Purpose
There are no robust data on hemoglobin (Hb), lactate dehydrogenase (LDH), and calcium variability for overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) treated ...with vascular endothelial growth factor (VEGF)-targeted therapy. We aim to evaluate prognostic implications of Hb, LDH, and calcium variability and establish a novel risk stratification model in RCC patients receiving targeted therapies.
Methods
We retrospectively studied an unselected cohort of patients with mRCC, who were treated with tyrosine kinase inhibitors. We assessed LDH variability, Ca variability, and Hb variability with various methods using standard deviation and fluctuation across thresholds. Kaplan–Meier and log-rank analyses were employed on OS and multivariate Cox proportional hazard model analyzed clinical parameters for their prognostic relevance.
Results
A total of 59 patients intermediate-risk group according to the Memorial Sloan-Kettering Cancer Center with mRCC who had early progressed after first-line therapy with interferon-α were included in this retrospective single-center study conducted between February 2008 and December 2011. The mean Hb was 12.4 g/dl (min–max 9.1–15.2) throughout the study. Multivariable-adjusted Cox regression showed that patients in the consistently low-Hb group and patients in the low-amplitude and high-amplitude groups had a statistically significant increase in risk compared with patients who were consistently on target (HR 4.1; 95 % CI 1.3–12.9 and HR 2.9; 95 % CI 1.05–8.1 and HR 4.4; 95 % CI 1.7–11.1, respectively). On the other hand, the higher mean LDH (LDH more than 1 >upper limit of normal) was associated with OS. LDH variability and Ca variability were not associated with mortality.
Conclusions
In patients with mRCC treated with VEGF-targeted therapy, Hb variability and mean LDH level might be associated with OS. This should be investigated prospectively.
The DNA damaging revolution Cetin, Bulent; Wabl, Chiara A.; Gumusay, Ozge
Critical reviews in oncology/hematology,
December 2020, 2020-12-00, Letnik:
156
Journal Article
Recenzirano
Display omitted
•PARP inhibitors are promising treatments for cancers with BRCA mutations and in other cancers with defective homologous recombination.•Inhibition of ATR/CHK1 signaling is a unique ...strategy to overcome PARP inhibitor resistance.•Novel biomarkers are potential candidates to predict response to PARP inhibitors.
Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme that plays a critical role in the repair of single-strand DNA damage via the base excision repair pathway. PARP inhibitors have substantial single-agent antitumor activity by inducing synthetic lethality. They have also emerged as promising anticancer targeted therapies, especially in tumors harboring deleterious germline or somatic breast cancer susceptibility gene (BRCA) mutations. PARP inhibition produces single-strand DNA breaks, which may be repaired by homologous recombination, a process partially dependent on BRCA1 and BRCA2. The PARP inhibitors olaparib, veliparib, talazoparib, niraparib, and rucaparib have predominantly been studied in patients with breast or ovarian cancers associated with deleterious germline mutations in BRCA1 and BRCA2. Ongoing clinical trials are evaluating the role of PARP inhibitors alone and in combination with other therapies, including selective inhibitors against key targets involved in the DNA damage response. In this review we summarize the use of PARP inhibitors in various tumor types, as well as possible approaches for overcoming resistance to PARP inhibitors.
Hormone receptor (HR)‐positive and human epidermal growth factor receptor 2 (HER2)‐negative breast cancer is defined by the presence of the estrogen receptor and/or the progesterone receptor and the ...absence of HER2 gene amplification. HR‐positive/HER2‐negative breast cancer accounts for 65%–70% of all breast cancers, and incidence increases with increasing age. Treatment varies by stage, and endocrine therapy is the mainstay of treatment in both early stage and late‐stage disease. Combinations with cyclin‐dependent kinase 4/6 inhibitors have reduced distant recurrence in the early stage setting and improved overall survival in the metastatic setting. Chemotherapy is used based on stage and tumor biology in the early stage setting and after endocrine resistance for advanced disease. New therapies, including novel endocrine agents and antibody‐drug conjugates, are now changing the treatment landscape. With the availability of new treatment options, it is important to define the optimal sequence of treatment to maximize clinical benefit while minimizing toxicity. In this review, the authors first discuss the pathologic and molecular features of HR‐positive/HER2‐negative breast cancer and mechanisms of endocrine resistance. Then, they discuss current and emerging therapies for both early stage and metastatic HR‐positive/HER2‐negative breast cancer, including treatment algorithms based on current data.
Bowel perforation is a rare but well-described complication of bevacizumab, a VEGF monoclonal antibody. However, bevacizumab associated abdominal wall perforation is a more serious complication. In ...here, a patient with recurrent epithelial ovarian cancer developing both bowel and abdominal wall perforation after bevacizumab treatment is reported with review of the literature to point out the clinical significance of this rare complication. To our knowledge, this is the first case with bevacizumab associated abdominal wall perforation.
Summary
Aim
The aim of the present study was to evaluate the effect of crizotinib on visceral organs in an experimental rat model.
Methods
Eighteen Wistar albino rats were divided into three groups: ...experimental toxicity was induced with crizotinib (10 mg/kg) administered for 28 days (Group 1), 42 days (Group 2) orally by gavage. Control group received only distilled water. Rats in Group 1 and Group 2 were sacrificed after the collection of blood and tissue samples on the 28th and 42nd days, respectively.
Results
Subjects in Group 1 and Group 2 had abnormal histology mainly in lung and liver. There were intraalveolar hemorrhage in lungs; mild portal inflammation, perivenular focal and confluent necrosis in liver; inflammatory reaction in renal pelvis and periureteral areas, and focal pancreatitis in pancreas.
Conclusion
This study is the first to evaluate the histopathological features of toxicity of crizotinib in a rat model.
