follow up. No significant financial relationships to disclose.
Treatment of newly diagnosed, inner-city multiple myeloma patients with low-dose thalidomide and dexamethasone and zoledronate
Authors: Klueppelberg U. H. , Kahn D. M. , Braunstein M. , Smith E. L. , Shapira I. , Batuman O. 
Published: March 2020

17555 Background: The incidence of multiple myeloma (MM) is high in African Americans (AA), who are underrepresented in clinical trials. This Phase II trial assessed thalidomide (100 mg/day), dexamethasone (10–40 mg for 4 days/week x3 for 6 months, then 4 days/month), and zoledronate (4 mg/4 weeks) (TDZ) in newly diagnosed AA patients with MM. TDZ was designed to be non-myelotoxic and compatible with HAART because of the high HIV infection rate in our patients. Because it mitigates tumor growth and angiogenesis and bone resorption, zoledronate was expected to boost the therapeutic effects of thal and dex. All newly diagnosed patients were eligible. Methods: Of 45 enrollees, 38 (22F/16M; median age = 61 years) were evaluable. All had bone disease, and baseline serum beta2-microglobulin (4.9 mg/dL) and albumin (3.3 mg/dL) indicated advanced disease. Eight patients (21%) were HIV+ (7F/1M; median age = 47 years). Patients with HIV were younger (P < .001) and had higher β2-microglobulin levels (P = .003), and 6 were on HAART. Patients were treated for 24 months or until disease progression. Results: Mean duration of treatment was 18 months (range = 3–24). Age-adjusted one-year survival was 74.4%, identical to SEER data (73.7%). Near-CR was achieved in 30% (7 HIV-/4 HIV+) and partial remission in 68% (22 HIV-/3 HIV+) of patients. Median time to maximum response was 4.5 months in HIV- patients and 2.5 months in HIV+ patients (P < .05). Overall cumulative survival at 24 months was 68% by Kaplan-Meier analysis, and was unaffected by HIV status, age, or sex. Creatinine clearance both for HIV+ and HIV- patients was normal, and was unaffected by TDZ. Despite daily ASA, thromboembolism occurred in 13% of patients. No other significant toxicity was observed. Ten patients died (9 HIV- and 1 HIV+); deaths were due to MM progression (n = 3), MM complications (n = 3), and causes unrelated to MM (n = 4). Conclusions: TDZ is safe and effective in the long-term management of MM, and is comparable to high-dose chemotherapy with stem cell rescue for both HIV- and HIV+ patients. TDZ is without renal or osteonecrotic side effects. The faster response to TDZ in HIV+ MM patients on HAART suggests a cooperative interaction between the two regimens. No significant financial relationships to disclose.
Multiple primary cancers in patients with non-Hodgkin’s lymphoma
Authors: Song H. , Do Y. , Lee W. , Lee J. 
Published: March 2020

17562 Background: Multiple primary malignant tumors have been documented with increased frequency over the last two decades. An analysis of other primary cancers in individuals with non-Hodgkin’s lymphoma (NHL) can help to elucidate this cancer epidemics and etiology. Methods: The occurrence of multiple malignancy was studied in patients with NHL from 1985 to 2005. Results: One or more additional cancers were observed in 19 patients. Seven were diagnosed prior to, 5 concomitantly with, and 7 after the diagnosis of NHL. The diagnosis of 5 synchronous primary cancer were rectal cancer, squamous cell esophageal cancer, prostatic cancer, transitional cell bladder cancer, and non-small cell lung cancer. Each cases of colon cancer, breast cancer, hepatoma, small cell lung cancer, stomach cancer, cervical cancer, and rhabdomyosarcoma were diagnosed prior to NHL, and the second primary cancers were two squamous skin cancer and each cases of melanoma, colon cancer, thyroid cancer, adenocarcinoma of the salivary gland, and cholangiocarcinoma. The mean age of synchronous cases was 68.2 ± 4.8 years-old, and all 5 cases were primary extranodal NHL (2 gastric, 1 nasopharynx, 1 nasal, 1 rectal) and pathologic diagnosis were diffuse large cell in 4 cases and extranasal NK/T cell type in one case. The mean age of the second primary NHL was 57.6 ± 11.4 years-old, and 5 of 7 cases were extranodal origin (each one case of colon, tonsil, tongue, stomach, and CNS), and were diagnosed 11, 19, 24, 72, 73, 101, 168 months after the diagnosis of variable cancers. The mean age of the second primary cancer was 46.9 ± 15.9 years-old, and 3 of 7 cases were extranodal origin (2 gastric and 1 tonsil), and were diagnosed 55, 73, 75, 99, 144, 156, 161 months after the diagnosis of NHL. Conclusions: The synchronous cases of NHL were more older and more frequent extranodal manifestations than metachronous cases. No significant financial relationships to disclose.