Immune checkpoint inhibitors in endometrial cancer.

The incidence of endometrial cancer (EC) is increasing worldwide. The prognosis for patients diagnosed with early-stage remains good, whereas for patients with recurrent or metastatic disease, the prognosis is poor and treatment options, until recently, were limited. In 2017, pembrolizumab was approved by the US Food and Drug Administration (FDA) for those patients with mistmach repair deficiency (MMRd) or high microsatellite instability (MSI-H) tumors. However, only 20-30 % of EC have MSI, and just over half of these patients benefit from treatment. In 2019, the FDA granted breakthrough therapy designation to lenvatinib in combination with pembrolizumab for the potential treatment of patients with advanced microsatellite stable EC that has progressed after treatment with at least one previous systemic therapy. It appears clear that immune check-point inhibitors will have a definite place in the management of EC, both as single agent or in combination with other targeted agents. In this review, we summarize the current evidence of immune check point blockade and the identification of potential biomarkers, beyond MSI-H or MMRd, that could help to predict response to this agents in correlation with the genomic EC subtypes.

Gene expression differences in primary colorectal tumors and matched liver metastases: chemotherapy related or tumoral heterogeneity?

Background: Treatment of metastatic colorectal cancer (mCRC) is generally based on genetic testing performed in primary tumor biopsies, but whether the genomic status of primary tumors is identical to that of metastases is not well known. We compared the gene expression profiles of formalin-fixed paraffin-embedded (FFPE) biopsies of colorectal primary tumors and matched liver metastases. Patients and methods: We compared the expression of 18 genes in FFPE CRC tumors and their matched liver metastases from 32 patients. The expression of each gene in CRC primary tumors and their matched liver metastases was tested using Student’s t test for paired samples. Pairwise correlations of each gene in the primary tumors and matched liver metastases were evaluated by Pearson’s correlation coefficient. Results: The expression of six genes was significantly different in primary tumors compared with their matched liver metastases [CXCR4 (p < 0.001), THBS1 (p = 0.007), MMP 9 (p = 0.048), GST Pi (p = 0.050), TYMP(p = 0.042) and DPYD (p < 0.001)]. For the remaining genes, where no significant differences were observed, only SMAD4 (r s = 0.447, p = 0.010), ERCC1 (r s = 0.423, p = 0.016) and VEGF A (r s = 0.453, p = 0.009) showed significant correlation in expression between the two tissues. Therefore, we only detected similar gene expression levels between the tumor and the metastases in these three markers. Conclusions: We only found similar gene expression levels between the tumor and the metastases in three genes (SMAD4, ERCC1, and VEGF A). However, our study could not assess whether the differences in gene expression were secondary to tumoral heterogeneity or to molecular changes induced by previous chemotherapy (AU)

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SMAD4 and TS expression might predict the risk of recurrence after resection of colorectal liver metastases

Purpose. Colorectal liver metastases (CLM) have significant molecular heterogeneity, which contributes to the risk of recurrence following surgery. Most of the traditional scores intended to predict recurrence is based on clinicopathological variables and it is unclear whether incorporating molecular biomarkers might improve our assessment of the risk of recurrence. Our aim was to determine if molecular biomarkers might be associated with the risk of recurrence after surgery of CLM. Patients and methods. A total of 121 patients diagnosed with colorectal cancer (CRC) with resected liver metastases were included. The role of several clinicopathological variables to predict patient’s outcome after resection of liver metastases was analyzed. Eighteen genes related to CRC pathogenesis were also included in the analyses. Univariate and multivariate stepwise Cox regression analyses were performed to identify factors associated with recurrence and the risk of death. Results. Eight prognostic factors for progression-free survival and nine factors for overall survival were identified in the univariate analyses. After adjusting for other risk factors, only the expression of two molecular factors was associated with the risk of recurrence: TS (HR 0.631, 95 % CI 0.422–0.944) and SMAD4 (HR 1.680, 95 % CI 1.047–2.695). None of the variables was significantly associated with the risk of death in the multivariate analyses. Conclusions. The prognostic significance of most traditional clinicopathological variables might be insufficient to define patients at risk for recurrence after liver metastases resection. Molecular biomarkers might improve the identification of patients with higher risk of recurrence (AU)

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SMAD4 and TS expression might predict the risk of recurrence after resection of colorectal liver metastases.

