bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and translational studies of depsipeptide (romidepsin), a histone deacetylase (HDAC) inhibitor, in patients with squamous cell carcinoma of the head and neck (SCCHN): New York Cancer Consortium Trial P6335
Authors: Haigentz M. , Kim M. , Sarta C. , Keresztes R. S. , Smith R. V. , Belbin T. J. , Mariadason J. M. , Greally J. M. , Shapiro G. I. , Haddad R. I. 
Published: March 2020

6065 Background: Unresectable recurrent and metastatic SCCHN is incurable and associated with dismal prognosis. Our objective is to evaluate the clinical activity of depsipeptide (DEP) and its effects of on PBMCs, SCCHN tumors and oral mucosa tissues in an NCI/CTEP sponsored phase II trial. Methods: Eligibility criteria include PS 0–2, any number of prior therapies and no history of significant cardiovascular disease. DEP was administered at 13 mg/m2 IV over 4 hrs on days 1, 8, and 15 of 28 day cycles. A two-stage design was utilized, with commencement to the second stage (total 46 pts) if at least 8 of 18 pts achieve disease control at 8 weeks by RECIST. Results: To date, 10 pts (7M/3F) have been accrued, all with samples for correlative studies. Two pretreated pts (2 and 4 prior therapies for recurrent/metastatic disease) have achieved disease stabilization, including one with clear histone H3 hyperacetylation in PBMCs immediately following the first 4 hr infusion of DEP. Common toxicities to date have included fatigue and weakness, usually mild. Myelosuppression is uncommon. Aside from G3 hypotension in 1 pt, no cardiovascular toxicities have been attributed to DEP. To date, 2 of 2 pairs of pre- and post-treatment (cycle 1, day 16) biopsy specimens have demonstrated increased expression of p21Waf1/Cip1 by immunohistochemistry post-DEP, consistent with HDAC inhibition by DEP in tumor cells. Additionally, 3 pairs of tumor biopsies and 4 pairs of mucosal brush biopsies have been analyzed by differential gene expression profiling using microarrays containing 27,323 cDNA clones; 208 cDNA clones of interest appear to be upregulated in response to DEP in at least 3 of the 7 comparisons. Analysis also includes CpG island methylation status of candidate tumor suppressor loci in tumor and mucosal tissues. Conclusions: DEP appears well tolerated by SCCHN pts, with infrequent myelosuppression and minimal if any cardiovascular toxicity in pts without pre-existing disease. Effects of DEP on PBMCs, tumor and mucosal tissues are consistent with HDAC inhibition in vivo. Accrual to the clinical trial is ongoing. Supported by ASCO Career Development Award, NIH CA110342 and N01-CM-62204. No significant financial relationships to disclose.
Clinical study of thyroid cancer among a pediatric population born after Chernobyl (first report)
Authors: Gorobeiko M. B. , Larin O. S. , Cherenko S. M. 
Published: March 2020

6069 Background: To evaluate the clinical and patologic results of surgical treatment of children born after Chernobyl and to compare these findings with well-known data of the group of patients who were children at the time of Chernobyl. To compare the clinical and pathologic features of thyroid cancer of children born after the Chernobyl versus those born prior to 1986. Methods: Comparison of clinical and pathologic result of surgical treatment of 141 patients born after Chernobyl (Group 1) and 589 patients (Group 2) aged 0–18 at the time of the disaster (1986) among the single institution clinical cohort within years 1995–2005. Results: In Group 1 there were 31 cancers (22%) vs. 243 (41%) in Group 2 (p<0.05 between Group 1 and Group 2). The rate of extrathyroid invasion was 69% vs. 36% (p<0.05 between Group 1 and Group 2). In Group 1, 17/21(80%) patients with extrathyroid invasion were found to have regional neck metastases (8 unilateral, 9 bilateral).The mean age in this subgroup was 13.4 ± 2.11 years but in the “benign subgroup” of Group 1 the mean age is 16.2 ± 0.77 years.In Group 2, 49/88 (55%) patients with extrathyroid invasion only had regional metastases. The mean age in this subgroup is 31.1 ± 4.7 years (p<0.05 between Group 1 and Group 2). We found cancer multifocality in 1 patient (3%, Group 1) vs. 55 (23%, Group 2).There were 19 cases (13.5%) of atypical adenomas in Group 1 vs. 46 (8%) in Group 2 (p<0.05 between Group 1 and Group 2). Histological types: solid follicular variant of papillary carcinoma (typical for radiation-induced children carcinomas with short latency) was found in 3 cases in Group 1 (9.5%) vs. 76 (31%) in the Group 2 (p<0.05 between Group 1 and Group 2). There was only one case of follicular thyroid cancer in Group 1 (3%) vs. 9% in Group 2. We did not find any relationship of cases of cancer in Group 1 to the Chernobyl-polluted area (only 3 patients − 10% from the nearest to Chernobyl regions) vs. 192 patients (80%) in Group 2 (p<0.05 between Group 1 and Group 2). Among patients with tumors of uncertain malignant potential 9 patients (6%) were from Chernobyl-polluted area vs.72% in Group 2 (p<0.05 between Group 1 and Group 2). Conclusions: Our data demonstrates higher likelihood of aggressive well-differentiated thyroid cancer among a pediatric population independently from Chernobyl irradiation and connected with another etiological factors of genesis of tumor.The solid-follicular variant of papillary cancer and multifocality are typical for radiation-induced carcinoma in children. No significant financial relationships to disclose.
Intraoperative radiotherapy (IORT) with low-energy x-rays for breast cancer
Authors: Kraus-Tiefenbacher U. S. , Herskind C. , Bauer L. , Scheda A. , Wenz F. 
Published: March 2020

