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Epithelial ovarian cancer (EOC) is the deadliest gynecological malignancy worldwide. Brain metastasis (BM) is quite an uncommon presentation. However, the likelihood of central nervous system (CNS) metastasization should be considered in the context of disseminated disease. The therapeutic management of BMs is an unmet clinical need, to date. We identified, across different cancer centers, six cases of both BRCA wild-type and BRCA-mutated EOCs spreading to the CNS. They presented either with a single brain lesion or with multiple lesions and most of them had intracranial-only disease. All cases received Poly-ADP ribose polymerase inhibitor (PARPi) maintenance, as per clinical practice, for a long time within a multimodal treatment approach. We also provide an insight into the available body of work regarding the management of this intriguing disease setting, with a glimpse of future therapeutic challenges. Despite the lack of unanimous guidelines, multimodal care pathways should be encouraged for the optimal disease control of this unfortunate patient subset. Albeit not being directly investigated in BM patients, PARPi maintenance is deemed to have a valuable role in this setting. Prospective research, aimed to implement worthwhile strategies in the multimodal patient journey of BMs from EOC, is eagerly awaited.
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Neoplasias Encefálicas , Carcinoma Epitelial do Ovário , Neoplasias Ovarianas , Inibidores de Poli(ADP-Ribose) Polimerases , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/tratamento farmacológico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/genética , Terapia Combinada , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/genética , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêuticoRESUMO
Sunitinib represents a reasonable therapeutic option for first-line treatment of poor-risk metastatic renal cell carcinoma and the treatment should aim at the delicate balance between managing side effects to improve the toxicity profile and patient compliance to treatment while maintaining anticancer efficacy. Achievement of a complete response, although rare, is possible, even in poor-risk patients. Treatment discontinuation represents a viable alternative for both tumour biology and patients' quality of life. To date, no molecular markers have been identified with prognostic and/or predictive value for guiding therapeutic decisions. Further research should aim at gaining in-depth knowledge of renal cell carcinoma biology for a tailored personalized therapy. We report a case of poor-risk metastatic renal cell carcinoma, with Von Hippel-Lindau loss of function, which achieved and maintained a complete remission after first-line therapy with sunitinib by using a reduced dosage and a modified schedule of treatment.
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Inibidores da Angiogênese/administração & dosagem , Carcinoma de Células Renais/tratamento farmacológico , Indóis/administração & dosagem , Neoplasias Renais/tratamento farmacológico , Proteínas Tirosina Quinases/antagonistas & inibidores , Pirróis/administração & dosagem , Idoso , Inibidores da Angiogênese/efeitos adversos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/secundário , Feminino , Humanos , Indóis/efeitos adversos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Mutação , Pirróis/efeitos adversos , Indução de Remissão , Risco , Sunitinibe , Proteína Supressora de Tumor Von Hippel-Lindau/genéticaRESUMO
2014 has been a year of significant innovations on kidney cancer treatments, the most relevant of which will be shown below. In particular, we analyzed the consolidated knowledge regarding the role of surgery in localized and advanced renal cell carcinoma and the targeted therapies already approved for metastatic renal cell carcinoma. Furthermore, we examined the outstanding issues, with particular reference to the choice of the second-line and the role of adjuvant and neoadjuvant treatments. Finally, we outlined the future therapeutic perspectives and those definitely abandoned.
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Neoplasias Renais/terapia , Gerenciamento Clínico , Humanos , Neoplasias Renais/diagnósticoRESUMO
The standard of care for patients with local advanced or metastatic urothelial carcinoma is chemotherapy. However, results with this are rather disappointing, and validated prognostic factors and biomarkers of tumor response, which are useful in the decision-making process, are still lacking. PubMed databases were searched for articles published until November 2013. Several promising clinical and biological candidate prognostic factors or markers of tumor response to first- or second-line therapy, such as hemoglobin, performance status, visceral metastasis and ERCC1, hENT1 and EMT markers, have been identified and described in this article. In summary, clinical parameters and molecular profiling could revolutionize the management of local advanced or metastatic urothelial cancer, but an improvement in individualized therapeutic approaches still seems distant.
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Carcinoma de Células de Transição/tratamento farmacológico , Cisplatino/uso terapêutico , Prognóstico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Carcinoma de Células de Transição/patologia , Humanos , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias da Bexiga Urinária/patologia , Urotélio/efeitos dos fármacos , Urotélio/patologiaRESUMO
2014 Genitourinary Cancers Symposium San Francisco, CA, USA, 30 January-1 February 2014 The American Society of Clinical Oncology symposium dedicated to genitourinary tumors represents an unmissable opportunity for the whole oncology community with a special interest in the diagnosis and treatment of genitorurinary tract malignancies, in particular kidney and prostate tumors. The 2014 Genitourinary Cancers Symposium focused attention on the need to find a personalized therapy for metastatic renal cell carcinoma and castration-resistant prostate cancer patients. The development of biomarkers for tumor response and/or resistance will represent a major step in this context and has been the focus of several researches at the symposium.
