bluuebunny/crossref_metadata_2025_split huggingface dataset:
A pilot study of modified neoadjuvant docetaxel/cisplatin/5-FU (TPF) to concomitant chemoradiotherapy (CT/RT) in locally advanced head and neck cancer (LAHNC): Preliminary results
Authors: Isla D. , Martínez-Trufero J. , Morales S. , Yubero A. , Lambea J. , Álvarez I. , Polo E. , Seguí M. A. , Pujol E. , Pastor P. 
Published: August 2020

6039 Background: Sequential treatment with induction CT followed by CT/RT is highly active and under study in ongoing randomized trials. We started a pilot phase II trial to explore the efficacy, toxicity profile and organ preservation of a modified neoadjuvant TPF to concurrent CT/RT in both resectable (R) and unresectable (UR) LAHNC. Methods: One hundred seventy patients(p) with stage III-IV, PS ECOG 0–2, were included to receive 3 cycles of docetaxel 75 mg/m2 iv day(d) 1, cisplatin(P) 75 mg/m2 iv d2 and 5-FU 750 mg/m2 iv continuous infusion d2–5, every 3 weeks with prophylactic ciprofloxacin 500 mg twice daily from d6–15 of each cycle and granulocyte colony-stimulating factor as secondary or primary setting, followed by P 100 mg/m2 iv d1, 22, 43 concomitant with RT (66–70 Gy, conventional fractionation). Neck dissection was planned for p with stage N2–3 after induction CT or salvage surgery for resectable p with persistent disease at the end of treatment. Results: Main p characteristics were: median age 58 years (39–77), male 89%, ECOG 0/1/2 47%/50.6%/2.4%, stage IV 62.7%, larynx/hipopharynx/oral cavity/oropharynx 45%/12%/17.3%/25.7% and R/UR 41.8%/58.2%. Median TPF/P cycles administered were 3/3. Neoadjuvant CT/total treatment overall response rate evaluation (R/UR): 70% (73%/68%)/86% (84%/88%). Neck dissection was performed in 16 p and salvage surgery in 6 p. Organ preservation was achieved in 90.8% of R p. Main G3–4 toxicity during TPF treatment was neutropenia 11.2%, febrile neutropenia 11.2%, mucositis 11.2%, and during CT/RT mucositis 16.5%, neutropenia 16.5%. Median time to progression was 19.5 m(R:15.6, UR:20.3), and median overall survival was not reached (R:not reached, UR:32.8). Conclusions: Preliminary results indicate that modified neoadjuvant TPF followed by CT/RT is an active and well tolerated regimen in LAHNC, with satisfactory organ preservation and survival. No significant financial relationships to disclose.
Phase II study of depsipeptide (DEP) in radioiodine (RAI)-refractory metastatic nonmedullary thyroid carcinoma
Authors: Sherman E. J. , Fury M. G. , Tuttle R. M. , Ghossein R. , Stambuk H. , Baum M. , Lisa D. , Su Y. B. , Shaha A. , Pfister D. G. 
Published: August 2020

6059 Background: Historically, systemic therapy for radioactive iodine (RAI)-refractory thyroid cancer has been understudied. Available drugs have modest efficacy. Depsipeptide (DEP) is a histone deacetylase inhibitor with potent anti-tumor effects both in vitro and in vivo. In thyroid cancer cell lines, DEP increases expression of both thyroglobulin and the sodium/iodine symporter messenger RNAs, offering the possibility of improved iodine concentrating ability of radioactive iodine (RAI)-resistant tumors. Methods: Eligible patients (pts) must have progressive, RAI-refractory, recurrent/metastatic, non-medullary, non-anaplastic thyroid cancer; RECIST measurable disease; and adequate organ/marrow function. Exclusionary criteria include prior chemotherapy in the recurrent/metastatic setting; cardiac disease or dysfunction; QTc prolongation or co-administration of drugs that prolong the QTc. DEP 13 mg/m2 IV is administered on days 1, 8, 15, every 28 days. The primary endpoint is response rate by RECIST criteria; change in RAI avidity is a secondary endpoint. The study closed early due to poor accrual after an unexpected grade 5 adverse event (AE) that prompted protocol suspension. Results: 20 pts were enrolled: female-50%; median age-64 years; histology-papillary (8)/follicular (1)/Hürthle (11). Grade 4–5 AE possibly related to drug: grade 5 sudden death (1); grade 4 -pulmonary embolus (1). Twelve of 20 subjects had a reported AE. No RECIST major responses have been seen. Evaluation of response: stable disease (10); progression (3); early death (1); unknown/inevaluable (6: 5 - temporary protocol suspension; 1 - withdrew consent). Restoration of RAI avidity was documented in 2 pts. For evaluable patients (14) only, median overall survival and time on study was 36 (.5–45+) months and 1.7 (0.46–12) months, respectively. Conclusions: We observed preliminary signs of in vivo reversal of RAI resistance after treatment with DEP. However, no major responses were observed and accrual was poor after the grade 5 AE. (Study funded by grant N01 CM 62206) No significant financial relationships to disclose.
Measuring the symptom burden of head and neck cancer patients undergoing concurrent chemotherapy and radiation therapy using area under the curve
Authors: Mendoza T. , Rosenthal D. , Wang X. , Mobley G. , Cleeland C. 
Published: August 2020

