bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cetuximab (C-mab) and chemo-radiation (CT-RT) for loco-regional advanced squamous cell carcinoma of the head and neck (HNC): A phase II study
Authors: Merlano M. C. , Numico G. , Russi E. G. , Benasso M. , Colantonio I. , Vigna Taglianti R. , Lanzilotta L. , Vigo V. , Bacigalupo A. 
Published: March 2020

6043 Background: C-mab is a monoclonal antibody targeting EGFR. C-mab combined with radiotherapy (RT) improved loco- regional control and overall survival over RT alone in HNC pts (Bonner 2006). Prior data of C-mab and CT-RT (Pfister 2006) were encouraging but the trial was stopped due to an excess of severe toxicities, suggesting the need for a less toxic scheduling. For these reasons we evaluate the safety and activity of C-mab combined with alternating CT-RT in HNC pts. Methods: The primary end-point is C.R. rate. The optimal two stage design was used: the calculated sample size is 45 pts. Eligible pts have locally advanced, measurable, untreated, stage III/IV HNC (excluding nasopharynx). Chemotherapy (CT) consists of Cis-PT 20 mg/m2/day and bolus 5Fu 200 mg/m2/day from day 1 to 5, repeated on days 22 and 43. RT, 2 Gy/day, 5 days a week, is given in the pauses between the chemotherapy courses and after the last CT week, up to a total dose of 70 Gy. Results: From 10/2005 to 12/2006 24 pts were enrolled: median age 59 (49–75); median ECOG P.S. 0 (0–1); Stage IV 73%; N1–3 86%; EGFR >80% cells: 55%; EGFR 3+: 91%; most pts had hypopharynx cancer, only 1 had oral cavity tumor. Toxicity is evaluable on 20 pts (4 ongoing). Grade 3–4 toxicities included febrile neutropenia (20%), diarrhea (20%), hypomagnesaemia (10%), mucositis (60%). Unexpected skin toxicity, starting as desquamating moist dermatitis and confined at the irradiated field, occurred in 18/20 pts, usually during the second part of the treatment. Acute colon diverticulitis with perforation (1 pt), gastric perforation (1 pt), fatal myocardial infarction (1 pt) and arterial thrombosis (1 pt) also occurred. Responses, evaluated 3 months after the treatment, are available for the first 16 pts. Objective responses were observed in all them (11 CR + 5 PR). Two PRs were then rendered disease free with salvage surgery. At a maximum follow-up of 15 months, 16/20 pts are alive and 16/20 progression free. Conclusions: This trial showed a skin toxicity not previously reported in other experiences of C-mab combined with RT or CT-RT. Preliminary activity data seems to confirm the Pfister experience. No significant financial relationships to disclose.
A randomized phase II study of concomitant CT (docetaxel±cisplatin) and (RT) in first-line treatment of locally advanced head and neck cancer (LAHNC)
Authors: Bouillet T. , Nizri D. , Zawadi A. , Herman D. , Cupissol D. , Demaux H. , Touboul E. , Cretin J. , Morere J. F. 
Published: March 2020

6047 Background: 4 randomized trials demonstrated superiority of concomitant CT and radiotherapy (CRT) versus RT. Radiosensitizing effect of docetaxel showed in vitro, phase I recommended docetaxel dose as weekly 20 mg/m2 with concomitant RT. Methods: (pts) with inoperable LAHNC (T3/T4); PS < 2.RT in both arms was 70 Gy. In arm A, pts received 7 cycles of weekly Docetaxel 20 mg/m2 before RT and cisplatin 20 mg/m2 D1–3 every three weeks (3 cycles). In arm B, docetaxel alone at the same dose as in arm A.G-CSF secondary prophylaxis and ciprofloxacin recommended in both arms. Primary objective was WHO objective response rate (ORR). Statistical analysis: 2 steps according to a Simon plan authorized early interruption in case of insufficient efficacy. Results: 82 pts treated (Arms A/B:35/47); Arm A stopped in the first step. 47 pts treated in arm B. M/F (%) (83/17), median age 56.6 y, PS 0/1 (%) 54/46, T2/T3/T4 (%) 2/36/62, N0–1/N2/N3 (%) 30/55/15, primary site (%): buccal cavity (38), hypo-oropharynx (47), larynx (11). Median nbr of cycles 7 (3–7), 85% of pts completed planned CRT. ITT ORR: 89 % [75–96], median TTP 31.3 [19.3 –42.4], median OS 36.8 [21.2–49.5] months. Main grade 3–4 toxicities were mucositis (31.9%),skin toxicity (21.3%). Grade 3–4 hematological, GI and neurological toxicities were not observed. Conclusions: In this study, concomitant RT and weekly 20 mg/m2 docetaxel is effective and well tolerated in LAHNC. The docetaxel/cisplatin arm was prematurely discontinued for insufficient efficacy. No significant financial relationships to disclose.
Phase II trial of pemetrexed (P) and bevacizumab (B) in patients (pts) with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC): An interim analysis
Authors: Karamouzis M. V. , Friedland D. , Johnson R. , Rajasenan K. , Branstetter B. , Argiris A. 
Published: March 2020

