bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a new mutation in the EGFR ligand-binding domain: Predictive factor for cetuximab antitumor activity in head and neck carcinoma?
Authors: Rixe Olivier , Ya-Qin Li , Wise-Draper Trisha , Deng Li , Wang Jiang , Darnell Colleen Marie , Salkeni Mohamad Adham , Wilson Keith , Wells Susanne I , Stambrook Peter , Bahassi El Mustapha 
Published: March 2020

e16017 Background: Cetuximab is an EGFR-blocking antibody that has been approved for the treatment of patients with head and neck squamous cell carcinoma (HNSCC) and metastatic colorectal cancer, but no predictive biomarkers of cetuximab activity have yet been identified. Methods: We report on a patient with HNSCC who had a complete tumor regression following treatment with cetuximab given as a single agent after initial surgery and radiation therapy. The EGFR protein expression level, gene copy number and sequence were assessed from both normal and tumor tissues from this patient. Results: Besides protein overexpression and gene amplification in the tumor tissue, sequencing of the EGFR gene from the patient revealed the presence of two somatic mutations, one in the kinase domain (R705G) and the other in the ligand binding domain (P546S). Cells that stably express these EGFR mutants were treated with cetuximab and their sensitivity to the drug was compared to cells expressing the wildtype gene. While the P546S mutation sensitized NIH-3T3 cells to cetuximab, R705G had a marginal effect. The double mutant (P546S/R705G) behaved the same as the P546S mutant, indicating that the mutation in the kinase domain does not contribute to the increased sensitivity to cetuximab. No mutations were found in K-RAS or B-RAF genes and there was no indication that the tumor was HPV-positive. Conclusions: Our results support a role for the P546S mutation in cetuximab sensitivity. To our knowledge, this is the first report of a somatic mutation in the EGFR ligand binding domain that may contribute to increased sensitivity to cetuximab. Other factors including EGFR copy number, EGFR over-expression and the immune response, as indicated by a very adverse side effect that correlated with the antitumor activity, may have also contributed to the observed response. It remains to be determined how frequently this mutation occurs in patients with HNSCCs and other cancers. Prospective evaluation of cetuximab anti-tumor activity in patients harboring P546S mutation needs to be clinically evaluated.
Concomitant chemoradiotherapy using docetaxel, cisplatin, and 5-FU for the patients with advanced squamous cell carcinoma of the temporal bone.
Authors: Shiga Kiyoto , Katagiri Katsunori , Ogawa Takenori , Kato Kengo , Asada Yukinori , Kobayashi Toshimitsu 
Published: March 2020

e16020 Background: Chemotherapy using TPF protocol has been showed efficacy in the neo-adjuvant setting for head and neck squamous cell carcinoma (SCC) so far. However, effectiveness of concomitant chemoradiotherapy (CCRT) using TPF protocol has not yet been clearly distinguished. On the other hand, prognoses of the patients with advanced stage SCC of the ear invading extra-temporal bone were very poor. The aim of this study was to determine the safety and efficacy of newly developed CCRT using TPF protocol in patients with SCC of the temporal bone. Methods: Patients with previously untreated T4 disease were eligible for the study. Eleven patients were enrolled between December 2001 and August 2010. Treatment consisted of radiotherapy administered once daily to a total dose of 70 Gy, concomitant with 120 hour infusions of 5-FU (600 mg/m2/day), docetaxel (50 mg/m2, day 2) and cisplatin (60 mg/m2, day 2) given during first and fifth weeks of radiotherapy. These drug doses were determined from the results of our former phase I study to assess the dose limiting toxicity of this protocol. Median follow-up period was 33 months. Results: Nine patients completed this protocol. Bone marrow suppression was the most common adverse event observed through this study. Grade 4 leukopenia and neutropenia were observed in 1 (9%) and 3 (27%) of the patients and also those grade 3 events were observed in 3 (27%) and 1 (9%) of the patients. Grade 3 lymphopenia and hemoglobin were observed in 7 (64%) and 1(9%) patients. Although all patients showed dermatitis and alopecia at any grade, other grade 3 or 4 adverse events were obviously less than in patients with oropharyngeal or hypopharyngeal cancer using the same treatment protocol during the same period. Complete remission of primary tumor was obtained in all patients but one who rejected second course of TPF. Local recurrences were observed in three patients and one of them underwent salvage surgery. The disease-specific and over-all survival rates at 60 months of the patients were 77.8% and 70.7%, respectively. Conclusions: Our data suggested that CCRT using TPF protocol was feasible and very effective in patients with advanced stage SCC of the ear and temporal bone.