PURPOSE: Colorectal liver metastases (CLM) have significant molecular heterogeneity, which contributes to the risk of recurrence following surgery. Most of the traditional scores intended to predict recurrence is based on clinicopathological variables and it is unclear whether incorporating molecular biomarkers might improve our assessment of the risk of recurrence. Our aim was to determine if molecular biomarkers might be associated with the risk of recurrence after surgery of CLM. PATIENTS AND METHODS: A total of 121 patients diagnosed with colorectal cancer (CRC) with resected liver metastases were included. The role of several clinicopathological variables to predict patient's outcome after resection of liver metastases was analyzed. Eighteen genes related to CRC pathogenesis were also included in the analyses. Univariate and multivariate stepwise Cox regression analyses were performed to identify factors associated with recurrence and the risk of death. RESULTS: Eight prognostic factors for progression-free survival and nine factors for overall survival were identified in the univariate analyses. After adjusting for other risk factors, only the expression of two molecular factors was associated with the risk of recurrence: TS (HR 0.631, 95 % CI 0.422-0.944) and SMAD4 (HR 1.680, 95 % CI 1.047-2.695). None of the variables was significantly associated with the risk of death in the multivariate analyses. CONCLUSIONS: The prognostic significance of most traditional clinicopathological variables might be insufficient to define patients at risk for recurrence after liver metastases resection. Molecular biomarkers might improve the identification of patients with higher risk of recurrence.

Gene expression differences in primary colorectal tumors and matched liver metastases: chemotherapy related or tumoral heterogeneity?

BACKGROUND: Treatment of metastatic colorectal cancer (mCRC) is generally based on genetic testing performed in primary tumor biopsies, but whether the genomic status of primary tumors is identical to that of metastases is not well known. We compared the gene expression profiles of formalin-fixed paraffin-embedded (FFPE) biopsies of colorectal primary tumors and matched liver metastases. PATIENTS AND METHODS: We compared the expression of 18 genes in FFPE CRC tumors and their matched liver metastases from 32 patients. The expression of each gene in CRC primary tumors and their matched liver metastases was tested using Student's t test for paired samples. Pairwise correlations of each gene in the primary tumors and matched liver metastases were evaluated by Pearson's correlation coefficient. RESULTS: The expression of six genes was significantly different in primary tumors compared with their matched liver metastases [CXCR4 (p < 0.001), THBS1 (p = 0.007), MMP 9 (p = 0.048), GST Pi (p = 0.050), TYMP (p = 0.042) and DPYD (p < 0.001)]. For the remaining genes, where no significant differences were observed, only SMAD4 (r s = 0.447, p = 0.010), ERCC1 (r s = 0.423, p = 0.016) and VEGF A (r s = 0.453, p = 0.009) showed significant correlation in expression between the two tissues. Therefore, we only detected similar gene expression levels between the tumor and the metastases in these three markers. CONCLUSIONS: We only found similar gene expression levels between the tumor and the metastases in three genes (SMAD4, ERCC1, and VEGF A). However, our study could not assess whether the differences in gene expression were secondary to tumoral heterogeneity or to molecular changes induced by previous chemotherapy.

MYH polyposis syndrome: clinical findings, genetics issues and management

Colorectal cancer (CRC) is one of the most frequent cancer in first world. Two hereditary CCR syndrome have been described: familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer. A recently described biallelic mutation of MYH, is responsible for adenomatous polyposis with an increased risk of CRC and is responsible for 30-40 % of adenomatous polyposis cases in which an APC mutation cannot be found. However, there is no clear consensus in the literature as whether a monoallelic mutation increases the risk for colorectal cancer. In addition, some authors have indicated that the spectrum of extracolonic lesions in MYH associated polyposis (MAP) might be far different from that observed in FAP and could be more similar to Lynch syndrome spectrum. In this review we are going to describe some general and specific aspects of MAP, including genetic topics, clinical features, different phenotypes and strategies to reduce CCR risk (AU)

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MYH polyposis syndrome: clinical findings, genetics issues and management.

Colorectal cancer (CRC) is one of the most frequent cancer in first world. Two hereditary CCR syndrome have been described: familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer. A recently described biallelic mutation of MYH, is responsible for adenomatous polyposis with an increased risk of CRC and is responsible for 30-40 % of adenomatous polyposis cases in which an APC mutation cannot be found. However, there is no clear consensus in the literature as whether a monoallelic mutation increases the risk for colorectal cancer. In addition, some authors have indicated that the spectrum of extracolonic lesions in MYH associated polyposis (MAP) might be far different from that observed in FAP and could be more similar to Lynch syndrome spectrum. In this review we are going to describe some general and specific aspects of MAP, including genetic topics, clinical features, different phenotypes and strategies to reduce CCR risk.

