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1.
Expert Rev Anticancer Ther ; : 1-9, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32779501

RESUMO

INTRODUCTION: Cancer of unknown primary (CUP) is a disease entity encompassing heterogeneous malignancies without a clinically-detectable anatomical primary. It is usually a poor prognosis malignancy with dismal prognosis where molecular and genetic testing were expected to be a major breakthrough. AREAS COVERED: In this review, we provide an overview of the advances in the understanding of the carcinogenesis, biology, diagnosis and treatment of patients with CUP. This review focuses on the advantages and inconveniences of immunohistochemistry and CUP classifiers in assessing the progress in the management of CUP. EXPERT OPINION: CUP classifiers were expected to gradually replace the classical multistep approach in identifying the culprit tumors to guide site-specific therapy. Immunohistochemistry staining led to the prediction of a single tissue of origin in 10.8-51%. CUP classifiers identified the primary site in 61-89% of these cases and were concordant with immunohistochemistry in 57.1-100%. Immunohistochemistry is cheap, fast and broadly available whereas CUP classifiers are less widely available and have not been validated in randomized control trials. The diagnostic recommendations consist of a standard pathology evaluation based on morphology and algorithmic immunohistochemistry assessment. Physicians should weigh in the input of the CUP classifier to the clinical picture and pathology investigations before performing additional investigations.

2.
Future Oncol ; 16(26): 1969-1976, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32567377

RESUMO

Aim: This article refers to the European School of Oncology Clinical Training Centers (CTCs) program, which is a granted Fellowships program dedicated to young oncologists in training. Materials & methods: A total of 74 fellowships were offered by several CTCs during the last 7 years. Candidates were enrolled for 3-6 months of training rotations as fellows or observers in more than 30 training programs in well known Cancer Centers around Europe. Fellowships were covering medical, surgical, radiation and pediatric oncology specialties, laboratory diagnostic training and experimental, translational and clinical research. Fellows originated from Europe, Latin America and Mediterranean Africa. Results: Analysis of the questionnaire assessment showed that 95.5% of the fellows evaluated CTC programs with an 'excellent' or 'very good' score, while 100% declare that they had reached their objectives. Conclusion: The European School of Oncology CTC program designed for an additional practical education abroad meets the needs of young oncologists.

3.
Crit Rev Oncol Hematol ; 151: 102976, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32389896

RESUMO

We investigated the impact of the European School of Oncology's (ESO) Masterclass (MCO) in Clinical Oncology on the career development of young participants. MCO represents the flagship educational activity of ESO and is organized annually, mostly in collaboration with the European Society for Medical Oncology (ESMO) in five different geographical regions. A questionnaire consisting of 21 questions was sent to all doctors who attended the ESO MCOs from 2009 to 2016. The 228 responders were mostly from European countries and hold the specialty of Medical Oncology. Ninety-five percent of them evaluated ESO MCOs as "extremely useful" or "useful" for their professional career. Around 60% were trained at University Hospitals or Cancer Institutes and currently, one-third of them are employed in Academic Centers. Eighty percent have performed translational or clinical research and 77.5% were able to publish in pertinent international journals. The contribution of ESO MCOs to trainees' career development in different oncology disciplines around the world is discussed.


Assuntos
Educação Médica Continuada , Educação Profissionalizante/organização & administração , Oncologia/educação , Neoplasias , Médicos , Europa (Continente) , Humanos , Oncologia/tendências , Inquéritos e Questionários
4.
Nat Rev Clin Oncol ; 17(9): 541-554, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32350398

RESUMO

Cancer of unknown primary (CUP) is an enigmatic disease entity encompassing heterogeneous malignancies without a detectable primary tumour, despite a thorough diagnostic workup. A minority of patients with CUP (15-20%) can be assigned a putative primary tissue of origin according to clinical and histopathological findings and typically have a more favourable prognosis with the use of corresponding tumour type-specific therapies. Thus, the majority of patients with CUP have disease that cannot be assigned to a culprit primary tumour, are treated with empirical chemotherapy and have a poor prognosis. In the molecular era, the use of (epi)genomic or transcriptomic CUP classifiers and DNA or RNA sequencing offers two, sometimes overlapping, therapeutic strategies: tumour type-specific therapy and biomarker-guided therapy. Published data reveal that the accuracy of site-of-origin predictions made using CUP classifiers ranges between 54% and 98% when compared with the assignment made according to the recommended clinicopathological criteria. These advances have led to promising results in non-randomized prospective studies evaluating the efficacy of tumour type-specific therapy; however, the favourable outcomes were not confirmed in randomized controlled studies comparing this approach with standard empirical chemotherapy. Currently, the evidence supporting the use of biomarker-guided therapies is limited to case reports and small case series. In this Review, we discuss the clinical management of CUP in the era of precision medicine. We focus on the advances in understanding the biology of CUP, the implications for the diagnosis and classification of CUP according to the tissue of origin and the shift away from empirical therapy towards tailored therapy.