Phase II study: Docetaxel-cisplatin and pro drug tegafur (TPF) as neoadjuvant treatment in advanced patients with head and neck cancer (HNC): Results and correlation between tandem magnesium/creatinine and toxicity.
Authors: Santos Ortega Manuel , Esquerdo Gaspar , Cervera Grau Jose Manuel , Barrajon Enrique , Rodriguez Villalva Silvia , De Piaggio Marina , Peiro Rafael , De Sanctis Rita , Espinoza Venegas Macarena Paz 
Published: March 2020

e16025 Background: Due to hospital control difficulties of patients with HNC, a phase II with oral fluoropyrimidines was conducted. Oral administration of 5-FU itself is not feasible owing to the high activity of dihydropyridine dehydrogenase (DPD) in the gut wall. To bypass this problem, oral fluoropyrimidine derivatives were developed in the form of 5-FU prodrugs. This phase II Trial focuses on the oral 5-FU prodrug tegafur to allow similar responses and toxicities. On the other hand a secondary objective was to correlate the effect of CDDP that induces renal injury through multiple pathways. For that reason, the correlation between Mg/Cr and Toxicity was studied. Methods: From 2006 to 2011 seventeen patients with locally advanced head and neck carcinomas were treated in our institution. A phase II clinical trial was conducted as neoadjuvant treatment [docetaxel 75 m2 d-1, cisplatin 75 mgm2 d-1, and tegafur 800 mg twice daily for 14 days, administered every 21 days with GCSF support]. If tumor response, patients received radiotherapy (RT) 70 Gy concomitant with weekly cisplatin 25mg/m2. If no response, palliative surgery or RT or/second line of chemotherapy was administered.) Results: Sixteen were male, one female, three died (2 sepsis secondary to neutropenia grade IV/ 1 secondary to direct tumor complication after 1st course of chemotherapy). Only 14 patients were evaluable for response [mean age was 54,24]. Toxicity grade >2 was present in a range [13,33-21,43%]. Partial responses (PR) were present in 9 patients (52,94%), complete response or no evidence of disease in 3 (17,63%). After RT witth weekly cisplatin the diseas control was 70,57%. An association trend was detected between hypomagnesaemia and a greater toxicity. Conclusions: The implementation of an oral chemotherapy regimen has been feasible and effective with similar results to other studies. The idiosyncrasy of patients with HNC have kept their prized autonomy and independence. A new study is in progress to assess more accurately magnesium levels as predictors of severe toxicities when platinum is used.
Triweekly carboplatin alone in the treatment of oropharyngeal carcinoma with definitive concurrent chemoradiation: Outcomes of 120 unselected patients and a comparison to the RTOG 0129 regimen results.
Authors: Iganej Shawn , Buchschacher Gary L. , Abdalla Iman A. 
