bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin resistance, estimated by serum C-peptide level, is associated with reduced event-free survival for postmenopausal women in NCIC CTG MA.14 adjuvant breast cancer trial
Authors: Pollak M. N. , Chapman J. W. , Shepherd L. , Meng D. , Richardson P. , Wilson C. , Orme B. , Pritchard K. I. 
Published: March 2020

524 Background: NCIC CTG MA.14 is a randomized multi-centre trial of tamoxifen versus combined tamoxifen and octreotide LAR therapy in the adjuvant treatment of breast cancer in post-menopausal women. Planned secondary analyses included investigation of baseline metabolic factors that might influence survival. Laboratory and clinical studies indicate that insulin resistance is associated with adverse outcome in breast cancer. Insulin resistance elevates C-peptide levels. Methods: In MA.14, trial patients with stage I or II postmenopausal breast cancer were randomized from September, 1996 until July, 2000 to receive 20 mg tamoxifen PO daily for 5 years with/without the administration of the somatostatin analogue Octreotide LAR 90 mg depot injection monthly for 2 years. Event-free survival (EFS), the trial’s primary outcome measure, was defined as time from randomization to time of recurrence of primary disease, time of second malignancy or death due to any cause. We investigated the effect of baseline IGF-I, IGFBP-3, and C-peptide levels on EFS. Kaplan-Meier univariate and Cox step-wise multivariate regressions were performed with/without adjustment for the stratification factors of adjuvant chemotherapy, nodal status, and hormone receptor status, and included patient age (years) and tumour size (T-status). Results: These results are based on analysis of patient serum for the trial’s 667 patients. Median follow-up for those alive is 6.1 years; patients experienced 165 events. Higher C-peptide levels were associated with significantly worse EFS in adjusted, and unadjusted, univariate and multivariate analyses. Final efficacy analyses are expected within a few months. Updated analyses for the effects of baseline metabolic markers and body mass index on EFS will be presented. Conclusions: This is the largest data set, and the first clinical trial, linking higher serum C-peptide levels to adverse outcome in patients with early breast cancer. These results raise concern in the context of increasing population prevalence of insulin resistance. Potential novel adjuvant therapies exist as insulin resistance is modifiable. [Table: see text]
Multivariate analysis of expression of the microtubule-associated protein, tau, predicts improved progression free and overall survival in patients with metastatic HER-2-negative breast cancers treated with docetaxel and vinorelbine plus filgrastim
Authors: Gown A. M. , Goldstein L. C. , Porter P. L. , Livingston R. B. , Tam S. , Yeh I. , Barlow W. E. , Gralow J. R. , Hayes D. F. 
Published: March 2020

543 Background: Drugs that poison the mitotic spindle, including taxanes and vinca alkaloids, are active agents against breast cancer. Preliminary evidence showed that high expression levels of tau predicted improved PFS and OS in patients with metastatic HER-2-negative breast cancers treated with docetaxel and vinorelbine plus filgrastim. We now tested whether levels of tau and another microtubule associated protein, beta-tubulin, could predict PFS and OS in multivariate analysis using other prognostic marker studies, including ER, PR, p53 and Ki-67 on a tissue microarray (TMA) obtained from patients in the SWOG S0102 trial. Materials and Methods: Immunohistochemistry (IHC) using antibodies to tau, beta-tubulin, ER, PR, p53, and Ki-67 was performed on a TMA constructed from the S0102 paraffin blocks. All markers were scored semiquantitatively from 0 to 3. Progression free survival (PFS) and overall survival (OS) were evaluated using multivariate analysis. Results: A total of 38 patients (41.3%) were evaluated. Tau was positively correlated with ER (r=0.36; p=0.0325) and PR (r=0.63; p<0.0001), but not with beta tubulin (p=0.34), Ki-67 (p=0.58), or age (p=0.73). Beta tubulin was not significantly correlated with any other markers. Adjusting for age, there was a significant effect of tau expression on OS (HR=0.667, p= 0.0193) and PFS (HR=0.653; p=0.0035), with higher tau associated with longer survival. When adjusted for both age and PR, there was a marginally significant effect of tau on OS (HR=0.582; p=0.056) and PFS (HR=0.604; p= 0.065). Beta tubulin was not associated with OS (HR=0.909; p=0.66) and PFS (HR=0.904; p=0.58) adjusted for age. Conclusions: In multivariate analysis, identification of breast cancer specimens showing high expression levels of tau predicts improved PFS and OS in patients with metastatic HER-2-negative breast cancers treated with docetaxel and vinorelbine plus filgrastim. High expression of tau also correlated with PR and ER expression. These results confirm and expand earlier studies of the predictive power of tau in a multivariate analysis using a panel of IHC markers for breast cancer. No significant financial relationships to disclose.
