Colorectal cancer remains one of the most frequent malignancies (third place at both genders) worldwide in the last decade, owing to significant changes in modern dietary habits. Approximately half ...of the patients develop metastases during the course of their disease. The available therapeutic armamentarium is constantly evolving, raising questions regarding the best approach for improving survival. Bevacizumab remains one of the most widely used therapies for treating metastatic colorectal cancer and can be used after progression. This study aimed to identify the best chemotherapy partner for bevacizumab after progression. We performed a retrospective analysis of patients with metastatic colorectal cancer who were treated with bevacizumab as first- and second-line chemotherapy. Data were collected for 151 patients, 40 of whom were treated with double-dose bevacizumab after the first progression. The two standard chemotherapy regimens combined with bevacizumab were FOLFIRI/CAPIRI and FOLFOX4/CAPEOX. The initiation of first-line treatment with irinotecan-based chemotherapy improved progression-free survival and time to treatment failure but not overall survival. After the first progression, retreatment with the same regimen as that used in the induction phase was the best approach for improving overall survival (median overall survival: 46.5 vs. 27.0 months for the same vs. switched strategy, respectively). No correlations were observed between the dose intensity of irinotecan, oxaliplatin, 5-fluorouracil, or bevacizumab and the overall survival, progression-free survival in the first-/second-line treatment, and time to treatment failure. Interaction between an irinotecan-based regimen as a second-line treatment and double-dose bevacizumab after progression was associated with an improved overall survival (p = 0.06). Initiating systemic treatment with an irinotecan-based regimen in combination with bevacizumab improved the progression-free survival in the first-line treatment and time to treatment failure. In terms of overall survival, bevacizumab treatment after the first progression is better partnered with the same regimen as that used in the induction phase.
Infantile hemangioma is one of the most common benign tumors affecting children, with ~10-15% requiring medical treatment. These tumors consist of endothelial cells and stromal components, including ...fibroblasts, pericytes and mast cells. Effects of propranolol treatment in combination with bevacizumab or vincristine on cell growth were compared in the current study using human umbilical vein endothelial cells (HUVECs) and BJ human normal fibroblasts (BJs) to determine potential synergic effects
. Inhibition of cell growth was investigated using MTT assays and cytotoxicity of the drugs in various combinations was expressed as half inhibitory concentration (IC
). Apoptosis was investigated using flow cytometry, with Alexa Fluor 488 and propidium iodide. Propranolol inhibited BJ and HUVEC growth in a dose-dependent manner, with increased response observed in BJs (IC50, 148,32 µg/ml; standard error logIC50, 0.07). Treatment with vincristine induced the strongest growth inhibition in HUVECs (IC50, 17,89 µg/ml; standard error log IC50, 0.07) and BJs (IC50, 24,81 µg/ml; standard error log IC50, 0.08) compared with propranolol (HUVEC IC50, 81,94 µg/ml; standard error log IC50, 0.06; BJ-IC50, 148,32 µg/ml; standard error logIC50, 0.07) or bevacizumab (HUVEC IC50 96,91 µg/ml; standard error log IC50, 0.06; BJ IC50, 182,70 µg/ml; standard error log IC50, 0.09) alone. Bevacizumab was the weakest cytotoxic agent. Combination treatment of vincristine with bevacizumab induced the highest levels of apoptosis in HUVECs compared with all other treatments and triple-drug therapy induced the levels of apoptosis in BJs. Single treatment with vincristine, propranolol or bevacizumab induced apoptosis in BJs and HUVECs. In BJs, triple treatment exhibited the greatest influence on apoptosis, compared with single and dual treatments and in HUVECs, vincristine and bevacizumab combination treatment induced apoptosis to the highest level. The present study offers novel perspectives in drug repurposing studies for the three drugs, particularly in diseases where the pathogenesis is based on healthy endothelial cell proliferation, including hemangiomas.
