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Purpose of review We review the new systemic treatment strategies for differentiated thyroid carcinoma, as well as the acquaintance of its molecular biology. Recent findings Multiple kinase inhibitor drugs have become the standard therapy for thyroid cancer, albeit several adverse effects. In the last few years, new molecules have raised with an overall safety profile. Most of them, are considered targeted therapies directed toward driven-molecules alterations, such as neurotrophic tyrosine kinase receptor (NTRK) inhibitors for NTRK-fusion thyroid cancer and rearranged during transfection (RET) inhibitors for RET-fusion thyroid cancer. Recently, promising outcomes and safety data have been presented. Furthermore, other novel strategies for advanced thyroid carcinoma are currently investigated in clinical trials.The ability to provide precision medicine to patients in routine clinical settings depends on the availability of molecular profiling test at their cancer centers. The impossibility to perform molecular characterization could turn out to be a diagnostic and treatment limitation for some patients. Summary The treatment of advanced differentiated thyroid carcinoma has undergone rapid evolution in the last decade. An emerging treatment era is coming. From now to then, we will need to face the different types of diagnostic tools for molecular characterization, their interpretation and, finally the access to targeted therapies.

Background Our previous phase-3 study (TTCC 2503) failed to show overall survival advantage of 2 induction chemotherapy (IC) regimens followed by standard concurrent chemoradiotherapy (CRT) over CRT alone in patients with unresectable locally advanced head and neck squamous-cell carcinoma (LAHNSCC). This study described the long-term survival of those patients. Materials and methods Long-term follow-up study of patients with untreated LAHNSCC assigned to IC (three cycles), with either docetaxel, cisplatin and 5-fluorouracil (TPF arm) or cisplatin and 5-fluorouracil (PF arm), followed by CRT, or CRT alone, included in the previous TTCC 2503 trial. Results In the intention-to-treat population (n = 439), the median OS times were 25.4 (95% CI, 16.8-34.4), 26.2 (95% CI, 18.2-36.6) and 25.4 months (95% CI, 17.4-36.0) in the TPF-CRT, PF-CRT and CRT arms, respectively (log-rankp = 0.51). In the per-protocol population (n = 355), patients with larynx-hypopharynx primary tumors treated with IC (TPF or PF) followed by CRT had a longer median PFS than those who received CRT alone. Moreover, patients with ECOG 0 treated with IC (TPF or PF) followed by CRT had a better TTF than those with CRT alone. There were no statistically significant differences in terms of OS, PFS or TTF, according to the tumor load or affected nodes. Conclusion After a long follow-up, the TTCC 2503 trial failed to show the benefit of IC-CRT in unresectable LAHNSCC regarding the primary end point. However, fit patients with ECOG 0 and primary larynx-hypopharyngeal tumors may benefit from the use of IC if administered by an experienced team. ClinicalTrials.gov identifierNCT00261703

To evaluate the importance of larynx compartments in the prognosis of T3-T4a laryngeal cancer treated with transoral laser microsurgery. Background: To evaluate the importance of larynx compartments in the prognosis of T3-T4a laryngeal cancer treated with transoral laser microsurgery. Methods: Two hundred and two consecutive pT3-T4a larynx carcinomas. Pre-epiglottic space involvement, anterior and posterior paraglottic space (PGS) involvement, vocal cord, and arytenoid mobility were determined. Local control with laser (LC), overall survival (OS), disease-specific survival (DSS), and laryngectomy-free survival (LFS) were evaluated. Results: The lowest LC was found in tumors with fixed arytenoid. In the multivariate analysis, positive margins (hazard ratio [HR] = 0.289 [0.085-0.979]) and anterior (HR = 0.278 [0.128-0.605]) and posterior (HR = 0.269 [0.115-0.630]) PGS invasion were independent factors of a reduced LC. Anterior (HR = 3.613 [1.537-8.495]) and posterior (HR = 5.195 [2.167-12.455]) PGS involvement were independent factors of total laryngectomy. Five-year OS, DSS, and LFS rates were 63.9%, 77.5%, and 77.5%, respectively. Patients with posterior PGS presented a reduced 5-year LFS. Conclusions: Tumor classification according to laryngeal compartmentalization depicts strong correlation with LC and LFS.

358 Background: Currently, no specific measures are used in Spain to evaluate quality of care in head and neck cancer, and programs such as the Quality Oncology Practice Initiative developed by the American Society of Clinical Oncology does not include head-and-neck-specific measures. Methods: A systematic literature review was carried out to identify measures useful for evaluating quality of care in head and neck cancer. A scientific committee, comprising 9 medical oncologists specialized in head and neck cancer, reviewed the literature findings and developed measures to be evaluated in a 2-step Delphi method. Experts in head and neck cancer practicing in Spain—specialized in medical oncology, radiotherapy oncology, maxillofacial surgery, pathology or otorhinolaryngology—participated in the Delphi, scoring the appropriateness of the measures using a 9-point Likert scale (1, extremely inappropriate; 9, extremely appropriate). Consensus was defined as at least two-thirds of Delphi respondents selecting a score sub-category (1–3, 4–6, or 7–9) that encompassed the median score of the group. Results: Out of the 833 documents found with the literature review, 20 were selected from to identify measures of interest. Fifty measures, covering diagnosis (13), treatment (28), follow-up (5), and outcome (4), were evaluated with the Delphi method. The 52 Delphi participants reached consensus on the appropriateness of using all 50 measures to evaluate the quality of care in head and neck cancer. Measures with lowest scores concerned re-hospitalization shortly after surgery and long hospitalization after surgery. Measures with highest scores regarded the use of imaging for follow-up, a histology study prior to treatment, and complete resection of the tumor. The scientific committee then selected 29 measures based on their applicability and cost-effectiveness and developed index cards with definitions, formulas, acceptable level of attainment, and rationale for their use in clinical practice. Conclusions: The goal of this study was to develop measures to evaluate and improve the quality of care in head and neck cancer. These results show unanimous consensus from a group of experts on the proposed measures for diagnosis, treatment, follow-up, and outcome. The index cards developed with measures are easy to follow and their use could improve quality of care.

Concurrent chemoradiotherapy is the standard treatment for patients with unresectable, locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN); induction chemotherapy (ICT) may provide survival benefits in some patients. This study aimed to demonstrate the noninferiority of concomitant cetuximab plus radiotherapy (cet+RT) vs cisplatin plus radiotherapy (cis+RT) in patients with unresectable LA-SCCHN who were responsive to ICT.This randomized, open-label, phase 3 trial studied patients with unresectable LA-SCCHN who received 3 cycles of ICT (docetaxel, cisplatin, and 5-fluorouracil; TPF) followed by cis+RT (standard arm) or cet+RT (experimental arm). The primary endpoint was noninferiority of the experimental arm vs the standard arm in terms of overall survival (OS), based on a hazard ratio (HR) of lt; 1.3. Secondary endpoints included progression-free survival, overall response, safety, and quality of life (QOL).Between July 15, 2008, and July 5, 2013, 519 patients were recruited and started ICT; 407 patients received post-ICT treatment (cis+RT, n = 205; cet+RT, n = 202). At a median follow-up of 43.9 (cis+RT) and 41.1 (cet+RT) months, median OS was 63.6 and 42.9 months with cis+RT and cet+RT, respectively (HR [90% CI] = 1.106 [0.888-1.378], P =.4492). There were no differences in progression-free survival, overall response rates, or adverse event rates between groups. There was greater late neurotoxicity with cis+RT than cet+RT (P =.0058). Several QOL dimensions improved with cet+RT vs cis+RT (physical functioning, P =.0287; appetite loss, P =.0248; social contact, P =.0153).Noninferiority of cet+RT over cis+RT was not demonstrated.

