bluuebunny/crossref_metadata_2025_split huggingface dataset:
RTOG 0131: Phase II trial of pre-irradiation and concurrent temozolomide in patients with newly diagnosed anaplastic oligodendrogliomas and mixed anaplastic oligodendrogliomas: Relationship between 1p/19q status and progression-free survival
Authors: Vogelbaum M. A. , Berkey B. , Peereboom D. , Giannini C. , Jenkins R. , Suh J. , Brown P. , Blumenthal D. , Biggs C. , Mehta M. 
Published: March 2020

1517 Background: In a previous report, we showed in patients with newly diagnosed anaplastic oligodendrogliomas (AOs) and mixed anaplastic oligoastrocytomas (MAOs) that temozolomide (TMZ) can be given concurrently with radiation therapy (RT) with acceptable toxicity. We have now evaluated the efficacy of this regimen and correlated durability of response with tumor 1p/19q genotype. Methods: A phase II study was performed to evaluate the use of pre-RT TMZ followed by concurrent RT and TMZ in patients with newly diagnosed AO or MAO. The primary endpoint was to determine the pre-RT TMZ six-month progression rate, and secondary endpoints included progression-free survival and overall survival. Results: 40 eligible patients were entered into the trial. Thirty-two patients completed 6 months of pre-RT TMZ and concurrent RT and TMZ. Of the remaining eight patients, 4 withdrew due to toxicity and 4 other patients withdrew from study without evidence of toxicity or pre-RT progression. 1p/19q data are available in 37 cases; 23 tumors had loss of heterozygosity (LOH) of both 1p and 19q (double-deleted) while 14 tumors had LOH of either 1p or 19q (n = 3), or no LOH (n = 11). To date, 11 patients have experienced tumor progression; 1p/19q data are available for 10 of these cases (2 are double-deleted (2/23 = 9%), 8 have at least one intact chromosome (8/14 = 57%). Kaplan-Meier analysis demonstrates that progression free survival is significantly better for the double-deleted group (median time to progression not reached) than for the intact group (median time to progression = 15.2 months, p = 0.001). Overall survival is 98% (39/40) with a median follow-up of 17.5 months (2.8 - 31.1 months). Conclusions: LOH of both 1p and 19q is strongly correlated with a durable response of AO and MAO to a combined regimen of chemotherapy and radiation therapy. Tumors that are intact at 1p and/or 19q progress early despite an aggressive therapeutic regimen. These results suggest that future clinical trials should be prospectively stratified by tumor 1p/19q genotype. [Table: see text]
NCCTG 96–94–53: Clinical variables associated with overall survival (OS), progression-free survival (PFS), 6 month progression-free survival (PFS6), immediate progression (ImmProg), and response in patients enrolled in recurrent glioma clinical trials
Authors: Buckner J. C. , Ballman K. , Schaefer P. , Furth A. F. , Giannini C. , Scheithauer B. W. , Galanis E. , Jaeckle K. A. 
Published: March 2020

1520 Background: Multiple variables may impact endpoints utilized to assess efficacy of investigational therapies for pts with recurrent gliomas. Understanding the nature of these variables should aid interpretation of results. Methods: 583 pts were enrolled to 15 consecutive recurrent glioma clinical trials conducted between 1980 and 2004. Identical patient, tumor, treatment and time variables were identified for each trial. Central neuropathology review was completed and pts were grouped by WHO diagnoses. Pts alive and progression-free at 6 months after start of treatment were a PFS6 ‘success’. Pts whose outcome was progression at first evaluation were classified as “Immediate Progression (ImmProg)”. Response was defined as regression, partial regression, or complete regression in the absence of worsening neurologic symptoms or increased corticosteroid dose. Univariable and multivariable Classification and Regression Trees (CART) models were used to identify factors associated with OS, PFS, PFS6, ImmProg, and Response. Results: Variables associated with outcomes for each endpoint assessed by CART models are shown in Table below. Conclusions: In clinical trials of recurrent glioma, age, PS, duration of disease, primary and recurrent histologic diagnosis, and primary and recurrent extent of resection are associated with outcomes. These variables should be validated in additional datasets for potential inclusion in reports of future clinical trials. [Table: see text] No significant financial relationships to disclose.
Concurrent weekly cisplatin and radiation therapy for nasopharyngeal carcinoma
Authors: Beldjillali Y. , Benhadji K. A. , Yekrou D. , Dali Youcef F. , Djellali L. , Yamouni M. 
Published: March 2020

