Nizar Tannir, MD, FACPDept of Genitourinary Medical Oncology. University of Texas MDACC; KCA Patient Conference; April 1. Treatment Options for Patients with Non- clear Cell Histology. Thank you all for coming, and thanks to the KCA for sponsoring this, which has become a yearly event. Candida diet foods; bac candidat. Becker Nevus Benign Familial Chronic Pemphigus Birt Hogg Dube Biting Excoriation Biting Fleas Biting. So, it's 2009 and I'm sitting here typing a Livejournal entry on my wireless keyboard and my display is a 47' 1080p HDTV. I have almost no bills to speak of, and my. Plain water consumption in relation to energy intake and diet quality. That is not one type of tumor, but a diverse group of tumors. But about 2. 0% have these diverse histological subtypes, with papillary 1 & 2 considered about 1. Oncocytoma is usually benign, rarely metastasizes but it is one of those non- clear cell types also. I added sarcomatoid dedifferentiation because it presents challenges to the treatment of patients with this dedifferentiation. It is characterized by considerable activation of the c- MET receptor. It is estimated that about 1. The other papillary type 2 is also an inherited syndrome, also characterized by the germline mutation of a tumor- suppressor gene, the fumarate hydratase gene. Individuals that have this, in addition to renal cell carcinoma, have leiomylomas. There is an inherited syndrome associated with this, called Birt- Hogg- Dube syndrome, and there is a mutation in BHD genes: follicular is one of these. Collecting Duct carcinoma of the kidney is highly aggressive, and it is a disease hybrid between renal cell carcinoma and transitional cell carcinoma TCC of the pelvis, which behaves like bladder cancer. Patients, young women and adolescents often present with advanced disease, with extensive lymph node metastases. The TFE 3 protein product of translocation has been studied. This is what the sarcomatoid RCC looks like, and again it is associated with both clear cell and non- clear cell RCC histologies. Chemotherapy plus targeted therapy trials are ongoing but prognosis remains guarded. Birt-Hogg-Dube Syndrome; Acromegaly. Outcome of Patients with Advanced ncc. RCCThis is historical data, from the pre- targeted therapy era, when chemotherapy, interferon and interleukin 2 were the mainstay of therapy of patients with RCC. This is a retrospective study from the Sloan Memorial in 6. The majority were reported as having collecting duct, then chromophobe, papillary and then unclassified. The median survival was about 2 . This is group (on the lower line) with the non- clear cell, the non- conventional.? I think that you may already have heard about this earlier from speakers. Temsirolimus was tested in patients in a phase III trial, with advanced poor- risk patients, with advanced RCC, and with multiple risk factors such as poor performance status, anemia, hypercalcemia, and high serum LDH. Survival was the primary endpoint of this study. This is an improvement of 4. The take home message on this retrospective analysis is that there was no central pathology review to really confirm that in fact, these patients had the reported pathology. Also, there was no central independent radiology review to confirm the responses. But the investigators reported a decent median progression free survival in patients with papillary, 7. RCC. Retrospective studies and again, patient selection biases are inherent in this. The French conducted a Phase II trial with Sunitinibin papillary RCC. They observed only one patient achieving a partial response, 1 among 2. None of the five patients with Type 1 had a response. The Sloan Memorial group published their experience. That brings up the point about the importance of patients.
The median PFS was just 5. The median age was typical of trials, about 6. Eight patients had prior systemic therapy. We did not exclude patients with brain metastases, if the brain metastases were controlled. HISTOLOGIES . Two of these responses were in chromophobe 2 of 5, that is, 4. That seemed to mirror the experience with conventional histology, and there was one patient each that had response, 1 of 2. The median response for PFS was 1. For all 5. 7 patients, the median overall survival was 1. Sunitinib. The median response for PFS was 1. For all 5. 7 patients, the median overall survival was 1. Sunitinib. The primary endpoint of the trial is progression free survival at 6 months, and secondary endpoints are disease control rate, objective response rate (ORR), and median progression free survival (PFS) and safety. Randomized Phase II Trial of Everolimus vs Sunitinib. There are two phase II trials of Everolimus versus Sunitinib, led by Duke and recruiting patients from Canada and the United Kingdom and one of our own, led by our institution with contributions from the Harvard Consortium. A Phase II trial of Everolimus vs Suntinib in Non- Clear Cell in MDACCThe two trials are very similar in design except the Duke study–the ESPEN trial–does ot have a cross- over at progression with first- line therapy. Evidence for EGFR over- expression or aberrant function has been reported in many of these epithelial malignancies. Rationale for EGFR Inhibition in RCCAnd there is a rationale for EGFR inhibition in RCC. This was work done by Dr. Mendelsohn, our former president here, where they transfected VHL into VHL- negative cell lines and showed that restoration of . Only 4. 5 patients were evaluable. Efficacy Median Follow Up. And this is the efficacy slide, with a median follow up of 2. There was an 1. 1% response rate with a wide confidence interval, as you see. We know very well that papillary RCC is not one disease, as I mentioned and that patients with tumors which have high grade have more aggressive disease than patients with lower grade. They also did not differentiate, did not characterize how many of those patients of the 4. Type I or Type II.? I think the story is similar to the story with non- small cell lung cancer, adenoma carcinoma of the lungs, where EGFR mutation has been linked to faster response among these patients. We need an ongoing, a future trial, looking again at Erlotinib (Tarceva) in patients with papillary RCC. The C- MET Signaling Pathway. Now an interesting pathway is the C- Met pathway. This pathway seems to be operational, operative in some patients with papillary RCC. You see that hepatocyte growth factor is the ligand that signals through the receptors–the MET receptor–and causes down- stream effects. I will focus now on one called Foretinib, XL8. Phase II and Biomarker of the Dual MET/VEGFR- 2 Inhibitor Foretinib in PRCCThis is a phase II trial that was conducted at multiple centers in the US. There was a biomarker initiative in this drug to study the effectiveness of the MET and how it was modulated and MET correlated with outcome. We have already covered that the oncogenic events in PRCC are unknown, but do not involve the VHL- HIF- VEGF axis.? It is a multi- tyrokinase inhibitor, and predominately blocks two pathways that may be critical in patients with papillary RCC, the C- MET pathway and the VEGF- R2 pathway. Based and encouraged by this, and on the rationale of blocking the MET pathway in papillary RCC, a phase II trial was then conducted. Study Design and Treatment. This is the study design, the treatment plan for Foretinib. You see that 5. 