Objectives: In the EXTREME trial, a combination of cisplatin or carboplatin plus 5-fluorouracil (5-FU) and cetuximab was superior to cisplatin/carboplatin plus 5-FU for first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). With the aim of improving fluoropyrimidine-related tolerance without decreasing its efficacy, the safety and efficacy of carboplatin plus the oral fluoropyrimidine tegafur and cetuximab were investigated. Methods: A retrospective analysis of 104 patients with recurrent or metastatic HNSCC was conducted. Patients were treated with carboplatin (area under the curve: 5 mg/mL/min) on day 1, oral tegafur (250 mg/m2 twice daily) for 21 consecutive days, and cetuximab (400 mg/m2 as an initial 2-hour intravenous infusion, then 250 mg/m2 as a 1-hour weekly infusion for 3 weeks) for ≤6 cycles. Patients who responded to the therapy then received weekly cetuximab maintenance therapy. Results: Treatment was well tolerated with a high level of compliance (relative dose intensity: 96%, 88%, and 81% for carboplatin, tegafur, and cetuximab, respectively). Grade 3-4 adverse events (AEs) were observed in 38% of patients (skin reactions in 17% of patients, anemia 4%, and neutropenia 3%). Grade 1-2 AEs included skin reactions (52% of patients), hypomagnesemia (20%), asthenia (19%), and anemia (13%). No venous thrombosis related to chemotherapy perfusion was observed. Over a median follow-up of 21 months, the median overall and progression-free survival were 11 and 6 months, respectively, and the overall response rate was 35%. Conclusions: Carboplatin plus oral tegafur and cetuximab is a safe, well-tolerated first-line therapy for recurrent or metastatic HNSCC.

Sinonasal tumors are rare neoplasms with distinctive clinical, aetiological and pathological features. The diagnosis and treatment of these tumors is challenging because of their low incidence, histological diversity and production of nonspecific symptoms in the early stages. They have a variable prognosis depending on their histology, origin and staging. Their location, close to neurocritical structures, which are of special relevance to surgery and postoperative treatment, makes their treatment difficult and complex, leading to high morbidity and mortality. Surgery followed by radiotherapy is the mainstay of treatment. To provide the best possible care, patients with sinonasal cancer should be treated in clinical referral centres specialising in skull-base pathologies. Such centres should include a multidisciplinary team led by otolaryngologist surgeons. This article outlines a consensus protocol for the management of these tumors devised by the Spanish Society of Otolaryngology in collaboration with the Spanish Society of Medical Oncology and the Spanish Society for Radiation Oncology.

Sinonasal tumors are rare neoplasms with distinctive clinical, aetiological and pathological features. The diagnosis and treatment of these tumours is challenging because of their low incidence, histological diversity and production of non-specific symptoms in the early stages. They have a variable prognosis depending on their histology, origin and staging. Their location, close to neurocritical structures, which are of special relevance to surgery and postoperative treatment, makes their treatment difficult and complex, leading to high morbidity and mortality. Surgery followed by radiotherapy is the mainstay of treatment. To provide the best possible care, patients with sinonasal cancer should be treated in clinical referral centres specializing in skull-base pathologies. Such centres should include a multidisciplinary team led by otolaryngologist surgeons. This article outlines a consensus protocol for the management of these tumours devised by the Spanish Society of Otolaryngology in collaboration with the Spanish Society of Medical Oncology and the Spanish Society for Radiation Oncology.

Objectives: To analyze the role of audiometry in considering change to a less ototoxic treatment in head and neck cancer (HNC) patients. Methods: Consecutive patients prescribed high-dose cisplatin (100 mg/m2) between January 2013 and February 2015 were enrolled. Audiometry was performed at baseline and before cisplatin. Change to a less ototoxic agent or reduced cisplatin dose was considered with audiometric decreases >25 dB. Results: A total of 103 patients were included; the median age of the patients was 59 years (range 18−75). Cisplatin was intended curative (58%), adjuvant (32%), or palliative (10%). Forty-two participants (41%) did not commence high-dose cisplatin because of baseline audiometric alterations. Of 61 patients treated with high-dose cisplatin, 40 (66%) showed marked ototoxicity at the end of treatment. The mean hearing loss between initial and final audiometries showed a hearing loss at 4 and 8 kHz in both ears (p = 0.002). Thirteen patients switched to carboplatin and 15 to a lower dose of cisplatin. The outcome was not significantly altered when cisplatin was replaced with carboplatin or cetuximab. Conclusions: Audiometric alterations are common in HNC with high-dose cisplatin, and switching to a less ototoxic regimen does not adversely affect outcome. Audiometric examination could help to prevent hearing loss in this population.

Among surgical procedures currently in use, tracheostomy has a particularly long history. The first written description of the procedure is due to Brasavola, and dates from 1546. Piero di Cosimo (1462-1522) was an early Renaissance painter who painted a work traditionally known as Cephalus and Procris or The Death of Procris (1495-1500). In this painting, a vertical tracheostomy can be observed in a young woman lying on the ground. A giant mass can be seen in the lower left neck with superficial venous vessels, suggesting a thyroid malignancy. This appears to be the first detailed depiction of a malignant cervical mass and a possibly therapeutic tracheostomy. We discuss the clinical differential diagnosis and also make some comments from an art history perspective.