Published: March 2020

e16031 Background: In 2002, due to the significant toxicities associated with triweekly high-dose cisplatin, we decided to routinely use triweekly carboplatin in the treatment of locally advanced head and neck cancer patients as our standard definitive concurrent chemoradiation drug, the outcomes of which are reported here. Methods: From August of 2002 through May of 2009, newly diagnosed patients with stage III (22%) or IVA/B (78%) oropharyngeal squamous carcinoma were treated with carboplatin (AUC=5) x 3 on days 1, 22 and 43 along with concurrent conventional RT (N=67) or IMRT (N=53) to 70 Gy. Individuals treated with induction chemotherapy or definitive surgery of any kind prior to concurrent chemoradiation, and surviving/recurrence-free patients with less than 24 months of follow-up were excluded, leaving 120 patients for this analysis. The median age was 58 (range 42-85). Feeding tubes were not placed prophylactically. Planned post chemoRT neck dissections were not performed. HPV/P16 status was not determined in any patients prior to treatment. Seventy-one patients (59%) had a significant history of tobacco use, 38 of whom were current smokers. Results: With a median follow-up of 64 months (range 32-108) for surviving patients, 15 (12.5%) had a loco-regional recurrence (LR), and a total of 9 patients (7.5%) failed distantly, including one with simultaneous LR. Only 26 (22%) patients required feeding tubes during or shortly after (< 90 days) chemoRT; 90% received 3 cycles of carboplatin and planned RT dose was delivered in 98%. The 3-year loco-regional control and overall survival rates for the entire group were 88% and 82%, respectively; these rates for 92 patients eligible for RTOG 0129 (T2N2-3, T3-4 any N) were 86% and 77%. At last follow-up, only 3% were feeding-tube dependent. Conclusions: This first ever report of concurrent triweekly carboplatin alone with radiotherapy at a large U.S. institution for locally advanced oropharyngeal carcinoma suggests that it is better tolerated and more feasible than concurrent triweekly high-dose cisplatin, with similar/favorable disease control and survival rates.
Rapidly alternating chemotherapy and radiotherapy in advanced laryngeal cancers.
Authors: Hasegawa Yasuhisa , Fujimoto Yasushi , Yoshino Kunitoshi , Hanai Nobuhiro , Ozawa Taijirou , Hirakawa Hitoshi , Suzuki Hidenori , Ijichi Kei 
Published: March 2020

e16032 Background: Rapidly alternating chemotherapy and radiotherapy (ACR) is a minor variation of concurrent chemoradiation (CCR). This scheduling and 5-fluorouracil (5-FU) pretreatment followed by cisplatin (FP) treatment have been tested in advanced laryngeal cancers. ACR allows the simultaneous administration of both treatment modalities without increasing toxicity, while pretreatment with 5-FU induces long arrest in S-phase, and enhances cisplatin cytotoxicity (Cancer Chemother Pharmacol, 2008). We conducted a phase II clinical trial to evaluate these hypotheses. Methods: Eligibility: histologically proven squamous cell carcinoma of larynx with stage III or IV, PS 0-1, age <= 75, adequate organ functions, and no prior chemotherapy. Chemotherapy consisted of administration of continuous infusion of 5-FU at 700 mg/m2/day on days 1-5, and 2-hour infusions of cisplatin at 80 mg/m2/day on day 6 (1st week). Once-daily radiotherapy of 36 Gy in 18 fractions was given starting on day 8 (2nd -5th week). Sequentially, FP treatment was repeated twice (6th week) for responders, and radiotherapy of 30 Gy in 15 fractions was given (7-9th week) in total 66 Gy. Results: From 4/2007 to 11/2010, 27 patients (pts) were enrolled. Patient characteristics were median age of 67 (49-74) years; gender, 26 male and 1 female; subsite, glottis 16 pts (59%) and supraglottis 11 (41%); stage, III 15 pts (56%), IV 12 (44%). 23 responders (85%) completed radiotherapy, and of them 20 pts (87%) received two courses of chemotherapy. 20 primary sites (74%) achieved CR by ACR. 4 non-responders (15%) underwent early salvage surgery. 7 pts had salvage surgery and neck dissection. Toxicity was assessed in all pts: 12 grade 3 events (44%; nausea 7, mucositis 4 (15%) and dermatitis 1). There have been no hematological grade 3 or 4 toxicities. The 3-year overall survival and laryngeal preservation rate were 88% and 65%, respectively. Conclusions: In this ACR trial, the rate of mucosal toxicity was equivalent to or less than those with radiotherapy alone, and the laryngeal preservation was equivalent to CCR in spite of 60% glottic carcinomas.