607 Background: IORT for breast cancer using either electrons or low-energy x-rays is of increasing interest over the last few years. In our institution, IORT is delivered by a mobile x-ray source (Intrabeam™) producing isotropic 50 kV x-ray fields. Because this treatment method includes single high doses to the normal breast tissue, careful and long-term evaluation of early and late toxicity is mandatory. To date there are still fewdata on long-term follow-up of patients treated with low-energy x-rays. Methods: Between 2/02 and 12/06 204 breast cancer patients received IORT either as a tumour-bed boost (133) followed by 46 Gy external beam radiotherapy (EBRT) or as partial breast irradiation (PBI) only (71). Median age was 66.4 years (35–95), median tumour size was 9 mm (1–45). Spherical applicators (median 4. 0 cm) were inserted into the tumour-cavity and a single dose of 20 Gy was given. Follow-up (f/u) included physical examination and ultrasound 1 week, 2 months, then every 6 months after therapy and mammography at yearly intervals. Radiobiological modelling of the expected spatial distribution of late reactions was done for typical cases using the linear-quadratic model with special consideration of relative biological effectiveness, spatial dose distribution and dose rate. Results: Median f/u was 28 months (1–56). Minor postoperative side effects included erythema (5%), delayed wound healing (4%), mastitis (1%) and hematoseroma (4%). A fibrotic induration of the tumour bed was observed in 9, 18, 24, 23, 26% and 24% of the patients at 2, 6 12, 24, 36 and 48 month f/u. These fibrosis rates were distributed equally in both groups. Reoperation was required in 2 patients after 10 (fibrosis) and 12 months (fat necrosis). Conclusions: Although two thirds of the patients were treated with a combination of IORT and EBRT, acute reactions in all patients were mild. A fibrotic induration confined to the tumourbed was observed in up to 25% of all patients after 2 years. The low level of clinically observed late reactions so far is in agreement with predictions from radiobiological modelling. No significant financial relationships to disclose.
Validation of weekly-dose cisplatin combined with radiation therapy in locally advanced head and neck cancer
Authors: Boulmay B. C. , Riggs C. E. , Lawson M. , Morris C. , Mendenhall W. M. 
Published: March 2020