Impact of age on treatment effect in locally advanced head and neck cancer (HNC): Two individual patient data meta-analyses
Authors: Bourhis J. , Le Maı̂tre A. , Pignon J. , Ang K. , Bernier J. , Overgaard J. , Tobias J. , Saunders M. , Adelstein D. , O’Sullivan B. 
Published: March 2020

5501 Background: The Meta-Analysis of Radiotherapy in Carcinomas of Head & Neck (MARCH; Bourhis J, ASTRO 2002) showed that altered fractionation radiotherapy (Alt-RT) could improve survival as compared to standard RT in patients with locally advanced HNC (pooled hazard ratio - HR -: 0.92, 95% confidence interval: 0.86–0.97). The Meta-Analysis of Chemotherapy in Head and Neck Cancer (MACH-NC; Bourhis J, ASCO 2004) demonstrated that concomitant chemotherapy (CT), added to RT, improved survival (HR: 0.82, 95% CI: 0.78–0.86). This study considers age as a potential modifier of the treatment effect. Methods: 15 randomized trials with 6,515 patients were included in MARCH (median follow up: 6.0 years), and 50 with 9,471 patients in concomitant part of MACH-NC (median follow up: 5.6 years). The interaction between age and treatment effect, using HR of death, was tested with heterogeneity test. Effect of prognostic factors on the interaction was analysed using Cox model. Results: The effect of Alt-RT in MARCH and of concomitant CT in MACH-NC on overall survival decreased with increased age ( table ). Patients aged 71+ had a lower performance status, less advanced stage, and more often laryngeal cancer than the younger patients; there were more women in the oldest patients group. However, adjusting on covariates did not modify the results. Causes of death was available in MARCH and in recent (1994–2000) trials of MACH-NC. The proportion of deaths not due to HNC increased with age, from 18% at age 50 to 41% at age 71+ in MARCH, and from 15% to 39% in MACH-NC. Conclusions: Treatment benefit decreases with increasing age. Patients aged 71+ did not benefit from Alt- RT nor from concomitant CT. The increasing risk of death from other causes with age may explain part of these observations. Supported by PHRC, ARC, LNCC [Table: see text] No significant financial relationships to disclose.
EGFr expression and clinical outcome in head and neck cancer patients treated with radiotherapy with or without cetuximab
Authors: Bonner J. A. , Harari P. M. , Giralt J. , Cohen R. B. , Baselga J. M. , Spencer S. A. , Azarnia N. , Rowinsky E. K. , Amellal N. , Ang K. K. 
