bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance and side effect evaluation of sequentially reduced radiotherapy doses in a phase II trial of induction chemotherapy (IndCT) followed by concomitant chemoradiotherapy (CTX) for advanced head and neck cancer (HNC)
Authors: List M. A. , Vokes E. E. , Cohen E. W. , Stenson K. M. , Karrison T. , Bruce B. E. , Witt M. , Haraf D. J. 
Published: March 2020

5558 Background: CTX regimens are often limited by severe acute toxicities and long-term functional impairment. This paper presents patient (pt) reported side effects and performance outcome in 3 sequential groups of stage IV HNC pts treated at the University of Chicago with IndCT and lowering radiation doses with the goal of maintaining survival while minimizing negative sequelae. Methods: Pts. were treated with IndCT followed by alternating weeks of concurrent CTX with lowering doses of radiotherapy to gross disease/ high risk microscopic/low risk microscopic disease: Group A - 75/60/45 Gy (n = 36 pts); Group B - 75/54/39 Gy (n = 34 pts); Group C - 72/51/36 Gy (n = 60 pts), respectively (treatment details & survival analyses presented separately). Pts were assessed for quality of life, performance (Performance Status Scale for HNC) and side effects (Radiotherapy Questionnaire) pretreatment, during CTX, at 3 & 12 months and annually thereafter. Controlling for baseline scores, differences between the groups were examined on- treatment and at 12-months. Results: Baseline and 12-month data were available for 81/114 pts. While all pts declined in performance (e.g., diet) and reported increased side effects (e.g., dry mouth, mouth pain, swallowing problems) on CTX, there were no statistically significant differences based on radiation dose. Similarly, there was improvement in most symptoms by 12 months with little difference among groups. In contrast, on normalcy of diet, fewer patients in Group C (20%) showed declines of more than 20 points from baseline compared to A (46%; p = .085) and B (45%, p = .09). Overall, 4% of patients were unable to take anything orally at 12-months with no difference among groups. Conclusions: This study showed no differences in pt reported symptoms on-treatment or at 12-months based on lowered radiation doses during CXT. On the other hand, while there continued to be some restriction in long-term diet, pts in the lowest radiation dose group showed somewhat less decline from baseline. These findings suggest the continued need to explore ways of decreasing both acute and long term toxicities in the use of CTX regimens. [Table: see text]
Intensity-modulated radiation therapy for head and neck cancer of unknown primary
Authors: Klem M. L. , Wolden S. L. , Zelefsky M. J. , Su Y. B. , Singh B. , Kraus D. , Shaha A. , Shah J. , Pfister D. G. , Lee N. 
Published: March 2020

5565 Background: Unknown primary head and neck cancers often require comprehensive mucosal and bilateral neck irradiation. With conventional techniques, significant toxicity can develop. Intensity modulated radiation therapy (IMRT) has the potential to minimize toxicity. Methods: From 2000–2005, 21 patients received IMRT for unknown primary head and neck cancer at our center. Median age was 57. Clinical stages were: TxN1: 43%; TxN2b:38%; TxN2c:5%; TxN3:14%. Five patients received IMRT with primary intent and 16 as postoperative therapy. Fourteen received concurrent chemotherapy, most with cisplatin (100mg/m2/cycle) or carboplatin (70mg/m2)/ 5FU (600mg/m2) every 3 weeks for 2–3 cycles. Seven received IMRT alone. Median dose was 66 Gy. PEG tube was placed in 13 patients. Toxicities were evaluated. Regional progression free survival (RPFS), distant metastases free survival (DMFS) and overall survival (OS) were calculated with Kaplan Meier curves. Results: Grade 1 and 2 xerostomia was seen in 57% and 43%. Salivary function improved with time. By 6 months, no patient had greater than grade 1 xerostomia. Grade 1, 2, and 3 acute skin toxicity and mucositis were seen in 67%, 29%, 5% and in 33%, 52%, 14%, respectively. PEG tube was required in 72% who had combined modality and 43% with IMRT alone. Of the 13 with PEG tubes, only 3 required PEG support at the time of last follow up. For those who had PEG removed, median time with PEG was 3.8 months from the end of RT. Two patients treated with combined modality and 1 treated with IMRT alone developed esophageal strictures, but all had improvement or resolution with dilation. Two patients had persistent disease after RT and 1 had late regional failure at 39 months. Two patients developed distant metastases and died. With a median follow up of 14.3 months (5.4–73.4), 2 year RPFS, DMFS, and OS were 88.9%, 89.4%, and 84.0%. Conclusions: Preliminary analysis of IMRT for unknown primary head and neck cancer shows acceptable toxicity and encouraging efficacy. Xerostomia was a common acute complication but patients had marked improvement by 6 months. Esophageal strictures were seen but effectively treated with dilation. Techniques to limit esophageal dose may help further minimize this complication. No significant financial relationships to disclose.
A phase II trial of PS-341 (bortezomib) followed by the addition of doxorubicin at progression in incurable adenoid cystic carcinoma of the head and neck: An Eastern Cooperative Oncology Group study
Authors: Argiris A. , Goldwasser M. A. , Burtness B. , Deconti R. , Axelrod R. , Van Waes C. , Forastiere A. 
Published: March 2020

