Real-World Evidence on the Use of Endocrine Therapy for Ductal Carcinoma In Situ in Patients Treated With Breast-Conserving Surgery Followed by Postoperative Radiation Therapy: A Brazilian Retrospective Cohort Study.

INTRODUCTION/BACKGROUND: This study aims to evaluate the reproducibility of findings from randomized controlled trials regarding adjuvant hormone therapy (HT) for breast ductal carcinoma in situ (DCIS) in a real-life scenario. MATERIALS/METHODS: This retrospective cohort study used Fundação Oncocentro de São Paulo database. It included DCIS patients DCIS who received breast-conserving surgery and postoperative radiation therapy. The endpoints were local control (LC), breast cancer-specific survival (BCSS), and overall survival (OS). RESULTS: We analyzed 2192 patients treated between 2000 and 2020. The median FU was 48.99 months. Most patients (53.33%; n = 1169) received adjuvant HT. Patients not receiving adjuvant HT tend to be older (P = .021) and have a lower educational level (P < .001). At the end of FU, 1.5% of patients had local recurrence, and there was no significant difference between groups (P = .19). The 10-year OS and BCSS were 89.4% and 97.5% for adjuvant HT versus 91.5% and 98.5% for no adjuvant HT, respectively, and there were no significant differences between groups. The 10-year OS was 93.25% for medium/high education level versus 87.31% for low (HR for death 0.51; 95% CI, 0.32-0.83; P = .007). CONCLUSIONS: The benefits of adjuvant HT for DCIS were not reproduced in a Brazilian cohort. Education significantly impacted survival and HT usage, reflecting the influence of socioeconomic factors. These findings can allow for more precise interventions.

Real-world treatment outcomes in HR+ HER2- metastatic breast cancer patients treated with CDK4/6 inhibitors: Results from a reference center in Brazil.

BACKGROUND: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have been recently developed and introduced into clinical practice. METHODS: We retrospectively analyzed data from patients with confirmed HR+/HER2 metastatic breast cancer treated with hormonal therapy in combination with ribociclib (R), palbociclib (P), or abemaciclib (A). OUTCOMES: median progression-free survival (mPFS), time to treatment discontinuation (mTTD), and objective response rate (ORR). RESULTS: Between January 2016 - June 2021, 142 patients were treated with an CDK4/6i (79 P, 42 R, 21 A). The median age was 59 years and 67.6% had recurrent disease. Roughly 35.2%, 36.6%, 28.2% of the patients had 1, 2 or 3+ metastatic sites, respectively, and 55.6% of the patients received CDK4/6i as a first-line treatment. The mPFS was 28m(R) vs. 14m(P) vs. 6m(A) (P = 0.002), with a higher proportion of patients receiving R in the first-line setting. However, no difference was seen when the analysis was restricted to the first-line scenario (P = 0.193). Sixty-four patients required one dose reduction, and 19 patients required two. ORR was 76.2% (R) vs 62% (P) vs 42.9% (A). More patients achieved a complete response with R and P, with no difference in the incidence of partial response and stable disease. Adverse events occurred in 94.4% of the population, with the most common grade 3-4 AE being neutropenia (59.1%). CONCLUSIONS: Our results confirm the efficacy and tolerability of CDK4/6i in routine clinical practice. This is the first real-world data describing and comparing the efficacy and toxicity of CDK4/6i in the Brazilian population.

Aberrant FGFR signaling mediates resistance to CDK4/6 inhibitors in ER+ breast cancer.

Using an ORF kinome screen in MCF-7 cells treated with the CDK4/6 inhibitor ribociclib plus fulvestrant, we identified FGFR1 as a mechanism of drug resistance. FGFR1-amplified/ER+ breast cancer cells and MCF-7 cells transduced with FGFR1 were resistant to fulvestrant ± ribociclib or palbociclib. This resistance was abrogated by treatment with the FGFR tyrosine kinase inhibitor (TKI) lucitanib. Addition of the FGFR TKI erdafitinib to palbociclib/fulvestrant induced complete responses of FGFR1-amplified/ER+ patient-derived-xenografts. Next generation sequencing of circulating tumor DNA (ctDNA) in 34 patients after progression on CDK4/6 inhibitors identified FGFR1/2 amplification or activating mutations in 14/34 (41%) post-progression specimens. Finally, ctDNA from patients enrolled in MONALEESA-2, the registration trial of ribociclib, showed that patients with FGFR1 amplification exhibited a shorter progression-free survival compared to patients with wild type FGFR1. Thus, we propose breast cancers with FGFR pathway alterations should be considered for trials using combinations of ER, CDK4/6 and FGFR antagonists.

