bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of patient performance between PEG/no PEG placement in head and neck cancer patients during chemoradiotherapy treatment.
Authors: Metcalfe-Klaw Robin , Husaini Hasan , Lazarus Cathy L , Harrison Louis Benjamin , Culliney Bruce , Li Zujun , Urken Mark L , Jacobson Adam , Buchbinder Daniel , Persky Mark , Tran Theresa , Pitman Michael , Concert Catherine , Palacios Daisy Maria , Bennett Bridget , Kumar Mahesh , Hu Kenneth 
Published: March 2020

6091 Background: Many head and neck cancer patients suffer from side effects of chemoradiotherapy that can result in reduced oral intake, and weight loss. To prevent this malnutrition they often undergo preventative percutaneous endoscopic gastrostomy (PEG) placement. We aim to determine whether PEG placement is necessary for successful patient performace during treatment. Methods: We compared 2 groups: patients that underwent PEG (Gp-1=P) (n=20), and those that did not undergo PEG (GP-2=NP) (n=47). All patients were treated with chemoradiotherapy. All were assessed at baseline (BL), and wk 5 of tx. WHO variables including weight loss, mucositis, dysphagia, and odynophagia ratings, along with patient-rated modified “distress thermometers”, were analyzed. Results: Patients with no PEGs had higher weights at BL (NP=193 vs P= 171, p=0.073) and at wk 5 (NP=179 vs P= 160, p=0.056). Weight loss in these groups were 8.09 % - P (p=0.000), 8.25% - NP (p=0.000) respectively from BL - wk 5. The median distress level of each group was 0-P and 1-NP at BL (p=0.302) and 6-P and 3-NP at wk 5 (p=0.086). 27 patients had a distress level of > = 4 at wk 5. Of these 27, 12 were PEG’d and 15 were not (p=0.008). 86 % of patients in the PEG group had distress >=4 and 44 % in the NP group had distress levels >=4. Patients that underwent PEG had slightly higher odds (NS) of associating their distress to nausea, fatigue and/or eating than patients that were not PEG’d. The wk 5 WHO toxicity scale assessment showed 15 PEG’d patients had Grade 1 (n=5), Grade 2 (n=9) & Grade 3 (n=1) dysphagia and 28 NP patients had Grade 1 (n=23) & Grade 2 (n=5) dysphagia (CHI square =11.66, p=0.009). Conclusions: Patients that underwent PEG placement before or during treatment performed worse in every assessment (weight loss, distress thermometer & toxicity scale) as compared to the no PEG group. Patients who have a normal or above average BMI are candidates to be monitored for PEG placement. However, both groups examined were able to complete treatment without significant treatment breaks. Close multidisciplinary monitoring and more intensive supportive care are needed when determining need for PEG placement during treatment.
Sequential TKI treatments for iodine-refractory differentiated thyroid carcinomas.
Authors: de la Fouchardiere Christelle , Massicotte Marie-Helene , Borget Isabelle , Brassard Maryse , Claude-Desroches Mederic , Giraudet Anne Laure , Docao Christine , Bonichon Francoise , Chougnet Cecile , Leboulleux Sophie , Baudin Eric , Schlumberger Martin 
Published: March 2020

6092 Background: Tyrosine kinase inhibitors (TKI) are currently used to treat patients with advanced iodine-refractory differentiated thyroid cancers (DTC) but none has been approved by the FDA or the EMA until now. Sometimes, patients are treated with off-label TKI when a clinical trial is not available or in second- and third-line therapy. Methods: We hereby report the efficacy of “off-label” sorafenib and sunitinib treatments as first-, second- and third-line therapy in metastatic DTC patients from the French TUTHYREF (TUmeurs THYroïdiennes REFractaires) network. Primary endpoints were progression free survival (PFS) and tumor response according to sequential TKI treatment. Secondary endpoint was organ-specific metastatic site analysis. Results: 45 patients with advanced iodine-refractory DTC treated with off-label TKI were included in this study (26 men, mean age: 62 years). 22 had papillary, 10 had follicular and 13 had poorly DTC. 24/45 patients were treated with two and 3/45 with three lines of TKIs. Sorafenib was the most frequently used (57%) followed by sunitinib (21.5%) and vandetanib (21.5%). Partial response (PR) rate was of 29% in the 21 patients who received first-line sorafenib therapy whereas PR was observed in 57% of the 7 first-line sunitinib patients. There was no PR with second- (n=24) and third-line (n=3) treatments. However, median progression free survival (PFS) was similar in second- as compared to first-line sorafenib or sunitinib treatment (6.7 vs. 7.6 months, HR 0.85 (95CI 0.45-1.61) p=0.6). Liver metastases were the most responsive to treatment (n=7; mean of -30%), followed by lung (n=57; mean of -19%) and lymph node (n=43; mean of -13%) metastases. Bone (n=14) and pleural (n=9) lesions were the most refractory to treatment (mean of -1% and -5%, respectively). Conclusions: Due to the small number of patients, we could not recommend a specific treatment sequence (sorafenib then sunitinib) over another (sunitinib then sorafenib). But TKI therapy appears to be beneficial in refractory DTC patients even in second- and third-line therapy, with similar PFS and stable disease as best response. Bone and pleural metastases were the most refractory and liver lesions the most responsive to treatment.
Completion of adjuvant trastuzumab for older patients with early-stage breast cancer (BC).
Authors: Freedman Rachel A. , Luis Ines Maria Vaz Duarte , Lin Nancy , Lii Joyce , Winer Eric P. , Keating Nancy Lynn 
Published: March 2020

