Efficacy and safety of induction chemotherapy in oral cavity cancer: An eight-year experience at a Portuguese reference center.

BACKGROUND: Induction chemotherapy has been described as an option in locally advanced oral cavity squamous cell carcinoma when the surgical morbidity is expected to be high. This work aimed to evaluate the outcome and safety of induction chemotherapy in this setting. METHODS: We performed a retrospective and observational study including patients with oral cavity squamous cell carcinoma, treated with induction chemotherapy between January 2010 and December 2018. Outcomes included induction chemotherapy toxicity, treatment response, disease-free survival and overall survival. RESULTS: A total of 108 oral cavity squamous cell carcinoma patients were included. Ninety-six (88.9%) had stage IV disease, while 12 (11.1%) had stage III. Eighty-four patients (80.8%) achieved at least a partial response to induction chemotherapy at clinical evaluation, and 75 (72.1%) at radiological evaluation. Seventy-eight patients have been proposed for subsequent definitive treatments, with no differences obtained in prognosis, when comparing surgical to non-surgical approaches. In patients treated with definitive treatments, improved five-year disease-free survival was obtained if at least a clinical (56.3%; p=0.001) or radiological (52.9%; p=0.001) partial response was achieved after induction chemotherapy. Similarly, superior five-year overall survival was verified for those achieving at least clinical (51.1%; p<0.0001) or radiological (52.6%; p=0.001) partial response. Also, accomplishing a pathologic complete response (n=22.6%) significantly improved disease-free survival (p=0.039) and overall survival (p=0.005). Grade 3 and 4 toxicities were observed in 52 patients (41.8%). CONCLUSION: Responses to induction chemotherapy predicted prognosis in our population, however important toxicities were observed. Further studies are necessary to identify induction chemotherapy response predictors and subgroups who may benefit from this approach.

Pioneering the implementation of a precision oncology strategy in Portugal: the Precision Oncology Platform trial.

BACKGROUND AND PURPOSE: The Precision Oncology Platform (POP) trial represents the effort of the Portuguese Oncology Institute of Porto (IPO Porto) for joining other leading European institutions in both 'Personalised Cancer Medicine for all EU citizens' (PCM4EU), and 'PRecisIon Cancer MEdicine RepurpOsing SystEm Using Pragmatic Clinical Trials' (PRIME-ROSE) consortia, enabling the development of the Portuguese version of the Drug Rediscovery Protocol (DRUP)-like Clinical Trial (DLCT), based on the experience of the DRUP trial developed in The Netherlands. PATIENTS/MATERIAL AND METHODS: The POP trial is a phase II, pragmatic multicentric, non-randomised, open-label study, designed entirely like the other DLCTs. Its primary objective is to describe anti-tumour activity of targeted anticancer drugs in patients with advanced malignancies harbouring actionable molecular alterations. The primary endpoint is disease control rate (DCR). Secondary endpoints encompass treatment-related grade ≥3 adverse events, objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Exploratory objectives will assess biomarkers, resource use and costs, and patient-reported outcome measures (PROMs). INTERPRETATION: The POP trial will offer access to innovative treatments for patients without further therapeutic options and provide evidence on efficacy and safety of molecularly-guided treatments. Methodologically, it represents a pioneer approach in Portugal, including a pay-for-performance model embedded in the clinical trial. The POP trial represents a unique opportunity to integrate clinical research within cancer care, pursuing an evidence-based precision oncology strategy, and facilitating its rational and cost-effective implementation into the Portuguese healthcare system.

Sample-comparison mapping and joint stimulus control.

A matching-to-sample task with a 3-sample, 2-comparison mapping has been found to engender joint control by the stimuli that signaled the samples (keylight) and the inter-trial interval (houselight), with a trade-off in the degree of control exerted by each stimulus. To learn about the boundary conditions for the establishment of that joint stimulus control, we trained pigeons in a similar task, but featuring a one-to-one sample-comparison mapping, with two samples and two comparisons. To assess their relative influences, we ran two tests where each of the stimuli was removed: in one test, no sample keylight was presented, and in the other, the ITI was spent in darkness. Results were consistent with both stimuli influencing choice but there was no clear evidence of a trade-off between them. These results suggest that sample-comparison mapping and/or total number of samples may influence how an animal directs its attention to the stimuli available.