Background Controversy exists regarding treatment of advanced laryngeal cancer. The purpose of this study was to evaluate the oncologic and functional outcomes of T3 to T4a supraglottic squamous carcinomas treated with transoral laser microsurgery (TLM). Methods We conducted a retrospective analysis from an SPSS database. Primary outcomes were: locoregional control, overall survival (OS), disease-specific survival (DSS), laryngectomy-free survival, and function-preservation rates. Secondary objectives were: rate of tracheostomies and gastrostomies according to age. Risk factors for local control and larynx preservation were also evaluated. Results One hundred fifty-four consecutive patients were chosen for this study. Median follow-up was 40.7 + /- 32.8 months. Five and 10-year OS, DSS, and laryngectomy-free survival were 55.6% and 47%, 67.6% and 58.6%, and 75.2% and 59.5%, respectively. Paraglottic involvement was an independent factor for larynx preservation. Six patients (3.9%) needed a definitive tracheostomy, a gastrostomy, or both. The gastrostomy rate was higher in the group of patients above 65 years of age (p = .03). Five-year laryngectomy-free survival with preserved function was 74.5%. Conclusion TLM constitutes a true alternative for organ preservation in locally advanced supraglottic carcinomas with good oncologic and functional outcomes. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

Purpose Despite treatment, prognosis of unresectable squamous cell carcinoma of the head and neck (SCCHC) is dismal. Cetuximab therapy has proven to increase the clinical activity of radiation therapy and chemotherapy in patients with locoregional advanced disease with an acceptable toxicity profile. We designed a phase 2 trial to evaluate the efficacy of docetaxel, cisplatin, and 5-fluorouracil (TPF) plus cetuximab (C-TPF) as an induction regimen in patients with unresectable SCCHN. Methods and Materials A single-arm phase 2 trial was conducted. Eligible patients included those with untreated unresectable SCCHC, World Health Organization performance status of 0 to 1, 18 to 70 years of age. Treatment consisted of four 21-day cycles of TPF (docetaxel, 75 mg/m 2 day 1; cisplatin, 75 mg/m 2 day 1; 5-fluorouracil [5-FU], 750 mg/m 2 day 1-5) and cetuximab, 250 mg/m 2 weekly (loading dose of 400 mg/m 2 ). Prophylactic granulocyte colony-stimulating factor and antibiotic support were given. After induction, sequential accelerated radiation therapy with concomitant boost (69.9 Gy) and weekly cetuximab therapy were delivered in the absence of disease progression. The primary endpoint was objective response rate (ORR) to C-TPF. Results Fifty patients were enrolled across 8 centers. Median age was 54 years; disease was stage IV; oropharynx and hypopharynx were the most common primary sites. Eighty-two percent received 4 cycles of C-TPF, and 86% started sequential treatment based on radiation therapy and cetuximab. ORR after C-TPF was 86% (95% confidence interval [CI]: 73%-94%) and 24% had complete response (CR). With a median follow-up of 40.7 months, median overall survival (OS) was 40.7 months. The 2-year actuarial locoregional control (LRC) rate was 57%. The most common drug-related grade 3 or 4 toxicities during induction were neutropenia (24%), neutropenic fever (24%), and diarrhea (20%). There were 3 treatment-related deaths (6%). Conclusions C-TPF yields high ORR and CR as induction treatment in unresectable SCCHN. However, hematologic toxicity is too high to recommend this regimen at the current dose.

Recurrent respiratory papillomatosis (RRP) is a chronic disease caused by human papillomavirus (HPV). RRP is a clinical challenge because of the high recurrence rate, poor surgery response, extension to tracheobronchial tree and because of the risk of malignancy in some cases. There is no consensus on which adjuvant therapy is better for those patients with highly recurrent course. Because papilloma cells overexpress the epidermal growth factor receptor (EGFR), together with an increased expression of COX-2 and prostaglandin E2, the combination of erlotinib and celecoxib seems plausible, and could be proposed for patients with poor response to previous lines of treatment.

Administration of external beam radiotherapy (EBRT) for a bulky recurrence or primary bulky tumor of differentiated thyroid carcinoma (DTC) is rare. No previous experience is available on the feasibility of administering EBRT simultaneously with systemic treatment with doxorubicin or sorafenib, or both. The present case study reported the results from two different institutions on 5 consecutive patients. Side effects and tolerance to radiotherapy plus systemic treatment with doxorubicin (20 mg/m2 intravenously weekly for 6/8 consecutive weeks) or sorafenib (400 mg/12 h orally for 8 weeks) or both, were analyzed in patients with DTC. The local response to radiotherapy and patient outcome was also analyzed. A total of 4 males and 1 female, aged 37–62 years with cervical bulky mass DTC were included. The pathological tumor types were papillary (2 patients), follicular (2 patients) and medullar thyroid carcinoma (1 patient). The radiated cervical mass was local recurrence in 3 cases and primary tumor in the other two. The total dose of radiotherapy ranged between 50 and 64.8 Gy. Three patients received sorafenib, 1 patient received doxorubicin and 1 patient received both treatments. The total planned dose of radiotherapy was administered to all patients. Grade 2 anemia and erythrodysesthesia was the most frequent toxicity. Only the patient who received doxorubicin plus sorafenib had grade 3 toxicity consisting of lymphopenia, folliculitis and mucositis. All but 1 patient had a good local response to radiotherapy. The administration of EBRT concurrently with sorafenib and doxorubicin to patients with DTC with a bulky cervical mass is feasible.

BACKGROUND Indications of transoral laser microsurgery (TLM) are conditioned by the risk of local relapse. OBJECTIVE To evaluate prognostic factors of local relapse and local control with TLM (LC-TLM). METHODS Local relapse and LC-TLM were evaluated in 1119 patients. Logistic regression and CHAID decision tree analysis were performed. RESULTS Local relapse correlated to previous radiotherapy failure (8.45, CI 95%: 2.64-27.03; P

Aim Electrochemotherapy is an effective local treatment for cutaneous tumours and metastases. In this prospective trial, six European institutions investigated electrochemotherapy in recurrent, mucosal head and neck tumours. Patient and methods Forty-three patients with recurrent mucosal head and neck tumours and no further curative or reasonably effective palliative treatment options were enrolled and treated with electrochemotherapy. Patients were treated in general anaesthesia using intravenous or local injection of bleomycin followed by delivery of electric pulses to the tumour area. Primary end-point was local tumour response. Secondary end-points were safety and toxicity, overall and progression free survival, and quality-of-life. Results Thirty-seven patients were evaluable for tumour response, pain score, side-effects and quality of life questionnaires. Six patients were not evaluable due to lost follow-up, disease progression or death before evaluation. Intention to treat analysis revealed an objective response of 56% (complete response 8 (19%), partial response 16 (37%), stable disease 10 (23%), progressive disease 3 (7%), and not evaluable 6 (14%)). Three patients (7%) remained in complete response at 30, 34, and 84 months post-treatment. The treatment procedure was generally well tolerated. Swelling of the mucosa was observed in the first days after treatment. Pain and use of pain medication rose temporarily; fatigue and dysphagia were also noted in the quality of life assessment. Conclusion Electrochemotherapy can be applied to mucosal head and neck recurrent tumours accessible to the procedure with promising objective response, survival and toxicity profile. Attention should be paid to post-treatment swelling and planning of pain medication. These favourable results indicate that electrochemotherapy could play a role in patients with recurrent head and neck cancer.

