bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gefitinib plus concomitant boost accelerated radiation (AFX-CB) and concurrent weekly cisplatin for locally advanced unresectable squamous cell head and neck carcinomas (SCCHN): A phase II study
Authors: Rueda A. , Medina J. A. , Mesía R. , Galiana R. , Vega M. E. , Collado A. , Cobo M. , Contreras J. , Marguelí M. , Alba E. 
Published: March 2020

6031 Background: Molecular inhibition of EGFR signaling represents one of the most promising current advances for the treatment of SCCHN. This study assesses the feasibility, toxicity and efficacy of gefitinib along with AFX-CB regimen and weekly cisplatin in treatment- naïve patients (pts) with locally advanced unresectable SCCHN. Methods: Eligible pts had stage III-IV SCCHN, exclusive of nasopharyngeal cancer. Tumors had to be considered unresectable by a multidisciplinary head/neck tumor board. AFX-CB dose was 72 Gy in 42 fractions over 6 weeks, delivered in 1 daily fraction of 1.8 Gy during the first 3.5 weeks and 2 fractions per day, 1.8 Gy and 1.5 Gy separated by a 6-hour interval, during the last 2.5 weeks. Cisplatin (40 mg/m2) was given weekly for the first 4 weeks. Gefitinib (250 mg PO OD) was started 1 day before radiochemotherapy (RCT) and continued 3 months after the end of AFX-CB. Response was evaluated 3 months after radiotherapy using RECIST criteria. Mucosal and skin toxicities were evaluated using the RTOG scale. Results: From Dec 2002 to Dec 2004, 46 pts with SCCHN, ECOG PS 0–1 and adequate hematologic and renal functions were included. Median age was 55 years (range, 39 to 75); T4, 73%; N2/3, 61%; stage IV disease, 93%. Four pts did not complete the concomitant treatment (1 PD/3 toxicity) and 8 pts did not complete the gefitinib monotherapy phase due to PD. Grade 3 and 4 toxicity was consistent with previous RCT or single agent gefitinib trials, and included mucositis (40% and 7%, respectively), radiation dermatitis (14% and 0%), skin rash (5% and 0%), and diarrhea (2% and 0%). Chemotherapy-associated toxicity was mild with only 2 cases of grade 3 neutropenia and 3 cases of grade 3 anaemia. Three months after AFX- CB, 24 pts (52%) achieved a complete remission, 5 pts (11%) a partial remission, and 17 pts (37%) were non-responders (SD, PD, and not evaluable). With a median follow-up of 23 months (range 1–43) 2-year PFS and OS are 47% and 56% respectively. Conclusions: The addition of gefitinib to radiochemotherapy appears tolerable and feasible. Efficacy is encouraging for this poor prognosis population, and further development of this targeted combined-modality paradigm is warranted. No significant financial relationships to disclose.
Surrogate endpoints for overall survival (OS) in head and neck squamous cell carcinoma (HNSCC): Evaluation using individual data of 23,737 patients
Authors: Michiels S. , Le Maître A. , Buyse M. , Burzykowski T. , Bogaerts J. , Vermorken J. B. , Budach W. , Ang K. , Pajak T. , Pignon J. P. 
Published: March 2020

6035 Background: The gold standard endpoint in randomized trials of HNSCC is OS. Our objective was to study if event-free survival (EFS) or loco-regional control (LRC) could be good surrogate endpoints to estimate the effect of radiotherapy (RT) and chemotherapy (CT) on OS. This would permit to decrease the duration and cost of the development of new treatments for HNSCC. Methods: EFS is the time from randomization to first event (loco-regional, distant recurrence or death), LRC the time from randomization to first loco-regional event. Individual patient data from two meta-analyses (MARCH; Bourhis, Lancet 2006, MACH-NC; Bourhis, ASCO 2004) were used. At the individual level, the rank correlation coefficient ρ between the surrogate endpoint (EFS or LRC) and OS was estimated from the bivariate distribution of these endpoints. At the trial level, the correlation coefficient R between treatment effects (estimated by log hazard ratios) on the surrogate endpoint and OS was estimated from a linear regression. EFS and LRC would be acceptable surrogates only if the correlation coefficients ρ and R were close to 1. Results: At the individual level, EFS was more strongly correlated with OS than LRC. For RT, treatment effects on both LRC and EFS were strongly correlated with those on OS. For CT, the correlation coefficients between treatment effects on EFS and OS were larger than those between LRC and OS. Conclusions: The preliminary analysis indicates that EFS can be used as a surrogate for OS to evaluate the treatment effect in randomized trials of patients with HNSCC. LRC is a possible alternative in RT alone trials. Unrestricted grants from ARC, LNCC, PHRC, Sanofi-Aventis. [Table: see text] [Table: see text]
Efficacy of neoadjuvant docetaxel and cisplatin followed by concurrent cisplatin-radiotherapy in locally advanced nasopharyngeal carcinoma (NPC): A randomized phase II study
Authors: Hui E. P. , Ma B. B. , Leung S. F. , King A. , Mo F. , Kam M. K. , Yu K. H. , Kwan W. H. , Zee B. C. , Chan A. T. 
Published: March 2020