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Neoplasias Urogenitais/diagnóstico , Neoplasias Urogenitais/terapia , Animais , HumanosRESUMO
Dual-energy CT (DECT) is an innovative technology that is increasingly widespread in clinical practice. DECT allows for tissue characterization beyond that of conventional CT as imaging is performed using different energy spectra that can help differentiate tissues based on their specific attenuation properties at different X-ray energies. The most employed post-processing applications of DECT include virtual monoenergetic images (VMIs), iodine density maps, virtual non-contrast images (VNC), and virtual non-calcium (VNCa) for bone marrow edema (BME) detection. The diverse array of images obtained through DECT acquisitions offers numerous benefits, including enhanced lesion detection and characterization, precise determination of material composition, decreased iodine dose, and reduced artifacts. These versatile applications play an increasingly significant role in tumor assessment and oncologic imaging, encompassing the diagnosis of primary tumors, local and metastatic staging, post-therapy evaluation, and complication management. This article provides a comprehensive review of the principal applications and post-processing techniques of DECT, with a specific focus on its utility in managing oncologic patients.
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Artefatos , Iodo , Humanos , Tomografia Computadorizada por Raios XRESUMO
There is an increasing trend towards using oral antitumoral agents in oncological patients. Compared to parenteral therapy, oral treatment offers convenience for both the patient and the healthcare system, with similar efficacy. However, the benefit deriving from oral drugs will be obtained only if patients adhere strictly to the treatment. Medical oncologists must therefore seek to optimize patient adherence. Breast cancer patients, particularly, are often treated with oral hormonal anticancer agents. In this review, we summarized evidence about adherence of breast cancer patients to oral hormonal anticancer agents and the consequences of poor compliance, the barriers to oral treatment and strategies to overcome them.
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Antineoplásicos , Neoplasias da Mama , Neoplasias Bucais , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Antineoplásicos Hormonais/uso terapêutico , Antineoplásicos/uso terapêutico , Cooperação do Paciente , Quimioterapia Adjuvante , Adesão à MedicaçãoRESUMO
Malnutrition affects up to 75% of cancer patients and results from a combination of anorexia and metabolic dysregulation. Metabolic and nutritional abnormalities in cancer patients can lead to cachexia, a multifactorial syndrome characterized by involuntary loss of skeletal muscle mass, systemic inflammation and increased protein catabolism. Cancer cachexia negatively affects patients' outcomes, response to anticancer treatments, quality of life, and survival. However, risk of malnutrition, and cachexia are still under-recognized in cancer patients. The Prevalence of Malnutrition in Oncology (PreMiO) study revealed that 51% of patients already had nutritional deficiencies at their first medical oncology visit. Here, we report the results of the subsequent retrospective, observational NUTRItional status at first medical oncology visit ON Clinical Outcomes (NUTRIONCO) study, aimed at assessing the impact of baseline nutritional and non-nutritional variables collected in the PreMiO study on the clinical outcomes of the same patients followed up from August 2019 to October 2021. We have highlighted a statistically significant association between baseline variables and patient death, rehospitalization, treatment toxicity, and disease progression at follow-up. We found a higher overall survival probability in the well-nourished general study population vs. malnourished patients (p < 0.001). Of major interest is the fact that patient stratification revealed that malnutrition decreased survival probability in non-metastatic patients but not in metastatic patients (p < 0.001). Multivariate analysis confirmed that baseline malnutrition (p = 0.004) and VAS score for appetite loss (p = 0.0104), in addition to albumin < 35 g/L (p < 0.0001) and neutrophil/lymphocyte ratio > 3 (p = 0.0007), were independently associated with the death of non-metastatic patients at follow-up. These findings highlight the importance of proactive, early management of malnutrition and cachexia in cancer patients, and in particular, in non-metastatic patients, from the perspective of a substantial improvement of their clinical outcomes.
