bluuebunny/crossref_metadata_2025_split huggingface dataset:
Esthesioneuroblastoma (ENB): A case report
Authors: Troncoso E. , Bonicatto S. , Mainella A. , Barbero A. , Lavezzaro M. , Zapata G. 
Published: March 2020

15546 Background: ENB is a rare embrionary tumor derived from neuroblasts of the olfactory sensory system. Polypoid mass with epistaxis or nasal obstruction are the most common clinical manifestations of this tumor. It’s invasive and it frequently causes regional and distant metastasis. ENB requires a multimodality therapy. The objective of this study is to describe the form of presentation, diagnosis, treatment and evolution of this tumor on a female patient (pt), as a casuistic contribution. Methods and Case Report: A 61 year old woman with a four month history of epistaxis, nasal pain and anosmia. CT shows nasal mass invading the entire nasal cavity and upper maxillary. Pt underwent nasal resection and reconstruction with frontal flaps. Anatomopathology: ENB invading the bone. Cromogranin (+), sinaptofisin (+), CK (−), NSE (−). Three months later: lesion on the right wing nasal and a mass in the soft palate. MRI: mass on the floor of the nasal fossa that involve the left maxillary sinus and the bone palate. Kadish stage C. We treated her with three cycles of chemotherapy using cisplatin 30 mg/sqM d 1–3 iv and etoposide 100 mg/sqM d 1–3 iv. After that, remission was observed in the wing nasal lesion but the the soft palate mass shows progression. MRI: mass in nasal fossa that destroys the left maxillary sinus and causes lysis of the upper maxillary and orbital floor. Pt was treated with radiotherapy (6000 cGy) showing complete remission of the nasal lession and partial response on the soft palate, verified by physical examination and RMI. Four months after the end of radiotherapy, she continues under control and maintains the response to therapy without evidence of progression. Conclusion: ENB is an unfrequent tumor without any standard treatment. In our case, the combination of surgery, CH and RT has been effective for local control of the disease with good tolerance and acceptable quality of life. No significant financial relationships to disclose.
Curative interstitial brachytherapy for early stage carcinoma of lip—A case report
Authors: Jha A. K. , Prasiko G. , Mod H. , Chaurasia P. P. , Shrivastava R. 
Published: March 2020

15547 Background: Brachytherapy is potentially useful in the treatment of carcinoma lip. Small cancers of the lip (less than 2 cm) are treated equally well with surgery or radiation therapy with excellent cosmetic and functional results seen in radiation therapy. Methods: We treated an 18-year old male diagnosed as stage 1 carcinoma lip with curative interstitial brachytherapy. Under anaesthesia, three catheters were inserted at 0.5 cm separation through the lesion. Patient was simulated, planned, treated in VARISOURCE (Varian, USA). He received dose of 3 Gy per fraction, two fractions per day at a minimum interval of 6 hours between the two fractions for 6 days. He therefore received a total dose of 36 Gy with High Dose Rate (HDR) Brachytherapy. During treatment, he received hyperalimentaion via naso-gastric tube with intravenous antibiotic prophylaxis. Results: Upper lip swelling occurred in first 12 hours of treatment and remained for 6 days that subsided subsequently. Catheters were removed on 6th day of treatment. Scar formation occurred over the lesion in 1 month’s follow up. In next one month’s follow up, there was no clinical evidence of disease. Cosmetic result was satisfactory. At two months follow, the patient is clinically disease free and has no complaints. Conclusions: Interstiatial brachytherapy is a excellent method for treating early stage carcinoma lips with excellent cosmetic outcome. This kind of treatment is now available in my country at our institution. No significant financial relationships to disclose.
A phase I study of temozolomide (TMZ) and the farnesyltransferase inhibitor (FTI), lonafarnib (Sarazar, SCH66336) in recurrent glioblastoma
Authors: Gilbert M. R. , Gaupp P. , Liu V. , Conrad C. , Colman H. , Groves M. , Puduvalli V. , Levin V. , Hsu S. , Horowitz J. , Yung W. 
Published: March 2020