Published: March 2020

5510 Background: Increased expression of epidermal growth factor receptor (EGFr) has been correlated with poor outcome for patients with squamous cell carcinoma of the head and neck (SCCHN). This analysis was performed to examine the prognostic significance of EGFr expression in patients with locoregionally advanced SCCHN treated with radiotherapy (R) with or without cetuximab (C, an IgG1 anti-EGFr monoclonal antibody). Methods: This correlative study was performed on tumor biopsy samples from patients with locoregionally advanced SCCHN who were randomized to R with or without C as previously described (ASTRO Abstract #120, 2005). Immunohistochemistry was utilized to assess the percentage of tumor cells that stained for EGFr (JCO 23:5568, 2005). Kaplan-Meier estimates of locoregional control and survival were derived, and Cox regression was used to adjust for differences in prognostic factors. Results: Tumor specimens were evaluated from 339 of the 424 randomized patients. The median percentage of EGFR-detectable tumor cells (EDTC) was 50%. 183 patients had ≤50% EDTC, whereas 156 patients had >50% EDTC. The addition of C to R resulted in improved locoregional control (LRC, p = 0.005) and survival (p = 0.03) in the overall study. The LRC and survival results are summarized for patients with ≤50% EDTC and patients with >50% EDTC. Medians are measured in months. These findings were not altered after adjusting for imbalances in known prognostic factors of Karnofsky score (90–100 vs. 60–80) and primary site (Oropharynx or Larynx vs. Hypopharynx). Conclusions: A high positive EGFr expression in SCCHN, as determined by current methodology, is not necessary for response to radiotherapy and cetuximab. These results warrant further evaluation. [Table: see text] [Table: see text]
Randomized phase II/III clinical trial of induction chemotherapy (ICT) with either cisplatin/5-fluorouracil (PF) or docetaxel/cisplatin/5-fluorouracil (TPF) followed by chemoradiotherapy (CRT) vs. crt alone for patients (pts) with unresectable locally advanced head and neck cancer (LAHNC)
Authors: Hitt R. , Grau J. , Lopez-Pousa A. , Berrocal A. , García-Giron C. , Belon J. , Sastre J. , Martinez-Trufero J. , Cortés-Funes H. , Cruz-Hernandez J. 
Published: March 2020

5515 Background: we have previously reported that ICT plus CRT is more active than CRT alone in pts with unresectable LAHNC (Hitt et al: ASCO 2005, abstract 5578). Here we present new data of efficacy and time to progression (TTP) in this trial. Methods: Patients: eligible pts included those with unresectable LAHNC, measurable disease, adequate organ function and ECOG 0–1. Pts were stratified according to primary tumor site. Treatment: Induction chemotherapy regimens (3 cycles): PF : P 100 mg/m2 day (d) 1, then F 1000 mg/m2 c.i. d1–5 q 21d; TPF: T 75 mg/m2 d1, P 75 mg/m2 d1, F 750 mg/m2 c.i. d 1–5 q 21 d plus G-CSF and ciprofloxacin. Chemoradiotherapy: conventional RT up to 70 Gy plus P 100 mg/m2 d 1–22–43 Results: Patients: a total of 310 pts have been accrued. Pts/tumor characteristics (ECOG, age, primary site, T/N stage) were well balanced among the three arms. T/N stage: T3–4 (88%); N2–3 (63%); pharynx-oropharynx site (62%). Treatment: Median number of cycles of ICT: 3; median dose of RT: 70 Gy, median number of cycles of P during RT in three arms: 3. Efficacy: Complete Response: 70% (ICT + CRT) vs. 49% (CRT alone) (p = 0.01). The response rate was similar between TPF and PF. Time to progression (TTP) in months: 16 (TPF + CRT); 12 (PF + CRT) vs 8 (CRT alone) (log-Rank= 0.02). G 3/4 toxicity (NCI criteria): Febrile neutropenia: 21% (TPF); mucositis: 10% (PF). Mucositis was observed in 55% (TPF + CRT), 60% (PF + CRT) and 36% (CRT alone) of the pts, respectively Conclusions: The results of the present randomised clinical trial demonstrate that the combination of ICT + CRT significantly increases the complete response rate and prolongs TTP when compared to CRT alone in patients with unresectable LAHNC. No significant financial relationships to disclose.
A phase I study of bevacizumab (B) with fluorouracil (F) and hydroxyurea (H) with concomitant radiotherapy (X) (B-FHX) for poor prognosis head and neck cancer (HNC)
Authors: Seiwert T. Y. , Haraf D. J. , Cohen E. E. , Stenson K. , Mauer A. M. , Dekker A. , Bajda C. , Weichselbaum R. R. , Chen H. X. , Vokes E. E. 