6049 Background: P is a multi-targeted antifolate with single-agent activity in recurrent or metastatic HNSCC (RR 26%, Pivot et al. Br J Cancer 2001;85:649–55) and a preferable toxicity profile compared with cisplatin or the taxanes. B is a monoclonal antibody against the vascular endothelial growth factor that has been successfully incorporated in the treatment of other advanced solid tumors. Methods: Eligible pts had pathologically documented HNSCC, ECOG performance status 0–1, measurable disease, no history of bleeding diathesis or hemoptysis, and were not on anticoagulation. Pts had no prior systemic therapy for recurrent or metastatic HNSCC; chemotherapy as part of initial potentially curative therapy, but without P or B, was allowed if completed >6 months earlier. Treatment consisted of P 500 mg/m2 and B 15 mg/Kg, both given intravenously every 21 days, until disease progression or intolerable toxicity. All patients received folic acid, vitamin B12, and corticosteroid prophylaxis. The primary endpoint was the time to progression (TTP) with a sample size of 40 pts (one stage design) with planned interim safety analysis after the first 6 and 12 pts. Results: 14 pts have been enrolled. Median age 64 years (35–84); male/female 13/1; PS 0/1: 7/7; prior chemotherapy: 8; primary site: oropharynx (7), larynx (4), oral cavity (3). Median number of cycles 5 (1–10). With a median follow up of 5.5 months, median TTP was 6 months (95% CI, 4–8). 11 pts were evaluable for response using RECIST. Best response was CR: 2, PR: 3, SD: 6, PD: 0, with ORR 45%. There were no grade 4 toxicities in 14 evaluable pts; 2 pts had grade 3 hemorrhagic events in the first cycle (1 tumor-related and 1 due to gastric ulcer post gastrostomy tube placement), and both discontinued treatment. 3 other pts had grade 1–2 hemorrhagic events. The relationship of these events to treatment was difficult to ascertain. Other grade 3 toxicities were stomatitis, dysphagia, and fatigue (all occurred in 1 pt). Conclusions: Preliminary results show that P plus B is a novel, highly active regimen that may represent a new treatment paradigm in HNSCC. However, bleeding complications were frequent in pts with susceptibility to such events. Study accrual continues. No significant financial relationships to disclose.
Phase II trial of docetaxel (T), cisplatin (P), and cetuximab (E) followed by concurrent radiation (RT), P, and E in locally advanced head and neck squamous cell carcinoma (HNSCC)
Authors: Argiris A. , Karamouzis M. V. , Heron D. E. , Smith R. , Ferris R. , Lai S. , Kim S. , Branstetter B. , Johnson J. , Grandis J. 
Published: March 2020