6067 Background: Patients with head and neck cancer (HNC) experience a significant treatment-related symptom burden during therapy that presents management challenges for both patients and treatment staff. Typical symptom measurement approaches have failed to capture the extent of this symptom burden over the course of therapy. We evaluated frequent symptom measurement summarized as area under the curve (AUC) as a way of portraying treatment related symptom burden in HNC patients, and explored this method for comparing symptoms produced by treatments that were expected to produce different levels of symptom impact. Methods: The M. D. Anderson Symptom Inventory - Head and Neck module - was administered at baseline and weekly for 10 weeks following the start of treatment to patients undergoing radiation therapy (XRT) as a single modality therapy (N = 49) and a second group receiving chemoradiotherapy CXRT (N = 53). We expected that treatment-related symptom burden would be greater for those patients receiving CXRT. A single value (AUC) was calculated based on the core symptoms reported by both groups of patients. Results: AUC comparisons for mean symptom severity for core symptom items demonstrated the expected greater symptom burden associated with CXRT (170.6 vs 120.9, p < 0.008). The AUC for symptom interference, as measured by the MDASI-HN, was also greater for the CXRT group (p < 0.002). AUCs for individual symptoms, such as fatigue (p < 0.002), sleep disturbance (p < 0.05) and lack of appetite (p < 0.02), were also significantly larger for the CXRT group. Conclusions: The AUC of individual and combined symptoms during cancer therapy present a useful summary of treatment related symptoms that can be used to compare treatment-related symptom burden between different treatment strategies used for the same disease. No significant financial relationships to disclose.
Expression of excision repair cross-complementation group 1 protein and outcome in patients with nasopharyngeal cancer
Authors: Lee H. , Hwang Y. , Han J. , Choi J. , Kang S. , Jeong S. , Ann M. , Oh Y. , Kim J. , Kim C. 
Published: August 2020

6085 Background: We evaluated the prognostic significance of thymidylate synthase (TS), and Excision Repair Cross-Complementation Group 1 protein (ERCC1) in patients (pts) with nasopharyngeal cancer (NPC) treated with concurrent chemoradiotherapy (CCRT). Methods: Pretreatment tumor biopsy specimens from 41 pts with locally advanced NPC were analyzed for TS and ERCC1 expression by immunohistochemistry. All patients were treated with 1 cycle of induction chemotherapy (5-fluorouracil 1,000 mg/m2/day and cisplatin 20 mg/m2/day, days 1–4) followed by CCRT starting on day 22. CCRT consisted of radiotherapy (70Gy/35 fractions for 7 weeks) with cisplatin 20mg/m2/day for 4 days on weeks 1, 4, 7 of radiotherapy. Results: Complete response and partial response were achieved in 34 pts (83%) and 6 pts (15%), respectively. Within median follow up duration of 101 months (26–147months) in survivors, 5-years overall survival (OS) of all pts was 50%. High expression of TS and ERCC1 was observed in 21 (51%) and 25 (60%) pts, respectively. High expression of ERCC1 was associated with WHO type 1 or 2 histology (p = 0.045). In univariate analysis, high expression of ERCC1 was associated with poor OS (5-year: 73% versus 35%; p = 0.005), while high expression of TS was not correlated with pts outcome (p = 0.867). In multivariate analysis, high expression of ERCC1 was a significant independent predictor of poor OS (p = 0.041) along with WHO type 1 or 2 histology (p = 0.004). Conclusions: High expression of ERCC1 protein may be useful for prediction of poor outcome in pts with NPC treated with CCRT. No significant financial relationships to disclose.
A prospective clinical study for molecular intra-operative detection of lymph node metastasis in breast cancer patients by one step nucleic acid amplification (OSNA) in comparison to intensive histological investigation
Authors: Di Filippo F. , Mottolese M. , Botti C. , Marandino F. , Psaila A. , Perri P. , Di Filippo S. , Pasqualoni R. , Ferranti F. , Buglioni S. 
Published: August 2020