6037 Background: The current standard treatment for locally advanced NPC is chemoradiation (CRT) ± adjuvant chemotherapy. However, adjuvant chemotherapy is often poorly tolerated after intensive CRT. Our previous study of neoadjuvant chemotherapy followed by CRT showed encouraging toxicity profile and disease control in advanced NPC (JCO 2004: 22: 3053–60). The current study compared the safety and efficacy of neoadjuvant chemotherapy (neoadj) followed by CRT. Methods: Newly diagnosed patients (pts) with stage III to IVB NPC were randomized (stratified by stage III vs IV) to: (1) Neoadj-CRT: docetaxel 75 mg/m2 D1, cisplatin 75 mg/m2 D1, q3w × 2 cycles, followed by cisplatin 40 mg/m2 weekly × 6–8 cycles concurrent with RT (= 66 Gy in 2-Gy fractions), or (2) CRT: cisplatin-RT (same as arm 1) without neoadj. The primary endpoint was toxicity. Secondary endpoints included survival and quality of life. Planned accrual was 30 pts per arm to detect a 20% difference in toxicity on one side of a 95% confidence interval (CI). Results: From 11/2002 to 11/2004, 65 pts were recruited. Five pts were excluded after randomization but before treatment started (three pts were subsequently found ineligible, and two pts withdrew consent). There was a higher rate of G3–4 neutropenia (100% vs 16%, p<0.001), but not neutropenic fever (3% vs 4%) or other non-hematologic toxicity in the neoadj-CRT vs CRT arm. The proportion of pts progressing at 2-yrs by group was compared by Fisher’s Exact Test (p=0.158). At median follow-up of 2.74 yrs, there were 10 deaths and 13 progressions. The 2-yr progression free survival for neoadj-CRT vs CRT was 80% vs 71% (hazard ratio 0.42; CI 0.14− 1.27; p=0.11). The 2-yr overall survival was 93% vs 76% (hazard ratio 0.17; CI 0.037–0.82; p=0.013). Conclusions: Neoadjuvant docetaxel and cisplatin followed by CRT was well tolerated with a manageable toxicity profile and allowed subsequent delivery of full dose CRT. Preliminary result suggested improved survival. A phase 3 study to definitively test this strategy is warranted. Acknowledgement: Sanofi-Aventis Hong Kong Ltd supported this study in part. No significant financial relationships to disclose.
A phase II trial of ZD 1869 for advanced cutaneous squamous cell carcinoma of the head and neck
Authors: Weber R. S. , Lustig R. , Glisson B. , Rosenthal D. , Kim E. , El-Naggar A. , Chalian A. , Hanna E. 
Published: March 2020

6038 Background: Advanced HN CSSC carries a 30–40% risk of death by 2 years with standard therapies. A number of patients (pts) with clinically aggressive CSCC tend to have a poor prognosis when treated with standard approaches using surgery and radiation (RT), thus novel therapies are needed. CSSC over expresses the epidermal growth factor receptor (EGFR) and these compounds have activity in head and neck cancers. We are studying the use of gefitinib as an induction therapy in a high-risk patient group prior to definitive therapy to determine the overall efficacy, toxicity and feasibility. Methods: Eligible pts must have HN CSSC >2cm, regional nodal metastases, peri-neural invasion, or deep invasion into cartilage, muscle or bone and must be candidates for definitive local-regional therapy with surgery and/or radiation. Two 30-day cycles of gefitinib 250mg administered orally are given daily prior to definitive therapy. Pts are assessed clinically after the first 30-day cycle. If a response is noted, gefitinib is continued. For patients with stable disease, the dose is escalated to 500mg daily. Pts with progressive disease go off study. Biomarker evaluations including EGFR and Akt expression prior to and after induction are planned. Results: To date, 14 pts have been enrolled. 10 are evaluable for response and 13 for toxicity. A complete clinical response (CR) was noted in 3 pts (30%, one pathological CR), partial response in 2 patients (20%), stable disease in 2 (20%) and progressive disease in 3 (30%). Therapy was well tolerated with 2 patients having grade 3 toxicity (rash, diarrhea, or elevated liver enzymes). Conclusions: Standard definitive surgery and RT are inadequate for patients with advanced HN CSSC. The emergence of targeted therapies has given new hope for many patients with high-risk cancers. The preliminary results from our study suggest that gefitinib is an active agent for HN CSCC, and is well tolerated. Correlative studies may help identify patients most likely to respond to anti- EGFR therapy. [Table: see text]
Impact of erythropoietin (EPO) on irradiation effect on the EPO receptor–positive head and neck cancer
Authors: Lo Nigro C. , Maffi M. , Fischel J. , Tonissi F. , Numico G. , Milano G. , Merlano M. 
Published: March 2020

