bluuebunny/crossref_metadata_2025 huggingface dataset:
High gene copy number of epidermal growth factor receptor by fluorescence in situ hybridization is frequent in head and neck squamous cell carcinomas and associates with worse recurrence-free survival
Authors: Chung C. H. , Ely K. , Carter J. , McGavran L. , Varella-Garcia M. , Nanney L. , Yi Y. , Slebos R. J. , Yarbrough W. , Hirsch F. R.
Published: March 2020

5502

Background: Epidermal growth factor receptor (EGFR) is expressed in 90–95% of head and neck squamous cell carcinoma (HNSCC). High EGFR gene copy number and activating mutations correlate with response and survival in lung cancer upon the treatment with EGFR tyrosine kinase inhibitors, but such findings have not been reported for HNSCC. A better understanding of the EGFR pathway may improve the use of EGFR inhibitors and provide a rationale for combination therapy. Methods: Tumor samples were obtained from 47 patients and analyzed for increased EGFR copy numbers by fluorescence in situ hybridization (FISH) (Vysis/Abbot) (N = 47), by immunohistochemistry (IHC) using antibodies against EGFR, phospho-EGFR (Tyr1173) and phospho-AKT (Ser473) (N = 31), for activating mutations in EGFR exons 18, 19 and 21 (N = 29), and for gene expression using Affymetrix Human 133U Plus 2.0 GeneChip (N = 18). Results from these assessments were tested for associations with patient characteristics and clinical endpoints. Univariate analysis was performed to test for differences in recurrence-free survival (RFS) and overall survival. Results: Twenty-six (63%) of 41 samples with FISH result demonstrated EGFR high polysomy and/or gene amplification (FISH+). The FISH(+) group did not differ from the FISH(−) group with regard to age, sex, race, tumor grade and site, disease stage, total EGFR, phospho-EGFR, or phospho-AKT, although the total EGFR protein score was close to significance (p = 0.10, Chi2-test for trend). The FISH(+) were associated with worse RFS, although this association did not reach significance (p = 0.057, Wilcoxon test). No activating EGFR point mutations were found. Using the FISH results as a supervising parameter, microarray data was interrogated and expression of genes involved in wnt signalling, cell motility, G-protein regulation and epithelial-mesenchymal transition pathways were found to be enhanced in the FISH(+) group (FDR <25%). Conclusions: High gene copy number of EGFR by FISH is frequent in HNSCC and may be a poor prognosticator. This data suggests that FISH(+) may be a marker of clinical benefit upon EGFR inhibition in HNSCC and further investigation is indicated.

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Postoperative concurrent radiochemotherapy versus radiotherapy in high-risk SCCA of the head and neck: Results of the German phase III trial ARO 96–3
Authors: Fietkau R. , Lautenschläger C. , Sauer R. , Dunst J. , Becker A. , Baumann M. , Wendt T. , Grüschow K. , Hess C. , Budach V. , Iro H.
Published: March 2020

5507

Background: Despite resection and postoperative irradiation high-risk (3 or more involved lymph nodes, extra-capsular disease and/or microscopically involved mucosal margins of resection) squamous cell carcinomas (SCCAs) of the head and neck frequently recur in the tumor bed. Postoperatively radiochemotherapy (RCT) with cis-Platin (CDDP)/5-FU versus radiotherapy (RT) alone was compared in a randomized trial. Methods: Between 5/97 and 12/04, 440 patients who had high-risk SCCAs of the head and neck were enrolled in this prospectively randomized phase III trial. Following resection and neck dissection, 214 patients were randomly assigned to RT (66 Gy/33 Fx/6.6 weeks) and 226 patients to identical RT plus CDDP (20 mg/m2 on day 1–5, 29–33) and 5-FU (600 mg/m2 on day 1–5, 29–33). Results: The 5 year local-regional control rate is 72.2 ± 3.7% following RT and 88.6 ± 2.4% for the RCT group (p = 0.00259; 5-year progression free survival 50.1 ± 4.0% and 62.4 ± 4.4% (p = 0.024) and 5-year overall survival 48.6 ± 4.4% vs. 58.1 ± 4.6% (p = 0.11). There was no difference in the 5 year incidence of distant metastases (19.3 ± 3.6% vs 25.5 ± 4.6%; p = 0.45). The incidence of grade 3+ acute toxicity was higher during RCT: mucositis 12.6% vs. 20.8% (p = 0.04), leucopenia 0% vs. 4.4% (p = 0.007). Conclusions: Acute toxicity is increased to an acceptable level by RCT. Postoperative RCT compared to RT improves locoregional control and progression free survival; thus survival as a trend is improved by 10% after 5 years. Supported by Deutsche Krebshilfe 70–2140.

No significant financial relationships to disclose.
Epidemiology of nasopharyngeal carcinoma (NPC) in California: Survival advantage of Chinese WHO Type 1 NPC patients resulted in Asian ethnicity as an independent and favorable prognostic factor of survival for NPC patients as a whole and for patients with the WHO histologic type 1
Authors: Ou S. I. , Zell J. A. , Ziogas A. , Anton-Culver H.
Published: March 2020

