bluuebunny/crossref_metadata_2025_split huggingface dataset:
Imatinib mesylate in the treatment of patients with recurrent high grade gliomas expressing PDGF-R
Authors: Marosi C. , Vedadinejad M. , Haberler C. , Hainfellner J. A. , Dieckmann K. , Rössler K. , Hassler M. R. 
Published: March 2020

1526 Background: Despite noticeable progress in the treatment of high-grade gliomas (HGG), most patients experience tumor recurrence after standard treatment consisting of surgery, radiotherapy and concomitant chemotherapy. Imatinib mesylate, a tyrosine kinase inhibitor of PDGFR-α, -β, c-kit, abl and arg, has been shown to produce tumor response in patients with recurrent gliomas (Raymond ProcASCO 2004, Dresemann ProcASCO 2004&2005, Reardon Proc ASCO 2005). We treated 34 patients with recurrent HGGs showing immunohistochemical expression of “imatinib targets” in the tumor tissue with imatinib. Methods: 34 patients, 16 women, 18 men, aged from 27 to 72 years, in median 49 years with recurrent HGG (GBM n= 23, AA n=11) were treated with imatinib 400 mg/day as continuous daily oral dosing. MRI was performed every three months or at clinical suspicion of progression. The median interval from diagnosis to the start of imatinib was 12.6 months (range 4.3 to 143 months). Imatinib was the 2nd line therapy in 15 patients, 3rd line in 13 and 4th line in 6 patients. ECOG performance score at start of imatinib was 1 in 9, 2 in 21 and 3 in 4 patients, respectively.Immunohistochemical analysis was performed on formalin fixed and paraffin embedded tumor tissue with antibodies against PDGFR-α, and -β. Results: The median treatment period with imatinib was 4 months (3 weeks to 17 months). The best response achieved was major response in 2 patients, partial remission in 6, stable disease in 12 and progressive disease in 14 patients. Eleven patients were free from tumor progression after 6 months (PFS-6 32,4%). The two patients with major response improved clinically and showed no more evidence of increased metabolism as well in MRI spectroscopy as in C11-methionine PET for 13 and 17 months, respectively. One of them showed widespread PDGF-R-α expression in the tumor tissue. In all patients with objective response to imatinib, a clinical benefit was noted within the first month of treatment. Conclusions: Compared to the results of Raymond et al, we observed a higher percentage of patients with progression free survival at 6 months. Detailed analysis of imatinib targets in tumor tissue of patients treated with imatinib will be helpful to explore the potential of imatinib as treatment option for patients with HGG. No significant financial relationships to disclose.
Detection of subclinical systemic disease in primary central nervous system lymphoma (PCNSL) by polymerase chain reaction (PCR) of the rearranged immunoglobulin heavy chain (IgH) genes
Authors: Jahnke K. , Hummel M. , Korfel A. , Burmeister T. , Mueller H. , Seide C. , Stein H. , Thiel E. 
Published: March 2020

1533 Background: An unresolved question is why some PCNSL spread systemically while most others do not. It was postulated that extracerebral relapse of PCNSL may represent a sequel of initial occult systemic disease rather than true extracerebral spread. Methods: To elucidate this question, we examined bone marrow and peripheral blood specimens of 24 patients with newly diagnosed PCNSL using PCR for the presence of clonally rearranged IgH genes. The applied IgH PCR method was recently developed by a European Concerted Action (BioMed-2). To all samples (50 ng DNA), three different FR primer sets (FR1, FR2 and FR3) were applied in conjunction with a JH consensus primer (JH22). Baseline routine staging procedures showed no evidence of systemic lymphoma manifestations in all patients. Results: The same dominant PCR products were found in bone marrow aspirates, blood samples and tumor biopsy specimens from three patients, indicating the presence of the same tumor cell population in the CNS as well as in extracerebral sites. No concordant dominant amplificates were detectable in the remaining 21 patients. To date, nine patients have relapsed intracerebrally and none systemically after a median follow-up of 25 months. Median overall survival was 30.5 months. Of the three patients with monoclonality outside the CNS, two are still in complete remission 24 and 25 months after diagnosis, respectively. The third patient relapsed intracerebrally 12 months after diagnosis, achieved complete remission after whole-brain irradiation and died in complete remission 16 months after diagnosis due to pulmonary embolism. Conclusions: Extracerebral disease not detectable by routine staging may be present in PCNSL patients. This finding may have an impact on the understanding of PCNSL pathogenesis and the extent of staging and treatment. No significant financial relationships to disclose.