Bevacizumab or cetuximab represent the standard treatment in association with classical chemotherapy in confirmed metastatic colorectal cancer (mCRC). Bevacizumab could be continued after the first ...disease progression with an overall survival (OS) advantage, compared to chemotherapy alone, but the optimal dose remains a debatable issue.
In a retrospective analysis of mCRC patients treated with bevacizumab, we selected patients with administration beyond progression, and stratified them according to the dose received- same dose bevacizumab (SDB) as first-line chemotherapy or double dose bevacizumab (DDB). For each group we evaluated OS, time to treatment failure (TTF) and progression-free survival in the first-line (PFS1) and in the second-line (PFS2).
In the first-line therapy, oxaliplatin backbone regimen was used in 73% SDB, compared with 22.5% DDB patients, while irinotecan was used in 75% DDB and 27% SDB patients. Second-line oxaliplatin was given to 50% DDB and 29.7% SDB patients, while irinotecan was administered to 47.5% DDB and 70.3% SDB patients. The median values were: OS - 41 months in the DDB group and 25 months in the SDB group (p = 0.01); TTF - 24 months in the DDB group and 19 months in the SDB group (p=0.009); PFS1 - 17 months in the DDB group and 12 months in the SDB group (p=0.008); PFS2 - 9 months in the DDB group and 5 months in the SDB group (p = 0.03).
Doubling the dose of bevacizumab at progression seems to provide OS and PFS advantage for mCRC patients.
•Paraneoplastic cerebellar degeneration may precede the diagnosis of cancer.•Early diagnosis of paraneoplastic cerebellar degeneration improve the prognosis.•Treatment includes immunotherapy, ...oncological therapy and supportive therapy.•Paraneoplastic cerebellar degeneration suspected in neurological symptoms in women.
Paraneoplastic neurologic syndromes (PNS) are a rare heterogeneous group of disorders associated with malignancy that can result in significant functional impairment. One syndrome in particular, paraneoplastic cerebellar degeneration (PCD), may be severely disabling. PCD is a rare neurological syndrome, associated with active or subclinical cancer, characterized by acute or subacute onset cerebellar ataxia due to tumor-induced autoimmunity against cerebellar antigens. Treatment of paraneoplastic syndromes is generally unsatisfactory, but early diagnosis and treatment of PCD, which includes neurological treatment, immunotherapy and oncological treatment of associated malignancy, may improve the neurological prognosis. We reported the case of a 59-year-old woman who presented PCD as the first sign of ovarian cancer. Laboratory investigations showed the presence of anti-Yo antibodies in the serum. The brain MRI revealed specific modifications for PCD. After oncological treatment, intravenous immunoglobulin therapy and corticosteroid therapy, the oncological response was satisfactory, but no improvement of the neurologic symptoms was achieved.
Recurrent vulvar squamous cell carcinoma with multiple site metastases is a rare entity - (up to 14.2% of the total number of recurrences), with a poor prognosis (only 15% of the patients alive at 5 ...years). Due to its "hard to find" character, there are no standardized guidelines available and the treatment is extrapolated from advanced cervical carcinoma, anal carcinoma and other squamous cell carcinomas. Immunotherapy has shown some positive results in vulvar carcinoma with PD-L1 positive, high TMB, high MSI or with MMR deficiency. An alternative for selected cases without therapeutic resources could be the HPV vaccine. We present the case of a 64-year-old woman diagnosed in 2014 with vulvar squamous cell carcinoma stage II for which she underwent radical vulvectomy with bilateral inguinal lymphadenectomy followed by external radiotherapy. In 2019 she developed local recurrence associated with lung, pleural, lymph nodes and subcutaneous metastasis, treated with three lines of chemotherapy: paclitaxel/carboplatin followed by cisplatin/5-fluorouracil and carboplatin/gemcitabine. The patient's general health status altered progressively, and she died after the 4
cycle of carboplatin/gemcitabine. This case's management could be a starting point for the vulvar carcinoma cases where the standard therapeutical options do not represent a choice anymore, providing the necessary example on how to approach it.