Published: March 2020

5530 Background: Increased VEGF levels are found in HNC. Preclinical data suggest synergistic antitumor activity of B with radiation and chemotherapy. We conducted a Phase I dose escalation study to determine the maximum tolerated dose and dose limiting toxicity (DLT) of B, when added to infusional 5-FU, Hydroxyurea (HU), and daily radiotherapy administered every other week in patients (pts) with poor prognosis HNC. Methods: Eligible pts had recurrent, or newly diagnosed HNC with high risk of recurrence, ± metastatic disease requiring local control, ECOG PS ≤2, and life expectancy >12 weeks. Two week cycles were repeated 6–7 times (see table ). Results: 43 pts were treated (34 completed). DLT was reached at level 3 with 2 pts having gr 3 transaminase elevations and one pt gr 4 neutropenia. Treatment of 7 (6 evaluable) pts on level 4 resulted in one DLT (SMV thrombosis) and this dose level was chosen for expanded evaluation. In all level 4 pts (N = 27) gr 3 mucositis occured in 73.1% and gr 3 hand-foot syndrome in 15.4%. Additional gr 3 or worse toxicities in the expanded level 4 included: esophageal bleed (tumor bed, grade 5), stroke (grade 4), carotid rupture (3 wks post RT, grade 5), and neck ulceration with need for carotid stent (3 months post RT, grade 4). One sudden death of unclear etiology occurred. Median overall survival is 389 days. One/two year survival is 52.1/26%. Median survival for patients treated with re-irradiation for recurrent, non-metastatic HNC is 314 days; one/two year survival is 45.9/17.2%. With a median follow-up of 317 days 13 patients are still alive (12 are cancer free). Conclusions: B can be integrated with FHX chemoradiotherapy at a dose of 10 mg/m2 every 2 weeks. While B related toxicities are seen, there appears to be no major synergistic toxicity. Long term activity is observed in this very high risk patient population. A randomized phase II trial of FHX with or without B in a lower risk population is ongoing. [Table: see text] No significant financial relationships to disclose.
Vitamin D deficiency: A threat to bone health in breast cancer patients during adjuvant treatment with aromatase inhibitors
Authors: Lonning P. , Geisler J. , Krag L. E. , Løkkevik E. , Risberg T. , Hagen A. I. , Schlichting E. , Eide G. E. , Di Salle E. 
Published: March 2020

554 Background: To evaluate potential detrimental effects of the aromatase inactivator exemestane on bone, 147 postmenopausal women with early breast cancer were randomised to receive either exemestane for 2 years or placebo (J. Clin. Oncol. 23 [22], 5126–5137, 2005). Exemestane increased the annual bone loss from the femoral neck (2.72%) compared to placebo (1.48%; P = 0.024) with a non-significant increase in the lumbar spine (exemestane 2.17% versus placebo 1.84%). The annual bone loss was higher than expected in the placebo arm. Methods: Various biomarkers involved in bone metabolism (25-hydroxyvitamin D, parathormone, calcium, estrogens, androgens) were analysed to elucidate their influence on bone status at baseline and BMD loss during treatment with exemestane compared to placebo. Results: Using a cut-off value of 30 ng/ml for 25-hydroxyvitamin D (J. Clin. Endocrinol. Metab. 90 [6], 3800–3801, 2005), the majority of study participants suffered from vitamin D deficiency (56 of 62 patients in the placebo group and 52 of 59 in the exemestane group). The mean levels (95% confidence interval) of vitamin D were 22.6 ng/ml (21.2 - 24.1) in the placebo group and 21.6 ng/ml (20.0 - 23.3) in the treatment group, revealing no differences between these groups. Low serum calcium levels at baseline were found to be significantly correlated to low BMD in the femoral neck in the exemestane group. However, individual levels of vitamin D, parathormone and estradiol at baseline were not correlated significantly to BMD. Conclusions: Considering an annual bone loss of 0.5% to be representative for postmenopausal women (Osteoporos. Int. 15, 881–886, 2004), our data indicate that vitamin D deficiency could be the most important factor elevating bone loss among patients treated with exemestane as well as in the placebo group. These findings, together with the observation of a moderate additional effect of exemestane on bone loss, underlines the need for proper vitamin D substitution of postmenopausal women in general and in breast cancer patients during treatment with aromatase inhibitors in particular. [Table: see text]
Accelerated fractionated radiation by concomitant boost (AFX-CB) with concurrent cis-platinum (CDDP) for advanced nasopharyngeal carcinoma
Authors: Choi W. , Huang H. , Sachdeva G. , Culliney B. , Malamud S. , Blum R. , Schantz S. , Li J. , Nishihori T. , Chow  , Harrison L. B. , Hu K. 