5514

Background: We have previously shown that Chinese race is an independent and favorable prognostic factor in NPC survival. We expanded our study to investigate whether Asian ethnicity has the same favorable survival characteristics and if there is a survival difference between Chinese and non-Chinese Asians. Methods: 1,657 newly diagnosed NPC patients from 1992 to 2002 were analysed from the population-based California Cancer Registry. Five year survival rate estimates and Kaplan-Meier curves were calculated. Cox proportional ratios were used to identify independent prognostic factor for survival. Results: The 5-year survival rate of Asian NPC patients was improved compared to non-Asian patients (62% vs 47%; P < .0001). By multivariate analyses, early age of diagnosis, localized stage at presentation (vs distant, HR = 0.41; P < .0001), WHO Type 3 histology (vs Type 1; HR = 0.64; P < .0001), socio-economic status (highest vs lowest quartile; HR = 0.71; P = .0012), use of radiation (vs none; HR = 0.55; P < .0001), and Asian ethnicity (vs Caucasian; HR = 0.82; P = .016) were associated with improved survival. Chinese composed the majority of the Asian ethnicity (49.1%) followed by Filipino (21.2%) and Vietnamese (14.9%). The 5-year survival rate of Chinese was better than non-Chinese Asians (67% vs 56%; P = .0005). When Asian ethnicity was analyzed separately as Chinese and non-Chinese, Chinese retained an overall favorable prognosis (HR = 0.72; P = .0016) whereas non-Chinese Asians did not (HR = 0.91; P = .34). Within each NPC WHO histologic type, early age of diagnosis, localized stage at presentation, and use of radiation were favorable prognostic factors. Chinese (HR = 0.62; P = .0006) but not non-Chinese Asian ethnicity (HR = 0.78; P = .053) was an additional favorable prognostic factor within WHO histologic Type 1. Conclusions: The significant survival advantage of Chinese WHO Type 1 NPC patients resulted in Asian ethnicity being an independent and favorable prognostic factor for survival in NPC. This observation may reflect underlying genetic difference among different racial groups with NPC WHO Type 1.

No significant financial relationships to disclose.
A randomized phase II study of BMS-247550 (ixabepilone) given daily x 5 days every 3 weeks or weekly in patients with metastatic or recurrent squamous cell cancer of the head and neck
Authors: Burtness B. , Goldwasser M. A. , Axelrod R. , Argiris A. , Forastiere A. A.
Published: March 2020

5532

Background: Ixabepilone is a novel tubulin-polymerizing agent, with potential activity in SCCHN. Methods: Patients (pts) were eligible who had incurable, measurable SCCHN. ≤ 2 prior regimens for metastatic/recurrent disease were permitted, including taxanes. ECOG PS 0 or 1, ANC ≥ 1500/ml and adequate renal/hepatic function were required. Pts were randomized to ixabepilone 6 mg/m2/d 60 minute (min) infusion x 5 days (d) q 21 d [Arm A], or 20 mg/m2 60 min infusion d1, 8, and 15 q 28 d [Arm B], with diphenhydramine premedication. Tumor assessment was q 6 weeks. Each arm accrued taxane-naive (Tax-N) and -exposed (Tax-E) patients as separate strata, in a 2-stage design. The primary endpoint was response.16 pts entered each group in the first stage. If 1 response was observed in any group, it continued to 32 pts. Results: 85 eligible pts entered. Male 69, ECOG PS (1) 58, metastatic disease 66. 15 Tax-E and 17 Tax-N eligible pts entered stage 1 of Arm A. There were no responses with this dose and schedule. 35 eligible Tax-N pts were accrued to Arm B and 5 had partial responses (14.3%, 90% CI 5.9%,28.2%), 11 stable and 9 progressive disease. 10 in this group were inevaluable (5 died before restaging, 2 were never treated).18 eligible Tax-E pts entered Arm B and none responded. On Arm A, 2/16 Tax-N pts developed grade (gd) 3/4 anemia (13%), and 4/16 (25%) developed gd 3 fatigue. Other gd 3/4 toxicities occurred in < 8% of pts on Arm A. On Arm B, 9/33 (27%) Tax-N pts experienced gd 3/4 leukopenia, 3/33 (9%) gd 3/4 anemia 7 gd 3/4 fatigue (21%), 4 gd 3 nausea (12%), 9 (27%) gd 3 sensory and 2 (6%) gd 3 motor neuropathy. 2/21 Tax-E pts on Arm B experienced gd 4 neutropenia (10%), 6 gd 3 fatigue (29%), 3 gd 3 motor (14%) and 2 gd 3 sensory neuropathy (10%). Median follow up for eligible pts is 31.5 months (mo). 75 have died. Median survival for Arm A Tax-N is 5.62 mo (CI 4.0, 10.0); for Arm A Tax-E is 6.5 mo (CI 2.7, 8.8); for Arm B Tax-N is 7.8 mo (CI 3.3, 8.9) and for Arm B Tax-E is 6.5 mo (CI 2.0, 11.3). Conclusions: Ixabepilone 20 mg/m2 d1,8,15 q 28 d is active and tolerable in taxane-naive pts with metastatic/recurrent SCCHN. A high incidence of motor and sensory gd 3 neuropathy results at this dose and schedule in patients with previous taxane exposure.

[Table: see text]
Oral mucositis (OM) related morbidity and resource utilization in a prospective study of head and neck cancer (HNC) patients
Authors: Isitt J. , Murphy B. A. , Beaumont J. L. , Garden A. S. , Gwede C. K. , Trotti A. , Meredith R. F. , Epstein J. B. , Le Q. , Brizel D. M.
Published: March 2020