5.
J Cancer Educ ; 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32303982

RESUMO

In this article, we report on the clinical case presentations that have been delivered during the ESO or ESO-ESMO Masterclasses in Clinical Oncology in the last 10 years. Masterclasses have been held in three different geographical continents including Europe, Middle East, and Latin America, in which participants had to submit a clinical case and present it either in front of a tumor board (multidisciplinary-like sessions) or in small groups. Clinical case presentation is a unique part of the educational program preparing young oncologists to present and discuss their own patients with distinguished experts. In each Masterclass, between 40 and 55 clinical cases-depending on the number of participants-are presented. All presentations are assessed and evaluated by faculty members as well as by the rest of the participants.

6.
Drugs R D ; 20(2): 55-73, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32215876

RESUMO

Genetic complexity and DNA damage repair defects are common in different cancer types and can induce tumor-specific vulnerabilities. Poly(ADP-ribose) polymerase (PARP) inhibitors exploit defects in the DNA repair pathway through synthetic lethality and have emerged as promising anticancer therapies, especially in tumors harboring deleterious germline or somatic breast cancer susceptibility gene (BRCA) mutations. However, the utility of PARP inhibitors could be expanded beyond germline BRCA1/2 mutated cancers by causing DNA damage with cytotoxic agents in the presence of a DNA repair inhibitor. US Food and Drug Administration (FDA)-approved PARP inhibitors include olaparib, rucaparib, and niraparib, while veliparib is in the late stage of clinical development. Talazoparib inhibits PARP catalytic activity, trapping PARP1/2 on damaged DNA, and it has been approved by the US FDA for the treatment of metastatic germline BRCA1/2 mutated breast cancers in October 2018. The talazoparib side effect profile more closely resembles traditional chemotherapeutics rather than other clinically approved PARP inhibitors. In this review, we discuss the scientific evidence that has emerged from both experimental and clinical studies in the development of talazoparib. Future directions will include optimizing combination therapy with chemotherapy, immunotherapies and targeted therapies, and in developing and validating biomarkers for patient selection and stratification, particularly in malignancies with 'BRCAness'.

7.
Br J Cancer ; 122(8): 1124-1132, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32042068

RESUMO

Cancer of unknown primary (CUP) affects a small percentage of the general population. Nonetheless, a substantial number of these patients have a poor prognosis and consequently succumb to their illness within a year of diagnosis. The natural history of CUP is characterised by early metastasis from the unknown primary site, aggressive course and resistance to conventional chemotherapy. Unfortunately, the processes by which this orphan disease originates and progresses have not been fully elucidated and its biology remain unclear. Despite the conceptual progress in genetic and molecular profiling made over the past decade, recognition of the genetic and molecular abnormalities involved in CUP, as well as the identification of the tissue of origin remain unresolved issues. This review will outline the biology of CUP by exploring the hallmarks of cancer in order to rationalise the complexities of this enigmatic syndrome. This approach will help the reader to understand where research efforts currently stand and the pitfalls of this quest.

8.
Crit Rev Oncol Hematol ; 147: 102882, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32106012

RESUMO

Cancers of Unknown Primary Site (CUP) account for approximately 1-3 % of all malignant neoplasms. It represents a heterogeneous group of malignancies without a detectable primary and is characterized by aggressive clinical behavior. Patients with CUP are presumably categorized into prognostic subsets according to their clinical and pathological characteristics. The majority of these patients are chemoresistant and treated with empiric chemotherapy regimens which yield limited survival. Recent diagnostic advances have led to the identification of a higher percentage of culprit primaries among which colorectal, lung and renal tumors. The empiric CUP regimens may be suboptimal in these patients which explain in part their poor prognosis. In the absence of prospective randomized studies to prove the benefit of site-specific therapy in these subsets, we reviewed the literature to assess whether CUP with colorectal, lung and renal - profiles should be treated similarly to the correspondent primary tumors.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Primárias Desconhecidas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/diagnóstico , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Primárias Desconhecidas/diagnóstico , Prognóstico
9.
Eur J Cancer ; 127: 118-122, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32007711