Although cetuximab plus radiotherapy is a standard treatment for patients with inoperable head and neck squamous cell carcinoma (HNSCC), its efficacy varies greatly among individuals. To identify predictive markers of efficacy, we examined the effects of single nucleotide polymorphisms (SNPs) in hypoxia-related and DNA repair genes on the clinical outcome and occurrence of skin toxicity. We analyzed 61 consecutive patients with HNSCC for the presence of specific SNPs (HIF-1α, HIF-2α, HIF-1β, VHL, FIH-1, XRCC1, and XRCC5). The results were then correlated with time to progression (TTP), overall survival (OS), and toxicity (epithelitis, mucositis, and folliculitis). The median TTP and OS were better in patients with severe vs mild mucositis (17 vs 7 months, p = 0.03; and 26 vs 12 months, p = 0.016, respectively) and folliculitis (10 vs 7 months, p = 0.01, and 26 vs 10 months, p

Background In the phase III LUX-Head & Neck 1 (LUX-H&N1) trial, second-line afatinib significantly improved progression-free survival (PFS) versus methotrexate in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Here, we evaluated association of prespecified biomarkers with efficacy outcomes in LUX-H&N1. Patients and methods Randomized patients with R/M HNSCC and progression following ≥2 cycles of platinum therapy received afatinib (40 mg/day) or methotrexate (40 mg/m2/week). Tumor/serum samples were collected at study entry for patients who volunteered for inclusion in biomarker analyses. Tumor biomarkers, including p16 (prespecified subgroup; all tumor subsites), EGFR, HER2, HER3, c-MET and PTEN, were assessed using tissue microarray cores and slides; serum protein was evaluated using the VeriStrat® test. Biomarkers were correlated with efficacy outcomes. Results Of 483 randomized patients, 326 (67%) were included in the biomarker analyses; baseline characteristics were consistent with the overall study population. Median PFS favored afatinib over methotrexate in patients with p16-negative [2.7 versus 1.6 months; HR 0.70 (95% CI 0.50–0.97)], EGFR-amplified [2.8 versus 1.5 months; HR 0.53 (0.33–0.85)], HER3-low [2.8 versus 1.8 months; HR 0.57 (0.37–0.88)], and PTEN-high [1.6 versus 1.4 months; HR 0.55 (0.29–1.05)] tumors. Afatinib also improved PFS in combined subsets of patients with p16-negative and EGFR-amplified tumors [2.7 versus 1.5 months; HR 0.47 (0.28–0.80)], and patients with p16-negative tumors who were EGFR therapy-naïve [4.0 versus 2.4 months; HR 0.55 (0.31–0.98)]. PFS was improved in afatinib-treated patients who were VeriStrat ‘Good’ versus ‘Poor’ [2.7 versus 1.5 months; HR 0.71 (0.49–0.94)], but no treatment interaction was observed. Afatinib improved tumor response versus methotrexate in all subsets analyzed except for those with p16-positive disease (n = 35). Conclusions Subgroups of HNSCC patients who may achieve increased benefit from afatinib were identified based on prespecified tumor biomarkers (p16-negative, EGFR-amplified, HER3-low, PTEN-high). Future studies are warranted to validate these findings. Clinical trial registration NCT01345682.

Background Axitinib, an antiangiogenic multikinase inhibitor (MKI), was evaluated in the compassionate use programme (CUP) in Spain (October 2012–November 2014). Subjects and Methods 47 patients with advanced radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC, n = 34) or medullary thyroid cancer (MTC, n = 13) with documented disease progression were treated with axitinib 5 mg b.i.d. The primary efficacy endpoint was objective response rate (ORR) by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. Progression-free survival (PFS) and adverse events (AEs) were secondary objectives. Regulatory authorities validated the CUP, and all patients signed informed consent form. Results Axitinib was administered as first-line therapy in 17 patients (36.2%), as second-line in 18 patients (38.3%) and as third/fourth-line in 12 patients (25.5%). With a median follow-up of 11.5 months (0–24.3), ORR was 27.7% (DTC: 29.4% and MTC: 23.1%) and median PFS was 8.1 months (95% CI: 4.1–12.2) (DTC: 7.4 months (95% CI: 3.1–11.8) and MTC: 9.4 months (95% CI: 4.8–13.9)). Better outcomes were reported with first-line axitinib, with an ORR of 53% and a median PFS of 13.6 months compared with 16.7% and 10.6 months as second-line treatment. Twelve (25.5%) patients required dose reduction to 3 mg b.i.d. All-grade AEs included asthenia (53.2%), diarrhoea (36.2%), hypertension (31.9%) and mucositis (29.8%); grade 3/4 AEs included anorexia (6.4%), diarrhoea (4.3%) and cardiac toxicity (4.3%). Conclusion Axitinib had a tolerable safety profile and clinically meaningful activity in refractory and progressive thyroid cancer regardless of histology as first-line therapy. To our knowledge, this is the first time that cross-resistance between MKIs is suggested in thyroid cancer, highlighting the importance of prospective sequential clinical studies.

Thyroid cancer (TC) is the most common type of endocrine malignancy and accounts for nearly 3 % of all malignancies. The incidence of TC in Spain was 5/100,000 in women and 1.9/100,000 in men in 2013. The diagnosis of TC usually follows the identification of a thyroid nodule on physical examination or as an incidental finding on diagnostic imaging performed for other reasons. In most of the cases, the prognosis is excellent but despite low mortality rates, local recurrence occurs in up to 20 %, and distant metastases can occur in approximately 10 % at 10 years. The better knowledge of molecular biology of TC has allowed to the development of new targeted agents directed to the main pathways involved in TC pathogenesis. Knowing all these new strategies will help us face the therapeutic management of TC more effectively.

Electrochemotherapy is an effective and safe method for local treatment of cutaneous and subcutaneous tumours, where electric pulses cause increased permeability of cell membranes in the tumour mass, enabling dramatically enhanced effectiveness of bleomycin and other hydrophilic drugs. Here, we report results of a European multi-institutional prospective study of the effectiveness of electrochemotherapy in the treatment of skin cancer of the head and neck (HN) area, where standard treatments had either failed or were not deemed suitable or declined by the patient. A total of 105 patients affected by primary or recurrent skin cancer of the HN area were enrolled; of these, 99 were eligible for evaluation of tumour response. By far, the majority (82%) were treated only once, and 18% of patients had a second treatment. The objective response was highest for basal cell carcinoma (97%) and for other histologies was 74%. Small, primary, and treatment-naive carcinomas responded significantly better (p Electrochemotherapy is an effective and safe method for local treatment of cutaneous and subcutaneous tumours, where electric pulses cause increased permeability of cell membranes in the tumour mass, enabling dramatically enhanced effectiveness of bleomycin and other hydrophilic drugs. Here, we report results of a European multi-institutional prospective study of the effectiveness of electrochemotherapy in the treatment of skin cancer of the head and neck (HN) area, where standard treatments had either failed or were not deemed suitable or declined by the patient. A total of 105 patients affected by primary or recurrent skin cancer of the HN area were enrolled; of these, 99 were eligible for evaluation of tumour response. By far, the majority (82%) were treated only once, and 18% of patients had a second treatment. The objective response was highest for basal cell carcinoma (97%) and for other histologies was 74%. Small, primary, and treatment-naive carcinomas responded significantly better (p < 0.05), as investigated by univariate analysis. Electrochemotherapy was well tolerated and led to a significant improvement of quality of life, estimated by the European Organisation for Research and Treatment of Cancer quality of life questionnaires. At 1-year follow-up, the percentages of overall and disease-free survival were 76% and 89%, respectively. Electrochemotherapy is an effective option for skin cancers of the HN area and can be considered a feasible alternative to standard treatments when such an alternative is appropriate. The precise role for electrochemotherapy in the treatment algorithm for non-melanoma skin cancer of the HN region requires data from future randomised controlled studies. (ISRCTN registry N. 30427).