A Rare Case of Glioblastoma Multiforme with Osseous Metastases.

Glioblastoma multiforme is the most common malignant primary central nervous system neoplasm in adults. It has a very aggressive natural history with a median overall survival estimated at 14.6 months despite multimodality treatment. Extracranial metastases are very rare with few case reports published to date. We report the case of a 65-year-old male who underwent maximal safe resection for a newly diagnosed brain mass after presentation with new neurologic symptoms. He then received standard postsurgical adjuvant treatment for glioblastoma. Subsequently, he underwent another resection for early progressive disease. Several months later, he was hospitalized for new-onset musculoskeletal complaints. Additional investigation revealed new metastatic osseous lesions which were initially felt to be a new malignancy. The patient opted for supportive care and died 12 days later. Despite choosing no treatment, he elected to undergo a bone biopsy to understand the new underlying process. Results were that of metastatic GBM and were reported after the patient expired. Physicians caring for patients with GBM and new nonneurologic symptoms may contemplate body imaging.

Chemotherapy for advanced non-small cell lung cancer in the elderly population.

BACKGROUND:: Approximately 50% of patients with newly diagnosed non-small cell lung cancer (NSCLC) are over 70 years of age at diagnosis. Despite this fact, these patients are underrepresented in randomized controlled trials (RCTs). As a consequence, the most appropriate regimens for these patients are controversial, and the role of single-agent or combination therapy is unclear. In this setting, a critical systematic review of RCTs in this group of patients is warranted. OBJECTIVES:: To assess the effectiveness and safety of different cytotoxic chemotherapy regimens for previously untreated elderly patients with advanced (stage IIIB and IV) NSCLC. To also assess the impact of cytotoxic chemotherapy on quality of life. METHODS:: Search methods: We searched the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 10), MEDLINE (1966 to 31 October 2014), EMBASE (1974 to 31 October 2014), and Latin American Caribbean Health Sciences Literature (LILACS) (1982 to 31 October 2014). In addition, we handsearched the proceedings of major conferences, reference lists from relevant resources, and the ClinicalTrial.gov database.Selection criteria: We included only RCTs that compared non-platinum single-agent therapy versus non-platinum combination therapy, or non-platinum therapy versus platinum combination therapy in patients over 70 years of age with advanced NSCLC. We allowed inclusion of RCTs specifically designed for the elderly population and those designed for elderly subgroup analyses.Data collection and analysis: Two review authors independently assessed search results, and a third review author resolved disagreements. We analyzed the following endpoints: overall survival (OS), one-year survival rate (1yOS), progression-free survival (PFS), objective response rate (ORR), major adverse events, and quality of life (QoL). MAIN RESULTS:: We included 51 trials in the review: non-platinum single-agent therapy versus non-platinum combination therapy (seven trials) and non-platinum combination therapy versus platinum combination therapy (44 trials).Non-platinum single-agent versus non-platinum combination therapyLow-quality evidence suggests that these treatments have similar effects on overall survival (hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.72 to 1.17; participants = 1062; five RCTs), 1yOS (risk ratio (RR) 0.88, 95% CI 0.73 to 1.07; participants = 992; four RCTs), and PFS (HR 0.94, 95% CI 0.83 to 1.07; participants = 942; four RCTs). Non-platinum combination therapy may better improve ORR compared with non-platinum single-agent therapy (RR 1.79, 95% CI 1.41 to 2.26; participants = 1014; five RCTs; low-quality evidence).Differences in effects on major adverse events between treatment groups were as follows: anemia: RR 1.10, 95% 0.53 to 2.31; participants = 983; four RCTs; very low-quality evidence; neutropenia: RR 1.26, 95% CI 0.96 to 1.65; participants = 983; four RCTs; low-quality evidence; and thrombocytopenia: RR 1.45, 95% CI 0.73 to 2.89; participants = 914; three RCTs; very low-quality evidence. Only two RCTs assessed quality of life; however, we were unable to perform a meta-analysis because of the paucity of available data.Non-platinum therapy versus platinum combination therapyPlatinum combination therapy probably improves OS (HR 0.76, 95% CI 0.69 to 0.85; participants = 1705; 13 RCTs; moderate-quality evidence), 1yOS (RR 0.89, 95% CI 0.82 to 0.96; participants = 813; 13 RCTs; moderate-quality evidence), and ORR (RR 1.57, 95% CI 1.32 to 1.85; participants = 1432; 11 RCTs; moderate-quality evidence) compared with non-platinum therapies. Platinum combination therapy may also improve PFS, although our confidence in this finding is limited because the quality of evidence was low (HR 0.76, 95% CI 0.61 to 0.93; participants = 1273; nine RCTs).Effects on major adverse events between treatment groups were as follows: anemia: RR 2.53, 95% CI 1.70 to 3.76; participants = 1437; 11 RCTs; low-quality evidence; thrombocytopenia: RR 3.59, 95% CI 2.22 to 5.82; participants = 1260; nine RCTs; low-quality evidence; fatigue: RR 1.56, 95% CI 1.02 to 2.38; participants = 1150; seven RCTs; emesis: RR 3.64, 95% CI 1.82 to 7.29; participants = 1193; eight RCTs; and peripheral neuropathy: RR 7.02, 95% CI 2.42 to 20.41; participants = 776; five RCTs; low-quality evidence. Only five RCTs assessed QoL; however, we were unable to perform a meta-analysis because of the paucity of available data. AUTHORS' CONCLUSIONS:: In people over the age of 70 with advanced NSCLC who do not have significant co-morbidities, increased survival with platinum combination therapy needs to be balanced against higher risk of major adverse events when compared with non-platinum therapy. For people who are not suitable candidates for platinum treatment, we have found low-quality evidence suggesting that non-platinum combination and single-agent therapy regimens have similar effects on survival. We are uncertain as to the comparability of their adverse event profiles. Additional evidence on quality of life gathered from additional studies is needed to help inform decision making.