616 Background: Few data are available about factors associated with completion of adjuvant trastuzumab in older women with BC. We examined rates and predictors of adjuvant trastuzumab completion for older women with early-stage BC. Methods: We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data to identify 1,319 patients ≥66 years with early-stage BC diagnosed between 1999-2007 who received trastuzumab. Completion of trastuzumab was defined as >270 days of therapy. We examined patient, clinical and geographic characteristics associated with trastuzumab completion using multivariable logistic regression. We also assessed rates of hospital admissions for cardiac events during treatment. Results: Most of the 1,319 women were aged ≤76 (70%) and had a comorbidity score=0 (88%); 37% and 23% received anthracyline-taxane-based and taxane-based therapy, respectively, and 16% received trastuzumab without chemotherapy. Overall, 982 women (74.5%) completed trastuzumab. Factors associated with completion are shown below. During treatment, 56 patients (4.2%) had 65 hospital admissions for cardiac events (3.0% in those who completed trastuzumab versus 8.0% in those who did not, p<.001). Conclusions: One-quarter of older patients who initiated adjuvant trastuzumab did not complete therapy. Older women, Hispanic women, those with more comorbidity, and those receiving anthracycline-taxane-based chemotherapy all had lower odds of completion. Rates of hosptializations for cardiac events were higher in those who did not complete therapy. [Table: see text]
Effect of afatinib alone and in combination with trastuzumab in HER2-positive breast cancer cell lines.
Authors: Canonici Alexandra , Pedersen Kasper , Browne Brigid , McDermott Martina , Walsh Naomi , Crown John , O'Donovan Norma 
Published: March 2020

632 Background: Trastuzumab and lapatinib have been shown to significantly improve the prognosis for HER2 positive breast cancer patients. However, resistance is a significant clinical problem. The aim of this study is to assess the activity of afatinib, an irreversible pan-HER tyrosine kinase inhibitor, in HER2 overexpressing breast cancer cell lines, including trastuzumab and/or lapatinib resistant cells. Methods: Using proliferation assays, the effect of afatinib was assessed alone and in combination with trastuzumab in HER2 positive cell lines. The effect of afatinib on HER2, Erk and Akt was determined by immunoblotting. Results: The eight HER2 positive breast cancer cell lines tested, including trastuzumab and/or lapatinib resistant cells, responded to afatinib with IC50values ranging from 5 to 80 nM. The combination of afatinib and trastuzumab was additive in four trastuzumab sensitive cell lines and one model of acquired trastuzumab resistant HER2 positive breast cancer. In the remaining three trastuzumab and/or lapatinib resistant cell lines, combined treatment with trastuzumab and afatinib showed no enhancement compared to afatinib alone. Finally, afatinib decreased the phosphorylation of HER2 and Erk in all cell lines tested. Conclusions: Our results suggest that afatinib has activity in HER2 positive breast cancer, including trastuzumab and/or lapatinib resistant breast cancer. We also demonstrate that afatinib in combination with trastuzumab may be more effective than either agent alone in trastuzumab sensitive breast cancer. [Table: see text]
Second-line treatment of HER2+ metastatic breast cancer (MBC): Trastuzumab (T) beyond progression or lapatinib (L)? A retrospective database study.
Authors: Yerushalmi Rinat , Feldhamer Ilan , Greenberg-Dotan Sari , Bitterman Haim , Hammerman Ariel 
Published: March 2020