1556 Background: Farnesylation is essential for the post-translational modification of several proteins that play a role in cell proliferation and growth. FTIs demonstrate antiproliferative effects in a variety of tumor cell lines and xenograft models and enhanced efficacy by combining lonafarnib with TMZ compared with TMZ alone. Clinical studies show that dose-intense TMZ may have better efficacy then conventional dosing (Wick, Neurology 2004). Objective: Determine the maximum tolerated dose of lonafarnib when combined with a dose-intensified schedule of TMZ. Eligibility criteria: Histologically proven GBM; evidence of relaspe or progression; up to 2 prior chemotherapy regimens, prior TMZ permitted; KPS ≥ 60. No enzyme-inducing anticonvulsants. Methods: TMZ was given at 150 mg/m2 days 1–7 and 15–21; lonafarnib escalated by cohort: 100 mg BID, 150 mg BID, 200 mg BID on days 8–14 and 22–28 of a 28-day cycle. Response: Toxicity measured after cycle 1 using NCI CTCAE v3. Patient (pt)accrual used a 3 + 3 design. Response was evaluated q2 cycles. Standard response criteria (MacDonald) were used. Results: 15 patients were accrued. Median age 47 yrs; median KPS 90. M:F ratio was 11:4. No DLTs in any dose cohort, a pt (cohort 1) died day 29 of unrelated cardiac disease. 4 pts demonstrated partial response, all with prior TMZ failure, 3 pts showed prolonged stable disease. 6-month PFS rate estimated at 33%, median PFS 14 weeks. Treatment was well tolerated: 1 episode each of grade 3 diarrhea, esophagitis, fatigue and hypokalemia; 3 episodes of grade 3/4 leukopenia, 2 episodes of grade 3/4 neutropenia, and 2 episodes of grade 4 thrombocytopenia. Seven pts had grade 3/4 lymphopenia, some with persistant lymphopenia from prior TMZ. 1 pt had grade 4 pneumonitis of uncertain etiology. Conclusions: The alternating week schedule of TMZ/lonafarnib was well tolerated. Preliminary results suggest anti-tumor activity even in pts who had failed prior TMZ. It is not certain whether this activity is due to the dose-intensified TMZ or the treatment combination. Studies are planned to evaluate potential predictors of response (i.e MGMT gene promoter methylation) and expand the trial to obtain pharmacokinetic and additional efficacy data. [Table: see text]
An update on phase I study of dose-escalating imatinib mesylate plus standard-dosed temozolomide for the treatment of patients with malignant glioma
Authors: Sathornsumetee S. , Reardon D. A. , Quinn J. A. , Rich J. N. , Vredenburgh J. J. , Desjardins A. , Gururangan S. , Egorin M. , Salvado A. , Friedman H. S. 
Published: March 2020

1560 Background: Imatinib mesylate, a kinase inhibitor of the PDGF receptor has been shown to decrease tumor interstitial pressure resulting in enhanced delivery of cytotoxic therapy. Recent phase II trial demonstrated promising anti-glioma activity of imatinib mesylate in combination with chemotherapy, hydroxyurea. Methods: The current phase I study is designed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of imatinib mesylate when combined with temozolomide, a DNA methylator with established efficacy against gliomas. Eligibility criteria include: histologically confirmed malignant glioma; age of at least 18 years; KPS of at least 60%; less than grade 2 intratumoral hemorrhage; adequate hepatic, renal, and bone marrow function and lack of prior failure or significant toxicity following treatment with either imatinib mesylate or temozolomide. Temozolomide is dosed at 200 mg/m2 on days 4–8 of each 28-day cycle. Imatinib mesylate is administered on days 1–8 of each cycle and the dose is escalated in successive cohorts of 3–6 patients via a standard “3+3” dose escalation design. Patients are stratified based on concurrent use of enzyme-inducing anticonvulsants (EIAC) and both strata are independently escalated. Results: To date 47 patients have been enrolled including 40 with GBM and 7 with anaplastic gliomas. Median age is 53.9 years (range 28 to 72); 66% are male and 51% are on EIAC. The MTD has yet to be defined for either stratum. To date DLT of ALT elevation has been observed in one patient from non-EIAC stratum. Two patients discontinued therapy due to toxicities with one asymptomatic intracerebral hemorrhage and one severe hematologic toxicity. Pharmacokinetic sampling has been performed in approximately half of the patients. One patient completed the study (12 cycles) with stable disease. Eleven patients remain on study with one partial response and three patients have undergone more than 10 cycles of therapy with stable disease. Twenty-eight patients (59%) have developed progressive disease and discontinued therapy. Conclusions: Combination of imatinib mesylate and temozolomide is safe and well tolerated. Further accrual and dose escalation are ongoing. [Table: see text]
A phase II study of temozolomide and oral VP-16 for adults with recurrent glioma—Final results
Authors: Korones D. N. , Benita-Weiss M. , Coyle T. , Bushunow P. , Mechtler L. , Friedman H. S. 
Published: March 2020