BRAZILIAN CONSENSUS FOR MULTIMODAL TREATMENT OF COLORECTAL LIVER METASTASES. MODULE 3: CONTROVERSIES AND UNRESECTABLE METASTASES.

In the last module of this consensus, controversial topics were discussed. Management of the disease after progression during first line chemotherapy was the first discussion. Next, the benefits of liver resection in the presence of extra-hepatic disease were debated, as soon as, the best sequence of treatment. Conversion chemotherapy in the presence of unresectable liver disease was also discussed in this module. Lastly, the approach to the unresectable disease was also discussed, focusing in the best chemotherapy regimens and hole of chemo-embolization.

Neste último módulo do consenso, abordou-se alguns temas controversos. O primeiro tópico discutido foi o manejo da doença após progressão na primeira linha de quimioterapia, com foco em se ainda haveria indicação cirúrgica neste cenário. A seguir, o painel debruçou-se sobre as situações de ressecção da doença hepática na presença de doença extra-hepática, assim como, qual a melhor sequência de tratamento. O tratamento de conversão para doença inicialmente irressecável também foi abordado neste módulo, incluindo as importantes definições de quando se pode esperar que a doença se torne ressecável e quais esquemas terapêuticos seriam mais efetivos à luz dos conhecimentos atuais sobre a biologia tumoral e taxas de resposta objetiva. Por último, o tratamento da doença não passível de ressecção foi discutida, focando-se nos melhores esquemas a serem empregados e seu sequenciamento, bem como o papel da quimioembolização no manejo destes pacientes.