609 Background: The aims of the study were 1) to assess the accuracy of a new intra-operative molecular diagnostic tool named OSNA, based on the measurement of cytokeratin 19 (CK19) mRNA, in the detection of axillary sentinel lymph node (SLN) metastases in patients with breast carcinoma 2) to determine the concordance of OSNA analysis with multilevel haematoxylin and eosin (H&E) and immunohistochemical (IHC) examination. Methods: A prospective series of 247 consecutive SLNs from 187 breast cancer patients was evaluated. The OSNA assay (Sysmex, Kobe - Japan) follows a short sample preparation step and subsequent rapid amplification of CK19 mRNA based on reverse transcription loop-mediated isothermal amplification. Each SLN was immediately divided into four slices. Two alternate slices were used for the intra-operative OSNA assay. The remaining two slices were investigated by six-level histopathology with 100 μm skip ribbons using routine H&E and CK19 IHC staining. The results of histology and OSNA were then compared. Results: Pts characteristics: infiltrating ductal/infiltrating lobular/mucinous/medullar/DCIS: 130/10/1/1/25. OSNA and histo-pathological methods identified 54 SLNs positive and 185 negative cases (2/3 contained isolated tumour cells). We found 8 discordant cases, 2 OSNA negative with micrometastasis found by IHC/H&E analysis, 5 OSNA positive for micrometastases but IHC/H&E negative and 1 case macrometastatic at OSNA, while negative at IHC/H&E analysis. The overall concordance of OSNA with histopathology was 96.7% with a specificity of 96.8% and sensitivity of 96.4%. These discordances could be due to sampling bias such that a micrometastasis was confined to the slices used for OSNA or the slices used for histology. Conclusions: The current study suggests that the performance provided by OSNA assay is comparable to intensive histopathological work-up even when using only half a lymph node. The method could be applied as a rapid and reliable intra-operative diagnostic tool thus preventing breast cancer patients from a diagnostic delay or second surgery due to a postoperatively diagnosed positive SLN. No significant financial relationships to disclose.
Use of quantitative RT-PCR assay to predict metastases size of sentinel node from breast cancer patients
Authors: Durbecq V. , Majjaj S. , Nogaret J. , Sirtaine N. , Schobbens J. , Noterman D. , Hertens D. , Filipov V. , Larsimont D. , Veys I. 
Published: August 2020