639 Background: L and T “beyond progression” (TBP) for MBC pts who progressed on 1st line therapy with T, are both reimbursed in Israel since 1/2010. The relative efficacy of L vs. T when combined with chemotherapy in 2nd line therapy for HER2+ MBC is unknown. In this retrospective database study we compared outcomes of 2ndline L or TBP, in the daily practice ("real life") in Israel. Methods: Using the computerized databases of Clalit Health Services' (CHS), Israel's largest health care provider, we identified all MBC pts that received 2nd line anti HER2 therapy, with either L or TBP after a 1stline protocol containing T, between 1/1/2010 and 31/12/2011. Pts characteristics and treatments were retrieved. The primary end point was overall survival (OS) defined as the time interval between date of initiation of 2nd line anti HER2 therapy and death or last day of follow-up. Secondary endpoint was progression free survival (PFS), defined as duration of 2nd line therapy. Results: The study population included 83 pts (28 L and 55 TBP). Mean age (59.9 vs. 61.4) and average Charlson co-morbidity index score (6.54 vs. 6.13) were similar between the cohorts. The groups differed in rates of prior adjuvant T (32.1% vs. 10.9%, p=0.017). The interim cutoff date for analysis was 31/12/2012 (allowing at least 12 months of follow-up). Median OS was 10.0 months for L pts (95% CI: 7.41–12.59) and was not reached for TBP, with a total of 31 deaths: 19 [67.9%] in the L group and 22 [40.0%] in the TBP group. A Cox regression showed an adjusted hazard ratio (HR) of 1.44 (95% CI 0.74-2.81), not significant (p=0.28).Prior adjuvant therapy with T was found to be a significant cofounder; HR=3.16 (95% CI 1.52-6.56). Median PFS was 6.0 months (95% CI: 4.31–7.69) for L and 7.0 months (95% CI: 4.30-9.70) for TBP, with a Cox regression adjusted HR of 0.87 (95% CI: 0.50-1.52), not statistically significant (p=0.87). Conclusions: In this retrospective database analysis, our interim results suggest no statistically significant difference in OS and PFS between L and TBP, as 2nd line therapy for HER2+ MBC, however the data showed a strong trend toward a survival benefit with TBP. A longer follow-up is required.
Impact of single and dual neoadjuvant HER2-directed therapy on clinical outcomes among patients with HER2-positive breast cancer (BC).
Authors: Reynolds Kerry Lynn , Bhatia Ashmeet , Cheng XingXing , Smith Barbara Lynn , Specht Michelle Connolly , Moy Beverly , Bardia Aditya 
Published: March 2020

647 Background: While the addition of trastuzumab to neoadjuvant chemotherapy (CTX) is well established for HER2+ BC, the use of dual agent HER2 blockade in the preoperative setting is not considered standard of care. We conducted a comprehensive systematic review and meta-analysis to evaluate the impact of neoadjuvant dual and single agent HER2 blockade on breast conserving surgery (BCS), pathological complete response (pCR) for estrogen receptor (ER)+ and ER- tumors, and impact of pCR on disease-free survival (DFS) and overall survival (OS) for HER2+ BC. Methods: Based on QUORUM guidelines, MEDLINE and Cochrane Controlled Clinical Trials Register databases were queried to identify eligible trials. Inclusion criteria were prospective, neoadjuvant trials that had at least one arm with HER2 directed therapy, and reported pCR. Pooled relative risk ratios (RRs) and 95% confidence intervals (CIs) were estimated for endpoints using the random effects model. Results: We identified 34 trials (N = 4064). High pCR rates (> 40%) were seen with anthracycline-based CTX and trastuzumab, as well as taxane based CTX alone with dual HER2 blockade. The addition of trastuzumab to CTX did not improve BCS rate (RR 1.40, CI: 0.89-2.22, p=.15), but significantly increased rates of pCR (RR 1.91, CI: 1.38-2.64, p=.0001). Similarly, dual HER2 blockade compared to trastuzumab alone did not improve BCS rate (RR 1.03, CI: 0.77-1.38, p=.84), but significantly increased rates of pCR overall (RR 1.38, CI: 1.24-1.53, p<0.00001), in both ER+ (RR 1.72, CI: 1.14-2.61, p=.01) and ER- subsets (RR 1.91, CI: 1.38-2.64, p=.0001). Higher pCR was associated with improved DFS (RR 2.29, CI: 1.27-4.12, p=.006) and OS (RR 4.61, CI: 1.46-14.56, p=.009). Conclusions: Neither the addition of trastuzumab to CTX, nor the dual-HER2 blockade compared to trastuzumab, improves rates of BCS, but both significantly improve rates of pCR, which is associated with improved DFS and OS. A subgroup of HER2+ BC patients can achieve pCR with dual HER2 blockade without dependence on anthracycline-based therapy. Predictive biomarkers are needed to improve patient selection and personalize the optimal regimen for HER2+ BC.
Participation in cancer pharmacogenomic studies in 8,456 patients registered to Cancer and Leukemia Group B (Alliance) clinical trials.
Authors: Dressler Lynn G. , Deal Allison Mary , Watson Dorothy , Hollis Donna , Owzar Kouros , Donohue Kathleen , Friedman Paula N. , Ratain Mark J. , McLeod Howard L. ,   Cancer and Leukemia Group B (Alliance)
Published: March 2020