6076 Background: Impressive outcomes have been achieved using multiagent neoadjuvant and concomitant chemotherapy combined with radiation in definitive treatment of head and neck cancer; these are associated with significant toxicities. The purpose of this study was to determine the efficacy and toxicities of single-agent weekly (CDDP) during curative-intent radiation therapy. Methods: 36 patients with AJCC Stage II (3%), Stage III (14%), Stage IV (83%) squamous cell carcinoma of the larynx, hypopharynx, oropharynx and oral cavity treated from 6/2000 to 11/2003 were retrospectively reviewed. Subjects received 72 Gy irradiation given either by hyperfractionation or IMRT technique with CDDP 30 mg/m2/wk throughout the radiation course. Cisplatin was held for Grade III/IV toxicities. The endpoints were best response, percentage of Grade III/IV toxicities, disease-free survival (DFS), overall survival (OS). Results: The median number of cycles of CDDP administered was 6. Grade III/IV toxicities: 11% of patients had anemia, 6% thrombocytopenia, 33% leukopenia, 0% renal failure, and 25% developed Grade III/IV mucositis; 1 patient (3%) died due to complications directly related to therapy. Responses to therapy included 72% CR, 17% PR, and 5% SD. Median follow-up for all patients was 19 months (34.5 months for living patients), DFS at 3 years (yrs.) was 59%, and OS at 3 yrs, was 40%. Nine patients died of disease up to 2.6 (median, 0.7) yrs. after treatment, while 11 died of intercurrent diseases up to 5.1 (median, 1.8) yrs. later. Fifteen are alive (2 with recurrence) at median 2.7 yrs. after treatment. Conclusion: Concomitant weekly CDDP with full-course radiation is feasible, tolerable, highly active, and comparable to more complex, costly and toxic regimens. Intercurrent disease was a significant contributor to mortality in our population. Our regimen is an attractive alternative to sequential chemoradiotherapy programs. No significant financial relationships to disclose.
Economic evaluation of the TAX 324 trial comparing docetaxel plus cisplatin and 5-fluorouracil (TPF) versus standard treatment with cisplatin and 5-fluorouracil (PF) as induction chemotherapy followed by concurrent chemoradiation therapy in locally advanced squamous cell carcinoma of the head and neck (SCCHN)
Authors: Parthan A. , Posner M. R. , Brammer C. , Beltran P. , Jansen J. 
Published: March 2020

6079 Background: The TAX 324 phase III trial showed that induction chemotherapy with TPF followed by chemoradiotherapy improves survival and time to progression in patients with locally advanced SCCHN compared with PF [Posner MR, et al. ASCO 2006]. A Markov state-transition model was developed to estimate the cost-effectiveness of TPF. Methods: The Markov model includes four health states (based on WHO criteria for measuring objective response): stable, responsive, progressive disease, and death. TAX 324 efficacy data were used to derive transition probabilities between health states. Adverse event rates were also derived from TAX 324. Data for resource utilization and costs from a UK perspective were derived from the literature and clinician inputs from an advisory board. The global score of the Health Related Quality of Life Questionnaire Core-30 (QLQ-C30) was mapped to the EQ-5D in order to derive utilities and quality adjusted life years (QALYs). Results: A patient in the TPF arm survived longer versus PF (5.4 vs. 2.7 years). Comparison of TPF vs. PF resulted in an incremental gain of 2.7 life years and 2.1 QALYs. The incremental discounted costs/QALY gained for TPF vs. PF was £1,988/QALY, which is below the £20,000 cost-effectiveness threshold suggested by NICE as a guide to the acceptability of a technology. At this threshold, there is a 96.1% probability that TPF is cost-effective compared with PF. Conclusion: Docetaxel, when given as induction chemotherapy followed by concurrent chemoradiotherapy in combination with cisplatin and 5-fluorouracil (TPF), leads to a substantial increase in life expectancy, and is cost-effective compared with PF for locally advanced SCCHN. No significant financial relationships to disclose.
Prognostic value of age in nasopharyngeal carcinoma patients: A single institution analysis
Authors: Downing N. L. , Wong P. , Petrik D. , Hara W. , Le Q. 
Published: March 2020

6080 Background: Nasopharyngeal carcinoma (NPC) has a bimodal age distribution with peaks at 15–25 and 40–50 years of age, though it is unclear if the prognosis differs significantly between the two age groups. Here, we compare treatment outcomes between two age groups of patients treated at a single institution. Methods: We retrospectively analyzed the data of 99 NPC patients who received definitive treatment at our institution between March 1985 and June 2004. All patients received a median dose of 66 Gy of external beam radiation therapy and 70% received either concurrent or induction chemotherapy. We compared patient, tumor, and treatment characteristics as well as treatment outcomes in juvenile patients (age = 25 years at diagnosis), versus adult patients (age > 25 years at diagnosis). Survival curves were estimated by the Kaplan-Meier method. Results: There was a significant difference in the ethnic composition between the age groups, with more Asians and fewer Whites and Hispanics in the adult group (see table ). Also, there was a significant difference between the groups in the proportion of patients receiving chemotherapy, especially induction chemotherapy (see table ). There was no difference in the distribution of tumor stage and WHO histology between the two age groups. At a median follow-up for all patients of 42 months (range 4 to 234), there were no statistically significant differences in treatment outcomes between the two age groups although the survival data numerically favored the juvenile patients (see table ). Conclusions: Although there were significant differences in racial distributions and treatment characteristics between the two age groups, treatment outcomes were similar. Aggressive treatment with radiotherapy and chemotherapy resulted in excellent outcomes for both patient populations. No significant financial relationships to disclose. [Table: see text]
Phase I study of panitumumab, chemotherapy and intensity-modulated radiotherapy (IMRT) for head and neck cancer (HNC): Early results
Authors: Wirth L. J. , Posner M. R. , TIshler R. B. , Haddad R. I. , Goguen L. , Clark J. R. , Allen A. M. 
Published: March 2020