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To evaluate the rate of early breast cancer (EBC) patients treated with neoadjuvant systemic therapy (NAT) in Italy, criteria of patient selection and types of therapies delivered, an analysis of 1276 patients with stage I-II-III was conducted out of 1633 patients enrolled in the multicenter prospective observational BRIDE study. A total of 177 patients (13.9%) were treated with NAT and 1099 (85.9%) with surgery; in multivariate analysis, menopausal status, cT, cN, grade, HER2-positive and Triple negative (TN) subgroups were significantly associated with the decision to administer NAT. The type of NAT delivered was influenced by EBC subtype. NAT was administered to 53.2% of HER2+/HR-negative, 27.9% of HER2+/HR+, 7.1% of HER2-negative/HR+ and 30.3% of TN EBC patients. The pCR rates were similar to the ones reported in the literature: 74.2% in HER2+/HR-negative, 52.3% in HER2+/HR+, 17.2% in HER2-negative/HR+ and 37.9% in TN. In clinical practice, patient and tumor characteristics influenced oncologists in the decision to administer NAT in EBC and in the choice of the type of systemic therapy, according to ESMO and AIOM Guidelines. Currently, it is recommended always to evaluate the use of NAT in EBC, mainly in HER2+ and TN patients, considering that pCR is associated with significantly better survival of the patient and that effective therapies are now available for residual disease.
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Introduction: The role of fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in early breast cancer treated with preoperative systemic therapy (PST) is not yet established in clinical practice. PET parameters have aroused great interest in the recent years, as non-invasive dynamic biological markers for predicting response to PST. Methods: In this retrospective study, we included 141 patients with stage II-III breast cancer who underwent surgery after PST. Using ROC analysis, we set optimal cutoff of FDG-PET/CT parameters predictive for pathological complete response (pCR). We investigated the correlation between FDG-PET/CT parameters and pCR, median disease-free survival (DFS), and median overall survival (mOS). Results: At multivariable analysis, baseline SUVmax (high vs low: OR 9.00, CI 1.85 - 61.9, p=0.012) and Delta SUVmax (high vs low: OR 9.64, CI 1.84, 69.2, p=0.012) were significantly associated with pCR rates. Interestingly, we found that a combined analysis of the metabolic parameter Delta SUVmax with the volume-based parameter Delta MTV, may help to identify patients with pCR, especially in the subgroup of hormone receptor positive breast cancer. Delta SUVmax was also an independent predictive marker for both mDFS (high vs low: HR 0.17, 95%CI 0.05-0.58, p=0.004) and mOS (high vs. low: HR 0.19, 95%CI 0.04-0.95, p=0.029). Discussion: Our results suggest that Delta SUVmax may predict survival of early BC patients treated with PST.
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The international literature emphasizes the importance of physical activity (PA) in the first steps after cancer surgery. The regular practice of physical exercise causes positive adaptations on several functional capacities, with positive consequences on patients' quality of life. This project aims to evaluate the effect of a post-operative training protocol, structured by taking into account both cancer-related issues and the presence of comorbidities, on functional capacities and quality of life of breast cancer survivors. Therefore, it was necessary to create a synergy between oncologists (referring physicians), sport medicine physicians (risk stratification and exercise prescription) and kinesiologists (trainers). Thirty-five post-surgery BC patients decided on a voluntary basis to attend an online Adapted PA (APA) protocol for 4 months, twice a week (APA Group) or Usual Care Group (UC Group). Functional capacity of the APA Group significantly increased, by 13.1% (p = 0.000), whereas perceived exertion decreased by 19.7% (p = 0.020). In the same group, the general health evaluated through the questionnaire EORTC-QLQ-C30 increased (p = 0.050). No differences were found in the UC Group. Operation Phalco, creating a network between oncologists, sports medicine physicians and kinesiologists, confirms the importance of structuring a post-operative path where APA should be included as early as possible in the cancer patient care.
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[This corrects the article DOI: 10.3389/fonc.2021.705927.].
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The role of a healthy diet in cancer prevention is well recognized. Recent data indicate that following the same advices can also improve cancer survivors' quality of life. Breast cancer (BC) patients are commonly concerned about diet and nutrition and frequently express the need to obtain health-related information and the will to change their diet and lifestyle. Hence, be aware of survivors' dietary changes and information needs is crucial for healthcare professionals to guide them toward optimal lifestyle choices. In order to investigate eating habits changes in a BC survivors' population, we conceived the cross-sectional multicentric study ECHO (Eating habits CHanges in Oncologic patients) Survey. Data were collected from 684 patients, diagnosed with invasive breast cancer, in order to investigate their changes in food consumption, use of supplements, or the beginning of a specific diet, after BC diagnosis. We also examined the sources of information used and if any modification in their diets was reported to the oncologist. We primarily observed that patients increased their consumption of vegetables, pulses, nuts, fruits, wholemeal bread/pasta, grains and fish; while decreasing red and processed meat, refined bread/pasta, baked good and animal fat consumption. Survivors also reported the use of dietary supplements, mainly vitamins, aimed at counteracting therapies' side effects. Changes in nutritional habits were often adopted without asking or informing the oncologist. Despite BC survivors made some positive changes in their nutritional habits, those modifications were mostly pursued by less than half of them, while the majority of patients consumed nutritional supplements after diagnosis. These results, as well as the failure to communicate with the physicians, reinforce the need to both improve the patient-healthcare professional relationship and to develop tailored nutrition counselling and intervention programs for cancer survivors.