1565 Background: Although temozolomide has proven activity in patients with high and low grade gliomas, many patients do not respond, and for those who do, responses are often short-lived. We therefore undertook a trial of temozolomide in combination with oral VP-16 (etoposide) for patients with recurrent glioma. Methods: Patients were eligible for the study if they had recurrence of a glioma (glioblastoma [GBM], anaplastic glioma, or low-grade glioma), were ≥ 18 years of age, had a WHO score of 0–2, and had not received prior therapy with temozolomide or oral VP-16. All patients received temozolomide, 150 mg/m2/d days 1–5 and oral VP-16, 50 mg/m2/d days 1–12 (based on the maximum tolerated dose established in a previous phase 1 study [Cancer 2003, 97 (8); 1963–68.]). Cycles were repeated every 28 days for up to 12 cycles. All patients received prophylaxis for pneumocystis. Results: Fifty-one patients were enrolled - 32 with glioblastoma, 12 with anaplastic gliomas, and 7 with low-grade glioma. Median age was 52 years (21–76), and 67% were male. Forty-one were enrolled at first and 10 at second recurrence. Fifty had had prior radiation, and 30 of these 50 patients had also received prior chemotherapy. Of the 32 subjects with GBM, 4 had a PR (12.5%), 13 (41%) SD, 13 (41%) PD, and 2 were not evaluable because of deterioration prior to imaging. The median progression-free survival (PFS) was 2 mo. (0–51+ mo), and the 6 mo. PFS was 19%. Of the 12 patients with anaplastic gliomas, 2 had a PR (16%), 7 SD (58%), 2 PD (16%) and one was not evaluable. Their median PFS was 5.5 mo, and the 6 mo. PFS was 50%. Of the seven subjects with low grade gliomas, 4 had a PR, 2 SD, and 1 PD. Their median PFS was 5 mo. (0–12) and 6 mo. PFS was 57%. Of the entire cohort, two patients developed fever and neutropenia and died of pseudomonas sepsis. Another two patients were prematurely withdrawn from the study due to toxicity (one for grade 4 neutropenia and a second for grade 2 diarrhea). Conclusions: In this population of previously treated patients with recurrent glioma, the combination of oral VP-16 and temozolomide has only modest efficacy and significant toxicity. The results of this study suggest that in this setting, the combination offers no advantage over either agent used alone. [Table: see text]
Results of G004, a phase IIb actively controlled clinical trial with the TGF-b2 targeted compound AP 12009 for recurrent anaplastic astrocytoma
Authors: Hau P. , Stockhammer G. , Kunst M. , Mahapatra A. , Sastry K. V. , Parfenov V. E. , Leshinsky V. G. , Jachimczak P. , Bogdahn U. , Schlingensiepen K. 
Published: March 2020

1566 Background: In 3 phase I/II dose-escalation studies the TGF-β2 specific compound AP 12009 proved to be well tolerated and revealed an excellent safety profile. Furthermore, antitumor activity including complete tumor remissions was observed. Methods: G004 is an international open-label, actively controlled, dose finding phase IIb trial in adult patients with histopathologically confirmed recurrent high-grade glioma. 145 patients with recurrent anaplastic astrocytoma (AA, WHO grade III) or glioblastoma (GBM, WHO grade IV) were enrolled into the study. Objective of the current phase IIb study is to compare the efficacy and safety of two doses of AP 12009 and standard treatment. Patients were randomized to receive either one of two doses of AP 12009 (10 μM or 80 μM) or standard chemotherapy (TMZ or PCV). AP 12009 was administered intratumorally by CED. 134 patients received treatment and all of them have completed active treatment. Primary endpoint is tumor response by local and central MRI reading and survival. Results: Here we report on patients with recurrent AA (for GBM see separate Abstract). 38 patients with AA (68% male, 32% female; median age 39, range 22–60; median Karnofsky performance status: 90, range 70–100) were treated. 26 patients received AP 12009 (10 μM or 80 μM), 12 patients were treated with TMZ or PCV. Up to now, in 89 patients treated with AP 12009 (both AA and GBM patients) 6 SAEs possibly related to the study drug and 37 procedure related SAEs (92% mild or moderate) were documented. Partial and complete tumor responses were observed. Exact response rates will be determined after central MRI reading is completed. Responses in the AP 12009 groups are long lasting. The results confirm the good safety profile of AP 12009 as well as the efficacy data seen in phase I studies. The median overall survival is not yet reached. Conclusions: The long-term tumor free survival of several patients may actually hint towards a potential to cure some patients with this devastating disease. Phase III clinical trials in both AA and GBM patients are currently in preparation. [Table: see text]
Outcomes of critically ill patients with lung cancer
Authors: Soares M. , Darmon M. , Ferreira C. G. , Salluh J. , De Miranda S. , Adda M. , Spector N. , Azoulay E. 
Published: March 2020