A New Era in Salivary Gland Carcinoma Treatment: A Case Report.

Salivary gland cancers are rare and heterogenous malignancies which makes it hard to standardize treatments with good evidence levels. The localized disease approach is well established, with surgery to the primary site and adjuvant radiation therapy in patients with high-risk features. Treatment of advanced disease should be multidisciplinary. Local approaches, which include radiation therapy, surgery, and thermoablation, among others, have the potential to achieve durable disease control with low toxicity. Chemotherapy has shown disappointing results, so systemic treatment should be guided by actionable genetic alterations, which in salivary gland cancers rely on the histologic type. When directed molecular tests are not useful, a multigene panel should be performed. This case is a good example of how to integrate all these possible tretaments in clinical practice, including molecular testing and target treatment.

Quality of Life With Pembrolizumab for Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: KEYNOTE-040.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) affects health-related quality of life (HRQoL); few treatments have demonstrated clinically meaningful HRQoL benefit. KEYNOTE-040 evaluated pembrolizumab vs standard of care (SOC) in patients with recurrent and/or metastatic HNSCC whose disease recurred or progressed after platinum-containing regimen. METHODS: Patients received pembrolizumab 200 mg or SOC (methotrexate, docetaxel, or cetuximab). Exploratory HRQoL analyses used European Organisation for Research and Treatment of Cancer (EORTC) 30 quality-of-life, EORTC 35-question quality-of-life head and neck cancer-specific module, and EuroQoL 5-dimensions questionnaires. RESULTS: The HRQoL population comprised 469 patients (pembrolizumab = 241, SOC = 228). HRQoL compliance for patients in the study at week 15 was 75.3% (116 of 154) for pembrolizumab and 74.6% (85 of 114) for SOC. The median time to deterioration in global health status (GHS) and QoL scores were 4.8 months with pembrolizumab and 2.8 months with SOC (hazard ratio = 0.79, 95% confidence interval [CI] = 0.59 to 1.05). At week 15, GHS / QoL scores were stable for pembrolizumab (least squares mean [LSM] = 0.39, 95% CI = -3.00 to 3.78) but worsened for SOC (LSM = -5.86, 95% CI = -9.68 to -2.04); the LSM between-group difference was 6.25 points (95% CI = 1.32 to 11.18; nominal 2-sided P = .01). A greater difference in the LSM for GHS / QoL score occurred with pembrolizumab vs docetaxel (10.23, 95% CI = 3.15 to 17.30) compared with pembrolizumab vs methotrexate (6.21, 95% CI = -4.57 to 16.99) or pembrolizumab vs cetuximab (-1.44, 95% CI = -11.43 to 8.56). Pembrolizumab-treated patients had stable functioning and symptoms at week 15, with no notable differences from SOC. CONCLUSIONS: GHS / QoL scores were stable with pembrolizumab but declined with SOC in patients at week 15, supporting the clinically meaningful benefit of pembrolizumab in recurrent and/or metastatic HNSCC.

A 10-year review of primary major salivary gland cancers.

Primary salivary gland cancers comprise a heterogeneous group of histological entities and represent less than 5% of head and neck malignancies. Surgical resection is the main treatment, and adjuvant radiotherapy is performed in selected cases. Chemotherapy is an option in metastatic or recurrent disease, with poor evidence. We aimed to review a 10-year experience of a cancer centre on major salivary gland cancers, focusing on clinical, pathological, treatment and patients' outcomes data. A total of 93 patients were identified, median age at diagnosis was 64 years (IQR, 23), and 51.6% were male. The parotid gland was the site of origin in 76.3% of cases. The most frequent histological type was salivary duct carcinoma (21.5%). All patients were submitted to surgery and adjuvant radiotherapy was performed in 74.2%. From 26 patients diagnosed with metastatic disease, 9 were treated with systemic therapy. At 8 years, disease-free survival was 54.6% and overall survival was 48.4%. Male sex, salivary duct carcinoma, stage pT3-4, stage pN2-3, high histologic grade, lymphovascular invasion and perineural invasion were negative prognostic indicators for disease-free survival and overall survival. Extracapsular spread was a negative prognostic indicator for overall survival. In the multivariable analysis, histological type-salivary duct carcinoma-kept significant negative impact in disease-free survival and high histologic grade in overall survival. The most frequent histological type was salivary duct carcinoma, which is estimated to represent only 9% of salivary tumours. Patients with salivary duct carcinoma relapsed more than other histological types. High histologic grade was a negative prognostic indicator for overall survival.