Relevance of breast cancer subtypes for magnetic resonance imaging response monitoring during neoadjuvant chemotherapy

Changes in magnetic resonance imaging (MRI) during neoadjuvant chemotherapy (NAC) have been reported as predictive of pathology outcome in triple-negative and HER2-positive breast cancer. The purpose of our study was to evaluate the relevance of breast cancer subtype for MRI response in 24 women before and during NAC in our centre. Our results show that a reduction greater than 23% is associated with a pathological complete response (pCR) in Her-2-positive and ER-negative/Her2-negative breast cancer, and suggest a trend correlation between higher ADC values and pCR in these subtypes in comparison with ER-positive/Her2-negative breast cancers. Higher proliferating tumours respond better to chemotherapy and our study suggests that changes in MRI during NAC are predictive of pCR in these breast cancer subtypes (AU)

Complete response with pegylated liposomal doxorubicin as a second-line therapy in metastatic ovarian carcinosarcoma: Significance of assessment of the response by FDG-PET.

► We present a case report of a patient with an ovarian carcinosarcoma who achieve a complete response with PLD as a second-line therapy. ► There is little evidence regarding the effectiveness of second-line therapies in ovarian carcinosarcoma. ► Our case illustrates that the RECIST criteria is unreliable in predicting the histopathological treatment response in carcinosarcomas. ► FDG-PET was significantly more accurate than size-based criteria.

Internet use by cancer patients: should oncologists 'prescribe' accurate web sites in combination with chemotherapy? A survey in a Spanish cohort.

BACKGROUND: Cancer patients search for information about prognosis and treatment. Internet has become a major source of medical information. Its impact on oncology patients is not well known. PATIENTS AND METHODS: Three hundred and eighty questionnaires were distributed to cancer patients and companions and 293 were returned. The type of information they obtained online, its usefulness, and its impact on the patient-physician relationship as well as other sources of searching were demanded. Student t-tests, chi-square tests, and multivariate regression logistic analysis were carried out. RESULTS: Internet use was low (27% patients, 58% relatives). Cancer-specific information was the principal research (41% and 70%). For 61% patients, the information had been useful. Information provided by clinicians was the primary reason to not use Internet (37% and 67%). Twenty-two percent patients discussed it with clinicians. Among other sources, health professional (62% and 51%) and printed materials (18% and 25%) were the most demanded. CONCLUSIONS: Cancer patients and carers reported a low use of the Internet for searching medical information, although it helps patients to better cope with cancer. To discuss this information may strengthen the patient-physician relationship. Physicians should ensure that their patients receive reliable online information.

Gastric tumours in hereditary cancer syndromes: clinical features, molecular biology and strategies for prevention

Gastric cancer is the major cause of cancer-related deaths worldwide. The majority of them are classified as sporadic, whereas the remaining 10% exhibit familial clustering. Hereditary diffuse gastric cancer (HDGC) syndrome is the most important condition that leads to hereditary gastric cancer. However, other hereditary cancer syndromes, such as hereditary non-polyposis colorectal cancer, familial adenomatous polyposis, Peutz-Jeghers syndrome, Li-Fraumeni syndrome and hereditary breast and ovarian cancer, entail a higher risk compared to the general population for developing this kind of neoplasia. In this review, we describe briefly the most important aspects related to clinical features, molecular biology and strategies for prevention in hereditary gastric associated to different cancer syndromes (AU)

Different patterns of toxicity after sequential administration of two anti-EGFR monoclonal antibodies

A 40-year-old woman with liver metastasis resulting from colorectal adenocarcinoma suffered from a severe hypersensitivity reaction to cetuximab. She also experienced grade 3 skin toxicity. The administration of cetuximab was suspended, and she was offered panitumumab as an alternative treatment. Whereas she did not experience another infusion reaction, her skin rash worsened with the administration of panitumumab, a fully human anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody (MAb) (AU)

Molecular characterization of ovarian cancer by gene-expression profiling.

Ovarian cancer is the second most common gynecologic malignancy, and represents the fifth most common cause of cancer death in women in the United States. The age at diagnosis, extent of disease, success of primary surgery, and the histopathological features of the tumor are important prognostic markers. Epithelial ovarian carcinomas are classified into four major categories: serous, mucinous, endometrioid, and clear cell. Each subtypes of ovarian carcinoma are known to have different clinical characteristics and biological behaviour and response to chemotherapy. Molecular studies have supported for the notion that the different histological types of ovarian cancer likely represent histopathologically, genetically, and biologically distinct diseases. Microarray-based profiling technologies have provided an opportunity to simultaneously examine the relationship between thousands of genes and clinical phenotypes. In this review, we will summarise the current gene-expression profiles that address the classification of ovarian cancer into molecular subtypes with different outcomes.