5539

Background: Few studies have reported the burden of oropharyngeal mucositis (OM) as well as the downstream resource consumption and risk of complications due to OM following standard therapy in head and neck cancer patients. This study was a prospective, multi-center, single-arm observational study of patients receiving radiation with or without chemotherapy for head and neck cancer. Methods: Over a 6-week period, the severity and impact of OM were assessed 5 times with the oral mucositis weekly questionnaire (OMWQ-HN) and patient resource use was collected bi-weekly. Seventy-five patients were enrolled from 6 centers in the United States. Hospitalization costs are reported from the Healthcare Utilization Project Nationwide Inpatient Sample (HUPNIS). Results: Sixty-seven percent (95% CI: 55%–77%) of the patients received concurrent chemoradiation. Seventy-six percent (95% CI: 65%–85%) of patients reported severe mouth and throat soreness. Eighty-five percent (95% CI: 75%-92%) were prescribed opioid analgesics. Mouth pain and throat pain accounted for 78% (95% CI: 68%–86%) of opioid uses. During weeks 1 and 2, 38% (95% CI: 26%-50%) of patients reported severe difficulty swallowing (59% by week 6); 67% (95% CI: 46%-83%) of these patients were taking opioids (84% by week 6). Over half of the patients (38/75; 51% [95% CI: 39%–62%]) had a feeding tube placed. Twenty-eight patients (37% [95% CI: 26%–49%]) were hospitalized, 30% (95% CI: 16%–49%) of hospitalizations were considered related to mucositis. Mean length of stay was 4.9 days (range: 1–16, SE: 0.72). National average cost for a 5-day hospitalization during this study period was approximately $23,000 (SE: $565.00 [HUPNIS]). Conclusions: Mucositis is a frequent, severe, and costly complication of treatment for head and neck cancer. Effective interventions may not only relieve patient suffering but also reduce healthcare consumption and downstream costs.

[Table: see text]
Cetuximab (C225) in recurrent and/or metastatic salivary gland carcinomas (RMSGCs): A monoinstitutional phase II study
Authors: Licitra L. F. , Locati L. D. , Potepan P. , Crippa F. , Bossi P. , Bergamini C. , Rinaldi G. , Liberatoscioli C. , Perrone F. , Losa M. , Pilotti S.
Published: March 2020

5547

Background: EGFR is expressed in 70% of salivary gland carcinomas (SGC). Investigations of anti EGFR treatment seems rational. Aim: To assess activity of C225 in patients with RMSGCs in terms of clinical benefit (CB), defined as occurrence of objective response (CR or PR) or stable disease (SD) for at least 6 months. To correlate treatment outcome with skin toxicity degree and EGFR analysis. Methods: One prior chemotherapy regimen was allowed, except for pts with adenoid cystic carcinoma (ACC) and acinic cell carcinoma for whom 2 lines were allowed. Prior exposure to targeted treatment was not allowed. C225 (Erbitux) was administered iv weekly at 400 mg/mq followed by 250 mg/mq until disease progression, major toxicity or voluntary discontinuation. MRI or CT and PET scan were performed every 6 weeks q4, and q12 thereafter. RECIST response criteria and CTC 3.0. were adopted. Results: From April to December 2005, 30 RMSGCs pts (20 F/10 M; median age 50 yrs), 50% with major SGC, were enrolled. Histotypes were: 23 ACC; 2 mucoepidermoid; 3 myoephitelial; 1 cystadenocarcinoma and 1 acinic cell carcinoma. Thirteen pts (43%) received prior chemotherapy. Localregional (LR) and metastatic (M) disease was present in 13 cases, M in 12, and LR in 5. A median number of 11 drug administration (range 2–31) was given. G2 skin toxicity was recorded in 24 cases. G2 fatigue in 2. At a median FU of 6 months (range 0–8), 2 pts died of PD. Of 22 pts evaluable for response with ≥ 3 months of potential FU, there were 11 SD, 9 PD, while 2 pts refused to continue after 1 months. Currently, 7 of these pts are progression-free at ≥ than 6 months, qualifying for CB definition according to study protocol. Preliminary EGFR analysis showed a high or intermediate expression score in 5 (3 ACC, 1 acinic cell, 1 cistoadenocarcinoma) out of 7 cases, no gene amplification nor chromosome 7 polisomy were found in 3 of 3 analysed ACC. PET results are under evaluation. Conclusions: Hints of activity of C225 in RMSGCs were observed. The early analysis for the CB rate in 23 pts is planned for April 2006, when all of them will have a potential follow-up of ≥ 6 months, and results thereof will be reported.

[Table: see text]
Preliminary results of the validation of a patient (pt) self-administered questionnaire (Oral Mucositis Weekly Questionnaire-Head and Neck [OMWQ-HN]) to assess the impact of OM on pain and functioning in head and neck cancer (HNC)
Authors: Epstein J. B. , Beaumont J. L. , Gwede C. K. , Trotti A. , McDowell M. , Murphy B. , Garden A. , Meredith R. , Quynh-Thu L. , Brizel D.
Published: March 2020

5548

Background: Pt self-reported questionnaires measuring acute and specific effects of OM are needed to assess effects of interventions and guide patient care. We evaluated the feasibility, validity, and reliability of the OMWQ-HN on OM and its impact on pts’ abilities to perform alimentary and other routine functions. Methods: Validity and reliability of the OMWQ-HN was assessed in 75 pts from a prospective multicenter study receiving radiotherapy ± chemotherapy (RTCT). Assessments included test-retest reliability, internal consistency reliability, and cross-sectional validity. The OMWQ-HN’s sensitivity to detect change was demonstrated by using the changes in the Performance Status Scale for HNC (PSS-HN) and the Functional Assessment of Cancer Therapy (FACT-HN) to form 3 independent groups (better, no change, worse) for comparison. Effect sizes (ES) were calculated for group comparisons to measure the clinical significance of differences. Results: Compliance rates were >90% throughout the study. The OMWQ-HN demonstrated good test-retest reliability (r = 0.89). Cronbach’s alpha was >0.85 and mouth, throat, and pain-related items correlated highly with each other (r>0.7). Cross-sectional analyses to assess validity showed that OMWQ-HN scores were different across levels of pain, with those in the worst pain category reporting the most severe OMWQ-HN scores (ES >0.5 for all comparisons). The OMWQ-HN was sensitive to change in FACT-HN and PSS-HN (p < 0.001 and p = 0.013, respectively). Patients reported increases in mouth and throat soreness (MTS) that corresponded with a steady decline in oral function. Conclusions: These results indicate the OMWQ-HN is a feasible, valid, and reliable instrument for assessing the impact of mucositis on patients receiving RTCT in the HNC patient care setting.