RESUMO

Cancers of unknown primary (CUP) are among the most common causes of death due to cancer, are associated with a poor prognosis and have few therapeutic options available. Molecularly-guided site-specific treatments were explored based on the assumption that CUP are similar in their response to treatment of predicted primary tumours. Given the discordant results between these studies, a meta-analysis using a random-effects model and the inverse variance method was performed. MEDLINE and conference abstracts of American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) meetings were searched from inception until November 2019. A trend towards improved OS was noted with site-specific versus empiric treatment for CUP (HR = 0.73; 95% confidence interval (CI) 0.52-1.02). There was significant heterogeneity across the four studies (I [2] = 79%; p = 0.002) but no significant difference was noted between the treatment effect in the two subgroups (randomised vs. non-randomised; p = 0.07). The test for overall effect for progression free survival, which had only been reported for the two randomised studies, was not statistically significant (HR = 0.93; 95% CI 0.74-1.17), with little heterogeneity between studies (I [2] = 0%; p = 0.77). The results of this meta-analysis highlight the significant heterogeneity between the prospective studies comparing molecularly tailored to empiric therapy for CUP and the need for other randomised studies including only primary tumors with available effective therapies.


Assuntos
Neoplasias Primárias Desconhecidas/patologia , Neoplasias Primárias Desconhecidas/terapia , Ensaios Clínicos como Assunto , Terapia Combinada , Humanos , Prognóstico , Taxa de Sobrevida
10.
Crit Rev Oncol Hematol ; 146: 102798, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31918958

RESUMO

In this review, we summarize the history of the 41 Masterclasses in Clinical Oncology (MCO) organized by ESO or ESO-ESMO during the last 17 years. MCOs have been held in five different geographical regions including: a) Central Europe, b) Eastern Europe and Balkans, c) Baltic and Euroasia, d) Arab World and Southern European Countries and e) Latin America. More than 2.000 young oncologists have attended and more than 250 distinguished faculty members have actively participated. The program exposes students to sessions covering all major tumors ("big killers") and to spotlights updating information on various important cancers and related topics. Participants are able to present their own clinical case in front of a tumor board or in parallel group sessions and are evaluated by a Learning Assessment Test (LAT) at the end of the event. They are asked to discuss the programme, using a questionnaire on the goals, quality and organization of the MCOs, which has been very highly scored by most of the participants. The Masterclass in Clinical Oncology has become the major educational event of ESO, intending to educate young oncologists from various countries within or outside Europe, providing an up-to-date interactive program based on solid evidence for all presented topics.


Assuntos
Educação de Pós-Graduação em Medicina/organização & administração , Oncologia/educação , Oncologistas/educação , Educação de Pós-Graduação em Medicina/tendências , Europa (Continente) , Humanos , Oncologia/tendências , Sociedades Médicas , Inquéritos e Questionários , Ensino
11.
Invest New Drugs ; 38(1): 181-193, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31650446

RESUMO

Epithelial ovarian cancer (EOC) accounts for nearly 90% of all ovarian malignancies. The standard therapeutic strategy includes cytoreductive surgery and neo (adjuvant) platinum-based chemotherapy. Relapse of advanced high grade serous ovarian cancer (HGSOC) is related to the development of drug resistance. A defective DNA damage response is a defining hallmark of HGSOC. Poly (ADP-ribose) polymerase (PARP) inhibitors exploit this deficiency through synthetic lethality and have emerged as promising anticancer therapies, especially in breast cancer gene (BRCA1 or BRCA2) mutation carriers. Apart from inducing synthetic lethality, PARP inhibitors have also been shown to trap PARP1 and PARP2 on DNA, leading to PARP-DNA complexes. This "PARP trapping" potentiates synergism between PARP inhibition and both alkylating agents and platinum-based chemotherapy. However, there are remarkable differences in the ability of PARP inhibitors to trap PARP, based on the size and structure of each separate molecule. Since monotherapy with PARP inhibitors is unlikely to induce cancer cell death in BRCA-proficient tumors, the efficacy of PARP inhibitors could be potentially optimized when combined with DNA-damaging agents, or with molecular targeted agents that also impair mechanisms of DNA repair. Olaparib, rucaparib, and niraparib have all obtained US Food and Drug Administration (FDA) and/or European Medicines Agency (EMA) approval in ovarian cancer in different settings. Veliparib does not yet have an approved label; nevertheless, there are currently promising results available in preclinical and early clinical settings. This comprehensive review summarizes the mechanism of action of veliparib and provides an overview of its early and ongoing clinical investigations.