6058 Background: Anemia frequently occurs in Head and Neck Squamous Cell Carcinoma (HNSCC) and has been associated with decreased quality of life, impaired treatment outcomes and shortened survival. Furthermore, anemia is a causative factor of tumor hypoxia, which compromises the efficacy of radiotherapy (RT). In order to circumvent the negative effects of anemia, several attempts have been made including the use of EPO, particularly in HNSCC. However, recent clinical data suggest a detrimental effect of EPO on survival for HNSCC patients treated with RT plus EPO. Methods: The HNSCC CAL-166 cell line, which is wild type p53 and expresses the EPO receptor (EPOR), was investigated in the present study; a MTT test was used to examine the effects of EPO on the cellular response to RT. Extended preliminary experiments were performed to standardize the conditions (time of exposure to hypoxia and time to return of normal culture conditions) and the administration of radiation (fractionated or in single dose) to optimize the effects of hypoxia on radiation response. Cells were exposed to a X-rays source at escalating doses from 2–20 Gy and showed classical dose- response curves. Hypoxia was mimed using a ‘Bug-Box‘ anaerobic workstation for 24–48 hours. Results: After a single RT dose of 10 Gy, the data confirmed the negative effect of hypoxia, directly related to the duration of hypoxia (% surviving cells when irradiated in normoxia: 43.95 ± 4.24; when irradiated after 24 hours of hypoxia, 62.4 ± 8.3 or after 48 hours, % surviving cells 70.8 ± 7.4; p = 0.001 versus RT in normoxia). The addition of EPO, from 24 hours before RT to 72 hours after, until MTT test, did not modify the cytotoxic effect of RT in hypoxic, but also in oxic conditions. Conclusions: These preliminary data do not support a direct negative effect of EPO when treating EPOR positive tumor cells with irradiation. Additional data concern the molecular impact of EPO on tumor cell lines with examination of EPOR, HIF-1 alpha and EGFR. No significant financial relationships to disclose.
Multi-center prospective study on sentinel node navigation surgery in early breast cancer
Authors: Imoto S. , Kitajima M. , Aikou T. , Kitagawa Y. 
Published: March 2020

606 Background: Sentinel node navigation surgery (SNNS) is a standard technique to identify lymph node metastases in clinically node-negative breast cancer. However, the dye and radiopharmaceuticals for lymphatic mapping commonly used in Western countries are not available in Japan. Methods: To assess the optimal lymphatic mapping and the outcome after SNNS, the Japanese society for SNNS conducted a non-randomized multi-center prospective study on SNNS in early breast cancer. Primary endpoint is to evaluate the success rates and adverse events associated with various lymphatic mapping and SNNS, and secondary endpoint is to observe the outcome of patients who underwent SNNS during 5 years. After the protocol was approved by institutional review board, SNNS had been registered between July 2004 and October 2005. Results: Fourteen hundred and sixty-eight cases had pre-registration from 65 investigators at 23 institutions. As 46 cases were withdrawn for some reasons and 11 cases were diagnosed as benign disease, 1,411 cases were finally entered in this study. Dyes used for lymphatic mapping were indigocarmine, indocyanin green, patent blue, and isosulfun blue, and radiopharmaceuticals were 99m-technetium-labelled tin colloid, human serum albumin, and phytate. In 19 cases, superparamagnetic iron oxide was used for MRI- guided SNNS. As of December 2006, 98% of clinical report forms were analyzed. Dye-guided SNNS was performed in 240 cases, radio-guided SNNS in 56 cases, and combined method in 1,016 cases. Overall success rate was 99%. SNNS alone was treated in 1,138 cases (82%) and SNNS followed by axillary lymph node dissection in 258 cases (12%). Breast-conserving surgery was undergone in 1,175 cases (85%) and total mastectomy in 217 cases (15%). Dye-induced allergic adverse events were not reported. Postoperative adverse events of bleeding, wound infection and seroma were observed in about 1 % of cases, respectively. Conclusions: Dye-guided and/or radio-guided SNNS proved reliable for lymphatic mapping in breast cancer. The prognosis of all cases will be observed until 2010. No significant financial relationships to disclose.
Retrospective analysis of the addition of cetuximab to induction chemotherapy (IC) with docetaxel, cisplatin, and 5-fluorouracil (TPF-C) for locally advanced squamous cell carcinoma of the head and neck (LA-HNSCC)
Authors: Kuperman D. I. , Nussenbaum B. , Thorstad W. , Haughey B. , Lewis J. , Adkins D. 
Published: March 2020