Chemotherapy for advanced non-small cell lung cancer in the elderly population

ABSTRACT BACKGROUND: Approximately 50% of patients with newly diagnosed non-small cell lung cancer (NSCLC) are over 70 years of age at diagnosis. Despite this fact, these patients are underrepresented in randomized controlled trials (RCTs). As a consequence, the most appropriate regimens for these patients are controversial, and the role of single-agent or combination therapy is unclear. In this setting, a critical systematic review of RCTs in this group of patients is warranted. OBJECTIVES: To assess the effectiveness and safety of different cytotoxic chemotherapy regimens for previously untreated elderly patients with advanced (stage IIIB and IV) NSCLC. To also assess the impact of cytotoxic chemotherapy on quality of life. METHODS: Search methods: We searched the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 10), MEDLINE (1966 to 31 October 2014), EMBASE (1974 to 31 October 2014), and Latin American Caribbean Health Sciences Literature (LILACS) (1982 to 31 October 2014). In addition, we handsearched the proceedings of major conferences, reference lists from relevant resources, and the ClinicalTrial.gov database. Selection criteria: We included only RCTs that compared non-platinum single-agent therapy versus non-platinum combination therapy, or non-platinum therapy versus platinum combination therapy in patients over 70 years of age with advanced NSCLC. We allowed inclusion of RCTs specifically designed for the elderly population and those designed for elderly subgroup analyses. Data collection and analysis: Two review authors independently assessed search results, and a third review author resolved disagreements. We analyzed the following endpoints: overall survival (OS), one-year survival rate (1yOS), progression-free survival (PFS), objective response rate (ORR), major adverse events, and quality of life (QoL). MAIN RESULTS: We included 51 trials in the review: non-platinum single-agent therapy versus non-platinum combination therapy (seven trials) and non-platinum combination therapy versus platinum combination therapy (44 trials). Non-platinum single-agent versus non-platinum combination therapy Low-quality evidence suggests that these treatments have similar effects on overall survival (hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.72 to 1.17; participants = 1062; five RCTs), 1yOS (risk ratio (RR) 0.88, 95% CI 0.73 to 1.07; participants = 992; four RCTs), and PFS (HR 0.94, 95% CI 0.83 to 1.07; participants = 942; four RCTs). Non-platinum combination therapy may better improve ORR compared with non-platinum single-agent therapy (RR 1.79, 95% CI 1.41 to 2.26; participants = 1014; five RCTs; low-quality evidence). Differences in effects on major adverse events between treatment groups were as follows: anemia: RR 1.10, 95% 0.53 to 2.31; participants = 983; four RCTs; very low-quality evidence; neutropenia: RR 1.26, 95% CI 0.96 to 1.65; participants = 983; four RCTs; low-quality evidence; and thrombocytopenia: RR 1.45, 95% CI 0.73 to 2.89; participants = 914; three RCTs; very low-quality evidence. Only two RCTs assessed quality of life; however, we were unable to perform a meta-analysis because of the paucity of available data. Non-platinum therapy versus platinum combination therapy Platinum combination therapy probably improves OS (HR 0.76, 95% CI 0.69 to 0.85; participants = 1705; 13 RCTs; moderate-quality evidence), 1yOS (RR 0.89, 95% CI 0.82 to 0.96; participants = 813; 13 RCTs; moderate-quality evidence), and ORR (RR 1.57, 95% CI 1.32 to 1.85; participants = 1432; 11 RCTs; moderate-quality evidence) compared with non-platinum therapies. Platinum combination therapy may also improve PFS, although our confidence in this finding is limited because the quality of evidence was low (HR 0.76, 95% CI 0.61 to 0.93; participants = 1273; nine RCTs). Effects on major adverse events between treatment groups were as follows: anemia: RR 2.53, 95% CI 1.70 to 3.76; participants = 1437; 11 RCTs; low-quality evidence; thrombocytopenia: RR 3.59, 95% CI 2.22 to 5.82; participants = 1260; nine RCTs; low-quality evidence; fatigue: RR 1.56, 95% CI 1.02 to 2.38; participants = 1150; seven RCTs; emesis: RR 3.64, 95% CI 1.82 to 7.29; participants = 1193; eight RCTs; and peripheral neuropathy: RR 7.02, 95% CI 2.42 to 20.41; participants = 776; five RCTs; low-quality evidence. Only five RCTs assessed QoL; however, we were unable to perform a meta-analysis because of the paucity of available data. AUTHORS' CONCLUSIONS: In people over the age of 70 with advanced NSCLC who do not have significant co-morbidities, increased survival with platinum combination therapy needs to be balanced against higher risk of major adverse events when compared with non-platinum therapy. For people who are not suitable candidates for platinum treatment, we have found low-quality evidence suggesting that non-platinum combination and single-agent therapy regimens have similar effects on survival. We are uncertain as to the comparability of their adverse event profiles. Additional evidence on quality of life gathered from additional studies is needed to help inform decision making

Brazilian consensus for multimodal treatment of colorectal liver metastases. module 3: controversies and unresectable metastases / Consenso brasileiro de tratamento multidisciplinar de metástase hepática de origem colorretal módulo 3: controvérsias e metástases irressecáveis

ABSTRACT In the last module of this consensus, controversial topics were discussed. Management of the disease after progression during first line chemotherapy was the first discussion. Next, the benefits of liver resection in the presence of extra-hepatic disease were debated, as soon as, the best sequence of treatment. Conversion chemotherapy in the presence of unresectable liver disease was also discussed in this module. Lastly, the approach to the unresectable disease was also discussed, focusing in the best chemotherapy regimens and hole of chemo-embolization.