Management of Locally Advanced Esthesioneuroblastoma in a Pregnant Woman.

Esthesioneuroblastoma (ENB) is a rare malignant tumor that commonly develops in the upper nasal cavity. Standard treatment is not established, especially in locally advanced disease which portends the worse prognosis. Hereby, we report a case of a 27-year-old, 23-week pregnant woman, with a 2-month history of progressively growing right cervical lymphadenopathy, nasal obstruction, anosmia, frequent episodes of epistaxis, and right frontal headache. Imagiological evaluation revealed a lesion with 7×5,2×3,2 cm in the nasal fossae with extension to the ethmoidal complex and right olfactive fend and invasion of the endocranial compartment associated with lymphadenopathy. The biopsy revealed a high-grade EBN. Neoadjuvant chemotherapy with cisplatin and etoposide was administrated during pregnancy and continued after delivery up to 6 cycles of treatment with partial response. Radiotherapy followed, with complete response. This case report is intended to highlight that a high grade of suspicion should be kept in the presence of nonspecific symptoms of nasal obstruction, anosmia, facial pain, and/or headache and focus that chemotherapy is an important component of a combined-treatment modality for locally advanced ENB that can be used during pregnancy in a lifesaving situation.

Afatinib vs Placebo as Adjuvant Therapy After Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck: A Randomized Clinical Trial.

IMPORTANCE: Locoregionally advanced head and neck squamous cell cancer (HNSCC) is treated curatively; however, risk of recurrence remains high among some patients. The ERBB family blocker afatinib has shown efficacy in recurrent or metastatic HNSCC. OBJECTIVE: To assess whether afatinib therapy after definitive chemoradiotherapy (CRT) improves disease-free survival (DFS) in patients with HNSCC. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, phase 3, double-blind randomized clinical trial (LUX-Head & Neck 2) studied 617 patients from November 2, 2011, to July 4, 2016. Patients who had complete response after CRT, comprising radiotherapy with cisplatin or carboplatin, with or without resection of residual disease, for locoregionally advanced high- or intermediate-risk HNSCC of the oral cavity, hypopharynx, larynx, or oropharynx were included in the study. Data analysis was of the intention-to-treat population. INTERVENTIONS: Patients were randomized (2:1) to treatment with afatinib (40 mg/d) or placebo, stratified by nodal status (N0-2a or N2b-3) and Eastern Cooperative Oncology Group performance status (0 or 1). Treatment continued for 18 months or until disease recurrence, unacceptable adverse events, or patient withdrawal. MAIN OUTCOMES AND MEASURES: The primary end point was DFS, defined as time from the date of randomization to the date of tumor recurrence or secondary primary tumor or death from any cause. Secondary end points were DFS at 2 years, overall survival (defined as time from the date of randomization to death), and health-related quality of life. RESULTS: A total of 617 patients were studied (mean [SD] age, 58 [8.4] years; 528 male [85.6%]). Recruitment was stopped after a preplanned interim futility analysis on July 4, 2016, on recommendation from an independent data monitoring committee. Treatment was discontinued. Median DFS was 43.4 months (95% CI, 37.4 months to not estimable) in the afatinib group and not estimable (95% CI, 40.1 months to not estimable) in the placebo group (hazard ratio, 1.13; 95% CI, 0.81-1.57; stratified log-rank test P = .48). The most common grade 3 and 4 drug-related adverse effects were acneiform rash (61 [14.8%] of 411 patients in the afatinib group vs 1 [0.5%] of 206 patients in the placebo group), stomatitis (55 [13.4%] in the afatinib group vs 1 [0.5%] in the placebo group), and diarrhea (32 [7.8%] in the afatinib group vs 1 [0.5%] in the placebo group). CONCLUSIONS AND RELEVANCE: This study's findings indicate that treatment with afatinib after CRT did not improve DFS and was associated with more adverse events than placebo in patients with primary, unresected, clinically high- to intermediate-risk HNSCC. The use of adjuvant afatinib after CRT is not recommended. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01345669.

Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study.

BACKGROUND: There are few effective treatment options for patients with recurrent or metastatic head-and-neck squamous cell carcinoma. Pembrolizumab showed antitumour activity and manageable toxicity in early-phase trials. We aimed to compare the efficacy and safety of pembrolizumab versus standard-of-care therapy for the treatment of head-and-neck squamous cell carcinoma. METHODS: We did a randomised, open-label, phase 3 study at 97 medical centres in 20 countries. Patients with head-and-neck squamous cell carcinoma that progressed during or after platinum-containing treatment for recurrent or metastatic disease (or both), or whose disease recurred or progressed within 3-6 months of previous multimodal therapy containing platinum for locally advanced disease, were randomly assigned (1:1) in blocks of four per stratum with an interactive voice-response and integrated web-response system to receive pembrolizumab 200 mg every 3 weeks intravenously or investigator's choice of standard doses of methotrexate, docetaxel, or cetuximab intravenously (standard-of-care group). The primary endpoint was overall survival in the intention-to-treat population. Safety was analysed in the as-treated population. This trial is registered with ClinicalTrials.gov, number NCT02252042, and is no longer enrolling patients. FINDINGS: Between Dec 24, 2014, and May 13, 2016, 247 patients were randomly allocated to pembrolizumab and 248 were randomly allocated to standard of care. As of May 15, 2017, 181 (73%) of 247 patients in the pembrolizumab group and 207 (83%) of 248 patients in the standard-of-care group had died. Median overall survival in the intention-to-treat population was 8·4 months (95% CI 6·4-9·4) with pembrolizumab and 6·9 months (5·9-8·0) with standard of care (hazard ratio 0·80, 0·65-0·98; nominal p=0·0161). Fewer patients treated with pembrolizumab than with standard of care had grade 3 or worse treatment-related adverse events (33 [13%] of 246 vs 85 [36%] of 234). The most common treatment-related adverse event was hypothyroidism with pembrolizumab (in 33 [13%] patients) and fatigue with standard of care (in 43 [18%]). Treatment-related death occurred in four patients treated with pembrolizumab (unspecified cause, large intestine perforation, malignant neoplasm progression, and Stevens-Johnson syndrome) and two patients treated with standard of care (malignant neoplasm progression and pneumonia). INTERPRETATION: The clinically meaningful prolongation of overall survival and favourable safety profile of pembrolizumab in patients with recurrent or metastatic head and neck squamous cell carcinoma support the further evaluation of pembrolizumab as a monotherapy and as part of combination therapy in earlier stages of disease. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co.

An open-label single-arm, phase II trial of zalutumumab, a human monoclonal anti-EGFR antibody, in patients with platinum-refractory squamous cell carcinoma of the head and neck.

PURPOSE: Treatment options for patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) are limited. The purpose of this study was to assess the efficacy and safety of zalutumumab in platinum-refractory R/M SCCHN. METHODS: Patients with platinum-refractory R/M SCCHN were enrolled if they had performance status of 0-2, age ≥18 years and adequate organ function. Patients received weekly infusions of zalutumumab individually titrated to a grade 2 skin rash. Primary objective was overall survival (OS), and secondary objectives were efficacy and safety. A subgroup analysis of OS and progression-free survival (PFS) was conducted for various demographic, disease-related and molecular factors. RESULTS: Ninety patients were enrolled. Twenty-three percent of patients had performance status (PS) 2 and 74 % had distant metastases. Median OS was 5.3 months (95 % CI [4.1, 7.1]), and median PFS was 2.1 months (95 % CI [2.0, 2.6]). Subgroup analysis by ECOG PS revealed median OS of 6.3 months for PS = 0-1 and 2.5 months for PS = 2. Objective response rate was 5.7 %, and disease control rate was 39.8 %. Grade 3-4 adverse events related to zalutumumab were observed in 19 % of patients and included skin rash (5 %), hypomagnesemia (4 %) and pneumonitis (1 %). The frequency of all-cause grade 3-4 AEs was 62 % and included infections (14 %), gastrointestinal disorders (12 %) and hypokalemia (6 %). Two deaths were deemed related to zalutumumab [ClinicalTrials.gov Identifier: NCT00542308]. CONCLUSIONS: Zalutumumab showed reasonable efficacy in platinum-refractory R/M SCCHN patients, and dose titration based on skin rash evaluation was feasible.