5573 Background: Adenoid cystic carcinoma (ACC) is usually resistant to chemotherapy. Bortezomib (B) is a highly selective inhibitor of the 26S proteasome which is central for the ubiquitin-proteasome degradation pathway. Inhibition of NF-κB activity achieved by B may be important for inhibition of the growth of ACC. Preclinical studies have shown synergy between B and doxorubicin (D). Methods: Eligibility criteria included incurable ACC, any number of prior therapies but without an anthracycline, unidimensionally measurable disease, ECOG performance status 0–2, ejection fraction within normal limits (WNL), absolute neutrophil count >1500/μL, platelets >100,000/μL, and total bilirubin WNL. Patients (pts) with stable disease (SD) for 9 months or more were excluded. Pts received B 1.3 mg/m2 IV push on days 1,4,8, and 11, every 21 days, until progression. Doxorubicin 20 mg/m2 IV on days 1 and 8 was added at the time of progression. Response assessment was performed after every 2 cycles using RECIST. Immunohistochemistry for biomarkers affected by the ubiquitin-proteasome pathway on baseline tumor and measurement of serum inflammatory and angiogenic cytokines before and in response to therapy were performed. Results: 25 pts were enrolled; 18 were females; median age was 56 years (26–73); distant metastatic sites: lung (21), liver (4), bone (2). Best response to single-agent B: 16 pts (64%) had SD, 7 progressed, and 2 were unevaluable (1 with symptomatic deterioration). The median progression-free survival was 8.5 months. In 4 evaluable pts who received B plus D, 1 partial response and 2 SD were observed. 1 pt died 7 months after starting treatment without documented progression. Worst grade (G) 3/4 toxicities with B alone in 22 evaluable pts were: G3 neutropenia 5%, G4 neutropenia 5%, G3 thrombocytopenia 5%, G3 sensory neuropathy 14%; G3 generalized weakness 5%, G3 fatigue 9%, G3 anorexia 5%, G3 diarrhea 5%, G3 hyponatremia 5%, G3 dyspnea 5%. Conclusions: B was well tolerated and resulted in disease stabilization in a high percentage of pts but no objective responses. Updated response data with the addition of D will be available. No significant financial relationships to disclose.
Acute myeloid leukemia (AML) in older women after adjuvant breast cancer therapy
Authors: Patt D. A. , Duan Z. , Hortobagyi G. , Giordano S. H. 
Published: March 2020

560 Background: Adjuvant chemotherapy for breast cancer is associated with the development of secondary AML, but this risk in an older population has not been previously quantified. Methods: We queried data from the Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database for women who were diagnosed with nonmetastatic breast cancer from 1992–1999. We compared the risk of AML in patients with and without adjuvant chemotherapy (C), and by differing C regimens. The primary endpoint was a claim with an inpatient or outpatient diagnosis of AML (ICD-09 codes 205–208). Risk of AML was estimated using the method of Kaplan-Meier. Cox proportional hazards models were used to determine factors independently associated with AML. Results: 36,904 patients were included in this observational study, 4,572 who had received adjuvant C and 32,332 who had not. The median patient age was 75.3 (66.0–103.3). The median follow up was 63 months (13–132). Patients who received C were significantly younger, had more advanced stage disease, and had lower comorbidity scores (p<0.001). The unadjusted risk of developing AML at 10 years after any adjuvant C for breast cancer was 1.6% versus 1.1% for women who had not received C. The adjusted HR for AML with adjuvant C was 1.72 (1.16–2.54) compared to women who did not receive C. HR for radiation was 1.21 (0.86–1.70). HR was higher with increasing age but p>0.05. An analysis was performed among women who received C. When compared to other C regimens, anthracycline-based therapy (A) conveyed a significantly higher hazard for AML HR 2.17 (1.08–4.38), while patients who received A plus taxanes (T) did not have a significant increase in risk HR1.29 (0.44–3.82) nor did patients who received T with some other C HR 1.50 (0.34–6.67). Another significant independent predictor of AML included GCSF use HR 2.21 (1.14–4.25). In addition, increasing A dose was associated with higher risk of AML (p<0.05). Conclusions: There is a small but real increase in AML after adjuvant chemotherapy for breast cancer in older women. The risk appears to be highest from A-based regimens, most of which also contained cyclophosphamide, and may be dose-dependent. T do not appear to increase risk. The role of GCSF should be further explored. No significant financial relationships to disclose.
Effect of treatment with sunitinib malate, a multitargeted tyrosine kinase inhibitor, on circulating plasma levels of VEGF, soluble VEGF receptors 2 and 3, and soluble KIT in patients with metastatic breast cancer
Authors: Deprimo S. E. , Friece C. , Huang X. , Smeraglia J. , Sherman L. , Collier M. , Baum C. , Elias A. D. , Burstein H. J. , Miller K. D. 
Published: March 2020