6083 Background: Both chemotherapy and epidermal growth factor receptor (EGFR) antibody therapy improve outcomes in HNC when added to radiotherapy. This phase I study investigates the addition of the fully human anti-EGFR antibody, panitumumab, to chemoradiotherapy (CRT) for HNC. Methods: Treatment naïve adults with stage III/IV HNC (primary sites include oropharynx and unknown primary) with normal hematologic, renal, and liver function are currently enrolling in a 2-part study. Part A determines the maximum tolerated dose (MTD) of paclitaxel in 2 dose levels (DLs) (15 and 30 mg/m2 wkly×7 wks) with fixed-dose carboplatin and panitumumab (AUC of 1.5 and 2.5 mg/kg wkly, respectively) plus IMRT (70 Gy). Patients (pts) are enrolled in sets of 3. Part B determines the MTD of 5-FU in 2 DLs (800 and 900 mg/m2 days 1–4, Q21d) with fixed-dose docetaxel, cisplatin and panitumumab (75 mg/m2, 100 mg/m2 and 9 mg/kg, Q21d, respectively) for 3 cycles followed by panitumumab + CRT, as determined in Part A. Results: To date, 8 pts (n=3 at DL 1, n=5 at DL 2) have enrolled in Part A. One dose-limiting toxicity has occurred in DL 2: grade (gr) 4 febrile neutropenia. Other adverse events include gr 3/4 mucositis (n=6), gr 3/4 radiation dermatitis (n=6), gr 2 acneiform rash (n=6), gr 3 dysphagia (n=6) and gr 2 oral pain (n=6). Dose-reduction has not been necessary thus far. Enrollment will continue in a cohort of 10 pts in DL 2. Of 4 pts evaluated for response, 4 had complete response in the primary and neck, and 1 had a residual neck mass. This pt had 1 positive node on neck dissection. Conclusions: Preliminary results suggest that panitumumab can be added to CRT for treatment of HNC without magnifying the expected toxicities with CRT. Part B will investigate panitumumab + sequential therapy for HNC once the MTD of Part A is established. No significant financial relationships to disclose.
Sequence-dependent cytoxicity of docetaxel and erlotinib in head and neck squamous cell carcinoma (HNSCC)
Authors: Glisson B. S. , Saigal B. , Xu Y. , Johnson F. M. 
Published: March 2020

6084 More effective systemic treatment is needed for HNSCC. The taxoids are the most efficacious single agents identified. Epidermal growth factor receptor (EGFR) is almost universally expressed by HNSCC tumors but inhibitors have only modest activity as single agents in clinical studies. However, the combination of the taxoids with EGFR inhibition has additive anti-tumor effects in HNSCC in vitro and in animals. Despite similar pre-clinical data in lung cancer, clinical trials showed no benefit when EGFR inhibitors were added to chemotherapy. In vitro studies in lung, breast and colon cancer cell lines demonstrate that the separation of EGFR TKI from chemotherapy and the order in which these agents are administered influences efficacy. We sought to determine if a similar sequence-dependent effect exists in HNSCC in order to help design future clinical trials with these agents. We chose three human HNSCC cell lines with diverse levels of basal EGFR expression and activation. None had EGFR mutations, which are very rare in HNSCC. Cells were treated with single agent docetaxel or erlotinib or combinations for 72 h and cytotoxicity was measured with an MTT assay. Concurrent treatment with docetaxel and erlotinib resulted in more cytotoxicity than single agents and calculated combination indices demonstrated additive effects. When erlotinib was added 4 to 24 h prior to docetaxel, the efficacy was similar to or less than that of concurrent therapy regardless of whether the erlotinib was washed off prior to the docetaxel or left in the cell medium. In contrast, when docetaxel was added ≥ 10 h prior to erlotinib, cytotoxicity was enhanced as compared to concurrent therapy. The most efficacious combination was docetaxel treatment for 24 h followed by erlotinib for 48 h. This combination was chosen for further analysis. Consistent with previously published studies in other cell types, erlotinib resulted in G1 cell cycle arrest and docetaxel in G2-M arrest. On-going studies to investigate the mechanism for the sequence-dependent cytotoxicity include examination of the effects of the sequence on cell cycle and apoptosis, tubulin expression, and cell signaling molecules that mediate pro-survival signals from EGFR. [Table: see text]
Intraoperative identification of sentinel lymph node guided by near-infrared fluorescence imaging for breast cancer patients
Authors: Tagaya N. 
Published: March 2020