The role of systemic and cranial 18Fluorodeoxyglucose positron emission tomography (FDG PET) in primary central nervous system lymphoma (PCNSL)
Authors: Mohile N. A. , Deangelis L. M. , Abrey L. E. 
Published: March 2020

1535 Background: The utility of body and brain FDG PET in staging and management of PCNSL is unknown. Methods: We performed a retrospective study of 166 PCNSL pts at Memorial Sloan-Kettering Cancer Center between January 2000 and August 2005. Pts. who underwent PET imaging were identified using the electronic medical record. PET reports and clinical data were reviewed to determine the reason for the study and impact on management. Results: 61 (37%) pts had ≥1 PET scans. Of 93 studies, 58 were body scans and 35 were brain scans. 72% (42/58) of body PET were done for systemic staging at diagnosis and 28% (16/58) at relapse. 19% (8/42) of scans done for initial staging had suspicious systemic foci. Lymphoma was found in 3 (37.5%), adrenal adenoma in 1 (12.5%), duodenal adenocarcinoma in 1 (12.5%) and non-diagnostic tissue in 1 (12.5%); biopsy was not pursued in 2 (25%). 31% (5/16) of scans done at relapse were abnormal. In 3 (19%) of these, biopsy revealed lymphoma; in 2 (12.5%), biopsy was not pursued. In 8% (4/50) of pts (SUV 12.8, 14.3, 22, 30.5), PET was the only study to demonstrate systemic lymphoma. 2 other pts found to have systemic disease had suspicious findings on conventional imaging in addition to positive body PET (SUV 3.8, 4.1). 43% (15/35) of brain PET were done at diagnosis and 57% (20/35) were done to evaluate residual MRI abnormalities after treatment. 14 brain PET at diagnosis were positive; SUV reported in 7 of these pts ranged from 7.5 to 26.8. The pt with a negative PET was receiving steroids. 10 brain PET done after treatment showed residual tumor and affected interpretation of MRI response. SUV reported in 7 of these pts. ranged from 8.1 to 29. Conclusions: Body PET imaging appears to be a sensitive tool for the detection of occult systemic lymphoma that may be missed with other diagnostics. While Brain PET at initial diagnosis did not yield incremental information, it may be useful in the interpretation of persistent MRI abnormalities after treatment. No significant financial relationships to disclose.
Differences in the distribution of methotrexate into high grade gliomas following intravenous administration, as monitored by microdialysis, are associated with blood brain barrier integrity
Authors: Olson J. J. , Blakeley J. O. , Grossman S. A. , Weingart J. , Rashid A. , Supko J. 