6072 Background: Achievement of a partial (PR) or complete (CR) tumor response at the primary site to IC has been used to predict for tumor sensitivity to definitive radiation (RT)-based treatment approaches in patients with LA-HNSCC. Three randomized trials of IC showed that TPF resulted in superior tumor response rates at the primary site in comparison to PF (TAX 323, TAX 324, and GORTEC). Based on the improved tumor response rate with the addition of cetuximab to cisplatin in metastatic HNSCC, TPF-C is a rational approach to improving tumor response rate to IC in LA-HNSCC. Methods: Between 2/06–12/06, 23 consecutive patients with LA-HNSCC were treated with IC that included TPF + cetuximab (400 mg/m2 loading dose followed by 250 mg/m2 weekly dose) for 1–3 cycles, followed by a standardized clinical assessment of tumor response at the primary site and at the regional nodes. TPF (docetaxel and cisplatin both 75 mg/m2 on day 1; 5-FU 750 mg/m2/d for 3 days) was given at every 3 week intervals. PR was defined as = 50% decrease and CR as complete resolution of tumor at the primary site. This is a retrospective analysis of the efficacy and the adverse effects (AE) of TPF-C in these patients. Results: Of 23 patients, 21 were evaluable for tumor response rate (RR). During IC, there were no deaths and grade 3–4 AE included: neutropenic fever (4), sepsis (1), and infusion reactions (4). Patients with favorable (PR or CR) tumor response to IC were treated with definitive RT-based therapy; whereas others were treated with surgery first. Conclusions: In this population of patients with LA-HNSCC with mostly (74%) T3 and T4 primary tumors, the tumor RR at the primary site to TPF-C was 71%. The addition of cetuximab to TPF was feasible. No significant financial relationships to disclose. [Table: see text]
Experience with cetuximab plus paclitaxel/carboplatinum in primary platinum-resistant recurrent head and neck cancer
Authors: Buentzel J. , de Vries A. , Micke O. 
Published: March 2020

6077 Background: In patients with platinum-resistant recurrent head and neck cancer the Anti-EGF-receptor antibody cetuximab could be used as a treatment option. Little is known about results of this therapeutic option. The objective of this study was to evaluate therapeutic benefit of this indication. Methods: 23 patients with histological confirmed recurrent head and neck cancer (18 male, 3 female, median age was 57 years) were included in this exploratory study. All recurrences had occurred after chemotherapy with platinum- derivates. 19 patients received radiation therapy during primary treatment. No surgical or radiotherapeutic option in recurrent disease was possible. Two patients were diagnosed with lung metastasis. The 2nd-line therapy consisted of carboplatinum (200 mg/m2) + paclitaxel (200 mg/m2) every three weeks (week 1, 4, and 7) and additionally cetuximab, which was given with 400 mg/m2 as loading dose in week 1 and 250 mg/m2 in week 2–6. Results: A significant tumor response was observed in 13/23 patients (56%). 7 partial, 5 minor and one complete remission were registered. The median survival time was 8 month (range 3–10), 4 patients are still alive. Median time to progression was 5 month (range 2–8). Side effects were rash (16/22), fever (9/22) and typical chemotherapy induced toxicities as neuropathy (7/22) and cytopenia (4/22). All side effects were moderate and easy to handle. Conclusions: The described combined chemoimmuntherapy with cetuximab and paclitaxel + carboplatinum seems to offer new strategies in 2nd and 3rd line chemotherapy for patients with platinum-resistant head and neck cancer, potentially overcoming primary platinum resistance. No significant financial relationships to disclose.
Phase III randomized trial of postoperative radiotherapy (RT) with or without carboplatin (Cb) in patients (pts) with head and neck squamous cell carcinoma (HNSCC)
Authors: Johnson J. T. , Agarwala S. S. , Karamouzis M. V. , Heron D. E. , Eibling D. E. , Cano E. , Urba S. , Gluckman J. , Wang Y. , Argiris A. 
Published: March 2020