INTRODUCTION: Local progression of papillary thyroid carcinoma (PTC) after failure of standard therapies may cause pain, ulceration, and bleeding. As patients are fully aware of the tumor growth, they might suffer high grade anxiety. Electrochemotherapy (ECT) is a new local palliative treatment for skin metastases of malignant melanoma or other tumors, including squamous head e neck cancer patients. OBJECTIVE: To evaluate the impact of ECT in patients with local progression of PTC. METHODS: Four patients with local progression of PTC were treated with ECT based on Bleomycin, and evaluated according to tumor response, local pain and side effects. RESULTS: In all cases, some grade of tumor response was observed, lasting 6, 7, 12 and 8 months, respectively. Also, reduction of local pain and anxiety was registered in all patients. Tumor infiltrated skin necrosis was the only collateral effect of the treatment. ECT induced a tumor response in all PTC patients with improvement of symptoms. CONCLUSIONS: ECT may be an option for local palliative treatment in PTC patients with local tumor progression. Resumo Introdução: A progressão local do carcinoma papilífero de tireoide (CPT) após a falha da terapia de rotina pode causar dor, ulceração e sangramento. Considerando que os pacientes estão perfeitamente cientes do crescimento tumoral, podem apresentar um alto grau de ansiedade. A eletroquimioterapia (EQT) é um novo tratamento paliativo para metástases de pele de melanoma maligno ou de outros tumores, inclusive em pacientes com carcinoma escamoso de cabeça e pescoço. Objetivo: Avaliar o impacto da EQT em pacientes com progressão local de CPT. Método: Quatro pacientes com progressão local de CPT foram tratados com EQT com base em bleomicina, e avaliados em relação ao grau de resposta tumoral, dor local, efeitos colaterais. Resultados: Em todos os casos, foi observado algum grau de resposta tumoral, que perdurou por 6, 7, 12 e 8 meses, respectivamente. Da mesma forma, foi registrada diminuição da dor local e da ansiedade em todos os pacientes. Necrose cutânea na infiltração tumoral foi o único efeito colateral do tratamento. EQT induziu resposta tumoral em todos os pacientes com CPT, com melhora dos sintomas. Conclusões: EQT pode ser uma opção para o tratamento paliativo tópico em pacientes com CPT com progressão tumoral local.

Background: Patients with head and neck squamous cell carcinoma (HNSCC) present different responses to chemotherapy and radiotherapy. One explanation may be the differences in the individual rates of stem cell-like cells. Methods: We included patients with HNSCC and tumor progression or relapse. Tumor samples were obtained before and after primary chemotherapy, and immunohistochemical analyses were performed for CD44, HLA class I (HLA-I), pancytokeratin, and phosphorylated epidermal growth factor receptor (p-EGFR). Differences in expression between the first and second specimens were assessed. Results: Expression between the first and second specimens varied as follows: CD44 increased by 14.67% (95% confidence interval, CI: 6.94 to 22.40; p < 0.01); HLA-I decreased by 16.72% (95% CI: -23.87 to -9.47; p < 0.01); pancytokeratin decreased by 24.91% (95% CI: -32.8 to -17.7; p < 0.01), and p-EFGR expression decreased by 12.30% (95% CI: -20.61 to -3.98; p < 0.005). Conclusions: Among patients with HNSCC, there is an enrichment of cells with stem-like markers in relapsed tumors when compared with the primary tumor. This finding should be considered when developing treatment strategies.

Resumen Objetivo Valorar el papel de la quimioterapia en el cancer avanzado de cavidad oral valorando su influencia en la supervivencia de los pacientes considerados como paliativos y su capacidad para mejorar las expectativas de cirugia curativa. Pacientes y metodo Noventa y nueve pacientes consecutivos fueron analizados para valorar su evolucion, los factores pronosticos de la progresion del tumor y la supervivencia global despues del tratamiento con dos regimenes diferentes de quimioterapia: cisplatino mas bleomicina (BLM) (n=45) o mas 5-fluorouracilo (5-FU) (n=52). El analisis se realizo dividiendo los pacientes de acuerdo con la finalidad del tratamiento: paliativo (n=41) o neoadyuvante (n=56). Resultados La tasa de respuesta fue del 56,7%. La respuesta fue mayor en el grupo neoadyuvante (73,2%) que en el grupo paliativo (36,6%) (p La supervivencia fue mayor en pacientes que recibieron BLM que en los que recibieron 5-FU (p=0,019) y en el estadio III que en el IV (p=0,013). En el grupo paliativo, la respuesta se asocio a una mayor supervivencia (p En el grupo neoadyuvante, 30 pacientes (53,6%) fueron intervenidos y la reseccion fue completa en 26 de ellos (86,7%). Dieciseis casos (61,5%) presentaron una recidiva. La respuesta a la quimioterapia no se asocio a la operabilidad. La supervivencia fue mayor en el grupo con una reseccion completa del tumor (p=0,041). Conclusiones La respuesta a la quimioterapia en los tumores de cavidad oral fue mayor en los pacientes con estadio III y en los que recibieron BLM. La quimioterapia puede mejorar la supervivencia en casos paliativos. En los casos neoadyuvantes no se demostro una gran influencia para convertir casos dudosos de cirugia en tributarios para cirugia.

Weekly paclitaxel may be an active and well tolerated chemotherapy regimen for patients with platin-resistant advanced head and neck cancer.Weekly paclitaxel should be an active and well tolerated regimen for palliative treatment of platin-resistant patients with recurrent or metastatic carcinoma of the head and neck. We analyzed the antitumor activity and toxicity profile.Sixty consecutive patients with advanced head and neck cancer were treated with 1 h infusion of paclitaxel, 80 mg/m(2) weekly, for 6 consecutive weeks. Patients who showed disease response or disease stabilization continued until progression of disease.A total of 719 doses of paclitaxel were administered to the 60 patients. No complete response was observed. Partial response and stable disease were observed in 26 (43.3%) and 9 (15%) patients, respectively. Median time to tumor progression for patients who responded to therapy was 6.2 months (SD=1.3; 95% CI, 3.7-8.6) and the overall median survival in this group of patients was 8.5 months (SD=1.4; 95% CI, 5.7-11.2). The main toxic effects were leukopenia (26.6%), anemia (43.3%), fatigue (37.4%), alopecia (18.7%), rash/desquamation (13.3%), and thrombophlebitis (6.8%).