Published: March 2020

1548 Background: Microdialysis (MD) is an accepted technique to monitor neurochemicals in pts with traumatic brain injury. This study was conducted to evaluate the use of MD to define the time course of intratumoral drug concentrations in pts with high grade gliomas (HGG) receiving systemic chemotherapy. Methods: MD catheters were placed in residual HGG following tumor debulking and infused with Ringer’s solution at 1 μL/min. MD probe location and integrity of the blood brain barrier (BBB) in adjacent tissue were determined by fused MRI/CT. Highdose (12g/m2) methotrexate (MTX), was given as a 4 h iv infusion the next day. MTX was measured in plasma and dialysate samples, collected at 30 min intervals from 1 h before to 24 h after dosing, with an LC/MS assay. Results: Six pts have been enrolled without any adverse events attributed to the MD catheter. Adequate pharmacokinetics (PK) were obtained in 4/6pts. MTX plasma pharmacokinetics (PK) were very consistent between the 4 evaluable pts and similar to published data. Time courses of the uncorrected MTX concentration in extracellular fluid (CECF) exhibited two distinctly different kinetic profiles. For 2pts in whom the MD probe resided within contrast enhancing tumor, CECF increased and decreased in parallel with drug levels in plasma, with a peak CECF of 189 ± 6 μM, an apparent elimination half-life in ECF of 4.44 ± 0.07 h, and an ECF/plasma AUCratio of 0.13 ± 0.01. The other 2pts had a much lower peak CECF (10.4 ± 0.4 μM) and AUC ratio (0.028 ± 0.020), with a more prolonged ECF half-life (11.4 ± 4.5 h). Fused images from 2 of these pts showed that the MD probe was located in nonenhancing tissue. Conclusions: MD is a clinically practical technique to monitor the distribution of systemically administered drugs to brain tumors in pts. It has the capability to elucidate variations in kinetic behavior that are consistent with regional differences in BBB integrity. Appropriate interpretation of data from MD studies to evaluate the distribution of investigational new drugs into brain tumors necessarily requires radiographic determination of the region of the tumor into which the probe has been placed. No significant financial relationships to disclose.
Toxicity and efficacy profiles of intrathecal injection of I-131 NaI via intraventricular (IVent) or intralumbar (Ilumb) route for leptomeningeal metastases (LM) therapy
Authors: Wong F. C. , Groves M. , Papadopoulos N. , Kim S. , Conrad C. , Meyers C. , Hsu S. , Kumar A. , Tummala S. , Kim E. 
Published: March 2020

1549 Background: LM is a fatal complication occurring in up to 30% of cancer patients. Intrathecal chemotherapy of LM is limited by diffusion while external beam irradiation is limited by neurotoxicity. Radioiodine I-131 may serve as a ablating agent because of its radiations transverse the meningeal thinkness but spare distant underlying nervous tissues. Two phase I studies are designed to determine MTD and to evaluate potential toxicity and efficacy of intrathecal I-131 sodium iodide (NaI) injected via IVent or the ILumb route. Methods: The IVent or Ilumb protocols each accured 5 groups of patients with cytology-confirmed LM from solid tumors. An injection of 15, 30, 60, 90 or 120 mCi of I-131 NaI was performed after thyroid blockade (Lugol solution and perchlorate), via an Ommaya reservoir (IVent) or lumbar puncture (ILumb). Patients underwent whole-body scintigraphy for biodistribution and radiation dosimetry. Follow-up studies consisted of serial CSF cytology, neuropsychology, ophthalmology, and serum tests (TSH and CBC) to 6 months. Results: The IVent and Ilumb studies accured 16 and 15 patients respectively with LM from melanoma, lung, breast and other tumors (13, 8, 6 and 4 of 31 patients). Because of re-entry into the protocols, one patient received a total of 407 mCi; the maximum radiation absorbed doses were estimated at 3716 cGy in the ventricular CSF and 54 cGy in the red marrow. No treatment-related NCI-Grade II/III/IV neurologic, hematologic or thyroid toxicity is noted. Transient improvements up to 6 weeks are noted in neuropsychologic tests (5/16 and 5/15), ophthalomologic test (3/16 and 1/15) and CSF cytology conversion (to negative) in 5/16 and 4/15 patients, respectively. Electrophysiology tests of 2 patients demonstrated normalization of P37 waves measured by somatosensory evoked potentials along with neuropsychologic test improvements. Conclusions: The MTD has not been reached up to 120 mCi on either the IVent or Ilumb protocol. Intrathecal I-131 NaI is likely to be efficacious to eradicate tumors in the CSF for LM therapy. Because of the low toxicity and likely efficacy, a phase II study with higher dosages is needed to fully explore therapeutic potentials of intrathecal I-131 NaI. No significant financial relationships to disclose.