12.
Int J Cancer ; 146(6): 1490-1498, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-31144291

RESUMO

Cancer of unknown primary (CUP) is a clinical challenge especially when it occurs in adolescents and young adults (AYA), aged 15-39 years, due to the sparse data in this population. The available data has not described the population-based epidemiological features of CUP among AYA. Therefore, we collected patient information from the Surveillance, Epidemiology and End Results (SEER) registry, 1990-2015. Age, gender, ethnic, five pathological classification groups were assessed along with an aggregate level socioeconomic status (SES) index and population density at the county level. Incidence rates, modeled relative risks and survival of AYA patients with CUP were assessed. Among 2,480 AYA patients, 907 met the definition of standard pathology classifications. The majority of AYA patients with CUP had a neuroendocrine, squamous cell and poorly differentiated carcinomas with 0.4 cases per 1,000,000 population. AYA living in areas with the highest SES level had the highest risks of CUP; adjusted relative risks (ARR) of 1.17 (95% CI 1.0-1.4) and 1.99 (95% CI 1.5-2.6), respectively. AYA living in nonmetropolitan areas had a lower risk of CUP (ARR = 0.16; 95% CI 0.1-0.2). The incidence of differentiated neoplasms has been decreasing slower than undifferentiated neoplasms since the early 1990s. The median overall survival (OS) was 11 months (95% CI 9-13 months) with squamous CUP having the longest median OS 16 years (95% CI 3-24 years). In conclusion, this analysis answers several gaps in the knowledge of CUP among AYA and provides a platform to better understand this disease and its management within this group.


Assuntos
Neoplasias Primárias Desconhecidas/epidemiologia , Adolescente , Adulto , Fatores Etários , Humanos , Incidência , Estimativa de Kaplan-Meier , Neoplasias Primárias Desconhecidas/patologia , Fatores de Risco , Programa de SEER/estatística & dados numéricos , Distribuição por Sexo , Classe Social , Fatores de Tempo , Estados Unidos/epidemiologia , Adulto Jovem
13.
J BUON ; 24(5): 2180-2197, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31786893

RESUMO

PURPOSE: Cancer is a leading cause of mortality worldwide. Its incidence is still increasing, particularly in developing countries. Recent progresses further strengthen the differences between low/middle and high-income countries. This situation calls for joint action to reduce inequities in cancer outcomes among the patients. The Association of Radiotherapy and Oncology of the Mediterranean Area (AROME) and the European School of Oncology (ESO), have initiated joint conferences devoted to access to innovations in oncology in the Mediterranean area. The heterogeneity of the economic, political and cultural situations of the different participating countries, offers the opportunity to develop consensus conference. METHODS: Cancer prevention and treatment strategies were discussed according to existing international guidelines. The Scientific committee prepared 111 questions with an objective to prioritize the access to treatments and innovations in low/middle-income Mediterranean countries. The results from the votes of 65 oncology experts, coming from 16 countries and 33 institutions have been analysed and access priorities classified accordingly. RESULTS: Ninety six percent of the proposed general recommendations concerning national health care strategies, oncology education, and treatment organization were considered to be high priorities. Regarding access to systemic treatments, 41% of the drugs without validated predictive markers and 53% of those with validated predictive markers were considered to be 1st level priority. Only 4 biological tests were considered to be 1st level priority to access to innovation. CONCLUSIONS: AROME-ESO consensus offers to cancer specialists from developing countries a basis for discussion with health authorities and payers on the prioritization of access to innovations in cancer care.


Assuntos
Assistência à Saúde/tendências , Oncologia/tendências , Neoplasias/epidemiologia , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Paris
14.
J Cancer Educ ; 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31845109

RESUMO

Masterclass in Clinical Oncology (MCO) represents the "key educational event" of European School of Oncology's (ESO) teaching program. MCO in collaboration with European Society for Medical Oncology (ESMO) is a multidisciplinary and clinical oriented educational event offered mainly to young oncologists worldwide. It provides full immersion in oncology with clinical case presentations and a Learning Self-Assessment Test (LSAT).LSAT is consisting of 45 multiple choice questions on an electronic platform referring to the material taught during the MCO. Three questions related to their topics are requested in advance from each faculty member. The major intentions of LSAT are the following: (a) the learning reflection of the massive information given during 4-5 days of intensive teaching and (b) to offer the opportunity to the participants to prepare themselves for their National Boards or for ESMO examination.In this article, we are analyzing and evaluating the results of LSAT from the ESO-ESMO Central European MCOs. We used the information of Central European MCOs for analysis due to the homogeneity of the available data. We assessed the level of participants' knowledge in relation to their oncology specialty or to their country of origin and the level of the quality of faculty teaching.