[Table: see text]
Re-irradiation with concurrent chemotherapy for recurrent head and neck cancer
Authors: Roman E. , Raez L. , Biagioli M. , Harvey M. , Blaya M. , Tolba K. , Bathia R. , Markoe A.
Published: March 2020

5559

Background: Despite aggressive therapy, over 70% of locally advanced squamous cell carcinomas of the head and neck (SCCHN) fail primary treatment. Salvage therapy with surgery, chemotherapy or brachytherapy alone or in combination has a 30–40% response rate, but few long-term survivors. Re-irradiation with concurrent chemotherapy for SCCHN has recently become a well established approach after two consecutive cooperative group studies were reported. Intensity Modulated Radiation Therapy (IMRT) is a new and safer way to deliver radiation therapy. This retrospective review evaluated the potential benefit and toxicity using every other week IMRT with concurrent chemotherapy. Design: Thirty-seven patients with locally recurrent SCCHN were evaluated. All patients received re-irradiation with IRMT every other week with concurrent weekly carboplatin (median AUC= 2) or cisplatin (60–100 mg/m2) ± 5-FU (800–1000 mg/m2) or paclitaxel 175mg/m2 every three weeks. Patients received 6000 cGy at 200 cGy per fraction. Results: The median follow-up time was 12 months. The overall response rate was 75.7% with a complete response (CR) and partial response (PR) of 56.8% and 18.9%, respectively. Among complete responders, 33% recurred locally in a median time of 5 months. The Kaplan-Meier estimate of disease-free survival, progression-free survival, and overall survival at 48 months is 58%, 45%, and 28%, respectively. At the time of last follow-up, 51.4% of patients were still alive and 27.8% of patients had no evidence of disease. Grade 3 or 4 acute toxicities occurred in 20% of patients of which 13.3% were hematologic requiring either growth factors or delay in chemotherapy. No deaths occurred during the course of treatment. Long-term complications consisted of one patient with an esophageal stricture requiring repeated dilations, 2 patients with chronic dysphagia, and 2 patients developing a pharyngeal-cutaneous fistula, one of which died from a carotid blowout occurring 6 months after treatment. Conclusions: IMRT delivered every other week with concurrent platinum based chemotherapy produces good responses with only moderate toxicity in patients previously treated with radiation therapy for recurrent head and neck cancer.

No significant financial relationships to disclose.
Minimally invasive laser-induced thermal therapy (LITT) for head and neck cancer: A comprehensive review
Authors: Paiva M. B. , Bublik M. , Wong S. , Blackwell K. E. , Sercarz J. A.
Published: March 2020

5572

Background: Laser induced thermal therapy (LITT) has been developed in a step-wise fashion at UCLA as a minimally invasive treatment for head and neck cancer. Initial Phase-I studies demonstrated the feasibility and safety of using the Nd:YAG laser (near infra-red nm) for thermal ablation of tumors as a palliative treatment in 62 patients. This was followed by the current Phase II study that confirmed such finding using higher laser power densities (P.D. = 1,600–2,200 J/cm2). Patients and Methods: This was a single group study in patients with recurrent carcinoma of the head and neck, who failed at least one treatment modality, and had a Karnofsky performance status ≥ 70%, and ECOG performance status ≤ 2. The primary end points of the study were objective tumor response, and survival. Prognostic values were assessed by uni- and multivariate analysis using the Kaplan-Meier method and Cox model, respectively. Results: In this Phase II study, we review our results on 104 patients with recurrent head and neck cancer that were treated by LITT. Best results were seen in oral cavity tumors where Kaplan Meyer curves showed average survival of 20.3 months (10.7–30 mo; 95% CI) compared to neck (avg. = 14.4 months, 7.5–20.7 mo; 95% CI) and other tumor sites, (avg. = 18 months, 13.8–22.3 mo; 95% CI). Further analysis of neck treatments showed that tumors away from the common carotid in cervical lymph nodes located in levels I, IV, and V had median survival of 25.9 months (mean = 37.7 mo), compared to 11.4 months (mean = 10.9 mo) in patients with tumors near, or encroaching the carotid in upper and lower jugular levels II and III. In univariate analysis, a trend toward a better survival was observed when tumor proximity to carotid artery was considered prognostic categories (log-rank P = .0007). However, in multivariate analysis, TNM stage, and reconstruction using free flap transfer, but not age and histology, were retained as independent prognostic variables (P < .001). Conclusion: LITT Patients tolerated LITT well on an outpatient basis, and were successfully palliated for periods ranging from 39 days to 90 months post-treatment. Based on the findings of this study it was possible to show that proximity to the carotid artery was the most relevant factor in projecting patient survival.