RESUMO Neste último módulo do consenso, abordou-se alguns temas controversos. O primeiro tópico discutido foi o manejo da doença após progressão na primeira linha de quimioterapia, com foco em se ainda haveria indicação cirúrgica neste cenário. A seguir, o painel debruçou-se sobre as situações de ressecção da doença hepática na presença de doença extra-hepática, assim como, qual a melhor sequência de tratamento. O tratamento de conversão para doença inicialmente irressecável também foi abordado neste módulo, incluindo as importantes definições de quando se pode esperar que a doença se torne ressecável e quais esquemas terapêuticos seriam mais efetivos à luz dos conhecimentos atuais sobre a biologia tumoral e taxas de resposta objetiva. Por último, o tratamento da doença não passível de ressecção foi discutida, focando-se nos melhores esquemas a serem empregados e seu sequenciamento, bem como o papel da quimioembolização no manejo destes pacientes.

Chemotherapy for Advanced Non-Small-Cell Lung Cancer in Elderly Patients.

CLINICAL QUESTION: Do patients above 70 years of age with newly diagnosed advanced non-small-cell lung cancer benefit from platinum-based combination or should they receive non-platinum agents either as single-agent or in combination? BOTTOM LINE: For fit elderly patients platinum-based combination is associated with better overall survival, progression-free survival, and objective response rate, however this improvement should be counter balanced against the higher risk of major adverse events (AE).

The role of the implementation of policies for the prevention of exposure to Radon in Brazil-a strategy for controlling the risk of developing lung cancer.

Lung cancer is the leading cause of cancer death in the United States and other industrialised countries. The most important risk factor is active smoking. However, given the increased incidence of lung cancer in non-smokers, it is necessary to improve knowledge regarding other risk factors. Radon (Rn) is a noble gas and is the most important natural source of human exposure to ionizing radiation. Exposure to high levels of this radioactive gas is related to an increased risk of developing lung cancer. The objective of this work is to highlight the importance of measuring indoor concentration of this gas and identify which steps should be taken for achieving radiological protection. A survey was conducted on the websites of the National Health Surveillance Agency (ANVISA), LAMIN (Mineral Analysis Laboratory), CPRM (Geological Survey of Brazil), Ministry of Health and PubMed. Using the words 'radon', 'lung', 'cancer', and PubMed®, 1,371 results were obtained; when using the words 'radon', 'lung', 'cancer', and with 'Brazil' or 'Brazilians', only six results were obtained. We emphasise that lung cancer is a major public health problem and the exposure to Rn indoors should be considered as a risk factor for lung cancer in non-smokers. Buildings or houses with high concentrations of Rn should be identified. However, currently in Brazil-a country with great potential for mineral extraction-there are no specific regulated recommendations to control indoor exposure to Rn.

Combination of afatinib with cetuximab in patients with EGFR-mutant non-small-cell lung cancer resistant to EGFR inhibitors.

Tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR) have shown effectiveness for advanced non-small-cell lung cancer (NSCLC) with activating mutations in the EGFR gene. However, resistance to the EGFR TKIs develops mostly secondary to T790M mutation in exon 20. The use of afatinib associated with cetuximab represents a new possibility of therapy following progression on gefitinib or erlotinib. We present two patients who acquired resistance to first-generation TKI and who underwent combination treatment with afatinib plus cetuximab as third-line therapy. Both patients presented partial response, and the time duration of disease control was 8 months and 10 months. The combined use of afatinib plus cetuximab emerges as a new possibility for the treatment of patients with advanced NSCLC harboring mutated EGFR after progression on first-generation EGFR TKIs with consequently acquired resistance to TKIs. Further studies are necessary to consolidate the data.