6078 Background: Postoperative RT plus cisplatin is a standard treatment in high-risk resected HNSCC. However, the role of Cb in the same setting has not been established. Methods: Eligible were pts with macroscopically resected stage III/IV HNSCC with high-risk pathologic features (=3 nodes, extracapsular extension, perineural or angiolymphatic invasion, or involved margins), ECOG performance status 0–2, and adequate laboratory parameters. Pts were randomized to receive RT 59.4 Gy (1.8 Gy/day) versus the same RT plus Cb 100 mg/m2 intravenously once weekly during RT. The primary endpoint was the 2-year disease-free survival (DFS); with a projected sample size 100 patients/arm, the power was 0.81 with alpha 0.1 to detect a 15% improvement (50% to 65%). Results: From 4/94 to 4/02, 76 pts were randomized, of whom 72 pts were eligible and analyzable (36/arm). The study was prematurely closed due to slow accrual. Median age 54 years (24–83); male/female: 60 pts/12 pts; primary sites: oral cavity (n=26), oropharynx (n=23), hypopharynx (n=8), larynx (n=15); stage III/IV: 6 pts/66 pts; ECOG performance status 0/1/2: 40 pts/30 pts/2 pts. Median follow-up was 5.3 years. The 2-, 3- and 5-year DFS with RT/Cb vs. RT was 70%, 60%, and 46% vs. 55% (p=0.21), 51% (p=0.48), and 43% (p=0.79) and the 2-, 3- and 5-year overall survival (OS) was 74%, 71%, and 47% vs. 51% (p=0.04), 51% (p=0.07) and 40% (p=0.59). There were no statistically significant differences in median DFS or OS. In the subset of pts with primary sites other than the oropharynx (n=49), RT/Cb resulted in better OS vs. RT (p=0.05, Wilcoxon; p=0.27, log-rank). RT/Cb was associated with infrequent grade III/IV toxicities, including leukopenia (RT/Cb 8% vs. RT 0%), stomatitis (11% vs. 3%), and dermatitis (6% vs. 3%). Gastrostomy tube was placed in 15 pts (RT/Cb 8 vs. RT 7). Conclusions: Our data do not show a statistically significant improvement in DFS with RT/Cb vs. RT but this may reflect insufficient sample size. The potential benefit of RT/Cb for a subset of pts merits further study. No significant financial relationships to disclose.
Trends in head and neck squamous cell carcinoma (HNSCC) clinical research as reported in the ASCO Proceedings from 1996- 2006
Authors: David K. A. , Rademaker A. , Agulnik M. 
Published: March 2020

6089 Background: The results of clinical research can be seen through the review of ASCO Proceedings abstracts. We aimed to identify treatment trends in HNSCC as reported at the ASCO annual meetings from 1996 to 2006 and to see if an improvement in patient survival occurred. Methods: All abstracts in the head and neck section of ASCO Proceedings from 1996 to 2006 were reviewed. Abstracts on locally advanced, recurrent or metastatic HNSCC were further explored. Descriptive summary information was recorded regarding number of authors, randomization, trial phase, presence of novel drug or combination therapies, timing of chemotherapy, and disease-free and overall survival. Results: From 1996 to 2006, there were a total of 1,043 Head and Neck Cancer abstracts. Out of 311 phase 2 and 3 abstracts, 207 were presented. Of these, 78 were presented in the first half of the study period (1996–2000) compared to 129 in the second half (2001–2006). The average number of authors over the 10-year period was 12.7. Randomized controlled study proportions fluctuated, ranging from 11.8% in 2005 to 47.1% in 2001. 60% of studies focused on locally advanced disease; 32% on metastatic or recurrent disease, and 7% on both. Induction chemotherapy accounted for 31% of presented abstracts, while only 4% presented adjuvant data. The majority of abstracts used concurrent chemoradiotherapy (57%); 36% studied drug therapy alone. Abstracts presenting new therapies or new therapy combinations decreased (75% in 1996 vs. 61% in 2006). 12 studies (6% of presented studies) showed a statistically significant survival benefit, with 9/12 presented since 2001. All 12 were of patients with locally advanced disease, with the majority (7/12) showing the survival benefit of radiation administered with chemotherapy or cetuximab. Two trials showed the survival benefit of induction docetaxel, cisplatin, and fluorouracil (TPF) compared to PF. Conclusions: Since 1996, the number of presented clinical trials of HNSCC has increased. Overall survival benefits have been shown in Phase III trials in locally advanced disease. The major therapeutic advance over the last decade has been the overall survival gain with the use of concurrent chemoradiotherapy in locally advanced HNSCC. No significant financial relationships to disclose.