No significant financial relationships to disclose.
Role of endocrine responsiveness and adjuvant therapy in very young women (< 35 years) with operable breast cancer and node negative disease
Authors: Orlando L. , Cardillo A. , Ghisini R. , Rotmensz N. , Peruzzotti G. , Maisonneuve P. , Viale G. , Goldhirsch A. , Colleoni M.
Published: March 2020

558

Background: Breast cancer rarely occurs in young women. There is limited knowledge about prognosis, and treatment effects in the population with node negative disease, largely dependent upon older series and extrapolation of data from older age cohorts. Methods: We evaluated biological features and adjuvant treatment recommendations for 841 premenopausal consecutive patients with pT1–3, pN0 and M0, operated and counseled for medical therapy from April 1997 to December 2001. We evaluated also, the prognostic role of age and adjuvant treatment. Median follow-up was 49.9. Results: Very young women (101, 12%) were more likely to have tumors with absent ER (42% v 17.6%, p < .0001) and PgR (48% v 23.2%, p < .0001), > 2 cm (36.7% v 24.8%; p = .002), grade 3 (53.9% v 33.5%; p = .0009) and elevated Ki-67 (68.5% v 51.6%; p = .002), when compared with older patients (740, 88%). Younger patients (compared with older patients) with endocrine responsive disease were prescribed more chemotherapy (67.2% v 44.3%; p = .0009) but endocrine adjuvant therapy was prescribed in a similar percentage in both groups (93.1% v 96% p = .30). A statistically significant difference in disease-free survival (DFS), risk of distant metastases and overall survival (OS) was observed at the multivariate analysis for younger patients (HR = 4.44; 95% CI, 2.53 to 7.78, p < .0001 for DFS; HR = 3.23; 95% CI, 1.32 to 7.94, p = .011 for distant metastases; HR = 2.89; 95% CI, 1.06 to 7.87, p = .038 for OS). An increased risk for younger age was observed for patients with endocrine responsive disease (ER ≥ 1%) (HR = 5.17; 95% CI, 2.72 to 9.83, p < .0001 for DFS) in particular if endocrine therapy was not performed (HR = 7.77; 95% CI, 1.98 to 30.6, p = .003 for DFS). Conclusions: We conclude that compared with less young premenopausal patients, the very young women presenting with breast cancer and ipsilateral axilla negative for disease, are at larger chance of relapse. Endocrine therapies are crucial in patients with endocrine responsive disease.

No significant financial relationships to disclose.
Longitudinal Oncology Registry of Head and Neck Carcinoma (LORHAN), a new national cancer registry
Authors: Curran W. , Chen A. , Harari P. , Murphy B. , Wong S. , Bellm L. , Gamber D. , Dawson D. , Ang K.
Published: March 2020

5583

Background: Registries can be invaluable for describing patterns of care for a population of patients (pts). Most cancer registries, however, do not possess sufficient breadth or depth to provide a complete and reliable picture of clinical practice. We report the launch of LORHAN, a new national registry of head and neck carcinoma (HNC) pts. LORHAN is designed to extend current cancer registries by providing detailed data on radiation and/or cancer drugs delivered to HNC pts in all practice settings. Methods: This is a prospective, multi-center, longitudinal, observational registry. Pts with newly diagnosed HNC, scheduled to receive radiotherapy or drug therapy, ≥18 years of age and providing written informed consent are being enrolled. Patients participating in clinical trials are eligible for LORHAN. The primary objective of the registry is to describe, in detail, patterns of care for HNC pts. The secondary objectives are to document outcome by treatment regimen, determine the incidence and severity of major toxicities and to identify supportive care received for managing treatment-related complications. Pts are entered in the registry from the time of initial diagnosis and are followed for at least 2 years and up to 10 years. Detailed information on initial treatment and re-treatment is collected. Data entry is electronic and incorporates encrypted point-to-point data transfer via secure HTTP protocols. Physician and patient confidentiality are strictly maintained. Participating practitioners can review and compare their data on a real-time basis to the database. Registry pts may be linked to the NDI to minimize lost to follow-up. Analyses of data are primarily descriptive. Results: LORHAN was launched in Oct. 2005, and as of Dec., 7 sites have received IRB approval and 3 pts have been enrolled. Of the 7 sites, 1 is an academic site and the remaining are community-based practices. An additional 21 sites (17 academic, 4 community) are at various stages of participation. More than 100 medical oncologists and radiation oncologists are anticipated to participate and approximately 26,000 pts will be eligible each year. Accrual status will be updated. Conclusions: LORHAN is a new national initiative that may further the understanding of the care of HNC pts across practice settings.

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Capecitabine (X) and taxanes in patients (pts) with anthracycline-pretreated metastatic breast cancer (MBC): Sequential vs. combined therapy results from a MOSG randomized phase III trial
Authors: Soto C. , Torrecillas L. , Reyes S. , Ramirez M. , Perez L. , Cervantes G. , Gonzalez F. , Tellez E. , Cortes P. , Benitez H.
Published: March 2020

570

Introduction: Capecitabine (Xeloda [X]) shows synergy with taxanes and adding X to docetaxel (T) extends overall survival (OS), response rate (RR) and progression free-survival (PFS) beyond T alone. Sequential single-agent therapy could confer convenience benefits and may be more appropriate than combination chemotherapy for some pts. Methods: Pts with anthracycline-pretreated MBC received 3-weekly cycles of 1 of the following regimens: X→taxane (X 1250mg/m2 bid d1–14, followed after progression (PD) by T 100mg/m2 or paclitaxel [P] 175mg/m2 day 1; X+P (X 825mg/m2 bid days 1–14 + P 175mg/m2 day 1) or X+T (X 825mg/m2 bid days 1–14 + T 75mg/m2 day 1). Results: Of the 368 pts enrolled, 91 are either still on therapy or not evaluable. The table shows baseline characteristics, efficacy and safety in evaluable pts. Median follow up is 15.5 months. Median doses for X in each arm (1st cycle vs. 8th cycle, mg/m2 bid): 1218 vs. 1054; 948 vs. 900; 846 vs. 751. Median doses for P and T (1st cycle vs. 8th cycle, mg/m2): 173 vs. 169 and 75 vs. 72, respectively. In the X→taxane arm, 58 pts (64%) received sequential taxane; the remainder did not receive a taxane, either because they were still on X, had CR or had rapid PD. Conclusions: RR is higher with XP and XT, but PFS and OS are similar at a median follow-up of 15.5 months. All regimens were well tolerated with minimal grade 4 AEs. Because there is no clear superiority of sequential vs. combined therapy, pt characteristics are likely to be used to decide which regimen is the most appropriate.