VEGF-A levels in bevacizumab-treated breast cancer patients: a systematic review and meta-analysis.

Bevacizumab may improve outcomes of patients with breast cancer, but the absence of an established biomarker hampers patient selection and researchers´ ability to demonstrate a clear survival benefit. Its putative target, circulating VEGF-A, emerged as the main candidate and we sought to identify the relationship between VEGF-A levels and outcomes through systematic review. We searched electronic databases and meeting proceedings for randomized controlled trials (RCTs) comparing the addition of bevacizumab to standard chemotherapy for breast cancer. RCTs were included if outcomes were presented separately according to VEGF-A plasma levels. Random-effects model were applied to calculate the pooled hazard ratios for progression-free survival, event-free survival (EFS), comprising disease recurrence, progression or any-cause death, and overall survival (OS), with respective confidence intervals (95 % CI). High and low VEGF-A levels subgroups followed each trial definition, and results were compared using the interaction test. Heterogeneity was calculated using χ (2) test (I (2)). Three trials enrolled a total of 3748 patients. 1713 patients had baseline VEGF-A levels in plasma available for assessment and were included. One trial added bevacizumab in the adjuvant setting (N = 2591) and two on first-line metastatic disease with taxane-based therapy (N = 1160) There was no interaction between VEGF-A levels and study setting (adjuvant vs. first line therapy). Bevacizumab improved PFS of patients with above median VEGF-A plasma levels (HR 0.56; 95 % CI 0.43-0.73; P < 0.001; I (2) = 0 %), but not of those with below median VEGF-A levels (HR 0.89; 95 % CI 0.68-1.15; P = 0.37; I (2) = 0 %), with relevant differences between these two groups, P-for interaction = 0.02. The same happened with EFS (VEGF-A above median HR 0.62; 95 % CI 0.39-0.79; P < 0.001; I (2) = 11 %; below median HR 0.89; 95 % CI 0.71-1.14; P = 0.98; I (2) = 17 %; P-for interaction = 0.03). OS data were not available. VEGF-A level is a reasonable candidate biomarker for bevacizumab in the treatment of breast cancer. Further studies have to confirm its surrogacy in overall survival and in other scenarios including other anti-angiogenic therapies.

Clinical Response to Sorafenib in a Patient with Metastatic Colorectal Cancer and FLT3 Amplification.

BACKGROUND: A considerable number of patients with metastatic colorectal cancer progress after exhausting all approved standard therapies but maintain an adequate performance status and could be candidates for further treatment. We aim at reviewing our experience with sorafenib treatment of a patient with FLT3 mutation in refractory metastatic colorectal cancer. METHODS: Treatment with sorafenib of a patient with metastatic colorectal cancer and FLT3 translocation who had previously been heavily treated. RESULTS: The patient with metastatic colorectal cancer, aged 51 years, showed significant symptomatic and laboratory improvement with sorafenib treatment (400 mg twice daily). CONCLUSION: The presented case illustrates how an aggressive and refractory colorectal tumor may respond well to targeted therapy.

Interpretation of PET/CT findings in patients with advanced lung cancer who have undergone pleurodesis.

A consensus has not yet been reached for the ideal moment to carry out pleurodesis in patients with malignant pleural effusion among the majority of centres, especially those which don't specialise in oncologic treatment. The PET (positron emission tomography)/CT (computed tomography) used in the staging of patients with non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) has caused controversy when used in the evaluation of therapeutical response and in detection of recurrence in patients with pleurodesis. For not distinguishing between inflammatory and neoplasic processes while using PET or CT, suspicion of pleural involvement can result in the indication for invasive diagnostic procedures or inadequate exchange of therapy. In such cases, the hypothesis of the inflammatory process must be included in the differential diagnoses for positive findings with the PET/CT in patients with NSCLC who have undergone pleurodesis, independently of time since the procedure. The reports of two patients with NSCLC have been presented in order to illustrate situations in which pleurodesis has been performed at the moment of diagnosis, outside of a cancer centre.