Purpose
In this study, we investigated the effect of lapatinib plus capecitabine treatment in HER2-positive breast cancer patients with brain metastasis.
Methods
Of 405 metastatic breast cancer ...patients with brain metastases at referral centers in Turkey, 46 were treated with lapatinib plus capecitabine only after the development of brain metastasis. Patients who only received trastuzumab-based therapy after the development of brain metastases were accepted as the historic control group for survival analyses (
n
= 65). Patients who received both drugs consecutively or sequentially were excluded from the analyses (
n
= 34).
Results
Median age among 46 patients who received lapatinib plus capecitabine therapy was 45 years (27–76), and median time for development of brain metastases was 11.9 months (0–69 months). Twenty-six out of 38 patients who received lapatinib plus capecitabine and had extracranial metastasis showed partial response or stable diseases (68.4 %). Grade 3-4 toxicity was observed in eight patients (17.3 %). Median overall survival (OS) in patients treated with lapatinib plus capecitabine was significantly increased compared to that in patients treated with trastuzumab-based therapy (19.1 vs. 12 months, respectively,
p
= 0.039). The incidence of cerebral death was slightly decreased in patients who received lapatinib plus capecitabine compared to those who received trastuzumab-based therapy (32 vs. 43.4 %,
p
= 0.332). In the multivariate analysis, lapatinib plus capecitabine therapy remained an independent positive predictor for survival odds ratio (OR), 0.57;
p
= 0.02.
Discussion
Although this retrospective multicenter study had several limitations, the results suggest that undergoing lapatinib plus capecitabine therapy after the diagnosis of brain metastasis may further improve survival compared to undergoing only trastuzumab-based therapy.
The aim of the present study was to evaluate the prevalence of thyroid lesions detected by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) incidentally, ...determine malignancy risk and its relationship with maximal standardized uptake value (SUVmax) and FDG uptake pattern.
Between February 2009 and February 2014, a total of 12713 patients underwent 18F-FDG PET/CT. Incidental thyroid uptake was seen in 710 patients and further diagnostic evaluation was performed on 147 patients with focal or diffuse FDG uptake. The 18F-FDG PET/CT findings of these patients and their association with malignancy were retrospectively reviewed.
The prevalence of thyroid incidentalomas detected by 18F-FDG PET/CT was 5.6% (710/12713). Of the 147 patients who underwent biopsy or thyroid surgery, histology was benign in 99 and malign in 48 patients. The malignancy risk of incidental thyroid lesions was calculated as 32.7% (48/147). The median SUVmax was 2.9 (0.6–27.4) in benign group, whereas 11.8 (2.4–72.9) in malign group and the difference between these groups was statistically significant (p < 0.001). According to the ROC analysis, a SUVmax above 6 was more likely to be malign with statistical significance (p < 0.001). The sensitivity, specificity, positive predictive value and negative predictive value were 87.4%, 81.7%, 70.1% and 93% respectively.
The malignancy risk of incidental thyroid lesions on 18F-FDG PET/CT is high. Although it is obvious that higher SUVmax values are tended to be malign, an overlap between benign and malign groups is still remaining. In case of absence of clinical contraindications, further examination should be recommended.
Opinion statementThe treatment of renal cell carcinoma (RCC) is one of the great success stories in the field of oncology, which was revolutionized with the development of therapies aimed at ...disrupting crucial pathways. Tumor biology of RCC has provided insight into the disease through elucidation of the role of vascular endothelial growth-factor (VEGF) and the mammalian target of rapamycin (mTOR). Targeted agents against VEGF and mTOR, as well as agents targeting relevant immunomodulatory pathways, have shown clinical benefit for advanced disease. The targeted agents are highly effective in achieving a response and survival, particularly in high-risk patients. These include the vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) axitinib and cabozantinib, and programmed cell death 1 protein (PD-1) immune checkpoint inhibitors (ICI) nivolumab and pembrolizumab. There is a wealth of evidence investigating different therapeutic options and combinations for first-line treatment of advanced RCC including the CheckMate 214 study, KEYNOTE-426, JAVELIN Renal 101, and CheckMate 9ER. Dual ICI and combination agents targeting the programmed cell death protein 1/programmed cell death protein ligand 1 (PD1/PDL1) and VEGF, began to demonstrate superiority over previously accepted standards in advanced clear-cell RCC. Data from a number of clinical studies are available to help physicians with evidence-based decisions for the sequence of second-line and future treatments for patients with progressive RCC. In this review, we focus on essentials for clinicians treating patients with clear-cell RCC.
In the head and neck mucosa, neuroendocrine carcinomas of the oral cavity is rare. Herein, we present the first report of a small cell neuroendocrine carcinoma in a 54-year-old man on the right ...lateral posterior tongue. It is important to remember that although neuroendocrine small cell carcinomas (SCCs) are most commonly seen in the lung, they rarely may arise in the extrapulmonary sites, including salivary glands, as well. As there is not any standard therapeutic regimen already existing, it is important to be aware of and to know how to deal with such rare cases.
Hormone receptor (HR)-positive, HER2-negative tumors represent the most common form of metastatic breast cancer (MBC), and endocrine therapy has been the mainstay treatment for several decades. ...Recently, a novel drug class called CDK4/6 inhibitors in combination with endocrine therapy have remarkably improved the outcome of patients with HR-positive, HER2-negative MBC by targeting the cell cycle machinery and overcoming aspects of endocrine resistance. Several potential cell-cycle-specific and nonspecific mechanisms of resistance to CDK4/6 inhibitors have been reported in recent studies. This review discusses potential resistance mechanisms to CDK4/6 inhibitors, the use of biomarkers to guide treatment for HR-positive, HER2-negative MBC and possible approaches to overcome resistance to CDK4/6 inhibitors.
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