578 Background: Sunitinib malate (SU11248) is a multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenic activity that specifically inhibits VEGFR, PDGFR, KIT, RET and FLT3. In a phase II trial of 64 patients with refractory, metastatic breast cancer, sunitinib treatment resulted in an ∼11% objective response rate (Miller et al, ASCO 2005). To characterize potential biomarkers of biological response to sunitinib, we analyzed plasma levels of a panel of soluble proteins from patients in this trial. Methods: Patients received sunitinib in 6-week cycles comprised of 50 mg/day for 4 weeks followed by 2 weeks off treatment. Pre-dose plasma samples from 62 patients were obtained on days 1, 14, and 28 of the first cycle and days 1 and 28 of subsequent cycles. Plasma levels of VEGF, soluble VEGF receptor 2 (sVEGFR-2), soluble KIT (sKIT), and a novel biomarker, sVEGFR-3, were measured via ELISA analysis. Results: Plasma levels of each protein were modulated in most patients during the course of treatment. At the end of the first cycle, VEGF levels were increased more than 3-fold relative to baseline in 73% of cases, while sVEGFR-2 levels decreased by at least 30% in 88% of cases, and by >20% in all but 4 cases. In addition, levels of sVEGFR-3 were decreased by >30% in 82% of cases during the first cycle. For each of these markers, levels tended to return to near-baseline after 2 weeks off treatment. Longitudinal decreases in sKIT were also observed; decreases >50% by the end of cycle 2 were correlated with treatment outcomes for time-to-progression (P < 0.001) and survival (P = 0.03). Further analysis of correlations with pharmacokinetic and clinical parameters is ongoing. Conclusions: Sunitinib therapy is associated with increases in plasma VEGF and decreases in soluble VEGFRs and KIT. This panel of circulating proteins may have utility as pharmacodynamic biomarkers of sunitinib activity in patients with metastatic breast cancer. sVEGFR-3 may be a novel biomarker of the biological activity of sunitinib, while sKIT may be correlated with clinical response. Analysis of these and other biomarkers in larger studies of sunitinib in breast cancer may be warranted. [Table: see text]
Prognosis of early-onset breast cancer based on BRCA1/2 mutation status in a French population-based cohort
Authors: Bonadona V. , Voirin N. , Sinilnikova O. , Mignotte H. , Bremond A. , Mathevet P. , Romestaing P. , Raudrant D. , Lenoir G. , Lasset C. 
Published: March 2020

591 Background: The debate concerning poorer survival for patients with breast cancer (BC) carrying a BRCA1 germline mutation is unresolved, and requires additional data from population-based studies. Methods: We followed 232 women with invasive BC under age 46, ascertained prospectively through a French population-based BC registry, and tested for BRCA1/2 mutations (median follow-up: 82 months). We compared tumour characteristics and survival rates between 21 BRCA1/2 deleterious mutation carriers and 211 non-carriers. Results: As compared to sporadic tumours, BRCA1/2 tumours showed higher grade (p = 0.02), fewer ductal carcinoma in situ (p = 0.02), more frequent medullary histology (p = 0.02), more frequent negative oestrogen and progesterone receptors (p = 0.001 each). At five years, BC-specific survival, metastasis-free survival, ipsilateral recurrence-free survival and contralateral BC-free survival rates for BRCA1/2 mutation carriers were 95.0%, 94.7%, 100% and 90.0% respectively, compared with 89.6%, 78.2%, 88.8% and 94.4% respectively, for non-carriers (not significant). Rates for women carrying only a BRCA1 mutation were 93.3%, 93.3%, 100%, 86.7%, respectively. 76% of BRCA1/2 carriers received chemotherapy. Conclusions: Despite unfavourable tumour features, we found no evidence for poorer short-term survival in BRCA1 mutation carriers compared to non-carriers in this prospective population-based cohort. The high rate of BRCA1 carriers who received chemotherapy for their BC should question the positive impact of this treatment, as suggested by preclinical studies showing increased chemosensitivity of BRCA1-associated tumours. No significant financial relationships to disclose.
A randomized controlled trial to evaluate the impact of an educational DVD on cancer patients considering participation in a phase I clinical trial
Authors: Strevel E. L. , Newman C. , Pond G. R. , Maclean M. , Siu L. L. 
Published: March 2020