Feasibility of 6 months of maintenance cetuximab after adjuvant concurrent chemoradiation plus cetuximab in squamous cell carcinoma of the head and neck (HNC).
Authors: Matuschek Christiane , Boelke Edwin , Debus Jürgen , Belka Claus , Welz Stephan , Henke Michael , Wendt Thomas , Ohmann Christian , Stegmaier Petra , Bamberg Michael , Wiegel Thomas , Budach Volker , Schipper Joerg , Budach Wilfried 
Published: March 2020

e16033 Background: The prognosis for HNC patients (pts) after surgical treatment and adjuvant chemoradiation (CRT) is unsatisfactory in case of close resection margin <5 mm (CM) or extra capsular extent at the lymph nodes (ECE). Therefore we conducted a multicenter phase II study to investigate the toxicity and efficacy of adjuvant radiotherapy (RT) in combination with concurrent cisplatin, 5- fluorouracil (5FU), and cetuximab (CTX) followed by maintenance therapy with CTX for 6 months. Here, we present the preliminary results on feasibility and toxicity. Methods: HNC pts after primary surgery were eligible for the study, if a CM or ECE was detected. Cisplatin [20 mg/m2 d1-5 and d29-33] and 5-FU (CI 600 mg/m2 d1-d5 + d29-33) were given concurrently to postoperative RT using an integrated boost IMRT-technique (1.8/2.0/2.2Gy QD) to a total dose of 61.6 Gy. CTX started 7 days prior CRT with a loading dose of 400 mg/m2 followed by weekly CTX (250 mg/m2) during CRT. Maintenance CTX started after completion of CRT plus CTX with 500 mg/m² every 2 weeks over a 6-month period. Results: 55 of 80 planned pts (46 male, 9 female, mean age 55.6, range 29-70 years) have finished CRT, 50 are evaluable for toxicity. Concurrent CRT plus CTX was associated with grade 3-4 (CTC 3.0) mucositis, radiation dermatitis, and skin reaction outside the radiation portals in 46%, 28%, and 14% of pts, respectively. One toxic death occurred (peritonitis at day 57). CTX was terminated in 10% of all pts (allergic reactions) after the first application. In 22% of all pts CTX was discontinued during the last 2 weeks or at the end of CRT. Of those pts embarking on maintenance therapy, 80% were still on CTX after 3 and 63% after 5 months. 48% completed 6 months maintenance therapy. Conclusions: Adjuvant CRT in combination with CTX followed by maintenance CTX is feasible with toxicity in the expected range. Compliance to maintenance CTX was satisfactory during the first 3-5 months.
Phase II study of postperative radiotherapy (RT), cisplatin (Ci), and cetuximab (Ce) in resected bad prognostic head and neck squamous cell carcinoma (HNSCC): Toxicity analysis.