Pathology Department of Hospital Cli´nic, Centre de Diagnostic Biome`dic (CDB), IDIBAPS (Augusto Pi i Sunyer Memorial Institute forBiomedical Research), and University of Barcelona, Barcelona, SpainBackgroundandObjectives: Single nucleotide polymorphisms ofdihydropyrimidine dehydrogenases gene(DPYD) inducesdihydropyrimidinedehydrogenase enzyme (DPD) deficiency resulting in increased activity of 5-fluorouracil derivatives. Cytidine-deaminase gene (CDA)polymorphisms have been involved in prognosis in experimental tumours.Methods: Analysis of 50 consecutive resected gastric cancer patients who received adjuvant chemotherapy with Tegafur for polymorphisms ofgenes DPYD1 (A/G; Ile543Val), DPYD2 (C/T; Arg29Cys) and CDA (A/C; Lys27Gin). The status of alleles (wild-type or at least onepolymorphism) was correlated with outcome and toxicity.Results:Polymorphismsfrequencieswild-type/non-wild-typewere36/14inDPYD1(A/G;Ile543Val);26/24inDPYD2(C/T;Arg29Cys);and17/23 in CDA (A/C; Lys27Gin) or between homozygous/heterozygous were 39/11 in DPYD1; 33/17 in DPYD2 and 26/24 in CDA respectively. After77 months of median follow-up (SD¼26.3), 18 patients died of tumour relapse. Better survival was observed in DPYD1 patients only, for non-wild-type over wild-type (P¼0.0214); and in patients with one or more heterozygous polymorphisms in any of the three genes tested(P¼0.0017). In 10 pts (20%) total dose was reduced by toxicity, only 3 of them were homozygous.Conclusions: Gene polymorphisms of DPYD and CDA predict survival of gastric cancer patients treated with 5-fluorouracil-based adjuvantchemotherapy.

Intramedullary spinal cord metastases (ISCM) are uncommon and present with rapidly progressing neurological deficits. The objective of this study was to determine the rate, duration of neurological response and survival after radiation therapy. We have retrospectively reviewed the clinical outcome of six cases with a diagnosis of ISCM from primary lung cancer, non-small cell (NSCLC) (n=3) and small cell (SCLC) (n=3). Total radiation dose ranged from 27 Gy/5 fr to 40 Gy/20 fr. Ambulation was preserved in 3 patients and partially recovered in one. Five out of the six patients (83%) showed improvement in neurological signs/symptoms with a mean duration of 17.2 days (max: 40 days; min: 6 days). Median survival time was 5 months (confidence interval (CI) 95%: 0-12) for NSCLC and 5 months (CI 95%: 4-6) for SCLC. Although radiation response rate is high, the interval free of neurological progression is very short. A therapeutic approach should be considered for each individual.

Cyclooxygenase-2 mRNA (COX2) levels are higher in head and neck cancer (HNC) patients than in controls and this correlates with tumor size and outcome. These findings suggest the use of this parameter as a future tumor marker.We analyzed the expression of COX2 mRNA in peripheral blood cells in HNC patients and in healthy controls and its relationship with outcome and progression-free survival.Blood samples were obtained from 41 consecutive HNC patients and 16 healthy controls and analyzed for COX2 mRNA with quantitative real-time polymerase chain reaction and compared with beta-actin as a house-keeping gene.Treatment consisted of surgery only (4 patients), chemoradiotherapy (18), chemotherapy followed by curative surgery (4) or palliative chemotherapy (15). COX2 mRNA levels were higher in patients with unfavorable outcome (mean 6.8, median 2.06) than those with favorable outcome (mean 1.2, median 1.31) (p=0.062). Both were higher than for healthy controls (mean 0.74, median 0.72; p0.001). In bulky tumors, the percentage of level over 6 in unfavorable outcome cases was higher than in the favorable outcome cases (p=0.005). In chemotherapy patients with levelor=1 no relapse or progression was observed (n=7), and progression-free survival was significantly better than those with level1 (n=19) (p=0.0138).

A combination of cisplatin and 5-fluorouracil (PF) is considered the standard induction chemotherapy regimen for squamous cell carcinoma of the head and neck (SCCHN). The present study compares the efficacy and safety of a new combination of cisplatin/docetaxel versus the PF regimen. A total of 83 chemotherapy-naive patients with locally advanced SCCHN were randomised to receive every 21 d (i) docetaxel 85 mg/m2 i.v. on day 1 and cisplatin 40 mg/m2 i.v. on days 1 and 2 (arm A) or (ii) cisplatin 100 mg/m2 i.v. on day 1 followed by 5-fluorouracil 1000 mg/m2 in 24 h continuous infusion for 5 d (arm B). A total of 287 cycles (range 1–3 per patient) were administered. Among 76 patients evaluable for response, the overall response rate in arm A was 70% (complete response (CR) 26%, partial response (PR) 44%) and in arm B 69% (CR 16%, PR 54%), respectively. Median survival in arm A was 7.6 months (95% CI: 5.8–11.1) and 9.9 months (95% CI: 7.4–14.6) for arm B. The most frequent grade 3/4 toxicity in arm A was neutropaenia (34.1%) and diarrhoea (9.8%) versus mucositis (29.3%) and neutropaenia (19.5%) in arm B. Both schedules present a similar efficacy, with different but acceptable toxicity patterns.

Background and Objectives We analyzed in a retrospective analysis whether adjuvant chemotherapy with mitomycin (MMC) alone or with Tegafur (TG) is associated with long-term survival benefit in resected gastric cancer. Other prognostic factors are compared. Methods From 1977 to 1998, 314 consecutive totally resected gastric adenocarcinoma patients have been included in a survival study. In 151 patients no adjuvant therapy was given. In 163 patients, four courses of adjuvant chemotherapy was given, 109 of them with MMC, 10–20 mg/m2 i.v. every 6 weeks and the other 54 with MMC plus TG, 500 mg/m2 p.o. day for 42 consecutive days. Univariate and multivariate survival analyses were performed. Results Survival benefit was seen in patients who had received adjuvant chemotherapy compared with the controls (52% vs. 30% alive at the end of the study, relative risk = 0.46, 95% CI: 0.33–0.62, P

Access to information on cancer prevention and treatment is often difficult for ethnic or low socio-economic groups. This study aimed to ascertain level of knowledge about cancer, and breast cancer in particular, in Spanish women from low socio-economic groups participating in literacy schemes. A study specific questionnaire was administered to 541 women All participants were married with a median of 2 children, and a total family income of less than 10,000 euros per year. The main themes covered: understanding of and access to screening, knowledge about cancer risk, diagnosis and prognosis. The majority of these women (66%) feel they have no control over getting cancer and 26% report that it can be caught from others. Most believe that a mammogram is the best method of diagnosis (87%) but a minority (14%) agree with the statement that breast cancer can be caused by breast feeding. In general, younger women are better informed and more optimistic about prognosis. In Spain there are problems in disseminating information about cancer to lower social-economic groups. These results confirm that more cancer education needs to be directed to low income and socially deprived groups. Copyright © 2003 John Wiley & Sons, Ltd.