Angiogenesis and ovarian cáncer

Ovarian carcinoma is the most important cause of gynaecological cancer-related mortality in Western societies. The age at diagnosis, extent of disease (as expressed by FIGO state), success of primary surgery and the histopathological features of the tumour are important prognostic markers. The majority of patients with ovarian cancer present with advanced disease (FIGO stage III/IV) and in this group of patients the median survival is only three years. New treatment approaches are therefore required to improve outcome in this disease. Angiogenesis, the development of a neovascular blood supply, is a critical step in the propagation of malignant tumour growth and metastasis and represents a promising target. This review will focus on angiogenesis, VEGF biology and the potential value of angiogenic factors with prognostic value in ovarian cancer (AU)

Idiopathic and recurrent thromboembolic phenomena in cancer patients

BACKGROUND: Venous thromboembolism (VTE) is one of the most common complications in cancer patients. It is not only associated with both reduced survival and a high number of recurrences, but an idiopathic VTE also increases the likelihood of a cancer diagnosis. METHODS: Between January 2000 and October 2005 we reviewed the medical history of 88 patients who were admitted to a tertiary hospital and presented both a diagnosis of VTE and any type of tumour. The information collected included the type of tumour, the temporal association between tumour diagnosis and VTE, anticoagulation treatment applied and percentage of recurrences. RESULTS: Ten patients (11.4%) presented the VTE prior to the cancer diagnosis; only half of them underwent a posterior tumour screening routine. Fifteen patients (17%) were diagnosed simultaneously and 71% presented the VTE after the tumour was detected. In 47 patients (53.4%) no risk factors for VTEs were detected. Twenty-nine patients (31.7%) presented a recurrent VTE, mainly during chemotherapy treatment (66%). Less than half of the patients (47.57%) were receiving treatment with low-molecular- weight heparins (LMWH). CONCLUSIONS: Idiopathic VTEs may be the first manifestation of an occult neoplasia, but tumour screening is scheduled in only a few patients. Regarding the high incidence of recurrent VTE in cancer populations, a high percentage is attributed to the underuse of LMWH, whose efficacy in preventing recurrent phenomena is superior to oral dicumarinics (AU)

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Retroperitoneal Castleman's disease with colon cancer. A rare association

Castleman's disease (CD) is a rare disorder of uncertain aetiology characterised by massive proliferation of lymphoid tissue usually localised as mediastinal masses, although abdominal involvement has been reported. Localised forms are usually associated with a good prognosis, but several more aggressive multifocal variants have been observed. Two different histologic subtypes have been described: the hyaline vascular type, more common in unicentric CD and usually asymptomatic, and the plasma cell form. Unicentric CD may be associated with an increased risk of lymphoma, but there was no reported increased risk of other malignancies. A patient with plasma cell subtype unicentric CD localised in retroperitoneum associated with an adenocarcinoma of ileocaecal valve and liver metastasis is reported (AU)

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Cirrhosis-like radiological pattern in patients with breast cancer

INTRODUCTION: Hepatic toxicity of breast cancer therapy is well known, usually consisting of elevation in the serum levels of hepatic enzymes or fatty infiltration of the liver. The chemotherapeutic agents most commonly linked to hepatotoxic effects are methotrexate, anthracyclines, taxanes and cyclophosphamide. There are few reports of patients with liver metastasis having radiological findings mimicking cirrhosis, both in the presence or the absence of prior systemic chemotherapy. Hepatotoxicity of antineoplastic drugs and cellular necrosis induced by response of liver metastases to chemotherapy may play a critical role in its physiopathology. MATERIALS AND METHODS: This article reports a series of ten women with breast cancer (nine with liver metastasis) treated with chemotherapy or hormonotherapy. RESULTS: They had low risk factors for hepatic disease, but developed a cirrhosis-like appearance in the computed tomography scan. The patient without liver metastasis is the second of this kind described in the literature. Relatively few reports have documented clinical sequelae of portal hypertension. In our series, three patients had oesophageal bleeding varices needing be hospitalised. To our knowledge, these are the first cases reported in the literature. CONCLUSIONS: This suggests that some manifestations of portal hypertension may develop in association with the cirrhosis- like pattern induced by breast cancer therapy (AU)

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Brain metastases as the first sign of colon cancer.

Cerebral metastases from colorectal cancer occur in 8% of cases. Diagnosis is usually made when primary disease and widespread metastases are already known. However, the detection of brain metastases as the first sign of colorectal carcinoma without any liver and/or lung involvement is extremely rare. Central nervous system metastases are more commonly seen in rectal cancer and often occur concurrently with lung metastasis. We report a case of a patient with brain metastases as the first clinical manifestation of an adenocarcinoma of caecum without any other organ involvement.

Brain metastases as the first sign of colon cancer

Cerebral metastases from colorectal cancer occur in 8% of cases. Diagnosis is usually made when primary disease and widespread metastases are already known. However, the detection of brain metastases as the first sign of colorectal carcinoma without any liver and/or lung involvement is extremely rare. Central nervous system metastases are more commonly seen in rectal cancer and often occur concurrently with lung metastasis. We report a case of a patient with brain metastases as the first clinical manifestation of an adenocarcinoma of caecum without any other organ involvement (AU)