Phase-2 study of imatinib in metastasized medullary thyroid carcinoma
Authors: Zonnenberg B. A. , Links T. , Quarles van Uffort P. , Lips C. , De Groot J. , Voest E. 
Published: March 2020

15500 Background: Medullary thyroid carcinoma (MTC) is a relatively rare tumor that metastasizes to regional lymph nodes, lung, liver and bone. When surgery is no longer a curative treatment option, no effective systemic therapy is currently available. In most cases a (somatic or germline) mutation in the RET (REarranged during Transfection) gene is considered to be an essential step in the pathogenesis of MTC. Imatinib is an oral inhibitor of several protein-tyrosine kinases including RET kinase. It has shown to be an effective drug in chronic myeloid leukemia and gastrointestinal stromal tumors. Methods: A two-step open label phase-2 study was initiated using 600 mg imatinib daily with a scheduled dose increase to 800 mg in case of minimal toxicity. Standard RECIST criteria were used for response evaluation using CT/MRI scans every 2 months. The two-step design allowed no further inclusion in the absence of objective responses in 15 patients. Results: 15 patients with metastasized MTC were included. No objective responses were observed but long term stable disease over 18 months was noted in 4 patients. However, toxicity was considerable. Emergency tracheotomy had to be performed in 2 cases due to mucosal swelling in patients with laryngeal nerve palsy and a narrow vocal cleft. In 3 cases the dose of Imatinib had to be decreased because of unacceptable toxicity (malaise, mucosal swelling (2) and fatigue). In 7 patients with a history of a thyreoidectomy, the dose of thyroxine had to be increased considerably to avoid serious hypothyroidism due to an incompletely understood interaction. Conclusion: Treatment with Imatinib yielded no objective responses and considerable toxicity in patients with MTC. Long-term stabilization of the disease was observed in only a minority of the patients. Patients with hypothyroidism and with laryngeal nerve palsy are at risk for serious adverse events and need special attention when treated with Imatinib. No significant financial relationships to disclose.
Phase II clinical trial preliminary report: Cetuximab, gemcitabine and simultaneous radiotherapy for locally advanced head and neck cancer: Preliminary report
Authors: De La Garza J. G. , Granados M. , Aguilar J. L. , Lavin J. , Cabrera G. , Maldonado F. , Moran A. , Cruz J. , Luna K. , Segura B. , Olvera G. 
Published: March 2020

15502 Background: Previous studies with cetuximab in SCCHN demonstrate to be clinically beneficial. In the present study we wished to evaluate the efficacy and safety of a chemotherapeutic scheme using gemcitabine, radiotherapy and cetuximab for SCCHN. Preliminary report of 20 of 40 enrolled patients into a phase II clinical trial. Methods: inclusion criteria; histological confirmation of epidermoid carcinoma, ages 18 to 70, K > 70%, normal renal, hepatic and haematologic functions, without previous treatment, surgically inoperable disease, or patients with operable disease that did not consent to surgery. All patients signed an informed consent form. Radiotherapy: 200 cGy/d/5/w until 70Gy were completed. Cetuximab: an initial dose of 400 mg/m2 one week prior to initiation of radiotherapy, followed by 250 mg/m2 weekly until completion of radiotherapy. Gemcitabine: 50 mg /m2 weeks 1–2, 4–5 and 7. Results: 20 patients were enrolled (16m/4f) from november of 2004 to november of 2005, (5 oral cavity, 5 oropharynx, 8 larynx, 1 hypopharynx and 1 paranasal sinus). Mean age 56 yrs (33–75). Tumor staging: 7/III, 8/IVa and 5/IVb. One female was excluded, 19 completed the study and were evaluated. GR 17/19 (89.5%), CR 13/17 (76.5%) and PR 4/17 (23.5%). 2/19 NR (10.5%). CR of the 1ary tumor 15/19 patients (78.9%); CR 6/11 patients with lymphatic disease at diagnosis (54.5%), PR 3/19 (27.3%). Toxicity: mucositis g/III-IV 8/19 patients; rash g/III 4 patients. 2/19 did not complete treatment with chemotherapy due to mucositis but did with radiotherapy. No relationship was found between clinical response and the severity of the rash. One patient developed leukopenia g/III. 4 patients developed disphagia g/II, one has not resolved after 8 month follow up. Xerostomia g/II was 7/19 patients. Dermatological toxicity resolved by the end of the treatment. Mean follow up: 6 months, 1 patient which did not respond died and 1 patient with a PR recurred. Conclusions: The scheme is safe and effective with tolerable toxicity. In our previously reported experience, the addition of cetuximab to gemcitabine and radiotherapy does not increment local toxicity, statistical validation of these findings require the completion of the 40 patient study. No significant financial relationships to disclose.