Published: March 2020

5540 Background: Recent data (RTOG 90–03 and RTOG 99–14) strongly suggest that concomitant boost radiation (AFX-CB) and concurrent chemoradiation offer a local control advantage in advanced head and neck cancer patients. Based on our previous experience treating unresectable head and neck cancer, we initiated a phase II trial delivering CDDP concurrent with AFX-CB for advanced nasopharyngeal carcinoma (NPC). Methods: From 2/99–7/05, 44 patients with newly diagnosed stage IIa-IV NPC were treated with AFX-CB to 70Gy/6 weeks (BID RT last 2 weeks with a 3D-conformal plan, 6 hr interfraction interval) with 2–3 cycles of concurrent CDDP (100mg/m2) on day 1, 22, 43 of radiation followed by adjuvant 5-Fluorouracil/CDDP. The median age was 46 (24 to 83) and 20 patients were male. Disease characteristics were as follows: 1997 AJCC stage: II-7; III-14 and IV-23, T3/T4 66%, N2/N3 55%. Results: With a median follow-up of 30 mo. (3–78 mo.), the crude local control rate (LC) was 93%, regional control (RC) was 98%, locoregional control (LRC) 91%, freedom from distant metastasis (FFDM) was 86%, disease-free survival (DFS) was 82%, and overall survival (OS) was 89%. Eighty-six percent of patients were able to receive 2–3 cycles of adjuvant chemotherapy. Four of the 6 distant metastases occurred after 3 years post-treatment. One of the 3 local failures was salvaged with additional chemoradiation and is without evidence of recurrence 23 months later. Thus, the total crude local control is 95%. Among 29 T3/T4 patients, local control was 93%. For all patients, the three year actuarial LC, RC, LRC, FFDM, DFS and OS were 95%, 98%, 93%, 94%, 86% and 87%, respectively. Major grade 3 acute toxicities include mucositis (59%), dysphagia (41%), vomiting (20%) and anemia (4.5%). Average hemoglobin drop was 2.3 gm (17.7%). Ninety percent of patients received erythropoietin support and near 20% required blood transfusion. Late toxicities included grade 3 tinnitus in 1, grade 2 serous otitis in 1, osteoradionecrosis in 1 and brain necrosis in 2. Conclusions: AFX-CB with concurrent and adjuvant chemotherapy for advanced NPC provides excellent locoregional control and acceptable toxicity. Future efforts will focus on decreasing toxicity and increasing systemic control. No significant financial relationships to disclose.
A pilot phase II study of consolidation chemotherapy with docetaxel and cisplatin following concurrent chemoradiotherapy (CCRT) for locoregionally advanced head and neck squamous cell carcinoma (HNSCC)
Authors: Lee Y. , Lee S. , Lee K. , Park S. , Cho E. , Shin D. 