Cetuximab plus platinum-based chemotherapy in head and neck squamous cell carcinoma: a retrospective study in a single comprehensive European cancer institution.

BACKGROUND: The use of cetuximab in combination with platinum (P) plus 5-fluorouracil (F) has previously been demonstrated to be effective in the treatment of metastatic squamous cell cancer of head and neck (SCCHN). We investigated the efficacy and outcome of this protocol as a first-line treatment for patients with recurrent or metastatic disease. We evaluated overall-survival (OS), progression-free-survival (PFS), overall response rate (ORR) and the treatment toxicity profile in a retrospective cohort. PATIENTS AND METHODS: This study enrolled 121 patients with untreated recurrent or metastatic SCCHN. The patients received PF+ cetuximab every 3 weeks for a maximum of 6 cycles. Patients with stable disease who received PF+ cetuximab continued to receive cetuximab until disease progressed or unacceptable toxic effects were experienced, whichever occurred first. RESULTS: The median patient age was 53 (37-78) years. The patient cohort was 86.8% male. The addition of cetuximab to PF in the recurrent or metastatic setting provided an OS of 11 months (Confidential Interval, CI, 95%, 8.684-13.316) and PFS of 8 months (CI 95%, 6.051-9.949). The disease control rate was 48.9%, and the ORR was 23.91%. The most common grade 3 or 4 adverse events in the PF+ cetuximab regimen were febrile neutropenia (5.7%), skin rash (3.8%) and mucosistis (3.8%). CONCLUSIONS: The results of this study suggest that cetuximab plus platinum-fluorouracil chemotherapy is a good option for systemic treatment in advanced SSCHN patients. This regimen has a well-tolerated toxicity profile.

Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with cisplatin therapy: randomized, double-blind study protocol--EASE.

PURPOSE: Addition of aprepitant, a neurokinin-1 receptor antagonist (NK1RA), to an ondansetron and dexamethasone regimen improves prevention of chemotherapy-induced nausea/vomiting (CINV), particularly during the delayed phase (DP; 25 to 120 hours). Therefore, recommended antiemetic regimens include multiple-day NK1RA administration. Preliminary data suggested that single-dose aprepitant before chemotherapy could provide CINV protection throughout the overall risk phase (OP; 0 to 120 hours). This study compared a 3-day oral aprepitant schedule to a regimen containing a single dose of the intravenous NK1RA fosaprepitant. PATIENTS AND METHODS: A randomized, double-blind, active-control design was used to test whether fosaprepitant is noninferior to aprepitant. Patients receiving cisplatin ≥ 70 mg/m(2) for the first time received ondansetron and dexamethasone with a standard aprepitant regimen (125 mg on day 1, 80 mg on day 2, 80 mg on day 3) or a single-dose fosaprepitant regimen (150 mg on day 1). The primary end point was complete response (CR; no vomiting, no rescue medication) during OP. Secondary end points were CR during DP and no vomiting during OP. Accrual of 1,113 evaluable patients per treatment arm was planned to confirm noninferiority with expected CR of 67.7% and noninferiority margin of minus 7 percentage points. RESULTS: A total of 2,322 patients were randomly assigned, and 2,247 were evaluable for efficacy. Antiemetic protection with aprepitant and fosaprepitant was equivalent within predefined bounds for noninferiority. Both regimens were well tolerated, although more frequent infusion site pain/erythema/thrombophlebitis was seen with fosaprepitant relative to aprepitant (2.7% v 0.3%, respectively). CONCLUSION: Given with ondansetron and dexamethasone, single-dose intravenous fosaprepitant (150 mg) was noninferior to standard 3-day oral aprepitant in preventing CINV during OP and DP.

[Hypertensive crisis in adolescence...what is it?]. / Crise hipertensiva em adolescente o que será?

Blood pressure in the pediatric age group is percentilated, depending on age, gender and height. Hypertension exists if either systolic or diastolic averages are greater than 95th percentile for age, gender and height. The prevalence of hypertension in the pediatric age group is about one to three percent, many of these patients are mildly affected. The most common cause of hypertension in prepubertal child is renal. By adolescence, the hypertension is primary or essential in majority of cases. We present a case of hypertension in an adolescent of secondary cause.