The effect of induction therapy with carboplatin-paclitaxel and low dose radiotherapy followed by hyperfractionated radiotherapy and intraarterial chemotherapy on advanced cancers of the head and neck
Authors: Warren G. W. , Arnold S. M. , Curtis G. , Valentino J. , Brill Y. , Regine W. F. , Spring P. M. , Mohiuddin M. , St. Clair W. H. , Kudrimoti M. R. 
Published: March 2020

15517 Background: The purpose of this study is to evaluate the potential benefits of induction therapy followed by intraarterial cisplatin and hyperfractionated radiation (HYPERRADPLAT) on patients with advanced head and neck tumors. Methods: 20 patients with Stage III-IV squamous cell carcinoma of the head and neck were treated with induction therapy consisting of 2 cycles of carboplatin (AUC 6) and paclitaxel (225 mg/m2) and 0.8 Gy BID on the day of and the day following chemotherapy. Induction therapy was given over 2 cycles separated by 3 weeks (previously described in ASCO 2002 abstract # 921 and 2004 abstract # 5593). Patients were then treated with the HYPERRADPLAT regimen consisting of external beam radiotherapy (74.4–81.6 Gy) delivered in 1.2 Gy BID fractions with intraarterial cisplatin (150 mg/m2) administered when patients had reached 60 Gy. Tumor response, disease free survival, overall survival, and toxicity were assessed for all patients according to NCI CTCAE criteria. Results: Of 20 patients, 9 had tumors of the oropharynx, 9-supralaryngeal, and 2-hypopharyngeal. Fifty percent of patients had T4 tumors and 35% had T3 tumors. Complete tumor response was observed in 80% of patients and 20% had a partial response. Three-year disease free survival was 75% and overall survival was 75%. Locoregional recurrence was noted in 25% of patients and 15% had distant failure. Overall recurrence was noted in 40% of patients with a median time to recurrence of 12 months (range 6–55 months). Median weight loss during treatment was 10% of initial body weight and 13 patients required a feeding tube within 6 months of starting treatment. Grade 3 mucositis was noted in 65% of patients and no patients developed Grade 4 toxicity. Conclusions: Two cycles of carboplatin-paclitaxel induction therapy followed by intraarterial cisplatin and hyperfractionated radiotherapy produces excellent tumor response and reduces distant failure. These results compare favorably with historical controls and produce tolerable toxicity profiles. [Table: see text]
Tumour thickness as a predictor of neck node metastasis at presentation in early T stage squamous cell carcinoma of oral tongue
Authors: Jamshed A. , Hussain R. , Azam M. , Hameed S. , Shah M. A. , Bilal M. , Khurram S. , Faruqui Z. 