Objectives: To determine outcomes in local-regional control and overall survival in patients with squamous locally advanced cancer of the oral cavity, based on intention-to-treat with neoadjuvant chemotherapy followed by surgery or radiation therapy. Methods: Two hundred and four out of 1,089 patients analyzed met the defined criteria. All had squamous cell carcinomas of the oral cavity in stage III or in nonmetastatic stage IV and were selected for surgery or radiation therapy (if located in the tonsils or in the base of the tongue). Chemotherapy was based on cisplatin 120 mg/m2 i.v. day 1 plus bleomycin 20 mg/m2 days 1–5 in continuous i.v. perfusion or plus 5-fluorouracil 1,000 mg/m2 days 1–5 in continuous i.v. perfusion. A total of 418 cycles were given to 204 patients (mean 2.049 per patient). Definitive surgery (n = 73; plus adjuvant radiation therapy) or definitive radiation therapy (n = 131) was performed. Results: One hundred thirty-five out of 204 (66%) patients were chemotherapy responders, 16% complete and 50% partial. One hundred ninety-four patients (95%) completed 2 courses of chemotherapy. After neoadjuvant chemotherapy, 34 out of 46 patients considered inoperable initially (74%) obtained a disease-free status with surgery. Eighty-three percent of surgical patients obtained a disease-free status (initial tumor control) versus 72% of radiation therapy patients. Disease-free survival rates at 5 years were 26 and 22%, respectively. A better prognosis was observed in stage III over IV (p = 0.02); primary tumor in the retromolar trigone, palate or buccal mucosa over tongue, tonsil or floor of the mouth (p = 0.0085); negative cervical nodes over positive (p = 0.0186); responders to chemotherapy over nonresponders (p = 0.0003); and adjuvant postsurgical radiation therapy (p = 0.0013). Causes of death were relapses in local area (86%), regional nodes (10.5%) or distant metastases (3.5%). Eleven patients (5%) died of a second primary. The main toxic effects were vomiting in 9% of patients and hemolytic-uremic syndrome in 3% of the patients treated with bleomycin. Conclusions: In locally advanced squamous cell carcinoma of the oral cavity, neoadjuvant chemotherapy induces a high response rate that may facilitate definitive surgery or radiotherapy. In this study, patients have an acceptable long-term survival.

The authors reviewed a series of 110 surgical specimens of primary non-small cell lung carcinomas from the Department of Pathology at the Hospital Clinic, University of Barcelona Medical School, between 1987 and 1997. The sample included 25 squamous cell carcinomas, 60 adenocarcinomas, 14 large cell carcinomas, and 11 neuroendocrine tumors. Electron microscopic subcellular characteristics of the lung cancer cells were studied to define the squamous, adenoid, or neuroendocrine differentiation in each tumor. An immunohistochemical study for Cyclin D1 was performed in 96 cases. In 71 cases (65%) the author found a single ultrastructural differentiation, and in 30 cases (27%) ultrastructural differentiation was double: 25 adenosquamous and 5 adeno-neuroendocrine. In 3 cases a triple adeno-squamous-neuroendocrine differentiation was found. There were no cases of squamous-neuroendocrine differentiation. In 6 cases no differentiation of any kind could be found. Cyclin D1 overexpression was found in 58% of all tumors. The positive expression rates in squamous cell carcinoma and adenocarcinoma were 72% and 62%, respectively. In purely adenoid-differentiated tumors there was a strong association between high Cyclin D1 overexpression and differentiation (p=.006). In bronchioloalveolar carcinoma the positivity rate was 70%; all were heavy expressers, compared with 25% of heavy expressers in adenocarcinomas as a whole (p

Background Adenoid cystic carcinoma (ACC) of the salivary gland frequently develops lung metastases. In cases in which chemotherapy is indicated, resistance is a common phenomenon. New drugs, such as cetuximab, have been chosen to avoid this chemoresistance. Methods and Results A 54-year-old man was diagnosed with ACC of the right submandibular gland. He underwent a submandibular gland resection with adjuvant radiotherapy. Three years later, bilateral lung metastases were diagnosed and treated with various chemotherapy schedules, including paclitaxel without success. We obtained radiographic response, followed by disease stabilization for more than 1 year with the addition of cetuximab to paclitaxel administered at low weekly doses (metronomic schedule). Conclusion This case demonstrates for the first time a reversion of primary resistance to chemotherapy in ACC that is currently considered chemoresistant by use of a combination of metronomic chemotherapy with new targeted agents such as cetuximab. Metronomic chemotherapy was also well tolerated and achieved long-term response. © 2011 Wiley Periodicals, Inc. Head Neck, 2013

Rubens was one of main baroque painters who practices realism, which means that he painted whatever his eyes capture. That fact has helped us with the visual aspect and the circumstances where such paintings were painted. This has allowed us to discover alterations in the breast of the models he painted, which suggest breast cancer. Such painting are 'The three Graces', 'Diana and her nymphs pursued by satyrs', 'Orpheus and Euridice'. In 'The three Graces' we can see that the model on the right has an open ulcer with reddening of the skin, nipple retraction, reduction of breast volume as well as axilar lymph nodes. This is a visual aspect of a locally advanced breast cancer. In Diana and her nymphs pursued by satyrs and in Orpheus and Euridice we can see a breast retraction in the same place as in 'The three Graces', which suggest breast cancer indirectly. The analysis of the tumor mass in the models of these pictures allow us to know more on the works, the social environment and the diseases happened in the years this painter lived.

Resumen Los tumores de glandulas salivares han sido considerados hasta hace pocos anos quimiorresistentes. El tratamiento con quimioterapia esta indicado en el contexto de enfermedad locorregional irresecable o enfermedad metastasica. La experiencia de quimioterapia en el carcinoma adenoide quistico de parotida se basa en estudios fase II; la mayoria con esquemas de quimioterapia en combinacion y a dosis plenas, y sin evidencia de que aumenten la supervivencia. Se conoce como quimioterapia metronomica a la administracion de agentes citotoxicos a bajas dosis y a intervalos cortos y regulares, sin interrupciones en el tratamiento. La mayoria de estudios demuestran una eficacia similar o incluso superior y una menor toxicidad que cuando se administra con la maxima dosis tolerada. Nuestro caso clinico muestra, por primera vez, la eficacia del paclitaxel y el cisplatino en monoterapia y a dosis metronomicas en el tratamiento del carcinoma adenoide quistico de parotida metastasico.

Formerly, salivary gland cancer was considered to be chemoresistant. Chemotherapy is indicated when distant metastases or inoperable locorregional disease are observed, although the chemotherapy schedule is not well defined. Data on chemotherapy treatment for adenoid cystic carcinoma consist of phaseII trials. Most of these studies analyze therapies with a combination of agents at full dose, although there is no clear evidence that such treatment improves survival. The administration of cytotoxic agents with low doses at frequent, regular intervals with no drug-free interruptions is known as metronomic chemotherapy. Most head-to-head studies show similar or even superior therapeutic results with metronomic scheduling than with a maximum tolerated dose regime. Our case report shows for first time the clinical activity of low-dose paclitaxel and cisplatin chemotherapy given separately as a single agent in metastatic adenoid cystic carcinoma of the parotid.