15507 Background: Platimum based chemotherapy and radiotherapy combinations are the corner stone of management of nasopharyngeal carcinoma. Concomitant chemoradiotherapy may increase activity of the treatment but also increase toxicity. The purpose of the present study was to evaluate both aspects in patients (pts) with nasopharyngeal carcinoma (NPC). Methods: Previously untreated patients with NPC and ECOG performance status 0–2, were enrolled in this study. Cisplatin was administered weekly, starting on day 1 as an intravenous infusion at 40 mg/m2 together with radiation therapy: 1.8–2.0 Gy per fraction, 5 fractions a week. The total dose delivered to the nasopharynx was 65 to 70 Gy and 45 Gy to lymph nodes with a boost of 15 Gy the node-bearing areas. Treatments were administered during 6 weeks. Results: 86 pts were enrolled in this study, 56 male and 30 female, with a median age of 41 years (range 16–69). 26 pts had stage IVb, 24 pts stage IVa, 17 pts stage III, 18 pts stage II and one pt stage I disease. 62 pts had undifferentiated, 22 poorly differentiated and 2 differentiated NPC. The complete response rate was 86% for all patients and the overall response rate was 93%, 7% of cases remained stable. After 494 cycles, grade 3 & 4 toxicity (NCI) were: neutropenia (1%), anemia (1%), nausea and vomiting (14%), dysphagia (12%). 4 pts had cutaneous induration/fibrosis. All pts presented hyposialosis. The disease free survival and overall survival at one year were 78% and 83% respectively. Conclusion: Concomitant chemotherapy and radiotherapy in pts with NPC result in a high complete response rate with an acceptable safety profile. Further follow-up is necessary to assess the curative potential of this combined modality. [Table: see text]
Induction chemotherapy followed by alternating chemo-radiotherapy in advanced undifferentiated nasopharyngeal carcinoma (UNPC)
Authors: Ponzanelli A. , Vigo V. , Bacigalupo A. , Marcenaro M. , Benasso M. 
Published: March 2020

15508 Background: Concomitant chemo-radiotherapy is the standard treatment for advanced UNPC. Induction chemotherapy may improve the results further by enhancing both locoregional and distant control. Methods: Fifty patients with previously untreated, locoregionally advanced UNPC were initially treated with 3 courses of epidoxorubicin, 90 mg/mq, day 1 and cisplatin, 40 mg/mq, days 1 and 2, every 3 weeks. After a radiological and clinical response assessment patients underwent 3 courses of cisplatin, 20 mg/mq/day, days 1–4 and fluorouracil, 200 mg/mq/day, days 1–4, i.v. bolus, (weeks 1,4,7) alternated to 3 splits of radiation (week 2–3, 5–6, 8–9-10), with a standard fractionation, up to 70 Gy. Histology was WHO type 1 in 1 pt (2%), WHO type 2 in 10 pt (20%), WHO type 3 in 39 pts (78%). All patients had stage IV disease (UICC 1992). Results: All the patients are evaluable for toxicity and response. All but one received 3 cycles of induction chemotherapy. Toxicities from induction chemoyherapy were: 2% grade 3 or 4 mucositis, 22% grade 3 or 4 nausea/vomiting, 6% grade 3 or 4 haematological toxicity and one episode of febrile neutropenia. At the end of induction phase 12% of CRs, 84% of PRs and 4% of SD were recorded. All patients but two had the planned number of chemotherapy courses in the alternating phase and all but one received the planned radiation dose. Toxicities from alternating chemo-radiotherapy were: 28% grade 3 or 4 mucositis, 8% grade 3 or 4 nausea/vomiting, 24% grade 3 or 4 haematological toxicity with no episodes of febrile neutropenia. At the final response evaluation 86% of CRs and 14% of PRs were observed. At a median follow up of 39 months, 14% of patients had locoregional failure, 20% had distant failure and 2% both. The 4-year actuarial progression free survival and overall survival rates were 71% and 81%. Conclusions: Treatment of locoregionally advanced UNPC with induction chemotherapy followed by alternating chemo-radiotherapy is feasible and patients’ compliance is optimal. 4-year outcomes seems better than those reported with concomitant chemo-radiotherapy alone. No significant financial relationships to disclose.
Phase II study of gefitinib in metastatic or locoregionally recurrent nasopharyngeal carcinoma (NPC)
Authors: Chan A. T. , Ma B. , Hui E. P. , King A. , Kam M. , Kwan W. H. , Mok T. , Leung S. F. 
Published: March 2020