Chromosome copy number changes carry prognostic information independent of KIT/PDGFRA point mutations in gastrointestinal stromal tumors.

BACKGROUND: Oncogenic point mutations in KIT or PDGFRA are recognized as the primary events responsible for the pathogenesis of most gastrointestinal stromal tumors (GIST), but additional genomic alterations are frequent and presumably required for tumor progression. The relative contribution of such alterations for the biology and clinical behavior of GIST, however, remains elusive. METHODS: In the present study, somatic mutations in KIT and PDGFRA were evaluated by direct sequencing analysis in a consecutive series of 80 GIST patients. For a subset of 29 tumors, comparative genomic hybridization was additionally used to screen for chromosome copy number aberrations. Genotype and genomic findings were cross-tabulated and compared with available clinical and follow-up data. RESULTS: We report an overall mutation frequency of 87.5%, with 76.25% of the tumors showing alterations in KIT and 11.25% in PDGFRA. Secondary KIT mutations were additionally found in two of four samples obtained after imatinib treatment. Chromosomal imbalances were detected in 25 out of 29 tumors (86%), namely losses at 14q (88% of abnormal cases), 22q (44%), 1p (44%), and 15q (36%), and gains at 1q (16%) and 12q (20%). In addition to clinico-pathological high-risk groups, patients with KIT mutations, genomic complexity, genomic gains and deletions at either 1p or 22q showed a significantly shorter disease-free survival. Furthermore, genomic complexity was the best predictor of disease progression in multivariate analysis. CONCLUSIONS: In addition to KIT/PDGFRA mutational status, our findings indicate that secondary chromosomal changes contribute significantly to tumor development and progression of GIST and that genomic complexity carries independent prognostic value that complements clinico-pathological and genotype information.

Hereditary gastrointestinal stromal tumors sharing the KIT Exon 17 germline mutation p.Asp820Tyr develop through different cytogenetic progression pathways.

Hereditary gastrointestinal stromal tumor (GIST) syndrome is a rare autosomal dominant genetic disorder originated by germline mutations in the KIT or PDGFRA genes. We report the third family with hereditary predisposition to GIST due to the KIT Exon 17 germline mutation p.Asp820Tyr and characterize the cytogenetic progression pathways followed by different GIST sharing the same primary genetic event, using a combination of chromosome banding, comparative genomic hybridization (CGH), and fluorescence in situ hybridization (FISH) analyses. The missense mutation p.Asp820Tyr was detected in the proband's rectal and gastric GIST, as well as in his aunt's GIST epiplon metastasis. The mutation p.Asp820Tyr was subsequently also found in the proband's peripheral blood DNA, as well as in that of 4 of 10 relatives thus far analyzed. CGH analysis revealed loss of 14q and 15q in the proband's gastric lesion, whereas FISH analysis of the proband's rectal GIST did not detect loss of 14q and 15q, but instead loss of 4q and 22q and gain of 20q, indicating that the two tumors were independent GIST. Chromosome banding and CGH analyses of the aunt's GIST epiplon metastasis revealed multiple cytogenetic alterations, including 1p loss, but none in common with the two proband's GIST. We conclude that, although the patients share the same KIT Exon 17 germline mutation, the multiple GIST analyzed followed different pathogenetic progression pathways, each of which did not significantly differ from what has been described in sporadic GIST.

[Biosimilars in oncology]. / Biossimilares em oncologia.

The development of biotechnology drugs represents one of the great advances in medical therapy and it was observed an exponential growth in its use. The resource to these drugs in Oncology and Hematology is no exception and it soon became an essential element of an integrated and directed therapy strategy. The expiry of the first biotechnology drugs patents has opened the door for the development and marketing of biosimilars, which entry in the Portuguese market was recently approved. This article was built on the analysis of the available state-of-the-art information on biotechnology drugs, biosimilars and current legislation and it expresses the opinion of Oncology and Hematology experts about the substituition of biological drugs by biosimilars in clinical practice.