Carcinoma metaplásico de mama: a importância da confirmação anatomopatológica / Metaplastic breast carcinoma: the importance of anatomopathologic confirmation

Objetivo: Comparar o diagnóstico inicial, geralmente a partir de serviços de patologia geral, com o laudo médico definitivo do serviço de patologia certificada. Métodos: Análise retrospectiva de pacientes em uma instituição com diagnóstico final de câncer de mama metaplásico (CMM) foi realizada entre janeiro de 2008 e janeiro de 2014. Resultados: Um total de 18 pacientes com diagnóstico de CMM do sexo feminino e idade média de 49,8 anos foi reportado. O tamanho tumoral foi menor do que 3,0 cm em 52,9% das pacientes. Linfadenopatia axilar não estava presente inicialmente em 72,2% das pacientes e, em nenhum caso, foi identificada metástase a distância ao diagnóstico. Diagnóstico prévio de carcinoma ductal invasivo (CDI) foi descrito em 60% dos casos. Cerca de 80% foram tratadas com quimioterapia neoadjuvante e apresentaram progressão. Apenas um caso com diagnóstico de CMM antes do início da terapia recebeu quimioterapia neoadjuvante com platina e apresentou resposta clínica. Conclusão: Devido às características histopatológicas de triplo-negativos, o CMM pode ter sido subdiagnosticado em serviços de patologia geral. Nos casos de ausência de resposta ou progressão da doença frente ao tratamento tradicional, o diagnóstico de CMM deve ser considerado e o laudo médico deve ser revisado.

Objective: To compare the initial diagnosis, usually from community pathology services, with the final pathology report from certified pathology service. Methods: A retrospective analysis of patients in an institution with final diagnosis of metaplastic breast cancer (MBC) was conducted from January 2008 to January 2014. Results: There were 18 female patients diagnosed with MBC. Median age was 49.8 years old; 52.9% of the patients had a tumor size less than 3.0 cm; 72.2% had no axillary lymphadenopathy at diagnosis. None of them had distant metastases at presentation. Initial diagnosis of invasive ductal carcinoma (IDC) occurred in 60% of patients. Eighty percent of patients were treated with neo-adjuvant chemotherapy and presented progression. Only one case with diagnosis of MBC prior to therapy was submitted to neo-adjuvant chemotherapy with a platinum-based regimen and presented clinical response. Conclusion: Due to the triple-negative histopathology features, MBC might have been underdiagnosed in community pathology services. In cases of non-response or progression of the disease regarding the traditional treatment, MBC diagnosis should be considered and the medical report must be reviewed.

Meningeal carcinomatosis in solid tumors / Carcinomatose meníngea em tumores sólidos

The involvement of the leptomeninges by metastatic tumors can be observed in solid tumors, in which case it is termed meningeal carcinomatosis (MC), and in lymphoproliferative malignant disease. It is more common in breast and lung cancer, as well as melanoma, with adenocarcinoma being the most frequent histological type. MC is usually a late event, with disseminated and progressive disease already present and, it is characterized by multifocal neurological signs and symptoms. Diagnosis is based on the evaluation of clinical presentation, cerebrospinal fluid and neuroimaging studies. The better systemic disease control is observed with new therapeutic agents, and the development of neuroimaging methods is responsible for the increasing incidence of such metastatic evolution. Intrathecal chemotherapy is generally the treatment of choice, although frequently palliative. Prognosis is guarded, although a higher performance status may indicate a subgroup of patients with a more favorable outcome.

O acometimento leptomeníngeo por metástases tumorais pode ocorrer em tumores sólidos, sendo chamado de carcinomatose meníngea (CM), e também em doenças linfoproliferativas. Tumores de mama, pulmão e melanoma são os principais responsáveis pelos casos, e adenocarcinoma é a histologia mais frequentemente encontrada. A CM é um evento tardio na evolução da doença e caracteriza-se por sinais e sintomas neurológicos multifocais. O diagnóstico se faz pela avaliação conjunta do quadro clínico, neuroimagem e estudo do líquido cefalorraquidiano. O maior controle da doença sistêmica obtido com as novas modalidades terapêuticas e a baixa penetração de drogas no sistema nervoso central, aliados ao desenvolvimento nos métodos de neuroimagem observado nas últimas décadas, são fatores que respondem por um aumento na incidência desta apresentação. A quimioterapia intratecal é o tratamento de escolha, porém, frequentemente paliativo. O prognóstico é reservado, sendo que o melhor performance status pode selecionar um subgrupo de pacientes com melhor evolução.

Meningeal carcinomatosis in breast cancer: prognostic factors and outcome.