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[Table: see text]
Results of an analysis of cardiac function in 2,812 patients treated with lapatinib
Authors: Perez E. A. , Byrne J. A. , Hammond I. W. , Rafi R. , Martin A. M. , Berger M. S. , Zaks T. Z. , Oliva C. R. , Roychowdhury D. F. , Stein S. H.
Published: March 2020

583

Background: Lapatinib is an orally bioavailable reversible, dual tyrosine kinase ErbB1 and ErbB2 inhibitor. Trastuzumab, an ErbB2 inhibitor, has been associated with cardiotoxicity. Methods: Left ventricular ejection fraction (LVEF) was monitored every 8 weeks using MUGA or echocardiogram. Cardiac risk factors including age, underlying cardiovascular disease, previous exposure to AC, trastuzumab, or mediastinal/left sided radiation (XRT) were also collected. LVEF data were evaluated for ≥ NCI CTC grade 3, or ≥ 20% decline relative to baseline (& below institutional LLN). Results: 1.3%, 37 of the 2812 subjects who have received lapatinib in all trials to date have experienced decreased LVEF. 22 of 37 patients received lapatinib monotherapy, the remaining 15 received lapatinib in combination with other chemotherapeutic agents. 68% (25/37) of patients were female, median age was 59 years. Decreased LVEF occurred within 9 weeks of treatment onset in 68% of cases. The event resolved/improved in 57% of cases: in 50% of these, lapatinib treatment was continued. Average event duration was 5 weeks. Four of 37 patients were symptomatic (0.1% incidence). Most symptomatic events responded promptly to standard CHF therapy. The majority of patients (92%, 34/37) had confounding factors that may have contributed to the event, including previous exposure to AC, trastuzumab or XRT, and/or medical history. 8 of 34 patients had a positive lapatinib dechallenge (LVEF recovered): 3 were symptomatic (signs of CHF) and 5 asymptomatic. 3 patients had no contributing factors: 1 experienced symptomatic decreased LVEF, the remaining 2 died due to disease progression whilst LVEF decrease was ongoing. 16 of 1307 patients participating in placebo controlled studies experienced decreased LVEF. Of these 8 are known to have received lapatinib, giving an incidence of 1.2% (8/654). Conclusions: Lapatinib-associated LVEF decrease is rarely symptomatic and generally reversible/non-progressive. Incidence was 1.3% in our population, less than the 3–6% incidence of asymptomatic LVEF decreases observed in the general population. Pharmacogenetic studies are ongoing to determine whether there is a link between ErbB2 polymorphisms and lapatinib cardiotoxicity.

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Understanding and preferences for receiving prognostic information: A comparison of the views of Australian and Canadian patients with metastatic cancer
Authors: Dimitry S. , Ellis P. M. , Butow P. N. , Hagerty R. G. , Tattersall M. H.
Published: March 2020

6014

Background: Previous research suggests that the majority of cancer patients desire full disclosure of their prognosis and treatment options. The current study compares the views of Australian (A) and Canadian (C) patients with metastatic cancer towards disclosure of prognostic information. Methods: Cross sectional studies were undertaken with A and C patients with newly diagnosed metastatic cancer to assess their preferences for and understanding of prognostic information. The primary outcome was patients’ preferences for the mode of delivery of prognostic information. Remaining analyses were primarily descriptive. Results: Survey response rate was A: 58% (n = 126) and C: 57% (n = 117). Patient mean age was 62.8yrs (A), 63.2yrs (C). 56% (A) and 39% (C) of patients were male. There were some differences in type of cancer: breast (25%A, 30%C), colorectal (18%A, 44%C), lung (10%A, 26%C) and other cancers (47%A). The main outcomes of the A and C surveys were very similar. The majority of all patients surveyed wanted to know prognostic information. Most patients preferred both words and numbers (46%A, 52%C), or words only (28%A, 31%C) for presenting prognostic information. Respondents were more likely to like words (66%A, 47%C), percentages (65%A, 45%C), or fractions (60%A, 47%C) for presenting prognostic information, than diagrams (37%A, 33%C), pie charts (42%A, 32%C) or graphs (33%A, 29%C). The majority of patients want to receive information on treatment goals and options when first given a metastatic diagnosis (84%A, 86%C). Fewer patients want to receive information on life expectancy at this time (59%A, 56%C) and only the minority want to discuss information about dying at this time (34%A, 36%C). Respondents indicated the specialist should just tell the patient (83%A, 74%C) rather than check first if the patient wants to know (15%A, 22%C). Conclusions: A and C patients have similar and strong preferences for receiving prognostic and treatment option information. However, more research is needed on the timing of delivery of this information.