6051 Background: E is a chimeric IgG1 monoclonal antibody against the external domain of the epidermal growth factor receptor that may enhance the efficacy of RT and chemotherapy. Our goal was to incorporate E in the induction and subsequent chemoradiotherapy of HNSCC. We report our preliminary results with TPE induction. Methods: Patients (pts) had pathologically documented HNSCC stage III/IV or selected stage II (base of tongue, hypopharynx, or nasopharynx), no prior therapy, ECOG PS 0–1, and adequate hematologic, kidney and liver laboratory parameters. Induction consisted of T 75 mg/m2 day 1, P 75 mg/m2 day 1, and E 250 mg/m2 days 1,8, and 15 (after an initial dose of 400 mg/m2 on cycle 1, day 1), repeated every 21 days × 3 cycles. Subsequently, pts received RT 70 Gy (2 Gy/day) with concurrent P 30 mg/m2 and E 250 mg/m2 weekly, followed by maintenance E for 6 months. Prophylactic antibiotics were given on days 5–14 of each TPE cycle. Tumor assessment was performed after induction (primary endpoint) and 8 weeks after RT. Sample size was 39; one-stage design; target overall response rate (ORR): 80%. Results: 21 pts have been enrolled to date: median age 55 (39–74); Male/Female: 18/3; primary site: oropharynx (n=13), larynx (n=5), and other (n=3); stage III/IV: 4/17. In 16 evaluable pts, ORR to TPE was 15/16 (94%), CR: 2, PR 13, SD 1. For the primary site (12 evaluable): CR 6, PR 5, SD 1; for the lymph nodes (14 evaluable): CR 1, PR: 12, SD 1. The pt with SD discontinued E in the first cycle due to recurring infusion reaction. Another patient had a grade (G) 3 infusion reaction on the first E administration and was removed from study. Other serious toxicities during TPE (n=20): grade (G) 3/4 neutropenia (n=4/n=7) without incidence of neutropenic fever, G 3 anemia (n=1), G 3 thrombocytopenia (n=1), G 3/4 hypomagnesemia (n=2/n=1), G 3 rash (n=1), G 3 fatigue (n=4), and G 3 diarrhea (n=1). 1 pt had sudden death due to myocardial infarction (autopsy) after the third cycle of TPE. Subsequent RT plus P and E was feasible. 10 pts completed RT and all remain progression-free. Conclusions: Preliminary results suggest that TPE has predictable and manageable toxicities and high activity in HNSCC. Accrual is ongoing and updated data will be available. No significant financial relationships to disclose.
Impact of chemoradiotherapy for locally advanced head and neck cancer on swallowing function
Authors: Burke E. , Goguen L. , Tishler R. , Wirth L. , Posner M. , Hempel E. , Allen A. , Costello R. , Haddad R. 
Published: March 2020

6054 Background: We examined the impact of chemoradiotherapy (CRT) on swallowing function in a group of patients treated for locally advanced head and neck cancer in an ongoing randomized phase II study with concurrent CRT, with or without Ethyol. Methods: Chemotherapy consisted of weekly carboplatin AUC 1.5 and paclitaxel at 45 /m2 for 4 weeks. Radiation was delivered using a 3 field technique with a concomitant boost schedule to a total dose of 72 Gy. Patients were randomized to receive or not receive daily subcutaneous Ethyol. Patients had video swallow studies at the start of radiation and 8, 12, 24 and 52 weeks post chemoradiotherapy. Dysphagia and weight loss were monitored. Video swallow study reports were collected and the incidence of penetration, aspiration, pharyngeal residue and upper esophageal narrowing analyzed. Results: Baseline data were available for 31 patients out of 43 enrolled. 29% of the patients penetrated, 6.4% aspirated and 29% had pharyngeal residue. Patients on both arms of the study had a steady decline in swallowing function from onset until 24 weeks post radiation. Penetration, aspiration and pharyngeal residue were consistently noted at all time points and improvements in deglutition were seen on the 52-week post radiation video swallow. Forty percent of the patients (17/43) had narrowing in the upper esophagus. On average, a third of the patients examined required dilations. The remaining patients with esophageal narrowing were able to advance their diet and have their feeding tubes removed without dilations. The average time from the end of the treatment to PEG removal was 219 days. Conclusion: Based on the video swallow studies that were conducted, patients had a gradual decline in swallowing function from initiation of CRT until 24 weeks post. Esophageal narrowing was common, often requiring dilation. Given that it takes 7 months on average for the feeding tubes to come out, we recommend that these patients undergo intensive swallowing therapy and continuous long term follow up and assessment at two and possibly three years post CRT. Study is ongoing. No significant financial relationships to disclose.
Clinical significance of ERCC1 expression in advanced squamous cell carcinoma of the head and neck treated with cisplatin- based concurrent chemoradiation
Authors: Jun H. , Ahn M. , Kim H. , Park B. , Han J. , Ahn Y. , Jeong H. , Son Y. , Baek J. , Park K. 
Published: March 2020