15.
Diagnostics (Basel) ; 9(3)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31374917

RESUMO

Poly (ADP-ribose) polymerase (PARP) inhibitors are the first clinically approved drugs designed to exploit synthetic lethality, and were first introduced as a cancer-targeting strategy in 2005. They have led to a major change in the treatment of advanced ovarian cancer, and altered the natural history of a disease with extreme genetic complexity and defective DNA repair via homologous recombination (HR) pathway. Furthermore, additional mechanisms apart from breast related cancer antigens 1 and 2 (BRCA1/2) mutations can also result in HR pathway alterations and consequently lead to a clinical benefit from PARP inhibitors. Novel combinations of PARP inhibitors with other anticancer therapies are challenging, and better understanding of PARP biology, DNA repair mechanisms, and PARP inhibitor mechanisms of action is crucial. It seems that PARP inhibitor and biologic agent combinations appear well tolerated and clinically effective in both BRCA-mutated and wild-type cancers. They target differing aberrant and exploitable pathways in ovarian cancer, and may induce greater DNA damage and HR deficiency. The input of immunotherapy in ovarian cancer is based on the observation that immunosuppressive microenvironments can affect tumour growth, metastasis, and even treatment resistance. Several biologic agents have been studied in combination with PARP inhibitors, including inhibitors of vascular endothelial growth factor (VEGF; bevacizumab, cediranib), and PD-1 or PD-L1 (durvalumab, pembrolizumab, nivolumab), anti-CTLA4 monoclonal antibodies (tremelimumab), mTOR-(vistusertib), AKT-(capivasertib), and PI3K inhibitors (buparlisib, alpelisib), as well as MEK 1/2, and WEE1 inhibitors (selumetinib and adavosertib, respectively). Olaparib and veliparib have also been combined with chemotherapy with the rationale of disrupting base excision repair via PARP inhibition. Olaparib has been investigated with carboplatin and paclitaxel, whereas veliparib has been tested additionally in combination with temozolomide vs. pegylated liposomal doxorubicin, as well as with oral cyclophosphamide, and topoisomerase inhibitors. However, overlapping myelosuppression observed with PARP inhibitor and chemotherapy combinations requires further investigation with dose escalation studies. In this review, we discuss multiple clinical trials that are underway examining the antitumor activity of such combination strategies.

16.
Future Oncol ; 15(23): 2759-2768, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31385529

RESUMO

Cancer of unknown primary accounts for 3-5% of all cancers for which an adequate investigation does not identify the primary tumor. The particular subset of brain metastasis in cancer of unknown primary (BMCUP) is a clinical challenge that lacks standardized diagnostic and therapeutic options. It is diagnosed predominantly in male patients in the sixth decade of age with complaints of headache, neurological dysfunction, cognitive and behavioral disturbances and seizures. The therapeutic approach to patients with BMCUP relies on local control and systemic treatment. Surgery or stereotactic radiosurgery and/or whole brain radiation therapy seems to be the cornerstone of the treatment approach to BMCUP. Systemic therapy remains essential as cancers of unknown primary are conceptually metastatic tumors. The benefits of chemotherapy were disappointing whereas those of targeted therapies and immune checkpoint inhibitors remain to be evaluated. In this Review, we address the advances in the diagnosis and treatment of BMCUP.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Neoplasias Primárias Desconhecidas/patologia , Radiocirurgia , Biomarcadores Tumorais/sangue , Neoplasias Encefálicas/patologia , Terapia Combinada , Humanos , Masculino
17.
Head Neck ; 41(10): 3700-3711, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31301162