16001 Background: Recent advances in oncology and critical care have resulted in improved survival in critically ill cancer patients. An appraisal of the prognosis of critically ill patients with lung cancer is timely. Methods: The aim of this study was to evaluate the outcomes and prognostic factors of critically ill cancer patients with lung cancer. From 2000 to 2005, patients with either small-cell (SCLC) or non-small-cell lung cancer (NSCLC) admitted at two intensive care units (ICU) in Brazil and France were included. Patients with postoperative care, ICU stay <24 h and readmissions were excluded. Demographics, clinical, cancer related and outcome variables were collected. Hospital mortality was the outcome variable of interest. Variables selected in the univariate analysis (p < 0.25) and those considered clinically relevant were entered in a multivariable logistic regression analysis [results were expressed as odds-ratios (OR), 95% confidence interval (CI)]. Results: A total of 132 patients were studied (INCA = 87, St Louis Hospital = 45). Their mean age was 61 ± 10 years and 73% were males. Twenty-five (19%) had SCLC and 107 (81%), NSCLC. The SAPS II score was 48 ± 21 points. The main reasons for ICU admission were severe sepsis (45%) and acute respiratory failure (33%). During ICU stay, 96 (73%) patients received mechanical ventilation, 76 (58%) vasopressors and 11 (8%) dialysis; 15 (11%) patients were treated with chemotherapy and 6 (5%), radiation therapy. Thirty-eight (29%) patients had end-of-life decisions. ICU and hospital mortality were 43% and 60%, respectively. Multivariable analysis identified three independent determinants of hospital mortality: airway obstruction/infiltration by cancer [OR = 2.87 (1.34–8.13), p < 0.001], number of organ failures [OR = 1.91 (1.01–2.74), p = 0.047] and performance status 3–4 before admission [OR = 2.90 (0.94–8.95), p = 0.065]. Conclusions: Improved survival in overall ICU cancer patients extends to patients with lung cancer, including those needing mechanical ventilation. Interestingly, the characteristics of the cancer are not associated with the outcome and should not be the grounds for the ICU decision making. Mortality is increased with the number of organ dysfunctions, in particular when respiratory failure is due to cancer progression. No significant financial relationships to disclose.
Access to specialized cancer care and clinical trials for cancer patients from non-urban areas is facilitated by a Cancer Network organization
Authors: Brunet J. , Martin B. , Del Barco S. , Juez I. , García A. , Viñas G. , Hernández X. , Arnedos M. , Borràs J. M. , Colomer R. 
Published: March 2020

16006 Background: In non-urban areas, there is a controversy about whether medical cancer treatments should be administered exclusively in referral cancer centers (CC) or in community hospitals (CH) (Br J Cancer 2004; 90: 1688). Limitations such as geographical distance or absence of treatment guidelines may reduce the access to specialized cancer care or clinical trials. A network organization that involves at the same time a CC and the CH from the same geographical area may provide an adequate balance between proximity, equity and quality of cancer services. Methods: We designed a cancer network in 2003 in order to consolidate all Oncology resources in an area covering a population of 700,000. A CC is placed adjacent to a general hospital in a centrally located urban area of 250,000. The remaining area is served by 6 CH. Our cancer network is based on: 1) approximately half of the Medical Oncology Dpt staff members work part-time at a CH, participating in outpatient clinic, chemotherapy treatments administration, and multidisciplinary meetings; and 2) other cancer health professionals are organized in network groups like the pharmacy group and the chemotherapy nursing group. Specialized medical cancer care included concomitant radio-chemotherapy, complex outpatient or inpatient therapies, genetic counseling and therapy for some pre-defined malignancies such as germ cell and ovarian cancers. Results: From January to December 2004, 1862 new patients were visited, 1013 (54%) at the CC (Medical Oncology Dpt.), and 849 (46%) at the CH. One-hundred ninety-three cancer patients were referred from the CH to the CC. In total, 141 of the cancer patients seen at the CC were included in clinical trials. It is remarkable that clinical trial participation was much enhanced by referrals, since 101 (72%) of patients in clinical trials came from non-urban areas. Conclusions: The establishment of a cancer network facilitates access to specialized cancer care and clinical trials for patients living in non-urban areas, therefore contributing to therapeutic equity. No significant financial relationships to disclose.
Using qualitative data to examine disparities in cancer outcomes: Results from interviews with African American (AA) and white (W) patients regarding health beliefs and perceptions of chemotherapy
Authors: Polite B. N. , Gehlert S. , Hlubocky F. , Smith D. , Daugherty C. K. 
Published: March 2020