621 Background: A RT-PCR Assay (GeneSearch, Veridex, LLC), FDA approved and CE marked to detect metastases > 0.2 mm in sentinel lymph nodes (SLNs) of breast cancer patients, has been in clinical use in our institute for 25 months. The assay gives qualitative (negative/positive) results by applying cutoff values to cycle times (Cts) of mammaglobin (MG) and cytokeratin 19 (CK19) (cutoff values = 30 / 31 Cts). This study evaluates if quantitative Ct values can be used to estimate the probable size of nodal metastases. Methods: To date 384 patients have been clinically tested with the BLN Assay at Institut Jules Bordet. An additional 74 patients were tested in a pilot study. Both sets had SLNs of breast cancer patients divided in ∼2 mm pieces. Alternating pieces were homogenized and intra-operatively processed by the assay. The remaining pieces were used for histological analysis (positive when > 0.2 mm). During clinical use, same-surgery complete axillary dissection was performed when the assay was positive (n=59). Results: Performance of the assay's qualitative results against permanent section H&E was similar for both groups (total N = 458), for a total sensitivity 89% (68/76), specificity 95% (364/382) and overall agreement 94%. The marker Ct values are correlated with metastases size as determined by H&E on adjacent node pieces (r = -0.74 for MG and -0.77 for CK19, p < 0.001). Lower Ct values indicate increased likelihood of macrometastases reported by H&E, as described in the table. Additionally, Assay Ct values in the SLN were predictive of metastases in non-SLN nodes. For example when CK19 and MG < 24 Cts, the non-SLN positivity rate jumps from 29% to 58%. Conclusions: The BLN Assay's high intra- operative qualitative performance minimizes the need for second surgeries for complete axillary dissections. Results from this investigational study examining the marker Ct values suggest that the assay may provide valuable individual tumor volume data intra- operatively or post-operatively. [Table: see text] [Table: see text]
Primary endocrine therapy for early operable primary breast cancer in elderly women: A large series from a single institution
Authors: Al-Khyatt W. , Syed B. M. , Morgan D. A. , Cheung K. L. 
Published: August 2020

630 Background: A recent Cochrane review of seven randomised trials involving 1,446 elderly women (unselected for oestrogen receptor (ER) status) has shown no significant difference in overall survival between surgery (with or without adjuvant tamoxifen) and primary endocrine therapy using tamoxifen. We report our experience of using primary endocrine therapy in a single centre with a dedicated elderly breast cancer service. Methods: Over a 20-year period, 825 elderly (>70 years) women with early operable primary breast cancer were treated with primary endocrine therapy (>80% using tamoxifen as first-line agent), due to patient choice or being unfit for surgery. All patients had disease assessable for response according to UICC criteria, and had treatment for ≥6 months unless the disease progressed prior. Results: Median age was 80 (range: 70–99) years. When the disease progressed, some patients received further lines of therapy and the overall results are summarised (Table). Conclusions: Compared to the general use of endocrine therapy reported in advanced breast cancer (where CB rate is around 70%), primary endocrine therapy in this context appears to produce superior results. They support its use as an excellent alternative in elderly women who refuse or are unfit for surgery. Its precise role compared to surgery is the focus of a national randomised trial in the UK. CR: complete response; PR: partial response; SD: stable disease; CB: clinical benefit = CR + PR + SD; PD: progressive disease; DoCB: duration of CB; TTP: time to progression (all in months). [Table: see text] No significant financial relationships to disclose.
Factors associated with bilateral versus single mastectomy in a diverse, population-based sample of breast cancer patients
Authors: Hawley S. , Jagsi R. , Hamilton A. S. , Graff J. , Griggs J. J. , Katz S. J. 
Published: August 2020

6502 Background: Rates of bilateral mastectomy are increasing in the U.S., even among women with cancer in only one breast. The goal of this analysis was to assess correlates of bilateral mastectomy in a large, racially/ethnically diverse sample of breast cancer patients. Methods: All women with ductal carcinoma-in-situ and a 20% random sample of women with invasive breast cancer aged < 79 years who were diagnosed in 2002 and reported to the Detroit and Los Angeles SEER registries were surveyed shortly after receipt of surgical treatment (response rate, 77.4%; n = 1,844). Patient survey data were merged with SEER data. The primary dependent variable, receipt of bilateral mastectomy, was obtained from patient report and validated by SEER. Independent variables included patient demographics, family history of breast cancer, tumor stage, and patient concerns about recurrence and body image. Logistic regression was used to evaluate factors associated with receipt of all mastectomy (including bilateral) vs. lumpectomy, and then to evaluate bilateral vs. single mastectomy. Results: The mean age was 60 years. 70% were white, 18% Black, and 12% Latina. Overall, 5% of women received bilateral mastectomy (13% of those getting mastectomy). The Table shows factors associated with receipt of any mastectomy vs. lumpectomy (model 1) and bilateral vs. single mastectomy (model 2). Advanced stage and concerns about recurrence were associated with increased odds of any mastectomy while body image concerns were associated with lumpectomy (P<0.05) (model 1). Model 2 shows family history (OR: 3.00; 95% CI 1.36–6.61) and concerns about recurrence (OR: 2.76, 95% CI 1.14–6.68) were associated with greater odds of receiving bilateral vs. single mastectomy. Conclusions: Decision making for any mastectomy vs. lumpectomy is quite different from that for bilateral vs. single mastectomy. The latter appears to be driven by genetic predisposition, but there continues to be a strong influence of women's concerns about recurrence. [Table: see text] No significant financial relationships to disclose.
Development of combination chemotherapy regimens: What is the yield of published phase II trials?
Authors: Hudoba C. , Maitland M. L. , Snider K. L. , Ratain M. J. 
Published: August 2020