The purpose of this clinical study was to analyze a long-term follow-up of all the patients with head and neck cancer in our institution. Between 1973 and 1993,1,355 consecutive cases of head and neck cancer were diagnosed, treated and followed up regularly. All were subjected to a multidisciplinary approach, and followed up until death or for 10 years with no event of disease. The local relapse rate was 20% and the node-regional relapse rate 15%. Distant metastases were observed in 6% of the patients mainly arising from the nasopharynx (23%) followed by the hypopharynx (11 %). The main organ involved was the lung (50%). Median follow-up of the group was 10 years (range 4 months to 15 years). Cancer cure was observed after 5 years in glottic and supraglottic laryngeal carcinoma, oral and nasopharyngeal cancer and after 2.5 years in patients with cancer of the oropharynx and hypopharynx. The highest cure rate was 80% in the glottis, followed by 70% in the supraglottic area, 45% in the mouth, 30% in the nasopharynx, 25% in the oropharynx, and 20% in the hypopharynx. A second primary tumor was observed in 7% of the patients and a third primary in 0.6% of the patients. Only in 7 patients, the second or third primary was seen after 5 years of follow-up. Curability should be observed after 5 years from definitive therapy of glottic, supraglottic, oral and nasopharyngeal and earlier in oropharyngeal and hypopharyngeal cancer. Further follow-up should be discontinued. Second and third neoplasias are the main problems after 5 years of follow-up but their incidence is low.

Head and neck cancer represents 5 % of oncologic cases in adults. Early stage treatments are local with surgery and/or radiotherapy. For locally advanced stages, treatment requires radiotherapy combined with platinum-based drugs or cetuximab. Induction chemotherapy should be considered for selected cases. In the case of metastatic disease, adjuvant or palliative treatment is based on platinum agents and cetuximab.

Nasopharyngeal carcinoma cases are not frequently encountered in our environment. Local stages are treated with radiotherapy. For advanced local stages, the association of chemotherapy with radiotherapy improves the rates of survival. In the case of metastatic disease stages, treatment requires platinum-based chemotherapy and patients may achieve a long survival time.

Few therapeutic options are available for recurrent/metastatic head and neck cancer when progression occurs after initial chemotherapy. We analyzed retrospectively the efficacy of weekly Paclitaxel plus Cetuximab as second line of palliative chemotherapy. Patients with squamous carcinoma of head and neck with documented progression after initial treatment were enrolled. Tumor response was evaluated through the response evaluation criteria in solid tumor criteria. The retrospective analysis focused on overall survival (OS) and progression-free survival (PFS). Between 2008 and 2011, 33 consecutive patients were treated. A response rate of 55% was observed, with median response duration of 5.0 months (95% CI 3.3-11.1). The median PFS was 4.0 months (95% CI 2.9-5.0) and the median OS time was 10.0 months (95% CI 7.9-12.0). Acne-like rash/Folliculitis and chronic anemia were the most common adverse events. A weekly schedule of Paclitaxel plus Cetuximab is a promising regimen for patients with advanced head and neck cancer after failure of platinum-based therapy. Good tolerance of this treatment suggests that would be used in fragile patients.

6001Background: CetRT has not been compared with CRT after ICT in phase III. Objective: To compare the impact on overall survival of CRT vs. CetRT after ICT in a Phase III randomized controlled cli...

e17553Background: Sequential therapy with MKIs in the management of refractory thyroid cancer cannot be standardized with data coming form randomized clinical trials. Methods: We retrospectively an...

Although thyroid cancer usually has an excellent prognosis, few therapeutic options are available in the refractory setting. Based on the recent results of phase II studies with tyrosine kinase inhibitors, we designed a retrospective analysis of patients with metastatic thyroid cancer treated with sorafenib in seven Spanish referral centers. Consecutive patients with progressive metastatic thyroid cancer (papillary, follicular, medullary, and anaplastic) not suitable for curative surgery, radioactive-iodine therapy, or radiotherapy were treated with sorafenib 400 mg twice a day. The primary end point was objective response rate (RR). Secondary end points included toxicity, median progression-free survival (mPFS), median overall survival (mOS), and correlation between tumor marker levels (thyroglobulin, calcitonin, and carcinoembryonic antigen) and efficacy. Between June 2006 and January 2010, 34 patients were included in the study. Sixteen patients presented differentiated thyroid carcinomas (DTC) of which seven (21%) were papillary, nine (26%) follicular, 15 (44%) medullary (MTC), and three (9%) were anaplastic (ATC). Eleven (32%) patients achieved partial response and 14 (41%) had stable disease beyond 6 months. Regarding histological subtype, RRs were 47% (seven of 15) for MTC, 19% (three of 16) for DTC, and 33% (one of three) for ATC. With a median follow-up of 11.5 months, mPFS were 13.5, 10.5, and 4.4 months for DTC, MTC, and ATC respectively. Tumor markers were evaluated in 22 patients, and a statistically significant association was observed between RR and decrease in tumor marker levels >50% (P=0.033). In this retrospective trial, sorafenib showed antitumor efficacy in all histological subtypes of thyroid cancer, warranting further development in this setting.

A review has been conducted of 1433 patients treated by the Lung Cancer Unit of our hospital to assess the association of age with clinical characteristics of patients with lung cancer. The factors evaluated were tobacco, stage of disease, treatment and survival of patients treated surgically. A comparison was made of patients aged 65 or less with those over 65. There was a similar prevalence of smokers in both age groups. The stage of disease at time of diagnosis was similar (33% of the patients aged 65 or less were Stage I or II versus 37% of the older patients). The distribution by histological type showed significant differences (p < 0.05) with a higher percentage of squamous carcinoma in the younger group (54% versus 44%). Surgery was performed in 30% of the patients aged 65 years or less but only in 19% of the older cases (p < 0.05). Among those patients treated surgically there was no difference in the survival of younger and older patients.

Background The efficacy and safety of a novel combination of weekly paclitaxel and the epidermal growth factor receptor (EGFR) monoclonal antibody cetuximab for the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck were investigated. Patients and methods Patients received paclitaxel (80 mg/m2) and cetuximab (400/250 mg/m2), weekly, until disease progression or unacceptable toxicity. The primary end point was response rate. Results Among 46 patients enrolled, the overall response rate was 54% [95% confidence interval (CI) 39% to 69%], with 10 (22%) complete responses and a disease control rate of 80%. Median progression-free and overall survival times were 4.2 (95% CI 2.9–5.5 months) and 8.1 months (95% CI 6.6–9.6 months), respectively. Common grade 3/4 adverse events were acne-like rash (24%), asthenia (17%) and neutropenia (13%). Prior chemotherapy and the development of acne-like rash were associated with tumor response but not survival. No association between tumor EGFR expression or EGFR gene copy number and response or survival was found. Conclusion The combination of cetuximab and weekly paclitaxel was active and well tolerated by these poor prognosis patients and may be an option for the treatment of medically unfit patients, particularly those for whom platinum is contraindicated.