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Small (pT1a-b), node-negative (pN0) breast cancer generally has a good prognosis. However, HER2-positive status is associated with an increased risk of relapse and decreased survival even in these tumors. Although there are only few data from prospective randomized trials, results of retrospective studies suggest adjuvant chemotherapy plus trastuzumab may improve outcomes of patients with pT1a-b pN0 HER2-positive breast cancer. On the other hand, trastuzumab is potentially associated with increased cardiac toxicity, especially when combined with anthracycline-based chemotherapy. A valid strategy for improving cardiac safety is the addition of trastuzumab to non-anthracycline chemotherapy, whereas a shorter duration of trastuzumab should be not routinely considered although might represent an option for selected patients at low risk of relapse and very high risk of cardiac events. Therefore, the choice of adjuvant treatment for patients with pT1a-b pN0 HER2-positive breast cancer should be done on individual basis, carefully weighing benefits and risks.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linfonodos/patologia , Receptor ErbB-2/sangue , Neoplasias da Mama/metabolismo , Feminino , Humanos , Estadiamento de Neoplasias , PrognósticoRESUMO
The objective response is an important endpoint to evaluate clinical activity of new anticancer drugs. Standardized criteria for evaluating response are needed for comparing results of different trials and represent the basis for advances in cancer therapy. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 are the most used in clinical practice and in clinical trials; however, they are not able to capture atypical responses seen with immunotherapy drugs. We describe the evolution of response criteria with a special focus on the immune-related criteria.
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Neoplasias/tratamento farmacológico , Neoplasias/terapia , Antineoplásicos/uso terapêutico , Ensaios Clínicos como Assunto , Humanos , Imunoterapia/métodos , Avaliação de Estado de Karnofsky , Critérios de Avaliação de Resposta em Tumores SólidosRESUMO
AIM: Monoclonal antibodies (mAbs) directed against PD-1/PD-L1 have recently entered the therapeutic algorithm of several solid tumors. Among treatment-related adverse events pulmonary toxicity (PT) is of particular interest. We assess the incidence and relative risk (RR) of PT in patients treated with anti-PD1/PD-L1 mAbs. RESULTS: 11 articles were selected. The incidence of any- and high-grade PT was low (2.9 and 1.0%, respectively). Compared with standard therapies, anti-PD-1 mAbs do not significantly increase the risk of both any-grade (RR: 2.65; p = 0.06) and high-grade PT (RR: 1.40; p = 0.25). Of note, the RR: of developing any-grade (RR: 3.13; p < 0.0001) and high-grade (RR: 2.42; p = 0.03) PT significantly increased when excluding the Checkmate-025 trial, with everolimus as control therapy. No differences were identified between the type of mAbs, the tumor type and treatment duration for both any-grade and high-grade PT.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Imunoterapia/métodos , Neoplasias Pulmonares/epidemiologia , Pulmão/efeitos dos fármacos , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Antígeno B7-H1/imunologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Humanos , Imunoterapia/efeitos adversos , Incidência , Pulmão/patologia , Neoplasias Pulmonares/tratamento farmacológico , Nivolumabe , Receptor de Morte Celular Programada 1/imunologia , RiscoRESUMO
Losses of chromosomes 9p and 14q are associated with worse outcomes in patients affected by clear-cell renal cell carcinoma (RCC) and are helpful for prognostic risk stratification. Both chromosomal loci harbor several hot-spot molecular pathways suitable for targeted therapeutic interventions. Intratumor heterogeneity may foster tumor adaptation and therapeutic failure. We sought to investigate the presence of losses of the hot spots of chromosomal loci 9p and 14q in primary clear-cell RCC and matched metastatic tissues. CD10 and CD13 were performed on 7 cases of clear-cell RCC with hematogenous tissue metastases. Cytogenetic fluorescence in situ hybridization analysis was performed on primary and matched metastatic tissues using specific probes mapping the 9p and the 14q loci. The loss of chromosome 9p was observed in 85% of both primary clear-cell RCCs and in matched metastases; 14% showed discordance between primary and matched metastases showing gains. The loss of chromosome 14q was observed in 58% of both primary and matched metastases. Only 3/7 (42%) did show an equal status of loss of chromosome 14q. Heterogeneity of the cytogenetic status between metastatic and primary clear-cell RCCs is observed for the loss of chromosome 14q rather than chromosome 9p. The impact of chromosome 14q cytogenetic status, harboring the HIF1 gene, a major driver for the angiogenenic switch, may drive the efficacy of targeted inhibitors, whereas the loss of chromosome 9p, harboring other hot-spot genes, seems to be related to the metastatic behavior per se, without cytogenetic modulation. Reprofiling the metastatic tissue, as compared with the primary tumor, in patients affected by metastatic RCC could be a novel approach to overcome resistance to VEGF(Rs)-targeting agents.