6501 Background: Clinically annotated specimens from cancer clinical trial participants offer an opportunity for discovery and validation of pharmacogenomic findings. This observational study assessed patient (pt) and institutional factors that may contribute to participation in pharmacogenomic components of prospective cancer clinical trials. No trial in the study used pharmacogenomic results to guide therapy, but germline DNA was collected from consenting pts for future study of potential heritable variations associated with clinical outcome. Methods: Pt demographic data (age, sex, diagnosis, self-reported race) and institutional characteristics (CALGB/CTSU site, diversity, accrual rate) were evaluated for 8546 pts enrolled in 7 CALGB phase III trials with a pharmacogenomic component. Participation was defined as pt consent specific to this component documented in the CALGB database. Results: Most pts (81%) enrolled on the clinical trials consented to participate in the pharmacogenomic component. In a multivariable analysis, site (CALGB vs CTSU), self-reported race (non-white vs white) and institutional diversity (% minority cancer pts on national trials) were significantly associated with participation. Pts from CALGB sites were more likely to participate than pts at CTSU sites (OR 2.09, CI 1.60-2.73, p<0.0001). Non-white pts were less likely to participate than white pts (OR 0.48, CI 0.41-0.56, p<0.0001). A significant interaction between site and race was observed (OR 0.41, CI 0.37-0.47, p<0.0001). As institutional diversity increased, likelihood of participation in the pharmacogenomic component decreased for both white (p=0.0001) and non-white pts (p=0.054). Conclusions: Pharmacogenomic studies are achievable in the context of multicenter cancer clinical trials, but optimization of pt and institution participation is needed. Institutional factorsappear to be more important than pt demographics. To promote equitable pt benefit, prospective studies should be conducted to understand barriers and incentives to participation in pharmacogenomic research at the patient, clinician and institutional levels.
A population-based analysis of outcomes in cancer patients who do not satisfy clinical trial eligibility criteria (CTEC).
Authors: Cheung Winson Y. , Kennecke Hagen F. , Lim Howard John , Renouf Daniel John , Gill Sharlene , Goktepe Ozge , Speers Caroline 
Published: March 2020

6502 Background: Trials have stringent inclusion and exclusion criteria to maintain internal validity. However, study findings are often applied to patients in routine practice who do not meet CTEC. Our aim was to characterize the outcomes and magnitude of treatment benefit in these patients. Methods: Patients diagnosed with stage III colon cancer from 2006 and 2008, referred to 1 of 5 regional cancer centers in British Columbia, and assessed for adjuvant chemotherapy (AC) within 12 weeks of surgery were analyzed. Patients were considered trial-eligible (TE) if aged 18 to 79 years, ECOG 0/1, CEA <10, did not receive prior chemotherapy or radiation, and had adequate blood counts and normal cardiac, liver and kidney function. All other patients were deemed trial-ineligible (TI). Results: A total of 820 patients were identified: median age was 69 years (range 60-76), 423 (52%) were men, 365 (45%) were ECOG 0/1 and 592 (72%) received AC. Among patients treated with AC, 370 (63%) were TE and 222 (37%) were TI. Compared to TI patients, those who were TE were younger (63 vs 70 years, p<0.01) and more likely to receive combination regimens rather than single agent AC (56 vs 33%, p<0.01). Outcomes were significantly different among patients who were TE, TI, and those who did not receive AC (Table). In multivariate analyses that adjusted for known prognostic factors such as age, ECOG and T and N stages, both TI patients and those not treated with AC had worse outcomes than TE patients (HR for colon cancer death 1.32, 95%CI 0.86-2.02 and 2.77, 95%CI 1.92-3.99, respectively, p trend <0.01; HR for all cause death 1.24, 95%CI 0.85-1.80 and 2.95, 95%CI 2.17-4.00, respectively, p trend <0.01). Conclusions: In this population-based cohort, colon cancer patients who did not fit CTEC were frequently treated with AC. Outcomes in this TI group were inferior to those in the TE group, but they were better than the subset that did not receive AC. Broadening CTEC to include a segment of the TI population should be considered as there appears to be benefit in selected individuals. [Table: see text]
Financial distress, communication, and cancer treatment decision making: Does cost matter?
Authors: Zafar Yousuf , Abernethy Amy Pickar , Tulsky James A , Ubel Peter A , Schrag Deborah , Rushing Christel , Chino Fumiko , Nicolla Jonathan , Altomare Ivy , Samsa Greg , Peppercorn Jeffrey M. 
Published: March 2020