No significant financial relationships to disclose.
Effect of distance to radiation treatment facility on use of radiation therapy after mastectomy in elderly women
Authors: Punglia R. S. , Weeks J. C. , Neville B. A. , Earle C. C.
Published: March 2020

6030

Background: Post-mastectomy radiation therapy (PMRT) has been shown to improve survival in patients at high risk for local or regional recurrence. However, radiation therapy necessitates daily travel to treatment centers for several weeks. We sought to study the effect of distance to the nearest radiation treatment facility on receipt of PMRT in elderly women. Methods: Using the linked Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database, we analyzed 19,787 women with Stage I or II breast cancer who received mastectomy as definitive surgery between 1991 and 1999. Multivariable logistic regression was used to investigate the association of travel distance with receipt of PMRT after adjusting for clinical and sociodemographic factors. Results: Overall, 2,075 (10.5%) patients treated with mastectomy received PMRT. In addition to cancer and patient characteristics, increasing distance from the nearest radiation treatment facility was independently associated with a decreased likelihood of receiving PMRT, (OR = 0.996 per additional mile, p = 0.01). The decline in PMRT use appeared at distances greater than 25 miles and was statistically significant for those patients living greater than 75 miles from the nearest radiation facility (odds of receiving PMRT of 0.58 [95% CI: 0.34–0.99] versus those living within 25 miles of such a facility). In secondary analyses, the effect of distance was only significant in women aged 75–80 years (OR = 0.992 per additional mile, p = 0.03), and those above the age of 80 (OR = 0.989, p = 0.02). When analyses were conducted separately by geographic region, the effect of distance was only significant in the Midwest (OR = 0.992, p = 0.014). The effect of distance was not significant (OR = 1.00, p = 0.87) among women with positive nodes, but was significant in women with no positive nodes (OR = 0.992, p = 0.013). Conclusions: Oncologists must be cognizant of the potential barrier to quality care that is posed by travel distance, especially for elderly patients. Mechanisms to ameliorate the effect of distance on receipt of radiation therapy by assisting individuals with transportation limitations or policies to decrease the centralization of RT services, may help to remove barriers to potentially life-saving treatment.

No significant financial relationships to disclose.
Direct-to-consumer advertising in oncology: A content analysis of print media
Authors: Abel G. A. , Lee S. J. , Viswanath V. , Weeks J. C.
Published: March 2020

6034

Background: Direct-to-consumer advertising (DTCA) is an increasingly prevalent and contentious medium of medical communication. Content analysis of cancer-related DTCA, with a focus on how benefit and risk/side effect information is presented, is essential to understanding its potential effect on oncology outcomes. Methods: We reviewed all product-specific DTCA for oncology-related medications appearing in the patient-focused cancer magazines CURE, Coping with Cancer, and MAMM: Women, Cancer and Community during 2005. We assessed the Flesch reading ease score (FRES), calculated with the formula [206.835 - (1.015 x average sentence length) - (84.6 x average syllables per word)], for the benefit and risk/side effect information presented in each advertisement. Ranging from 0 to 100, a FRES of 65 or higher is considered understandable for the average person. We also assessed the largest type size (in mm) and the placement (first, middle or final third of text) of benefits and risks/side effects, as well as the ads’ use of appeals to clinical trial data, cost, celebrity endorsement, physician endorsement, and implied patient testimonials (visual and written). Results: Of 75 ads reviewed, many were repeated, such that 15 unique ads were analyzed. The mean FRES for benefit information was 40.64, while the mean FRES for risks/side effects was 32.30, a difference of 8.34 [95% CI: 1.16, 15.52]. The mean largest benefit type size was 7.10 mm, while the mean largest risk/side effect type size was 2.33 mm, a difference of 4.77 mm [95% CI: 2.35, 7.17]. No ads mentioned cost, and none contained a celebrity or physician endorsement. 53% referenced clinical trials, and 60% offered an implied patient testimonial. In their first third of text, 93% presented benefits; 13% presented risks/side effects. In their final third of text, 27% presented benefits; 93% presented risks/side effects. Conclusion: Oncology print DTCA is difficult to read, as assessed by a standard readability measure. Moreover, compared to risks/side effects, benefits are presented in a larger typeface, earlier in the text, and in language that is modestly easier to read. Oncology providers should be aware of such differences, as they may influence patients’ perceptions of cancer-related medications.

No significant financial relationships to disclose.
Cancer clinical trial accrual patterns among community cancer centers in the United States
Authors: Lee J. A. , Mathiason M. A. , Czeczok C. A. , Keller J. K. , Go R. S.
Published: March 2020

6041

Background: Most cancer patients are diagnosed and treated in the community but clinical trial accrual rate is low. Published data on trial accrual from community-based cancer centers throughout the U.S. are limited. The Association of Community Cancer Centers (ACCC) is a national multidisciplinary education and advocacy organization that maintains a membership caring for over 60% of all patients with cancer in the U.S. In order to determine the clinical trial accrual patterns in the community across various geographic regions in the U.S., we performed a retrospective study utilizing the data from ACCC membership maintained at their web site. Methods: Data available from the most recent year (2003–2005) were obtained from 621 centers throughout the U.S., representing 49 states (no data for WY) and the DC. We investigated the number of patients (new and old) accrued into trials per year relative to the number of new analytical patients seen in the same year, a value we termed accrual ratio (AR). In addition, we studied the effects of geographic location, size of the cancer program, number of affiliations with National Cancer Institute sponsored cancer cooperative groups, and the number of medical/support/data management staffs on trial accrual. Results: A total of 670,215 new patients were seen across the ACCC membership with 43,743 patients accrued into trials for a median AR of 6.5% (range, 0.3–16.9). The top and bottom 5 accruing states were VT, MD, SD, LA, ID and KS, ND, VA, NH, AR, respectively. Regionally, the AR for Midwest, Middle Atlantic, West, South, Southwest, and New England were as follows: 7.4%, 7.0%, 6.2%, 6.0%, 5.7%, and 5.4% (p < 0.001). One hundred (16.1%) centers representing 11.8% of all new patients were not affiliated with any of the cooperative groups. This group had the lowest AR (3.1%). AR increased when centers were affiliated with more cooperative groups (p < 0.001) or cared for more new patients (p < 0.001). The number of medical, support, and data management staffs did not influence accrual. Conclusions: Overall, clinical trial accrual in the U.S. community cancer centers is low. Accrual patterns differed significantly among various geographic locations. Better access to trials is needed in order to improve participation of cancer patients.