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Carcinoma de Células Renais/genética , Cromossomos Humanos Par 14 , Cromossomos Humanos Par 9 , Neoplasias Renais/genética , Metástase Neoplásica/genética , Carcinoma de Células Renais/patologia , Humanos , Hibridização in Situ Fluorescente , Neoplasias Renais/patologiaRESUMO
BACKGROUND: The lysosomal cysteine protease cathepsin K is involved in bone remodeling and is also expressed in the peritumoral stroma of carcinomas arising from different organs. A new generation of cathepsin K inhibitors blocking the RANKL/RANK pathway are being developed. We sought to investigate cathepsin K expression in a cohort of castration-resistant prostate carcinomas. METHODS: Sixteen cases of castration-resistant disease with at least 5 years of follow-up were selected from a cohort of 280 patients who underwent surgery. Cathepsin K was evaluated on formalin-fixed and paraffin-embedded tissue microarrays with 5 tissue spots per case. These were scored as high 2+ (≥30% of cells), low 1+ (<30% of cells) or zero (absence), distinguishing tumor cells and peritumoral stroma cells. Low (1+) and absence (0) of scoring were interpreted as negative, and high (2+) as positive. RESULTS: The castration-resistant group was composed of 15 acinar adenocarcinomas and 1 neuroendocrine carcinoma, and all showed at least Gleason score 8 at prostatectomy. Two out of 16 cases (12%) scored positive for cathepsin K in tumor cells; and 5 of 16 cases (31%) scored positive in peritumoral stroma cells. The neuroendocrine and acinar subtypes of carcinoma with positive immunoexpression in neoplastic cells developed bone metastases after 4 and 5 years, respectively, and subsequently died. CONCLUSIONS: Patients affected by castration-resistant prostate carcinoma may be tested for cathepsin K, and a positive strong expression (2+) could be a useful predictive biomarker of response to targeted agents, aiding in the selection of patients eligible for these treatments.
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Neoplasias Ósseas/genética , Carcinoma/genética , Catepsina K/genética , Neoplasias de Próstata Resistentes à Castração/genética , Idoso , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Carcinoma/tratamento farmacológico , Carcinoma/patologia , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Metástase Neoplásica , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Análise Serial de TecidosRESUMO
Chemotherapy is the mainstay of treatment of advanced non-small cell lung cancer (NSCLC) without molecular drivers. Despite a low penetration of central nervous system (CNS), chemotherapy drugs demonstrated encouraging activity against CNS metastases from NSCLC. Based on the available data, chemotherapy should be considered as an important part of the multidisciplinary treatment of CNS metastases. Particularly, platinum-based regimens represent the most active combinations and pemetrexed is associated with a meaningful clinical benefit for patients with non-squamous histology. How to integrate chemotherapy and radiotherapy for newly diagnosed brain metastases (BMs) is still debated. Although flawed by some limitations, the available evidence suggests a role for upfront chemotherapy for the treatment of NSCLC patients with synchronous, asymptomatic BMs, thus allowing a delay of radiotherapy. Despite the introduction of modern and more effective chemotherapy, however, the prognosis of NSCLC patients with CNS metastases remains poor, especially for those with progressive BMs or leptomeningeal carcinomatosis (LC).
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Despite recent advances that have been made in the therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC), effective management of bone metastases remains a key goal not yet reached. The receptor tyrosine kinase MET and the vascular endothelial growth factor receptor (VEGFR) seem to play an important role in prostate cancer progression and pathological bone turnover, representing potential targets for improving clinical outcomes in mCRPC. Studies evaluating agents that target one or both these pathways have demonstrated modest activity but no improvement in overall survival. Nevertheless, this therapeutic strategy seems to still be a promising and engaging area of prostate cancer research and the interest in better understanding the MET/VEGFR axis and the mechanism of action of these inhibitors is growing. This review describes the rationale for targeting MET and VEGFR pathway in mCRPC and provides the clinical data available to date and an update on ongoing trials.