Authors: Benezery Karen , Righini Christian , Chamorey Emmanuel , Lallemant Benjamin , le Caer Herve , Darloy Franck , Guelfucci Bruno , Dupuis Charlotte , Dassonville Olivier , Peyrade Frederic 
Published: March 2020

e16051 Background: Despite toxic multimodal about 60% of resected HNSCC relapse. The addition of both Ce or Ci to RT improved overall survival of patients with HNSCC. Consequently, we designed a prospective phase II study, to evaluate the feasibility and efficacy of concomitant RT-Ci and Ce in bad prognostic resected HNSCC. Methods: Patients have resected HNSCC of the oral cavity , oropharynx, larynx or hypopharynx, and at least one of the following adverse prognostic factors: microscopically incomplete resection, >2 metastatic lymph nodes and/or >1 lymph node with extracapsular spread, vascular and/or lymphatic emboli, >2 perineural invasion, positive margins and pT4. All patients received: RT 70-72Gy in 7 weeks concurrent with Ce 250mg/m² weekly (6-7 weeks), after a loading dose of 400mg/m², and Ci 75mg/m² every 3 weeks x3 cycles. The primary endpoint is the 2 years disease-free survival. Results: 45 patients (35 Male) were enrolled, and 44 were evaluable for toxicity. Median age was 56 years (27-70). The tumor site was oral cavity (21), oropharynx (17), hypopharynx (3) and larynx (4). 39% of the patients had stage T2, 14% stage T3 and 27% stage T4. The nodal status was 0-2b in 80% of cases. The main adverse prognostic factors were the nodal involvement and microscopical positive resection (80% of patients). The RT-Ce-Ci regimen was discontinued in 11 cases including 7 due to toxicity. Among the 352 cycles (ie Ce+/-Ci) initially planned, 301 were delivered. Cutaneous and mucosal toxicity were the most common grade 3/4 side effects, accounting for 35% and 33%, respectively, and remained manageable. Grade 3 lymphopenia has been noted in 25% of cases. No treatment-related death was recorded. Conclusions: The triple association of RT-Ce-Ci appears to be safe and feasible in patients with bad prognostic resected HNSCC. The toxicity profile is comparable to that reported for RT-Ci or RT-Ce alone. Longer follow-up is required to evaluate the impact of addition of Ce to RT-Ci on survival.
Prospective analysis of qol in patients undergoing concurrent chemotherapy and radiation therapy for locally advanced head and neck cancer.
Authors: Blakaj Dukagjin , Godoy-Scripes Paola , Skinner William Kempton , Viswanathan Shankar , Haynes Hilda , Eng Yoko , Sarta Catherine , Haigentz Missak , Schiff Bradley A. , Smith Richard V. , Guha Chandan , Kalnicki Shalom , Garg Madhur 
Published: March 2020

e16058 Background: This is a prospective analysis of quality of life (QoL) in patients undergoing concurrent chemotherapy and IMRT for locally advanced head and neck cancers. Methods: In a prospective IRB approved study, patients undergoing concurrent chemotradio therapy for head and neck cancers at AECOM/MMC completed a QoL survey (EORTC QLQ-C30 and QLQ-H&N 35) pretreatment, during radiation therapy, and at 1, 3 and 6 months after completion. The patients were re-simulated for adaptive planning midway through their treatment. Patients were treated to 66-70Gy (2-2.12 Gy/Fraction) to the primary and 54 to 60Gy (1.64-1.8 Gy/fraction) to the subclinical and high risk areas. Swallowing complex (SC) (base of tongue, constrictor muscles, proximal esophagus and oral cavity) were contoured as avoidance structures along with other critical structures. QoL scores were correlated with radiation dose to swallowing complex to evaluate relationships. Results: The Global Heath Status and Physical Functioning scores fell (mean 58.33 SD 35.36) during the first week of therapy before recovering at the end of second week. There is a 2nd dip in functioning scores at 4th week subsequent to which the scores rise and stabilized. The nausea/vomiting scores correlate with the timing of chemotherapy whereas the pain scores are highest at the second week mark before declining gradually. The mean swallowing specific score is worst at 5 weeks (61.11 SD 31.43) and recover gradually thereafter to level better than pre-RT score at 6-months follow-up. Conclusions: Most studies have reported QoL changes before and after treatment and have not looked at the changes during RT. One would imagine that QoL scores would gradually deteriorate throughout radiation therapy and should be the worst towards the end. In our experience, most of the QoL scores stabilize during the latter half of radiation therapy. This may be a result of multidisciplinary patient care, adaptive radiation therapy as well as tumor response to chemo-radiation therapy. Matched pair analysis is underway to compare dosimetric data and correlate this with QoL results.
Disparities in quality-of-life outcomes in immigrant cancer patients.