6061 Background: The cytotoxic effect of cisplatin is based on the DNA cross linking. Nucleotide excision repair is associated with resistant to platinum-based chemotherapy. The excision repair cross-complementation group 1 (ERCC1) enzyme plays a rate-limiting role in nucleotide excision repair pathway. We evaluated the expression of ERCC1 as a predictive factor for survival in patients of squamous cell carcinoma of the head and neck (SCCHN) treated with cisplatin-based concurrent chemoradiotherapy (CCRT). Methods: We reviewed the clinical records and pathologic specimens of locally advanced SCCHN patients who had been treated with cisplatin-based definitive CCRT between 1995 and 2005. ERCC1 expression of the biopsy specimen was assessed by immunohistochemical (IHC) staining and a semi- quantitative grading system (H-score) was used for the evaluation. The median value of the H-score was chosen as the cutoff point for positive ERCC1 expression. Results: A total of 44 specimens and clinical data of the patients were reviewed. The median age was 59 years (range; 27–75), and 81.8% were male; 94.2% had ECOG performance status 0–1. The positive ERCC1 expression rate was 54.5% of all specimens (N=24/44). Overall tumor response rate for CCRT was 90.9% (CR=65.9%; PR=25.0%). With a median follow-up of 45.9 months (range; 5.4–133.0), 5-year progression free survival (PFS) rate was 58.0% and 5-year overall survival (OS) rate was 57.2%. Patients in group of positive ERCC1 expression showed poor survival in terms of PFS and OS (p=0.04; p=0.05), compared with negative ERCC1 expression group. Conclusions: The positive ERCC1 expression might be a predictive factor for poor survival and early progression in patients with locally advanced SCCHN treated with cisplatin-based CCRT. No significant financial relationships to disclose.
Deriving valid utilities for comparing treatments in clinical trials using standard quality-of-life (QoL) questionnaires
Authors: Grimison P. S. , Simes R. J. , Stockler M. R. 
Published: March 2020

6500 Background: Treatments for cancer have a myriad of beneficial and harmful effects. Benefits include prolonging survival and relieving cancer symptoms. Harms include side effects, inconvenience and costs. Assessing the overall impact of treatments requires a single, precise measure of net benefit, which combines information about health-related QoL, disease control and survival. Our aim is to develop a system for converting data from a QoL questionnaire into valid utilities, which allows comparison of treatments tested in clinical trials using utility measures and quality-adjusted survival analysis. Methods: 200 cancer patients previously completed the Utility-Based Questionnaire-Cancer (UBQ-C), a validated cancer-specific QoL measure which includes scales of health status (1 item), overall QoL (1 item), disabilities (12 items) and distresses (20 items); and were interviewed to elicit utilities using time trade-off (TTO) techniques. Scores were standardized to a scale bounded by 0 (worst outcome or death) and 1 (best possible health). A global QoL measure was derived from a weighted combination of the UBQ-C scales. Linear regression of overall health status on scales determined the weights. An equation to convert global QoL into utility was derived. Results: The global QoL measure as derived from the UBQ-C scales was more precise than the single- item scales. Median scores (IQR) were much lower for the global QoL measure: 0.77 (0.65–0.85) than for the direct measure of utility: TTO 0.98 (0.85 to 1.0). The best model to predict utility from derived global QoL was a power transformation: TTO=1-(1-global QoL)2.1. The mean absolute error in predicting utilities was 0.02. Conclusions: QoL measures underestimate utilities. A global QoL measure based on a weighted combination of the single item scales is more precise than single-item QoL scales. Our work enables QoL data obtained with a simple questionnaire to be converted into valid utilities that can be used in clinical trials to (i) describe the effects of cancer treatments on QoL (accounting for trade-offs between disparate aspects), (ii) evaluate trade-offs between quality and quantity of life, and (iii) do cost- effectiveness analysis. No significant financial relationships to disclose.
Risk-based care in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS)
Authors: Nathan P. C. , Greenberg M. L. , Ness K. K. , Mahoney M. C. , Gurney J. G. , Hudson M. M. , Donaldson S. S. , Leisenring W. M. , Robison L. L. , Oeffinger K. C. 
Published: March 2020

6502 Background: Childhood cancer survivors are at significant risk of morbidity as a result of their therapy. Thus, they require regular medical follow-up focused on their specific long-term risks. We examined the frequency and type of care received by a cohort of adult survivors of childhood cancer and examined the predictors of the receipt of appropriate risk-based care. Methods: Eligible subjects were members of the CCSS, a multi-institutional study of patients who have survived at least 5 years after being diagnosed with childhood cancer between 1970 and 1986. Participants completed a baseline survey and a subsequent survey on health care contact within the preceding 2 years. Contact was classified hierarchically as general care, cancer-related care, basic risk-based care and optimal risk-based care. Optimal risk-based care was assessed only in patients whose therapy is associated with a substantial risk of cardiac disease (=300 mg/m2 of an anthracycline, or any anthracycline plus chest radiation) or breast cancer (females who received chest radiation who are =27 years). Univariate and multivariable analyses were performed to assess associations between demographic/treatment variables and health care outcomes using logistic regression models. Results: The health care questionnaire was completed by 8,448 survivors. Median age (range) at diagnosis was 6.8 (0–21.0) years and at assessment was 31.4 (17.5–54.1) years. 87% reported general medical contact, 31% cancer- related care and 12% basic risk-based cancer care. Amongst patients at increased risk of cardiac disease (N=1,798) or breast cancer (N=852), only 28% reported receiving an echocardiogram and 49% a mammogram, respectively. Patients without health insurance (odds ratio [OR]=2.22, 95% confidence interval [CI]=1.56–3.13, p<0.0001 by Wald statistic), males (OR=1.19, 95% CI=1.03–1.37, p=0.02), younger patients (OR=1.03, 95% CI=1.02–1.04, p<0.0001) and those who perceived their health as good/excellent (OR=1.37, 95% CI=1.13–1.65, p=0.001) were at increased risk of not having received basic risk-based care. Conclusions: Despite a significant risk of late effects after cancer therapy, the majority of adult survivors of childhood cancer do not receive appropriate risk-based health care. No significant financial relationships to disclose.
Hope and prognostic disclosure
Authors: Mack J. W. , Cook E. F. , Wolfe J. , Grier H. E. , Cleary P. D. , Weeks J. C. 
Published: March 2020