6510 Background: Although combination therapy presents an opportunity to advance cancer care, how well typical phase II development methods screen for regimens that improve care is not known. Since single arm phase II trials have fundamental flaws that could be magnified in combination treatment studies, we hypothesized that these phase II trials would have a low positive predictive value. Methods: We searched medline for phase II combination chemotherapy clinical trials published in 2001 and 2002, and selected for those which tested only systemic therapies in oncology patients, yielding 364 published trials. These studies were rated as positive, negative, or inconclusive based on review of abstract and text statements by the authors. The Web of Science Index (Thomson Reuters, NY, NY) was searched for all articles published between 2003 and October 2007 that cited at least one of these 364 source papers. Results: Of 364 published phase II combination chemotherapy trials (including 16,033 subjects), 262 were declared to be positive. The Web of Science search identified 3,764 unique subsequent citing papers. Of these, 20 reported randomized phase III trials testing the same combination in the same disease as the source paper, and 9 studies resulted in findings that improved standards of care. Based on these data, for any published, reported positive, phase II combination chemotherapy trial the likelihood that it will result in a published, confirmatory randomized trial demonstrating an improvement in standard of care within 5 years is 0.034 (95% confidence interval - 0.016, 0.064). Conclusions: For combination chemotherapy phase II trials performed by standards of published studies in 2001–02, the positive predictive value is low despite the participation of a large number of subjects. Historical approaches to the development of combination chemotherapy regimens have been an inefficient use of patient resources. Future phase II studies of combination regimens require better methods to screen for treatments most likely to improve standards of care. [Table: see text]
Electronic patient-reported data capture as the foundation of a learning health care system
Authors: Abernethy A. P. , Zafar S. Y. , Coeytaux R. , Rowe K. , Wheeler J. L. , Lyerly H. K. 
Published: August 2020

6522 Background: In a “learning healthcare system” clinical decisions are supported by accurate information delivered at point of care; information gathered today iteratively informs future care and research. Methods: Customized software on wireless tablet personal computers presented a review of systems (ROS) instrument, validated research surveys (e.g., quality of life [QOL]), and a satisfaction survey, tailored by user. The system was piloted in the Duke Cancer Clinics and affiliated hospitals. We previously demonstrated equivalence of electronic and paper survey data. We conducted a series of studies using similar procedures to evaluate feasibility, acceptability, and utility. Results: First, we assessed the ability to collect ROS data at point of care to inform the clinic visit for participating breast (n = 65), gastrointestinal (n = 113), and lung (n = 97) cancer patients. Duke physicians reported that the system's clinical reports informed care and increased dictation efficiency. Second, we assessed patient satisfaction in the breast cancer cohort. Participants found the computers easy to read (94%), navigate (99%), and use (98%); the system helped 74% remember forgotten concerns to report to their clinician. Third, we assessed whether these data could contribute to current research. If the patient was on another clinical trial, PRO data (e.g., pain, QOL) were delivered to the investigator for research purposes in real time; data governance rules provided assurance to investigators. Fourth, we identified whether the PRO data could inform future research directions. Symptoms monitored longitudinally in aggregate uncovered unmet needs. Sexual distress was an underserved concern; intervention studies were initiated. Warehoused PRO data were integrated with clinical trials, genomic, biomarker, radiology, and administrative datasets for analyses. The approach has been scaled to 4 clinics and 3 hospitals. Conclusions: An integrated, real-time, electronic data capture system that interdigitates PROs with clinical and other data allows creation of a learning oncology environment that continuously improves care and research. Advantages include: patient-centeredness, description of the PRO phenotype, interoperability, and interface with caBIG infrastructure. No significant financial relationships to disclose.