Ovarian Germ Cell Tumors Treatment (PDQ®)
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Dr Kurian disclosed research funding from Ambry Genetics, GenDx, Genomic Health, Invitae, and Myriad Genetics. Dr Idos disclosed research funding from Myriad. Dr Isaacs disclosed honoraria from Genentech/Roche, Pfizer, Genentech, and Novartis. Dr Weitzel has disclosed no relevant financial relationships.I think it is really important to think about an individual's preference and their tolerance for ambiguity," said Dr Isaacs. "In June 2016, there is still a reasonable chance if you send someone for multigene panel testing that you will find a mutation in a moderate penetrance gene or you will get a VUS, and you have to make sure the patient feels comfortable with that. I think the technology has outpaced our medical knowledge, but our medical knowledge will catch up."
Importance A 2009 randomized clinical trial demonstrated that using cancer antigen 125 (CA-125) tests for routine surveillance in ovarian cancer increases the use of chemotherapy and decreases patients’ quality of life without improving survival, compared with clinical observation. The Society of Gynecologic Oncology guidelines categorize CA-125 testing as optional and discourage the use of radiographic imaging for routine surveillance. To date, few studies have examined the use of CA-125 tests in clinical practice.
These results therefore run contrary to the "timing hypothesis" that suggests a benefit to hormone therapy if taken early in menopause as opposed to later on.
Limitations to the study include that generalizability may be limited to healthy postmenopausal women, and that it was not designed to examine short-term effects on estradiol or effects on the risks of mild cognitive impairment or Alzheimer's disease.
Approximately 5% to 10% of patients with cancer will develop a life-threatening condition that necessitates ICU admission.[9-12]
However, caution is needed when interpreting the results in the literature on ICU treatment for patients with cancer and when deriving conclusions for clinical practice. The vast majority of studies is retrospective and demonstrates considerable heterogeneity. It remains controversial whether the observed improvements in survival of critically ill patients with cancer are solely the result of advances in treatment of the underlying malignancy and progress in critical care.[38-40] Part of the improvements that were seen could be because of selection bias or earlier ICU admission of critically ill patients with cancer. Furthermore, there are substantial practice variations at the physician, hospital, country, and temporal levels. Thus, published data concerning cancer critical care, such as changes in ICU survival of patients with cancer, may be confounded by differences in clinical practice, case mix, and admission policies.[41]
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Infections |
• Pneumonia |
• Sepsis |
Oncologic emergencies |
• Superior vena cava syndrome |
• Tumor lysis syndrome |
• Hypercalcemia |
Noninfectious ARF |
• TRALI |
• TACO |
• Pneumonitis |
• Alveolar hemorrhage |
• Engraftment syndrome |
Surgery |
• Regular postsurgical care |
• Postsurgical complications, eg, bleeding |
Adverse drug reactions |
• Anaphylaxis |
• Cytokine release syndrome |
• ATRA syndrome |
• Thrombotic microangiopathy |
Neurologic complications |
• Seizures |
• PRES |
Cardiovascular disease |
• Myocardial infarction |
• Congestive heart failure |
• Arrhythmias |
• Pulmonary thromboembolism |
Results Of the 143 people registered for the conference, 137 provided valid email addresses. There was a wide range of attendees, with the 3 most common groups being plastic surgeons (28 [19.6%]), general surgeons (19 [13.3%]), and researchers (25 [17.5%])....
Franklin died of ovarian cancer in 1958, four years before the Nobel prize was awarded to Watson, Crick and Wilkins for their work on DNA structure. She never learned the full extent to which Watson and Crick had relied on her data to make their model......
For eight out of the ten patients tested, junctions identified in DNA of the primary tumor were also detected in the cfDNA derived from pre-surgical plasma (Table 1). Of these eight, three demonstrated a continued presence of the ctDNA post-surgery, consistent with the presence of disease, which was documented at the time of the blood draw. In five patients, ctDNA could not be detected post-surgery, in accord with the lack of detectable disease observed at the time of the blood draw. Thus, for these eight cases, perfect concordance was observed between ctDNA detection and clinical presentation at the time of the blood draw. In two of the ten cases, somatic rearrangements could not be detected in the patient plasma.
Recently, ctDNA increases in breast cancer were found to indicate recurrence earlier than rises in CTCs or CA 15-3. Furthermore, detection of ctDNA in half of these cases was possible an average of 5 months before radiologically confirmed disease progression was observed3,25. Similar results have been reported in gynecological cancer18. More work will need to be done in OC patients to study how fluctuations in ctDNA% correlate with other clinical indicators of recurrence over multiple time-points.
The study was done on 10 patients in advanced stages of ovarian cancer.
When post-surgery DNA matched that of the tumor, patients were later found to have had a recurrence of ovarian cancer. However, when the post-surgery DNA did not match the DNA of the tumor, patients were found to be in remission.
CRLX101 is being evaluated in combination with weekly paclitaxel for the treatment of recurrent platinum-resistant ovarian carcinoma in a Phase 1b/2 clinical trial. Data from the Phase 1b portion of the trial were the subject of an oral presentation at the Gynecologic Oncology 2016 Conference in May. These data showed that five of the first nine patients (56%) enrolled in the trial achieved partial responses. Of note, five of the nine patients enrolled in the Phase 1b trial previously failed Avastin® (bevacizumab) and three of these five patients achieved partial responses. Cerulean is conducting this trial in collaboration with the GOG and expects to provide an update at the European Society for Medical Oncology 2016 Congress.
In 2015, CRLX101 was granted Orphan Drug designation for the treatment of ovarian cancer.
The present case may represent many recurrent ovarian cancer patients who have benefited greatly from emerging target therapies, such as bevacizumab, and have survived longer with an improved quality of life, but also later developed adverse effects including cardiovascular disease.
To reap the benefits of long term bevacizumab treatment, efforts should be made to diagnose cardiovascular complications and to treat them aggressively to minimize the deleterious adverse effects of cancer therapy.