Solid pseudopapillary tumor (SPT) of the pancreas is a rare pathological condition, representing less than 3% of all exocrine pancreatic tumors. SPT usually occurs in young females, without notable ...symptoms, with a low malignant potential and excellent prognosis.
We conducted a retrospective study during the period January 2005 - January 2015. SPT patients admitted in our institution were reviewed by describing demographic data, clinico-pathologic and radiological features, therapeutic management and prognosis records.
Thirteen patients with SPT were identified (10 females), with a median age of 30 years. The main clinical presentation was abdominal pain (92.3%). The tumor was mostly located in the body or tail of the pancreas (77%), and the mean size was 8.2 cm. Regarding the surgical approach there were 5 distal pancreatectomies with splenectomy, 3 body and tail pancreatectomies, 2 body and tail pancreatectomies with splenectomy, 2 pancreato-duodenectomy, 1 partial enucleation and of all only 2 partial resections. Postoperative hematoxylin- eosin staining and immunohistochemistry confirmed the diagnosis in all cases. None of the patients had lymph nodes metastases. Only one local invasion. There was one case of death due to postoperative complications. Four cases followed adjuvant systemic chemotherapy. The mean follow-up was 18 months, without evidence of recurrence during this period.
SPT should always be considered in the differential diagnosis in young women with a pancreatic tumor. Complete surgical excision is the treatment of choice, and is usually curative. The decision to administer systemic therapy must be individualized. Malignant behavior and late recurrences mandates long-term follow-up for patients with SPT.
A normal evolution of the cell-cycle phases consists of multiple consecutive events, which makes it a highly complex process. Its preservation is regulated by Cyclin-Cdks (cyclin-dependent kinases) ...interactions and protein degradation, which is often controlled by the ubiquitin-mediated proteolysis. The goal of this review is to emphasize the most important features of the regulation of the cell-cycle involved in cancerogenesis, by presenting the involvement of E3 ubiquitin ligases SCF (Skp1-Cul1-F-box protein) and APC/C (Anaphase-promoting complex/cyclosome) in human malignancies. Also, we discuss the importance of the ubiquitin proteasome pathway blockade in cancer treatment. We know that a better understanding of the regulatory biology of the cell cycle can lead to the development of new target therapies for cancer.
The aim of this study was to evaluate the impact of the interval between surgery and adjuvant treatments regarding the overall survival and recurrence-free survival in patients from a developing ...country. For stages II and III rectal cancer, international guidelines recommend neoadjuvant chemoradiotherapy (CRT) regardless of the tumor location. In the developing countries there is a shortage of radiotherapy centers, specialists, which lead to long waiting lists for radiotherapy. These problems might lead to protocol deviations.
We conducted a retrospective study on 161 patients with rectal cancer treated with surgery, postoperative CRT and with or without chemotherapy for a total of 6 months, at The Oncology Institute Cluj-Napoca between 2006-2010. All patients had 5 years of follow-up.
A total of 161 patients were enrolled in this study. The majority of patients were locally advanced stages (89.44%). The well known prognostic factors, such as TNM stage, performance status, CEA serum level, perineural, vascular and lymphatic invasion, and node capsular effraction had a statistically significant influence on overall survival. In 21.12% of patients the first adjuvant treatment was started in the first 4 weeks after surgery. Only 13.04% of patients started the concomitant CRT within the limit of 6 weeks after surgery. Concerning the time between surgery and CRT, we did not observe a statistically significantly difference in OS if the radiotherapy started after the first 6 weeks (p=0.701). The OS rate for locally advanced rectal cancer patients was 69.44%.
In rectal cancer, the importance of the first therapeutic act is crucial. Following international guidelines provides a survival advantage and a better quality of life. In case of adjuvant treatment, it is recommended to start this treatment as soon as the local infrastructure allows it.
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