Authors: Goldstein David , Sze Ming , Bell Melanie , King Madeleine , Jefford Michael , Eisenbruch Maurice , Girgis Afaf , Vaccaro Lisa , Butow Phyllis Noemi 
Published: March 2020

e16507 Background: Immigration is increasing world-wide. We explored disparities in quality of life outcomes for immigrant (IM) versus Anglo-Australian (AA) cancer patients having anti-cancer treatment. Methods: In a cross-sectional design, cancer patients were recruited through outpatient Oncology clinics in New South Wales, Victoria, and the Northern Territory in Australia. IM participants, their parents and grand parents were born in a country where Chinese, Greek, or Arabic is spoken and spoke one of those languages. AAs were born in Australia and spoke English. All were diagnosed with cancer < 1 year previously. Questionnaires (completed in preferred language) included the Hospital Anxiety and Depression Scale (anxiety/depression), FACT-G (quality of life) and the Supportive Care Needs Survey (unmet needs). Adjusted regression models comparing AA and IM groups included age, gender, socio-economic status, education, marital status, religion, time since diagnosis, and cancer type (colorectal, breast, lung, other). Results: There were 910 participants (response rate 57%). IM were similar to AA, except that IM were more likely to be married (76 vs 67 %, p = 0.01) and in the low and the highly educated groups (p < 0.0001). In adjusted analyses, IMs had clinically significant higher anxiety, greater unmet information and physical needs and lower quality of life than AAs (see table). The possible ranges are 0-21 for anxiety and depression, and 0-100 otherwise. Conclusions: In this hospital-based study with a high rate of advanced disease, immigrants with cancer experienced poorer quality of life outcomes, even after adjusting for socio-economic, demographic, and disease variables. Interventions are required to improve their experience of cancer care. Results highlight areas of unmet need that might be better addressed by the health system (particularly with regards to provision of information and meeting support and physical needs). [Table: see text]
Did FDA safety warnings and CMS coverage restrictions improve guideline adherence for ESA use for patients with myelodysplastic syndromes?
Authors: Hendrick Franklin , Baer Maria R. , Gore Steven , Weiss Smith Sheila , Davidoff Amy J. 
Published: March 2020

e16519 Background: ESAs are used to treat anemia associated with MDS as an off-label indication. Our prior research demonstrated poor adherence to MDS treatment guidelines in US Medicare-insured patients. Concerns of adverse events including tumor progression led the FDA to release safety alerts and mandate label changes in early ‘07. In a rare move, CMS implemented a National Coverage Determination (NCD) in August ‘07, dramatically restricting ESA coverage based on specific clinical parameters (e.g. baseline hemoglobin). As MDS patients were not directly targeted by the NCD, we sought to examine if ESA use changed following these actions. Methods: We selected Medicare beneficiaries with MDS diagnostic codes and receiving a bone marrow aspirate based on 100% enrollment and claims data from 2004-2008. Patients were observed from diagnosis until death or end of study. Through procedures codes on claims we determined the receipt of any ESA within 6 months of diagnosis, whether serum EPO level was measured prior to ESA initiation, whether treatment was of therapeutic duration (>=8 weeks), and whether patients had low transfusion needs (defined based on a measure of transfusion dependence) at ESA initiation. Logistic regression models tested the effect of time (half-year increments pre-post the August ‘07 CMS NCD implementation), controlling for demographics, health status, and supplemental insurance Results: The sample included 36,537 MDS patients; 23,351 (64%) with ESA use. Regression results indicate that relative to Jan-June 2005, ESA use increased through ‘06 (OR 1.22, 95% CI 1.12, 1.33), and declined beginning in August ‘07 (OR 0.71,CI:0.65,0.77). Assessment of serum EPO levels increased beginning in January ‘06, preceding the FDA/CMS actions, ESA use increased among transfusion-users throughout the study period (Jan-June ’08 OR 1.59; CI 1.43, 1.77) though the proportion of patients receiving therapeutic-duration episodes began declining in Jan ‘07 (OR 0.82; CI 0.73-0.91). Conclusions: These results suggest a mixed pattern of change in the face of the FDA safety warnings and CMS NCD in MDS.