15509 Background: Our preclinical work has shown that epidermal growth factor receptor (EGFR) is expressed in ∼ 80% of undifferentiated NPC & gefitinib is a small molecule inhibitor against EGFR with anti-proliferative activity in NPC in vitro. Methods: We report the preliminary result of a phase II study of gefitinib in patients (pts) who progressed after 1–2 lines of chemotherapy (at least 1 line had to contain platinum) for metastatic or locoregionally recurrent NPC. Fourteen Chinese pts were accrued, of whom the median age was 48 years (range 34–64 years), 12 were males, 9 had metastatic & 5 had locoregionally recurrent NPC. All received gefitinib at 500mg/day orally, every 28 days with radiological assessment performed every 2 cycles for a maximum of 8 cycles. Ten pts had 1 line & 5 pts had 2 lines of prior chemotherapy. Results: The median number of administered cycles was 2 (range 1–8). Of the 14 pts evaluable for toxicity, the most commonly reported were acneiform rash (86%, grade 1–2, n = 10; grade 3, n = 4), dry skin (86%, grade 1–2), diarrhea (71%, grade 1–2), fatigue (64%, grade 1–2), anorexia (64%, grade 1–2) & nausea (20%, grade 2). Other grade 3–4 toxicities included fever (n = 2, skin cellulitis, infective pneumonia), hyponatremia (n = 2), near-syncope (n = 2), anemia (n = 1). Dose reduction to 250mg/day was required in 4 pts who encountered grade 3 skin rash. Of the 11 pts evaluable for response, 2 had stable disease (SD) for ≥ 6 months (m) (mean 6.8 m) 9 progressed and no partial responders. Five pts have died mostly of progressive disease & there were no treatment-related deaths. Conclusions: Gefitinib is well tolerated in pts with advanced NPC with some pts experiencing disease stabilization for over 6 months & study accrual is ongoing. No significant financial relationships to disclose.
Modulation of integrin α5 in head and neck cancer cells by epidermal growth factor and its contribution to the malignant phenotype
Authors: Kertsman J. , Cohen E. , Abdellatif M. , Wieder R. 
Published: March 2020

15512 Background: The primary therapy for head and neck cancer consists of combination treatment with radiation and chemotherapy. While this combined modality approach is often curative, a significant fraction of patients have residual viable tumor cells after treatment that can result in progressive disease or relapse. We hypothesize that a significant contribution of cell survival results from interaction of cancer cells with the tumor microenvironment that includes soluble ligands of growth factor receptors and structural ligands of cell surface adhesion molecules. One of the growth factors with reported tumor survival effects is epidermal growth factor (EGF). We investigated the contribution of EGF to the relationship of 1483 head and neck cancer cells with their microenvironment. Methods: We treated 1483 head and neck cancer cells with variable concentrations of EGF from 0.1 to 20 nM and carried out western blots and flow cytometry to determine the expression of relevant integrins. Effects of interventions were evaluated by soft agar colony assays, proliferation and survival in tissue culture and adhesion to culture plates coated with integrin ligands. Results: Western blots demonstrated an EGF-induced increase in the expression of intgerin α5 but no change in the expression of integrins α2 or β1. The presence of dissolved fibronectin, a ligand of integrin α5β1, but not of collagen I, a ligand of integrin α2β1, provided a survival advantage to colonies in soft agar in EGF-treated cells. Experiments are determining whether this survival advantage translates to a shift in the dose-response curve to paclitaxel and ionizing radiation, on activation of caspases 3 and 8 and cleavage of poly (ADP- ribose) polymerase (PARP). These data are being correlated with EGF-induced modulation of adhesion to fibronectin, collagen and control plates. We have constructed adenoviral vectors expressing short hairpin RNA (shRNA) sequences to integrins α5 and α2 to confirm the role of integrin α5 expression in the EGF-induced modulation of survival. Conclusions: These data support a potential contribution to survival of head and neck cancer cells by modulation of integrins by EGF through interaction with their ligands in the microenvironment. No significant financial relationships to disclose.
Chemotherapy alternating gemcitabine and cisplatin concomitant with radiotherapy in locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN)
Authors: Tellez Bernal E. , Aguilar J. L. , Cruz J. , Granados M. , Maldonado F. , Moran A. , Martinez J. , Cabrera G. , Martinez-Said H. , Frias-Mendivil M. , Herrera A. 
Published: March 2020