No significant financial relationships to disclose.
Early closure of clinical trials: The experience of the National Cancer Institute of Canada Clinical Trials Group
Authors: Parulekar W. , Pater J. L.
Published: March 2020

6053

Background: Phase III studies require a significant commitment on behalf of researchers and patients. Closure of a study before the originally planned number of patients have been enrolled may be due to a number of reasons such as poor accrual, information within the study that precludes continuation such as excess toxicity, an interim futility or extreme efficacy analysis or data from outside sources that render the study question obsolete. Methods: We reviewed the phase III activity of our group since inception. Reasons for early closure were classified in the following manner: accrual failure (AF), external information (EI), internal information (II). Studies were grouped by site and time period of study activation to demonstrate any trends over time. Results: 94 phase III studies led by our group were identified from our roster. Reasons for early closure are presented below. Other sites include brain with an early closure due to AF, head/neck where 1 of 3 studies closed due to AF, melanoma where 1 of 3 studies closed due to EI and sarcoma where 2 studies were successfully completed. Several of the studies that closed for accrual failure were nevertheless published either singly or as part of a meta-analysis. Conclusions: Slightly over one third of studies closed prior to achievement of the targeted sample size. Accrual failure continues to be the main cause of early study closure (27/34 or 80%) with a trend towards decreasing frequency of occurrence over time. Emerging data within or external to a study leading to study closure are important but relatively rare reasons for early closure.

[Table: see text]

No significant financial relationships to disclose.
What can we glean from linking registry and Medicaid claims data?
Authors: Schrag D. , Virnig B. , Xu F. , Allen M. , Warren J. L.
Published: March 2020

6055

Background: Cancer quality of care problems are concentrated among the indigent. Although Medicare claims linked to tumor registry data have become an important source for evaluating cancer care, parallel efforts to use Medicaid claims are not well developed. Objective: To evaluate the feasibility and potential value of linking the California state cancer registry with Medicaid claims for health services research. Methods: Cases reported to the California Cancer Registry (CCR) between 1988 and 2000 were matched with California Medicaid enrollment and claims data. We assessed the number of cancer cases that appeared in the Medicaid enrollment data. We evaluated the sensitivity of Medicaid claims to capture cancer diagnoses and treatments reported in the registry data. Results: 6,800 patients ages 18–64 had records in the 1998 CCR data that were matched to the 1998 Medicaid enrollment file; Medicaid enrollees accounted for 34.4% of patients with hepatoma and 21.1% of patients with cervix cancer, but only 8.9% of breast and 8.9% of testicular cancer patients in this age bracket. Medicaid data had only modest sensitivity to capture cancer diagnoses and procedures. For 5 cancers, Medicaid claims included procedure codes for about 70% of surgeries reported in the registry data. Missing diagnoses and procedures could be attributed to discontinuous enrollment, Medicare crossover and enrollment in pre-paid health plans. Conclusion: Linkage of CCR and Medicaid enrollment data identified sizable populations of indigent patients. However, the modest sensitivity of Medicaid claims to capture cancer diagnoses and procedures currently limits the utility of Medicaid data to assess cancer treatment and outcomes.

No significant financial relationships to disclose.
Cancer clinical trials available in the community setting: A 5-year analysis from 1999–2004
Authors: Keller J. K. , Bowman J. , Lee J. A. , Mathiason M. A. , Frisby K. A. , Meyer C. M. , Meyer L. A. , Wright L. J. , Go R. S.
Published: March 2020

6056

Background: Less than 5% of newly diagnosed cancer patients are accrued into clinical trials. In the community setting, the lack of appropriate clinical trials is a major barrier. Our prospective study in 2004 determined that 58% of newly diagnosed adult cancer patients at our community-based cancer center didn’t have a clinical trial available appropriate for their disease stage. Among those with clinical trials, 23% were subsequently found to be ineligible (Go RS, et al. Cancer 2006, in press). However, the availability of clinical trials may vary from year to year. Methods: A retrospective study was conducted to determine what clinical trials were available for newly diagnosed adult cancer patients at our institution from June 1999-July 2004. The study also investigated the proportions of newly diagnosed patients who had a clinical trial available appropriate for type and stage of disease and patients accrued. Results: Over the 5-year period, 207 (82, 87, 99, 102, 117, years 1–5, respectively) trials were available. Most (50.7%) trials were for the following cancers: breast (15.5%), lung (13.5%), head and neck (7.7%), colorectal (7.2%) and lymphoma (6.8%). ECOG (53%), RTOG (26%), and CTSU (9%) provided the majority of the trials. A total of 5,776 new adult cancer patients were seen during this period. Overall, 60% of the patients had a trial available appropriate for type and stage of their cancer, but only 103 (3%) were enrolled. There was a significant upward trend in the proportions of patients with available trials over the years (60.2%, 55.9%, 59.2%, 60.7%, 63.9%, years 1–5, respectively; Mantel-Haenszel P=.008). The proportion of patients with a trial available was highest for prostate (97.3%), lung (90.9%), and breast (73.9%), and lowest for melanoma (17.1%), renal (11.6%), and bladder (7.2%). The majority of patients accrued to trials had the following cancers: breast (32%), lung (17%), lymphoma (9%), colon (7%), and prostate (5%). Conclusions: Nearly half of the newly diagnosed adult patients at our center had no trials available appropriate for type and stage of their cancers. It is likely that if strict clinical trial eligibility criteria were applied, approximately 2/3 of our patients would not be eligible for a clinical trial.

No significant financial relationships to disclose.