Published: March 2020

5549 Background: With the improvement seen with CCRT in the management of locoregionally advanced HNSCC, distant failures have become a more relevant problem in terms of survival. As a consequence, more effective strategies including consolidation chemotherapy are warranted. The primary objective of this pilot phase II study was to assess the feasibility and efficacy of docetaxel and cisplatin consolidation following primary CCRT for HNSCC. Methods: Thirty-three patients with previously untreated, stage III/IV HNSCC participated in this study. CCRT consisted of cisplatin 100 mg/m2 on day 1, 22 and 43. Concurrent radiotherapy (70 Gy) to the primary tumor and neck was performed over a period of 7 weeks. After completion of CCRT, patients with no evidence of disease progression received an additional 4 cycles of consolidation chemotherapy with docetaxel 75 mg/m2 and cisplatin 75 mg/m2 every 3 weeks. To minimize the expected accrual into unacceptable treatment, either in terms of clinical response or toxicity, a total of 35 patients would be required in a two-stage design. Results: Baseline characteristics were: male (22), median age (60 years), ECOG performance status 0/1 (15/18), stage III/IV (10/23). Of these, 27 (81%) patients completed CCRT. After CCRT, 3 complete and 19 partial responses were recorded, giving an overall response rate of 67% (95% CI, 51–83%). Of the 19 patients who went to consolidation phase, only 4 (21%) completed all 4 cycles of docetaxel and cisplatin. Failure to consolidation chemotherapy was attributed to the following causes: toxicity (11 including 3 treatment-related deaths), disease progression (4). During consolidation chemotherapy, 13 patients (68%) had grade 3/4 neutropenia and febrile neutropenia occurred in 6 (32%). With consolidation chemotherapy, one patient with initial stable disease achieved a partial response. Median survival in all patients was 11.0 months, and 8.3 months for those treated with consolidation chemotherapy. Conclusions: The poor compliance and the high incidence of severe toxicities, including 3 treatment-related deaths, prompted no further evaluation of this consolidation chemotherapy following CCRT. No significant financial relationships to disclose.
Quality of life assessment in patients above 60, below 50 years of age during and after curative radiotherapy in head and neck cancers
Authors: Turaka A. , Mohanti B. K. , Chander S. , Deo S. V. , Jena R. , Rath G. K. 
Published: March 2020

5552 Background: To evaluate the Quality of life in patients above 60 and below 50 years during and after curative radiotherapy in head and neck cancers. Methods: Head and Neck cancer patients who are to undergo curative radiotherapy (RT) were divided into two groups, 49 patients (Group A,above 60 years) and 40 patients (Group B,below 50). Quality of life assessment was done using EORTC QLQ C-30 version-2 at 4 phases;Pretreatment-Phase I,during RT-Phase II,1-month post RT-Phase III and 6 months post RT-Phase IV.Statistical analysis was done with mean scores using ’t’ test. Results: Physical functioning (PF)scores in both groups were highest in phase I (69.4;77.5, p < 0.035) and lowest in phase II (40; 50, p < 0.008) and the difference was statistically significant. Although PF scores declined in both groups in phase II, overall PF score remained higher in group B than in group A in all phases.Role functioning score remained low in both groups and the difference were not statistically significant at all phases. Emotional functioning score was highest in phase I (68.37; 69.15), but declined as treatment progressed, consequent to depression.The values improved over time, restored to near pretreatment values at phase IV. Cognitive functioning scores in both groups was also highest in phase I (70.07; 79.17). Social functioning of both groups declined during RT (42.52; 45)compared to pre RT values (73.47; 77.09). The mean Global Health Status score was higher in group B compared to group A at all phases, yet there was no statistical significance.The scores declined during RT (66.87 vs 35.62 & 64.79 vs 34.01), improved overtime but did not reach pre RT scores.The symptom scores were all higher for elderly patients compared with younger patients at all phases, implying elderly patients experienced more symptoms, with greater experience of symptoms during RT. Conclusions: Quality of Life of elderly patients was lower compared to younger patients at phase II in terms of physical functioning, social and emotional functioning. Global Health Status score was higher for younger patients than elderly at all phases, and declined in phase II. No significant financial relationships to disclose.