<p>In patients treated with vorinostat and everolimus, there was a longer median progression-free survival in patients with normal LDH compared to patients with high LDH (5.8 months, 4.4 - 7.2 vs. 1.6 months, 95% CI 1.3-1.9; P < 0.001).</p>
Introduction: Kaposi’s sarcoma is an angio-proliferative disorder that is caused by HHV-8. Gastrointestinal KS is an under-diagnosed entity in HIV population. This case underlines the importance of endoscopic interventions in patients with HIV with multisystem involvement with higher CD4 count. Case Description/Methods: A 31-year man with history of HIV was admitted to the hospital with persistent cough for 2 months, back pain, loss of appetite and diarrhea. He was suspected to have disseminated MAC despite a CD4 count of 375 cells/mm3. Physical exam showed a lethargic man with hepatosplenomegaly with no tenderness in the abdomen. Labs revealed hemoglobin 8.6, alkaline phosphatase 1223, total bilirubin 5.6, AST 90. He developed an empyema requiring chest tube. GI was called to investigate up trending liver enzymes and diarrhea. Patient underwent EGD and colonoscopy. EGD showed 3 lesions. Two of them were fleshy masses in the antral area of 8mm and 15mm and the third was 18mm, raised and centrally necrotic at the body. The biopsy specimens from the stomach revealed Kaposi sarcoma. Patient was treated during hospitalization for disseminated MAC, restarted HIV medications, and followed up as outpatient to start paclitaxel for Kaposi sarcoma (Figure 1). Discussion: Kaposi's sarcoma is the most common gastrointestinal malignancy in AIDS and is often asymptomatic. There have been recent reports in the literature of rising cases of Kaposi's sarcoma among patients with CD4 count > 350 cells/mm3. Patient might present with abdominal pain, SOB, dizziness, anemia or, in rare cases, with frank hemorrhage. However, when the patients with HIV and disseminated conditions, the above symptoms may be obscured. Physicians need high level of suspicion to evaluate the endoluminal. Endoscopically, lesions may resemble benign lesions as well as malignant lesions, as in our case. Biopsy is confirmatory with spindle cell proliferation and presence of HHV 8. Visceral involvement of KS is associated with poor prognosis. Treatment options include antiretroviral medications, chemotherapy, radiotherapy, or combination therapy. Visceral KS is an underdiagnosed entity and high index of suspicion in susceptible populations may increase the early diagnosis and treatment.Figure 1.: A: Retroflex view of the body and incisura, 2 fleshy lesions noted (yellow arrows) B: Direct view of one of the lesions, raised and centrally necrotic appearance C: H&E,10x magnification. Slit like spaces and associated neoplastic spindle cells (green arrow) with surrounding hemorrhage. D: H&E,40x magnification. Abnormally formed vessels by neoplastic spindle cells (green arrow). Background of extravasated red blood cells and occasional fragments of hemosiderin. E: CD31 immunostaining. Highlight neoplastic endothelial cells (blue arrow) forming anastomosing and slit-like vascular spaces. F: HHV8 immunostaining. Diffusely expressed in neoplastic endothelial cells (blue arrow).
mutations occur in about 30% of patients with cholangiocarcinoma. Analysis of mutations in circulating tumor DNA (ctDNA) can be performed by droplet digital polymerase chain reaction (ddPCR). The analysis of ctDNA is a feasible approach to detect
Oncogenic mutations in PIK3CA are prevalent in diverse cancers and can be targeted with inhibitors of the phosphoinositide-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway. Analysis of circulating tumor DNA (ctDNA) provides a minimally invasive approach to detect clinically actionable PIK3CA mutations.We analyzed PIK3CA hotspot mutation frequency by droplet digital PCR (QX 200; BioRad) using 16 ng of unamplified plasma-derived cell-free DNA from 68 patients with advanced solid tumors (breast cancer, n = 41; colorectal cancer, n = 13; other tumor types, n = 14). Results quantified as variant allele frequencies (VAFs) were compared with previous testing of archival tumor tissue and with patient outcomes.Of 68 patients, 58 (85%) had PIK3CA mutations in tumor tissue and 43 (74%) PIK3CA mutations in ctDNA with an overall concordance of 72% (49/68, κ = 0.38). In a subset analysis, which excluded samples from 26 patients known not to have disease progression at the time of sample collection, we found an overall concordance of 91% (38/42; κ = 0.74). PIK3CA-mutated ctDNA VAF of ≤8.5% (5% trimmed mean) showed a longer median survival compared with patients with a higher VAF (15.9 versus 9.4 months; 95% confidence interval 6.7-17.1 months; P = 0.014). Longitudinal analysis of ctDNA in 18 patients with serial plasma collections (range 2-22 time points, median 5) showed that those with a decrease in PIK3CA VAF had a longer time to treatment failure (TTF) compared with patients with an increase or no change (10.7 versus 2.6 months; P = 0.048).Detection of PIK3CA mutations in ctDNA is concordant with testing of archival tumor tissue. Low quantity of PIK3CA-mutant ctDNA is associated with longer survival and a decrease in PIK3CA-mutant ctDNA on therapy is associated with longer TTF.
<p>Clinical Study Protocol: A Phase I Trial of Sirolimus or Everolimus or Temsirolimus (mTOR inhibitor) and Vorinostat (Histone Deacetylase Inhibitor) in Patients with Advanced Cancer</p>
<p>In patients treated with vorinostat and everolimus, there was a longer median progression-free survival in patients with normal albumin compared to patients with low albumin (5.8 months, 4.4 - 7.2 vs. 1.6 months, 95% CI 1.3-1.9; P < 0.001).</p>
Malignant peripheral nerve sheath tumors (MPNSTs) are growths that arise in conjunction with a peripheral nerve and are believed to originate from neural crest cells. These tumors can arise sporadically but are often associated with the cancer-predisposing genetic condition, neurofibromatosis type 1 (NF-1). The clinical presentation of an enlarging mass, pain, paresthesias, and neurologic deficits can mirror that of other soft tissue sarcomas. Thus, clinical suspicion should remain high for an MPNST when this aggregation of symptoms arises, particularly in those with a genetic proclivity. We report the case of metastatic MPNST in a 44-year-old female with a long history of NF-1. She was first seen for evaluation of progressive forearm and hand weakness associated with numbness and paresthesias in her second through fourth digits which prompted a need for an MRI. A forearm mass was discovered, and she underwent surgical intervention which revealed an MPSNT with positive margins. The patient completed radiation therapy for this lesion, but ultimately her forearm lesion recurred and progressed with metastasis to the lungs. Local recurrence was managed with a trans-humeral amputation and her systemic involvement necessitated chemotherapy. She was ultimately enrolled in a clinical trial for adult patients with recurrent advanced solid tumors. Given the potentially fatal course of NF-1-associated MPNSTs, clinical suspicion should remain high and early diagnosis and intervention with regular clinical surveillance are of utmost importance in this patient population.