[Characterization of oncological disease: racional, objectives and methodology - perfil study]. / Perfil da doença oncológica em Portugal racional, objectivos e metodologia - estudo perfil.

Oncologic disease is one of the main causes of death in Portugal, as well as a high morbidity rate. Over the past few years, these diseases have been targeted with several strategies which aims at optimizing the use of available therapeutic and diagnostic options. Nevertheless, the amount of quantitative information available regarding the disease, patient profile, and treatment and monitoring practices is very low. In order to optimise the implementation of health policies specifically directed at oncologic diseases reliable and up-to-date information is needed, permitting optimisation and balancing of costs and benefits. The PERFIL national epidemiologic study is a multi-centre, retrospective cohort study which aims at evaluating the clinical practice regarding treatment of 6 neoplasias -colorectal, gastric, breast, prostate, lung, and lymphoma, in Portugal, between 2003 and 2007. This study is based upon data collection from the clinical files of patients being followed in the participating centres from 2003 to 2007. Qualitative evaluation (diagnosis and stage) was collected from the clinical records of all patients seen in each participating centre on a given month in each year from 2003 to 2007. The characterization of both patient profile and treatment and monitoring patterns will be based on a far-reaching analysis of 10,000 of those files, selected in a random and stratified sampling. This article describes the PERFIL study rationale, its objectives, and methodology.

[Guidelines for prevention of febrile neutropenia]. / Orientações para a prevenção da neutropenia febril em doentes submetidos a quimioterapia.

Neutropenia and febrile neutropenia are common consequences of some cytotoxic chemotherapy regimens. This situation leads to modifications of the therapeutic regimen, conducting to either dose reduction or cycle delays. Granulocyte colony stimulating factors are commonly used to minimize chemotherapy cytotoxic effect on the granulocytic series. The objective of this study is to assess the available evidence in what concerns the efficacy and safety of granulocyte colony stimulating factors, in several settings of their use. An extensive bibliographic review was performed, including clinical trials, observational studies, systematic reviews, and international guidelines for neutropenia prophylaxis, which aims to establish recommendations on their use, in adequacy to the National reality.

Genotypes at the APOE and SCA2 loci do not predict the course of multiple sclerosis in patients of Portuguese origin.

Multiple sclerosis (MS) is a demyelinating disease that affects about one in 500 young Europeans. In order to test the previously proposed influence of the APOE and SCA2 loci on susceptibility to MS, we studied these loci in 243 Portuguese patients and 192 healthy controls and both parents of 92 patients. We did not detect any significant difference when APOE and SCA2 allele frequencies of cases and controls were compared, or when we compared cases with different forms of the disease. Disequilibrium of transmission was tested for both loci in the 92 trios, and we did not observe segregation distortion. To test the influence of the APOE epsilon4 and SCA2 22 CAGs alleles on severity of disease, we compared age at onset and progression rate between groups with and without those alleles. We did not observe an association of the epsilon4 or the 22 CAGs alleles with rate of progression in our total patient population; allele epsilon4 was associated with increased rate of progression of MS in a subset of patients with less than 10 years of the disease. However, globally in the Portuguese population, the APOE and SCA2 genes do not seem to be useful in the clinical context as prognostic markers of this disorder.

Tratamento cirúrgico no hipertireoidismo: análise prospectiva de 20 pacientes / Surgical treatment of hiperthyroidism: a prospective analysis of 20 patients

Os autores analisam prospectivamente 100 pacientes submetidos à tireoidectomia no período de out. 1994 a maio de 1997. A indicação cirúrgica em 20 pacientes foi por hipotireoidismo, sendo 10 com bócio tóxico multinodular, 5 com nnódulo tóxico solitário e 5 com Doença de Graves. Dos 20 pacientes deste grupo, 14 sofreram tireoidectomia subtotal e 6, tireoidectomia total. Todos retornaram ao ambulatório periódicamente para acompanhamento pós-operatório com controle hormonal. Foram encontrados 6 pacientes no estado eutireoideo, 8 em hipotireoidismo sub-clínico e 6 em hipotireoidismo. Um paciente evoluiu para hipoparatireoídismo e não houve nenhuma lesão de nervo laríngeo recorrente. Os autores concluem que a cirurgia constitui um método eficaz e seguro no tratamento de hipertireoidísmo