6011 Background: Informed consent for phase I trials is controversial; gaps in patient (pt) knowledge regarding the purpose of these studies are central to this debate. This study assessed the impact of viewing an educational DVD on pt knowledge and satisfaction in cancer pts newly referred to a phase I trials clinic. Methods: Prior to physician (MD) appointment, 49 pts were randomly assigned to view either an educational DVD (n = 22) which provided information about phase I trials, or a placebo DVD (n = 27) which described research achievements by local scientists. Upon completion of DVD viewing, pts completed a self-administered questionnaire addressing their understanding of phase I trials (knowledge) and their satisfaction with the DVD (perception). The interviewing MD (n = 8), who was blinded to the intervention, also rated the pt’s understanding of phase I trials upon completion of the clinic appointment. Results: The mean pt age was 56 and 61% were male. Prior to attending the phase I clinic, most pts (86%) had previously heard of clinical trials, but only 49% were aware of phase I trials. Pts who viewed the educational DVD were less likely to believe that the goal of phase I trials is to determine the efficacy of a new drug (p = 0.019), more likely to correctly assess that drugs undergoing phase I evaluations have not been thoroughly studied in humans (p = 0.003), and less likely to believe that phase I drugs have proven activity against human cancers (p = 0.008). More pts who viewed the educational DVD than the placebo DVD agreed/strongly agreed that the DVD provided useful information (p < 0.001), believed that they had a good knowledge of phase I trials (p = 0.031), felt that the DVD helped them decide whether to enter a phase I trial (p = 0.011), and perceived that they would have more questions for their physicians as a result of watching the DVD (p = 0.017). No statistically significant differences in MD satisfaction was observed. Conclusions: Exposure to an educational DVD increased both objective measures of pt knowledge as well as pt satisfaction regarding participation in phase I clinical trials. The educational DVD did not significantly impact MD perception of pt understanding. No significant financial relationships to disclose.
NCIC CTG MA.17: Tolerability of letrozole among ethnic minority women
Authors: Moy B. , Tu D. , Shepherd L. E. , Pater J. L. , Whelan T. J. , Ingle J. N. , Goss P. E. 
Published: March 2020

6018 Background: Disease free survival was significantly improved in women receiving letrozole after standard adjuvant tamoxifen in the MA.17 trial. Based on the results of MA.17 and of other trials of aromatase inhibitors in early stage breast cancer, chronic aromatase inhibitor therapy, in postmenopausal women free of breast cancer recurrence, is now being widely employed. We analyzed the toxicity of letrozole according to ethnic status among women enrolled in MA.17. Methods: The chi-square test was used for comparison of rates of side effects between the two groups, Caucasian vs. ethnic minority (defined as all non-Caucasians). In a subset of women, quality of life (QOL) was assessed by the SF-36 Health Survey. Mean change scores in QOL from baseline were compared between groups for summary measures and domains using the Wilcoxon test. Results: 352 minority women and 4,708 Caucasians were enrolled in MA.17, of which 183 minority women and 2,339 Caucasians were randomized to receive letrozole. Caucasians were older than minority women and had a slightly longer duration of treatment with prior tamoxifen. Tumor size and nodal status were not significantly different between the two groups. In women who received letrozole, minority women had significantly lower incidence of hot flashes (49% vs. 58%; p = 0.02), fatigue (29% vs. 39%; p = 0.005), and arthritis (2% vs. 7%; p = 0.006) compared with Caucasians. Mean QOL change scores of SF-36 domains for women who received letrozole were not different but minority women had better mental health at 6 month assessment (p = 0.02) and worse bodily pain at 12 month assessment (p = 0.046). Conclusions: Minority women tolerated letrozole considerably better than Caucasians in the MA.17 trial. These preliminary findings suggest that minority women respond differently to letrozole in terms of toxicity. Recent demonstration of genotypic variations in the aromatase gene in different ethnic groups plus likely pharmacogenomic differences suggests that further research is needed to clarify the clinical outcomes of aromatase inhibition in women of diverse ethnicities. Future research strategies should focus on examining in vivo genotype-phenotype correlations to determine the effects of genetic variation on response to anticancer therapy and on toxicities and end-organ effects. [Table: see text]
Predictors of complications following prostate brachytherapy
Authors: Chen A. B. , D’Amico A. V. , Neville B. A. , Earle C. C. 
Published: March 2020