6510 Background: Physicians sometimes selectively convey prognostic information to support patients’ hopes. However, the relationship between prognostic disclosure and hope is not known. Methods: We surveyed 194 parents of children with cancer (overall response rate 70%) in their first year of cancer treatment at the Dana-Farber Cancer Institute and Children’s Hospital, Boston, Mass, and the children’s physicians. We evaluated relationships between parents’ recall of prognostic disclosure by the physician and the extent to which physician communications “always” made them feel hopeful. A five-item index of prognostic disclosure assessed whether prognostic information was provided in any form, in quantitative terms, and in written form, whether the physician gave prognostic information before the parent asked, and whether parents wanted additional prognostic information beyond what they had already received. Results: Parents were less likely to report hopeful communication when the child’s likelihood of cure was low (OR .70 per category of decreasing likelihood of cure, P=.0003). However, parents who reported having received more extensive prognostic information were more likely to report hopeful communication, even when the prognosis was poor. In a multivariable model, parental report that physician communication “always” made them feel hopeful was associated with increased prognostic disclosure (OR 1.67 per element of disclosure, P=.009) and higher perceived communication quality (OR 5.39, P<.0001). In contrast, communication-related hope was inversely associated with the child’s likelihood of cure (OR .67, P=.006). Conclusions: Although physicians sometimes selectively convey prognostic information to preserve hope, we found no evidence that prognostic disclosure makes parents less hopeful. Instead, disclosure of prognosis by the physician can support hope for parents of children with cancer, even when the child’s prognosis is poor. No significant financial relationships to disclose. [Table: see text]
Randomized trials in oncology stopped early for benefit: A systematic review
Authors: Wilcox R. A. , Guyatt G. H. , Montori V. M. 
Published: March 2020

6513 Background: Investigators finding a large treatment effect in an interim analysis may terminate a randomized trial (RCT) earlier than planned. A systematic review (Montori et. al., JAMA 2005; 294: 2203–2209) found that RCTs stopped early for benefit are poorly reported and may overestimate the true treatment affect. The extent to which RCTs in oncology stopped early for benefit share similar concerns remains unclear. Methods: We selected RCTs in oncology which had been reported in the original systematic review and reviewed the study characteristics, features related to the decision to monitor and stop the study early (sample size, interim analyses, monitoring and stopping rules), and the number of events and the estimated treatment effects. Results: We found 29 RCTs in malignant hematology (n=6) and oncology (n=23), 52% published in 2000–2004 and 41% in 3 high-impact medical journals (New England Journal of Medicine, Lancet, JAMA). The majority (79%) of trials reported a planned sample size and, on average, recruited 67% of the planned sample size (SD 31%). RCTs reported (1) the planned sample size (n=20), (2) the interim analysis at which the study was terminated (n=16), and (3) whether the decision to stop the study prematurely was informed by a stopping rule (n=16); only 13 reported all three. There was a highly significant correlation between the number of events and the treatment effect (r=0.68, p=0.0007). The odds of finding a large treatment effect (a relative risk < median of 0.54, IQR 0.3–0.7) when studies stopped after a few events (no. events < median of 54 events, IQR 22–125) was 6.2 times greater than when studies stopped later. Conclusions: RCTs in oncology stopped early for benefit tend to report large treatment effects that may overestimate the true treatment effect, particularly when the number of events driving study termination is small. Also, information pertinent to the decision to stop early was inconsistently reported. Clinicians and policymakers should interpret such studies with caution, especially when information about the decision to stop early is not provided and few events occurred. No significant financial relationships to disclose.