Meningeal carcinomatosis (MC) occurs in up to 5% of breast cancer patients. Few studies have evaluated prognostic markers in breast cancer patients with MC. Our aim was to describe the treatment of breast cancer patients with MC, and identify prognostic factors related to survival. Sixty breast cancer patients that had a diagnosis of MC between January 2003 and December 2009 were included. The median age was 46 years (range 27-76). Most patients had invasive ductal carcinoma (78.3%) and high histological/nuclear grade (61.7/53.3%). Estrogen and progesterone receptors were positive in 51.7 and 43.3% of patients, respectively, and 15% were HER-2-positive. Symptoms at presentation were headache, cranial nerve dysfunction, seizures, and intracranial hypertension signals. Diagnosis was made by CSF cytology in 66.7% of cases and by MRI in 71.7%. Intrathecal (IT) chemotherapy was used in 68.3% of patients, and 21.6% received a new systemic treatment (chemo- or hormone therapy). Median survival was 3.3 months (range 0.03-90.4). There was no survival difference according to age, nuclear grade, hormonal and HER-2 status, CSF features, sites of metastasis, systemic and IT chemotherapy, or radiotherapy. However, histological grade and performance status had a significant impact on survival in the multivariate analysis. Only four papers have addressed prognostic factors in breast cancer patients with MC in the last two decades. The results of those reports are discussed here. High histological grade and poor performance status seem to impact survival of breast cancer patients with MC. Prospective studies are necessary to clarify the role of IT and systemic treatment in the treatment of those patients.

Meningeal carcinomatosis in solid tumors.

The involvement of the leptomeninges by metastatic tumors can be observed in solid tumors, in which case it is termed meningeal carcinomatosis (MC), and in lymphoproliferative malignant disease. It is more common in breast and lung cancer, as well as melanoma, with adenocarcinoma being the most frequent histological type. MC is usually a late event, with disseminated and progressive disease already present and, it is characterized by multifocal neurological signs and symptoms. Diagnosis is based on the evaluation of clinical presentation, cerebrospinal fluid and neuroimaging studies. The better systemic disease control is observed with new therapeutic agents, and the development of neuroimaging methods is responsible for the increasing incidence of such metastatic evolution. Intrathecal chemotherapy is generally the treatment of choice, although frequently palliative. Prognosis is guarded, although a higher performance status may indicate a subgroup of patients with a more favorable outcome.

Gefitinibe no tratamento de pacientes com câncer avançado de não-pequenas células do pulmão em um programa de acesso expandido: experiência de uma única instituição / Gefitinib for patients with advanced non-small cell lung cancer treated on the expanded access program: a single institution experience

Relatamos uma análise retrospectiva dos pacientes com câncer de pulmão não-pequenas células avançado tratados com gefitinib no programa de acesso expandido. Pacientes com câncer de pulmão não-pequenas células avançado e “performance status” de Karnofsky ≥ 50% foram selecionados para receber gefitinib 250 mg uma vez ao dia. Nenhum outro tratamento sistêmicoantineoplásico era permitido. De junho/2002 a abril/2003, foram incluídos 31 pacientes com idade entre 38 e 84 anos, sendo 20 homens e 11 mulheres. O “performance status” de Karnofsky mediano foi 80% e 25 pacientes tinham história de tabagismo. Trinta pacientes apresentavam estádio clínico IV e 1 paciente apresentava estádio clínico IIIB. A taxa de resposta objetiva foi de 14%. Não houve respostacompleta. Dez pacientes apresentaram doença estável por mais de 6 meses, proporcionando uma taxa de resposta mais doença estável de 50%. A sobrevida mediana livre de progressão foi de 3,6 meses, e a sobrevida global mediana foi de 4 meses. A taxa de sobrevida em um ano foi de 19%. O perfil de toxicidade em geral foi leve, com diarréia grau 1 (42%) e 2 (11%) e rash cutâneo grau 1 (16%) sendo osefeitos colaterais mais observados. Embora seja uma pequena amostra de pacientes, nossos dados são similares aos dados de estudos publicados, confirmando a eficácia e segurança do gefitinib em um grupo de pacientes previamente tratados. Neste estudo, ospacientes selecionados apresentavam apenas alguns critérios essenciais de elegibilidade, o que torna nossos dados reprodutíveis e aplicáveis aos pacientes atendidos na comunidade.