6021 Background: Prior studies on complications from prostate brachytherapy have reported on single institution experiences. We assessed the prevalence and predictors of complications following brachytherapy for prostate cancer on a population basis. Methods: We analyzed the claims of Medicare-enrolled men over age 65 living in SEER surveillance areas diagnosed with locoregional prostate cancer from 1991–1999 who underwent brachytherapy as initial treatment. Two-year complications were identified using Medicare diagnosis and procedure codes from the time of brachytherapy through 2001. Results: We identified 6,879 men who had brachytherapy as initial treatment for locoregional prostate cancer, 5,682 of whom had at least two years follow-up. Of these patients, 54.63% had at least one diagnosis or procedure associated with rectal, urinary, or erectile dysfunction, and 14.33% underwent at least one invasive surgical procedure for treating bowel, urinary, or erectile morbidity within two years of brachytherapy. 10.30% of men had procedures for urinary obstruction, 0.18% had procedures for urinary incontinence, 0.77% had rectal procedures, and 4.08% had invasive procedures for erectile dysfunction. Predictors of two-year complication procedures on multivariable analysis are shown in the Table . Conclusions: A significant proportion of men have diagnoses associated with rectal, urinary, or erectile morbidity following prostate brachytherapy. Though procedures for urinary obstruction are common following brachytherapy, invasive interventions for rectal complications, urinary incontinence, and erectile dysfunction are rare. Procedures for complications following brachytherapy appear to have declined over the 1990s. [Table: see text] No significant financial relationships to disclose.
Cost-effectiveness analysis of trastuzumab in the adjuvant setting for treatment of HER2+ breast cancer
Authors: Garrison L. P. , Perez E. A. , Dueck A. , Lalla D. , Paton V. , Lubeck D. 
Published: March 2020

6023 Background: The addition of trastuzumab (H) to a standard adjuvant therapy regimen (doxorubicin, cyclophosphamide, and paclitaxel; AC→T) is associated with a 52% reduction in risk (p < 0.0001) of disease recurrence in patients with HER2 positive operable breast cancer (Romond et al, NEJM 2005). A cost-effectiveness analysis was performed to assess the lifetime clinical and economic implications of this important clinical finding. Methods: A Markov model with three health states (disease-free survival [DFS], recurrence, and death) was used to estimate the likely cost-effectiveness (CE) for a 50 yr old woman. Efficacy results from both trials (NCCTG N9831/NSABP B-31) were used through 4 years, and projections of time to recurrence and death were based on the literature (EBCTCG, Lancet 2005). After 4 years, annual transition probabilities to recurrence and death are assumed to be the same in both arms. Cardiotoxicity was higher with H (Perez EA, ASCO 2005). Actual total dose of H was used which was lower than scheduled dose. Incremental costs associated with addition of H to adjuvant therapy were estimated using average wholesale prices, Medicare reimbursement rates and other published data. These costs included testing for HER2 status, drug and administration costs for H, cardiac monitoring, treatment of cardiotoxicity, treatment following recurrence, and end-of-life costs for dying patients. Utility estimates were derived from the literature. Results: Over a lifetime, the cost per quality-adjusted life year gained (QALY; discount rate 3%) is $27,800, with a range of $17,900 to $39,100 under multi-way sensitivity analysis. Projected life expectancy from the Markov model is 3 years longer for H patients (19.4 v 16.4 yrs). Over a 20-year horizon, addition of H to AC→T is estimated to cost an additional $46,300 on average, with an expected gain of 1.28 QALYs-a cost/QALY of $36,100. The key drivers of CE are the cost of treatment and the improvement in DFS. Conclusion: The model projects a cost-utility ratio that is below that of many treatments used for oncology patients. The use of trastuzumab in the adjuvant setting for HER2+ breast cancer is projected to be cost-effective. [Table: see text]