6506 Background: Financial distress (FD) increases the burden of living with cancer. Even insured patients may experience considerable FD, but little is known about whether patients want to include cost discussions in treatment decision-making. Methods: This is an ongoing cross-sectional study of insured adults with solid tumors on anticancer therapy for ≥1 month. Consecutive patients were surveyed, in person, at a referral center and 3 rural oncology clinics. Participants were asked about FD (via a validated measure), out-of-pocket (OOP) costs, discussion of costs with their doctor, and decision-making. Medical records were reviewed for disease and treatment data. Logistic regression assessed the relationship between FD and cost communication. Results: 119 participants (85% response) had a median age of 60 years (range 27-86). 54% were men, 29% non-white, and 96% completed high school. 81% had incurable cancer. 58% had private insurance. Median income was $50,000/yr. Median OOP costs were $480/mo. The mean FD score (6.7, SD 2.5) corresponded to moderate FD. 19% reported high/overwhelming FD. Overall, 48% (n=57) expressed any desire to discuss costs with their doctor, but only 21% (n=25) had actually done so. Of the 19% with highest FD, 36% (n=8) had discussed costs with a doctor, and 68% (n=15) expressed any desire to discuss costs. The most common reasons for not discussing costs with doctors were: “no problems with costs” (n=47); “want best care regardless of cost” (n=36); and “doctors shouldn’t have to worry about costs” (n=19). Of those who discussed costs with their doctor, 48% (n=12) felt the discussion helped decrease costs. 54% (n=64) wanted their doctors to account for costs in cancer treatment decision-making; 20% (n=24) always wanted costs considered in decision-making. High FD was the only variable associated with greater willingness to discuss costs (adjusted OR 2.81; 95%CI 1.05-7.50; p=0.04). Conclusions: FD was prevalent among insured cancer patients. A large proportion wanted costs discussed with doctors and included in treatment decision-making. Discussing finances may lower costs, but the discussion rarely occurs. Communication and decision-making present a potential focus for intervening on FD.
Beyond Jeopardy!: Harnessing IBM's Watson to improve oncology decision making.
Authors: Bach Peter , Zauderer Marjorie Glass , Gucalp Ayca , Epstein Andrew S. , Norton Larry , Seidman Andrew David , Caroline Aryeh , Grigorenko Alexander , Bartashnik Aleksandra , Wagner Isaac , Keesing Jeffrey , Kohn Martin , Hsiao Franny , Megerian Mark , Stevens Rick J , Malin Jennifer , Whitney John , Kris Mark G. 
Published: March 2020

6508 Background: Electronic decision support is increasingly prevalent in clinical practice. Traditional tools map guidelines into an interactive platform. An alternative method builds on experience-based learning. Methods: Memorial Sloan-Kettering (MSK), IBM and WellPoint teamed to develop IBM Watson – a cognitive computing system leveraging natural language processing (NLP), machine learning (ML) and massive parallel processing – to help inform clinical decision making. We made a prototype for lung cancers using manufactured and anonymized patient cases. We configured this tool to read medical language and extract specific attributes from each case to identify appropriate treatment options benchmarked against MSK expertise, anonymized patient cases and published evidence. Treatment options reflect consensus guidelines and MSK best practices where guidelines are not granular enough to match treatments to unique patients. Analysis and building accuracy is ongoing and iterative. Results: 420 manufactured and 525 anonymized patient cases trained the initial models. Early results show accuracy improvement in NLP and ML in identifying treatment options (Table). All treatment plans were guideline adherent. A proportion of cases showed the need to incorporate tailored treatment plans reflecting MSK’s practice beyond guidelines – e.g. 11% of cases required addressing a site of critical metastasis before initiating guideline supported treatment. Conclusions: IBM Watson is extracting information from free text medical records that supports building ML models to assist in selecting treatments for persons with lung cancers. This tool can select treatment options from consensus guidelines, and, through ML, it will identify personalized treatment plans. Training is ongoing to improve individualized decision making and optimize the web-based tool that connects with IBM Watson. [Table: see text]