615 Background: Recently, radioactive tracer, a vital dye, or a combination of both has been applied intraoperatively to detect sentinel lymph nodes (SLN) for patients with early breast cancers. We present a novel method of SLN identification using near-infrared fluorescence imaging that provides with high detection and low false-negative rates. Materials and Methods: This study enrolled 52 patients with a tumor less than 3 cm in diameter. Their mean age was 54.7 years. Preoperative TNM stage was I in 35 cases, IIa in 12, and IIb in 5, respectively. Initially the combination dye of indocyanine green and indigocarmine was injected subdermally in the areola. Fluorescence imaging (photodynamic eye: Hamamatsu Photonics Co.) was obtained using a charge coupled device camera with a cut filter as the detector, and light emitting diodes at 760 nm as the light source. Subcutaneous lymphatic channels draining from the areola to the axilla or other directions were visible by fluorescence imagings immediately. After incising the axillary skin 1 cm cranial side from the disappeared point of fluorescence image, SLN was then dissected under the guidance of fluorescence. Results: In all but one patient, lymphatic channels and SLN were successfully visualized (identification rate: 98.1%). SLN was observed before skin incision in two patients. The number of fluorescence SLN ranged from 0 to 11 (mean: 4.7) and blue dyed SLN ranged from o to 6 (mean: 2.0). SLN was not identified in one patient in the former and 7 patients in the latter. Twelve patients had lymph node metastases pathologically. All of them were recognized by fluorescence imaging, however, three patients with metastatic LN were not identified by a vital dye. Conclusions: This method is feasible and safe to detect SLN intraoperatively with less invasive, real-time observation and no requirement of training. We are convinced that this method will provide with high detection and low false-negative rates in SLN navigation surgery. No significant financial relationships to disclose.
A randomized trial of computer and pamphlet-based versions of the Decision Board (DB)
Authors: Whelan T. J. , Gafni A. , Julian J. , Sebaldt R. J. , Tozer R. , Heller B. , Ellis P. , Hodgson N. , Mukherjee S. , Levine M. N. 
Published: March 2020

6508 Background: Many women with breast cancer want to be involved in treatment decision making. The DB is a visual aid poster board which sequentially presents written and graphical information from clinical trials regarding treatment options for early breast cancer. The physician presents the DB to the patient during the consultation. Randomized trials have demonstrated that the standard version of the DB improves patient comprehension, satisfaction and comfort with decision making. The standard DB is cumbersome to use and hard to update. Computer based instruments are attractive as they provide more flexibility in presenting information, and can be easily updated and accessed via the Internet. On the other hand pamphlet based versions may be easier to use. We developed computer versions of the DB for breast cancer surgery and adjuvant chemotherapy options using a Windows type format. Pamphlet versions were also developed. The objective of this study was to compare the computer and pamphlet versions of the DB to the proven standard version. Methods: 309 women were randomized to the physician consultation plus the standard (105), computer (103) or pamphlet (101) versions of the DB. Patients were stratified according to type of decision: surgical treatment or adjuvant chemotherapy. Patients were evaluated following the consultation for their knowledge about the breast cancer treatments offered, decisional conflict, and satisfaction with preparation for decision making using established validated instruments. Usefulness of the instrument for the patient and physician was also assessed. Results: Study outcomes were similar between the three versions of the DB ( Table ). Usefulness of the instrument for the patient and physician was also similar for the different versions. Conclusions: The different versions of the DB appeared equally effective in facilitating shared decision making. Physicians and patients now have the option of choosing which instrument best suits their needs. Such versatility may encourage wider use of the DB. No significant financial relationships to disclose. [Table: see text]