16016 Background: Prior data indicate African Americans are less likely to receive appropriate and timely therapy for breast, colon, and lung cancers. The reasons for this may involve differences in how AA patients (pts) perceive the risks and benefits of available therapies. In general, little is known about the beliefs of pts, and about AA’s in particular, toward the risks and benefits of chemotherapy. Methods: Semi-structured qualitative interviews are being conducted on pts who have been referred to receive chemotherapy for breast, colon, and lung cancer. Results: To date, 18 patients have been interviewed: 9AA, 9W; median age 61 (range 35–77); 11 lung, 4 breast, 3 colon (11 for adjuvant therapy and 7 with metastatic disease). Pts provided their beliefs on the role of chemotherapy. Many described the advantages of chemotherapy indicating the possibility of cure or remission. Others expressed a degree of skepticism about the curative intent of chemotherapy. Many indicated an expectation of moderate to severe side effects that may have lasting effects on the body. Trust in one’s physician and the role of religion/spirituality are also emerging themes. One AA pt described that chemotherapy was a way for physicians to experiment on patients. Others believed that trust in one’s physician was implicit and essential. Many indicated a belief in God but few believed that his/her religious beliefs affected his/her approach to treatment. Conclusions: Consistent with the health beliefs’ model, perceived benefits and perceived barriers (one’s belief about the tangible and psychological costs of the advised action) shape pts’ perceptions of chemotherapy. In this ongoing analysis, the perceived benefits are tempered by a degree of skepticism. The perceived barriers include concerns about the overall impact of chemotherapy on the body and spirit rather than specific short-term side effects. Also, belief in the use of chemotherapy as an experiment is potentially consistent with some African American patients’ perceptions. No significant financial relationships to disclose.
Health state utility and toxicities in metastatic lung cancer: A qualitative study
Authors: Nafees B. , Stafford M. , Bhalla S. , Watkins J. 
Published: March 2020

16017 Background: In metastatic lung cancer, it is expected that quality of life is impacted both by the efficacy and toxicity of therapy. Previous research has reported health states either based on response to therapy or on toxicity, but not in combination. Using methodology applied in breast cancer (Narewska 2005), we developed health state descriptions for advanced non-small cell lung cancer (NSCLC) for use in cost-utility analyses. Methods: An interview discussion and content validation guide was produced based on literature review and clinical input. Response to therapy was described as responding disease, stable disease, or progressive disease. The most common toxicities were selected based on randomized clinical trials. Descriptions of health states were reviewed by clinical specialists. Final health states will be piloted and then used in a societal-based valuation study using standard gamble technique. The contributory effect of disease state and toxicity will be estimated using a mixed model analysis and compared with the data from the previous breast cancer utility study. Results: Eight toxicities were identified: alopecia and grade 3/4 neutropenia, febrile neutropenia, hand-foot syndrome, gastrointestinal (diarrhea/vomiting), rash, stomatitis and fatigue. These were combined with response to therapy to yield 19 health states: 9 responding disease (one with each toxicity plus one with no toxicity), 9 stable disease (one with each toxicity plus one with no toxicity) and one progressive disease (toxicity not included). These health states were reviewed by 6 pulmonary oncologists and 3 specialist nurses. Conclusions: Development of health states that combine both efficacy and toxicity will be useful in evaluating the relative value of therapies for advanced NSCLC and comparison with other diseases. Input by clinical experts has provided validation for the proposed health states. Evaluation of these health states by members of society will provide appropriate perspective for economic evaluations. [Table: see text]