15514 Background: In the Pignon’s meta-analysis, the OS benefit was 8% with chemoradiation in LA SCCHN. Unfortunately it is still unclear what scheme is the best, cisplatin (CDDP) being the most widely used drug. Other drugs such as gemcitabine (GMZ) has promising results, although toxicity has been severe but tolerable. We have published an initial study using GMZ and radiotherapy (ann oncol. 2004;15:301). In the present study we wished to determine if a scheme in which GMZ is alternated with CDDP and concomitant radiotherapy reduced toxicity yet maintains our previously described therapeutic effectiveness. This is a preliminary report with a short follow-up period. Methods: Inclusion criteria: patients with SCCHN (EC: III, IVa and IVb ) or with recurring disease, and no sytemic metastases or patients rejection of surgery between 03/2003 and 09/2004. Chemotherapy scheme consisted of GMZ at 100 mg/m2 once a w, ws 1, 3, 5, 7 and CDDP at 50 mg/m2 once a w, ws 2, 4, y 6. Radiotherapy consisted of 2 Gy/day, for a total of 70 Gy during the 7 ws. Toxicity evaluation focused on mucositis, xerostomia, dysphagia y leukopenia. Results: 28 patients were treated. 7 (25%)/ stage III, 11 (39.3%) IVa, 10 (35.7%) IVb. The tumor sites distribution was as follows: 9 patients with oropharynx and larynx disease (32.1%), 6 patients with oral cavity disease (21.4%), 3 patients with paranasal sinus disease (10.7%), and 1 hypopharinx (3.5%). A CCR was observed in 21 patients (75%), a partial response was observed in 5 patients (17%). Organ preservation was achieved in 68% of the patients. Toxicity: mucositis Grade 3–4 was in 42% of patients, leucopenia grade III in 29%, dysphagia in 19% and xerostomia in 10%. 40%of the patients stopped treatment for one or two weeks due to toxicity without affecting the doses of both treatments. Conclusions: The scheme with alternating GMZ and CDDP concomitant with radiotherapy is safe and effective. We observed a lower incidence in mucositis and few systemic toxic effects. Our findings support further studies in which alternating chemotherapeutic schemes are utilized given that tumor response is increased without an increment in toxicity. No significant financial relationships to disclose.
Intra-arterial chemotherapy with docetaxel and cysplatin in combined treatment of patients with locally advanced squamouse cell head and neck cancer (SCHNC)
Authors: Adilbayev G. , Adilbay D. , Kim G. , Ahmetov D. 
Published: March 2020

15528 Background: Currently the main role in chemotherapy of head and neck cancer from the 90ths is related to taxans. To elevate the effect of combination docetaxel + cysplatin and to reduce their toxic influence to the organism we have studied intra-arterial path of delivery at the combined therapy of head and neck cancer. Methods: We treated 53 patients with locally advanced SCHNC(T3, T4). All patients received 2 courses of intra-arterial chemotherapy by catheterization the feeding arteries of tumor through the external carotid artery: docetaxel-80 mg/m2, cysplatin-100 mg/m2. Further, depending on the results of chemotherapy, there were performed radiotherapy and surgical treatment in necessary volumes. Results: By analyzing the effect of docetaxel + cysplatin combination in different tumor localizations, we have concluded that the best results have been achieved in oral cavity cancer: 9 (29.1%) patients with CR and 16 (51.6%) patients with PR. Worst results have been achieved in maxilla cancer: 0 CR and 14 PR (63.6%). Hematologic toxicity of chemotherapy has manifested only in 18.8% patients (I, II grade). Non-hemathologic toxicity: alopecia 67.9%; periphery neuropathy 11.3; mucositis 5.3%. Performing radiotherapy as the second stage after chemotherapy has increased the number of patients with CR, in patients with oral cancer up to 45.1% and with maxilla cancer up to 18.1%. All results has been confirmed by cytomorphology. As of now surgical treatment has been performed for 30 patients (56.6%). 86.8% patients have been followed up for 6 to 30 months. Conclusion: This neoadjuvant intra-arterial chemotherapy with docetaxel + cysplatin allows both increasing the results of combined therapy and reducing the toxicity of chemotherapy. No significant financial relationships to disclose.
Pilot study of paclitaxel and carboplatin (P/C) with concurrent radiation therapy (RT) in high risk salivary gland carcinomas (SGC)
Authors: Langston M. , Farray D. , Ruzich J. C. , Emami B. , Petruzzelli G. , Clark J. I. 
Published: March 2020