Published: March 2020

15518 Background: Pakistan has one of the highest incidence of oral cancer in the world. Twenty to thirty percent of the patients have occult neck nodal metastasis at presentation. Elective treatment of neck in early T stage tongue cancer is controversial. The study was conducted to determine the risk of neck node metastasis in patients with T1 or T2 carcinoma tongue on the basis of pathological tumour thickness. Methods: The study group consisted of 20 patients with early T stage carcinoma oral tongue treated at Shaukat Khanum Memorial Hospital and Research Centre between December 2003 - October 2005. There were 10 males and 10 female patients. The median age for the group was 54 years. All patients underwent partial glossectomy with modified neck dissection. Histopathological reports were analysed to stage the patients according to AJCC 2002 system. The glossectomy specimen were serially sectioned to determine histological thickness. Nine patients (45%) had pT1 and 11 patients (55%) had pT2 disease. Patients were divided in to three groups based on tumour thickness; Group I (tumor < or = 3 mm), Group II (> 3 mm but < or = 9 mm) and Group III (> 9 mm). Results: In patients with pT1 lesions there were 2, 3 and 4 patients in group I, II and III respectively. Pathological neck nodal metastasis were seen in 0/2 patients in group I, 1/3 patients in group II and 1/4 in group III. With pT2 lesions there were 0, 4 and 7 patients in group I, II and III respectively. Neck nodal metastasis were found in 3/4 and 3/7 in group II and III patients. The risk of neck node metastasis in patients with tumor thickness more than 3 mm was 28% (2/7 patients) for pT1 patients and 55% (6/11 patients) for patients with pT2 disease. Conclusions: Tumor thickness more than 3 mm in patients with early T stage squamous cell carcinoma oral tongue carries a high risk of neck nodal metastasis. Elective neck treatment should be considered for this group of patients. No significant financial relationships to disclose.
Phase II study of concurrent chemoradiation with gemcitabine (GEM) in locally advanced squamous cell carcinoma of the head and neck (SCCHN): Preliminary result
Authors: Sirisinha T. , Sirilertrakul S. , Kraiphibul P. , Dangprasert S. , Sirachainanm E. , Ativitavas T. , Ratanatarathorn V. 
Published: March 2020

15519 Background: Concurrent chemoradiation is effective in the treatment of unresectable SCCHN. Cisplatin is the most frequently used agent but has significant toxicity and also requires hospitalization for hydration. Due to above limiting factors and the known radiosensitization effect of GEM, this study was initiated to evaluate the feasibility, safety and antitumor activity of low dose GEM concomitant with radiation (RT) in locally advanced (LA) SCCHN. Methods: Patients (pts) with LA SCCHN with no prior radiotherapy, adequate organ function and signed informed consent were eligible. RT was given at 65–70 Gy over 6.5–7 weeks concurrently with 7 weekly GEM at 4 dose levels (30 mg/m2, 50 mg/m2, 60 mg/m2 or 75 mg/m2) before RT. Results: Between 11/01–12/05, 26 pts (22 men, 4 women) were enrolled; median age 55 (range 33–77); 24 with primary tumors and 2 with recurrent disease following prior resection; stage III/IV: 5/19; T2–3/T4: 18/7; N 0–1/ 2–3: 9/17 and ECOG 0–1/2: 23/3. Four pts received GEM at 30 mg/m2, 3, 4 and 15 pts received 50, 60 and 75 mg/m2, respectively, with a median of 6 GEM doses (range 3–7) and a median RT of 70 Gy (range 45–75). Two pts who are currently receiving chemoradiation and one patient who died during chemoradiation from COPD exacerbation were not included in the analysis. Grade 3/4 acute toxicity were: mucositis 13/3, acute dermatitis 1/0, fatigue 1/1, neutropenia 1/0 and anemia requiring transfusion or erythropoietin use in 5 pts, 17 pts required enteral feeding during the treatment and median weight loss was 3.5 kg. RT was interrupted briefly in 12 pts, mostly due to grade 3/4 mucositis but treatment was completed in 87%. Nineteen pts (83%) responded (9CR, 10PR) with 3SD and 1PD. Eleven pts have relapsed or progressed. With the median F/U time of 16 months (range 2–31), the median overall survival was 28.3 months (95% CI 16.3, 40.2). Conclusions: Concurrent chemoradiation with GEM is feasible and effective with moderate but manageable treatment-related toxicity. No significant financial relationships to disclose.