RESUMO

BACKGROUND: Human papillomavirus (HPV)-related squamous cell carcinoma of unknown primary (SCCUP) is currently rising in incidence but lacks a validated management approach. AIMS: This paper reviews the clinical presentation, diagnosis, and treatment of HPV-related SCCUP. MATERIALS AND METHODS: The Medline/Pubmed database was searched by using the following keywords "CUP", "cancer of unknown primary", "HPV", "human papilloma virus", and "head and neck". The references of the publications of interest were also screened for relevant papers. RESULTS: The clinical assessment of HPV-related SCCUP includes a complete clinical examination, an endoscopic evaluation with white-light and narrow band imaging, and radiologic assessment using morphologic and metabolic imaging. If the diagnosis remains unconfirmed, endoscopic examination under anesthesia with tonsillectomy ± base of tongue mucosectomy is performed. The therapeutic rationale aims to eradicate the involved lymph nodes and potential primary tumor with a sequence of chemoradiotherapy and neck dissection. DISCUSSION: As a general approach, p16-negative SCCUP are truly HPV negative, whereas p16-positive specimens require confirmation with HPV in situ hybridization or polymerase chain reaction to confirm HPV infection. If a cervical metastasis is considered HPV positive, the primary lesion is likely in the oropharynx, and further diagnostic interventions such as tonsillectomy seems to be mandatory. Whether the optimal treatment is neck dissection followed by adjuvant radiotherapy or concomitant chemoradiotherapy (CRT) (in case of extranodal extension or advanced lymph node stages) or definitive CRT followed by neck dissection (in case of positive 18 F-FDG-PET/CT) remains a matter of debate. Solid scientific evidence supporting treatment de-escalation in HPV-related SCCUP is lacking, and the results of ongoing trials are at the brink of reporting. CONCLUSION: Currently, the treatment of patients with HPV-related SCCUP should not differ from the standard treatment of other SCCUP patients and is similarly based on the staging of the disease and general condition of the patient.

18.
Cancer Epidemiol ; 61: 139-141, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31254795

RESUMO

Cancer of unknown primary (CUP) is a heterogeneous group of metastatic cancers for which a primary tumor cannot be identified after a standardized work-up. The biology of CUP has not been fully elucidated and epidemiologic data may be helpful in this regard. The variations in the incidence-rate over time and between countries reflect changes in the risk factors for CUP, incidence trends of the primary tumors that potentially contribute to the burden of CUP and changes in the diagnostic technologies and practice. CUP accounted for 3-5% of cancers in the historical series but its incidence seems to decline in the recent publications. This paper reviews the published cancer-registry studies in order to identify and understand the variations in the incidence-rates of CUP.


Assuntos
Neoplasias Primárias Desconhecidas/epidemiologia , Feminino , Humanos , Incidência , Masculino , Sistema de Registros , Fatores de Risco
19.
Immunotherapy ; 11(10): 913-920, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31188048

RESUMO

The hypothesis that the interaction of chemotherapy and immune checkpoint inhibitors (ICIs) is synergistic has not been formally validated. The frontline ICI Phase II/III trials in advanced non-small-cell lung cancer were reviewed for the objective response rates (ORRs) and grade 3-5 adverse events (AEs) of ICI-chemotherapy combinations and those of each individual drug. The expected ORR and grade 3-5 AE of ICI-chemotherapy combinations were computed as the arithmetic sum of the pooled effects of each drug. Statistical pooling was performed using a double arcsine transformation and a random-effects model. Our findings suggest an enhanced effect that is less than additive for the ICI-chemotherapy combinations since the actual ORR and grade 3-5 AE were found to be less than the expected additive effect.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas , Imunoterapia , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/terapia , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Terapia Combinada , Feminino , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Masculino
20.
Int J Clin Oncol ; 24(10): 1328-1331, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31203526

RESUMO

Cancer of unknown primary site (CUP) is a deadly disease diagnosed through metastases at various organs without primary tumor identification. Despite the major molecular and technological advances, the carcinogenesis of CUP remains enigmatic which hampers adequate study design of treatments leading to survival improvement. To date, the pathogenesis of CUP is still debatable with one hypothesis considering CUP simply a group of metastatic tumors with unidentified primaries and another considering it a distinct entity with specific genetic and phenotypic aberrations. Familial CUP seems to favor the first hypothesis due to common genetic predisposition factors between known primaries and CUP. Two clinical implications may be withdrawn from the pathogenesis of familial clustering of CUP. The detailed family history and environmental risk factors may orient towards the primary tumor identification. Smoking avoidance and adherence to general population guidelines for cancer screening would be strongly encouraged.


Assuntos
Adenocarcinoma/patologia , Carcinoma Neuroendócrino/patologia , Carcinoma de Células Escamosas/patologia , Predisposição Genética para Doença , Neoplasias Primárias Desconhecidas/patologia , Adenocarcinoma/genética , Idoso , Carcinoma Neuroendócrino/genética , Carcinoma de Células Escamosas/genética , Feminino , Humanos , Masculino , Metanálise como Assunto , Neoplasias Primárias Desconhecidas/genética
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