15538 Background: Standard therapy for high risk SGC includes surgical resection with adjuvant RT, but a high risk of recurrence exists. The role of chemotherapy in this setting has not been fully defined. Methods: This limited institution pilot study evaluated the use of P/C with concurrent RT as adjuvant treatment of high risk SGC. The primary objective was to assess toxicity of this treatment in anticipation of a larger cooperative group phase II study. Eligible patients (pts.) had a Southwest Oncology Group (SWOG) performance status (PS) of 0–2 who after surgical resection of their SGC had high risk features including positive surgical margins, perineural invasion, multiple lymph node (LN) metastases, or extracapsular extension. Treatment included P = 40 mg/m2 intravenously followed by C = AUC of 2 concurrently on days 1, 8, 15, 22, 29, 36 of RT. RT consisted of a total dose of 60 Gy in 30 fractions to the primary and regional LN sites of disease. Results: Five pts. were enrolled 4 with adenoid cystic CA and 1 with high grade mucoepidermoid CA. Median age was 59 years (32–69), all with SWOG PS = 0. Four pts. completed the full 6 cycle P/C chemotherapy; all completed RT per protocol. Grade III/IV mucositis, the most common toxicity, occurred in 6 of 30 (20%) P/C cycles, leading to alteration of therapy in 1 pt. There was no reported neuropathy or significant laboratory abnormalities. Median follow up was 17.5 months (mos.); most were disease free at last follow up (13 to 37 mos.); 1 recurred at 14 mos.; this pt. accounts for the only death observed. One year survival was 100%. Conclusions: The regimen of P/C with concurrent RT, as defined, was tolerated well. Grade III/IV mucositis was the main toxicity. Based on the overall tolerability of this regimen, we believe that this postoperative combined modality therapy deserves further study in a larger cooperative group phase II trial to further define its toxicity and efficacy in high risk SGC. We thank Bristol Myers Squibb for support of this study. No significant financial relationships to disclose.
Phase II trial of imatinib mesylate and hydroxyurea for grade III malignant gliomas
Authors: Desjardins A. , Reardon D. A. , Quinn J. A. , Rich J. N. , Vredenburgh J. J. , Sathornsumetee S. , Salvado A. , Friedman H. S. 
Published: March 2020

1573 Background: We evaluated the combination of imatinib mesylate (Gleevec) and hydroxyurea in WHO grade III malignant gliomas following the encouraging response of this combination demonstrated in glioblastoma multiforme. Methods: Eligibility: adult patients with recurrent/relapsing AA or AO with measurable disease; 2 weeks since surgical resection or 4 weeks since radiotherapy or chemotherapy; Karnofsky 60% and adequate organ function. Imatinib and hydroxyurea were given orally daily. Imatinib was administered at 400 mg daily to patients not on enzyme inducing antiepileptic drugs (EIAED) while those on EIAED received 500 mg twice a day. Hydroxyurea was administered to all patients at 500 mg twice a day. Each cycle was 28 days of therapy. Results: Thirty-nine patients with recurrent AA (n= 32) or AO (n=7), following prior radiation therapy and chemotherapy, have been enrolled, including 21 (54%) not on EIAED and 18 (46%) on EIAED. Patient characteristics were comparable between both strata. Median age was 39 years (range, 21–59 years). The most frequent grade III-IV toxicities were neutropenia (n=11), leukopenia (n=8), thrombocytopenia (n=6), deep venous thrombosis (n=3), fatigue (n=2) and pulmonary edema (n=2). One patient presented grade V brain hemorrhage at the time of disease progression. Four patients achieved a partial response, for an overall response rate of 10%. Thirteen patients (33%) achieved disease stabilization. Twelve patients (67%) not on EIAED had progressive disease as their best response compared to only 4 patients (27%) on EIAED. The median time to progression for all patients, and for those not on EAIED and on EIAED was 14.1 weeks, 10.9 weeks and 26.0 weeks, respectively. Conclusions: Daily imitanib mesylate plus hydroxyurea demonstrates encouraging activity and is well tolerated among patients with recurrent AA or AO. As observed with glioblastoma multiforme patients, patients on EAIED seem to demonstrate a better response. [Table: see text]