0 of 6. When you look at the tumor shrinkage, I think this is impressive to see this in a disease where we have no established therapy. MET Status and Outcome. Now I think this is very important slide, as it illustrates a proof of concept, that when you target a particular pathway that drives the disease such as the type I where you have the germline MET mutation, five of ten patients, that is 5. So I think this represents a progress, a map forward, to try to bring this company to sponsor a large trial, testing this in a large number of patients. I told you I would mention sarcomatoid because it presents challenges to our management of sarcomatoid RCC. Phase II Doxorubincin/Gemcitabine. Just briefly, the backbone of treatment for sarcomatoid treatment remains chemotherapy. This is the backbone of the treatment, two cytotoxics. In this trial conducted by ECOG, published in Medical Oncology Journal lately, the response rate and efficacy were not very encouraging. We just recently closed this trial with 3. Gemcitabine and Capecitabine, two cytotoxics with Bevacizumab, a targeted agent blocking VGEF. Mc. Dermott say earlier. There is no place where this is more urgent than patients with non- clear cell RCC, because the other FDA- approved treatments that work with conventional clear cell cancer, unfortunately do not work as well in non- clear cell. I show you this scan of Pedro. Pedro came in with a large family, 1. This was ten years ago when we did not have any of these therapies. Pedro wanted to be treated, his family supported him and we treated him with what we had at the time. That was chemotherapy with F/U, Gemcitabine, and low dose interferon. He is celebrating ten years. Tannir, and any help with papillary would be great, and XL8. XL 1. 84 I think represents a lot of promise for papillary and also clear cell, in making those medications, making them available for our patient group, for patients with clinical trials and off label, where they are approved for other types of cancer. Tannir; . This now politics, but insurance companies, when you have gone through all the standards of care, you think that there is drug that might help them and they deny that. Skin Tags: Removal, Causes and Treatments. A skin tag is a small (benign) tag of skin which may have a peduncle (stalk) - they look like a small piece of soft, hanging skin. Skin tags are also known as an acrochordon, cutaneous papilloma, cutaneous tag, fibroepithelial polyp, fibroma molluscum, fibroma pendulum, soft fibroma, and Templeton skin tags. Skin tags can appear on any part of the surface of the body (skin), but most occur in areas where skin may rub against skin or clothing, such as the: 1. Eyelids. Axillae (armpits) Under the breasts. Groin. Upper chest. Neck (papilloma colli). Fast facts on skin tags. Here are some key points about skin tags. More detail and supporting information is in the main article. Skin tags are benign tumors of the skin. Some people are more susceptible to skin tags than others. Skin tags commonly occur in creases or folds of the skin. Obesity and diabetes may increase the risk of skin tags developing. Skin tags are typically removed for aesthetic and cosmetic reasons. Methods of skin tag removal include excision and cryotherapy. There are some over- the- counter solutions available for skin tags. There is no evidence to suggest that removing a skin tag causes more to develop. What are skin tags? Skin tags are invariably benign - non cancerous - tumors of the skin which cause no symptoms, unless it is repeatedly rubbed or scratched, as may happen with clothing, jewelry, or when shaving. Very large skin tags may burst under pressure. Skin tags are composed of a core of fibers and ducts, nerve cells, fat cells, and a covering or epidermis. Some people inherit an increased susceptibility to skin tags, and being obese or overweight also appears to increase the likelihood of developing this skin anomaly. Skin tags affect people of all genders equally, but are more likely to occur in people who are pregnant and/or who have diabetes and have been associated with hyperinsulinaemia. Some people may have had skin tags and never noticed them - they would have rubbed or fallen off painlessly. In most cases, however, they do not fall off. The surface of skin tags may be smooth or irregular in appearance, they are often raised from the surface of the skin on fleshy peduncles (stalks). They are usually flesh- colored or slightly brownish. Initially they are quite small, flattened like a pinhead bump. They are said to be caused by bunches of collagen and blood vessels which are trapped inside thicker bits of skin. They are believed to be the result of skin rubbing against skin. That is why they are generally found in skin creases and folds. Risk factors for skin tags. A risk factor is something which increases the likelihood of developing a condition or disease. For example, obesity significantly raises the risk of developing diabetes type 2. Therefore, obesity is a risk factor for diabetes type 2. This association between skin tags and insulin resistance was also found in a survey of 1. The same survey found that skin tags were also associated with obesity, dyslipidemia (such as high cholesterol levels), hypertension (high blood pressure), and elevated high- sensitive C- reactive protein (a marker for inflammation). This suggests that skin tags may offer an external sign of an increased risk of atherosclerosis and cardiovascular disease. According to the NIH (National Institutes of Health), USA, approximately 4. Around 5. 9% of people have skin tags by the time they are 7. A causal genetic component is thought to exist, i. People with close family members who have skin tags are more likely to develop them themselves. Skin tags are rarely associated with: Birt- Hogg- Dub. Patients with BHD tend to also develop carcinomas (cancerous tumors) in the kidneys and colon. On the next page, we look at the options for removing and treating skin tags.
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