The clinical application of plasma Kaposi sarcoma herpesvirus viral load as a tumour biomarker: results from 704 patients.

OBJECTIVES: The aim of the study was to evaluate the role of plasma Kaposi sarcoma herpesvirus (KSHV) as a diagnostic and prognostic biomarker in people living with HIV (PLWH) and diagnosed with KSHV-associated diseases. METHODS: Using quantitative nested polymerase chain reaction (PCR) targeting the open reading frame-26 gene of KSHV, plasma levels of KSHV were measured in consecutive PLWH with KSHV-associated diseases or as part of the investigation of lymphadenopathy. RESULTS: Plasma KSHV assays were performed on samples from 684 PLWH and 20 HIV-seronegative people with KSHV-associated malignancies. In PLWH, plasma KSHV was detected in 39% of those with KS, 99% of those with multicentric Castleman disease (MCD), 9% of those with non-Hodgkin lymphoma (NHL), 2% of those with non-AIDS-defining malignancies and 0% of those with nonmalignant lymphadenopathy. There was no significant difference in plasma KSHV viral load among those with KS, MCD and KSHV-associated NHL. The 5-year overall survival rate from KS diagnosis of 335 PLWH was 95.2% (95% confidence interval 92.6-97.8%). Plasma KSHV viraemia did not predict overall survival in those with KS (P = 0.73), nor when those with T0 stage KS (P = 0.52) or T1 stage KS (P = 0.62) were analysed separately. CONCLUSIONS: Measuring the plasma levels of KSHV as a biomarker in KSHV-associated disease has a very limited value in either diagnosis or prognostication. The only potential role of clinical value is the suggestion that an undetectable plasma KSHV excludes a diagnosis of MCD in PLWH.

Liposomal anthracycline chemotherapy and the risk of second malignancies in patients with Kaposi's sarcoma (KS).

PURPOSE: People living with HIV (PLWH) are at increased risk of cancer, both non-AIDS- and AIDS-defining malignancies (NADM and ADM). Systemic chemotherapy also predisposes to secondary cancers. The potential contribution of systemic liposomal anthracycline chemotherapy (SLAC) to the development of second cancers in PLWH is unknown. METHODS: Since 1998, we have treated 495 PLWH and Kaposi's sarcoma (KS) with a stage-stratified approach including 163 who received SLAC as first-line treatment for KS. Subsequent ADM and NADM diagnosed in this population were recorded. RESULTS: More patients who received SLAC had T1 stage disease (p < 0.0001) and lower CD4 cell counts (p < 0.0001) in line with the stage-stratified treatment, but there were no significant differences in age (p = 0.29), gender (p = 0.18), prior AIDS-defining illness (p = 0.45), plasma HIV viral load (p = 0.15), or HHV8 viral load (p = 0.39) between the two groups. During a median follow-up of 4.6 years (maximum 15 years) from KS diagnosis, 28 patients developed a second cancer (5 ADM and 23 NADM). The 5-year cumulative risk of second cancer is 5.8 % (95 % CI 3.0-8.6 %), and there is no significant difference in the rate between those treated with SLAC and those not (log rank p = 0.19). Most patients (n = 131) were treated with daunoxome (liposomal daunorubicin) chemotherapy, and there was no significant correlation between risk of second cancer and cumulative dose of daunoxome (p = 0.23). CONCLUSION: Although the risk of second cancer after a diagnosis of KS in PLWH is high, systemic liposomal anthracycline chemotherapy does not appear to increase the risk.

Malignant spinal cord compression: NICE guidance, improvements and challenges.

BACKGROUND AND AIM: Malignant spinal cord compression (mSCC) is one of the most serious complications of cancer. Recent NICE guidance has aimed to improve patient pathways and outcomes for patients with mSCC. We have examined the current presentations, management and outcomes for patients with mSCC in West London following the implementation of the NICE guidance. MATERIALS AND METHODS: The electronic records and clinical notes were reviewed for all patients assessed for confirmed or potential mSCC at Charing Cross Hospital in 2012. Details on the number of referrals, the proportion with confirmed mSCC, the cancer diagnosis, treatment and outcome were analysed. RESULTS: 191 patients were reviewed with 127 (66%) cases of confirmed mSCC. The commonest tumour types were prostate cancer (26 cases), lung cancer (26), breast cancer (21) and kidney cancer (15). 21% of the patients had no previous cancer diagnosis; mSCC was their presenting diagnostic event. Radiotherapy was the predominant management, 24% of the patients had first line surgical treatment. At presentation 62% of patients were either chair or bed bound. Treatment brought important mobility benefits to all patients groups with 20% of the initially chair or bed bound patients leaving the hospital with independent mobility. CONCLUSION: Enhanced patients pathways with ease of access, rapid assessment and prompt treatment can improve outcomes. Despite these pathways many patients still present with gross motor impairment and over 20% have no previous diagnosis of cancer. Ongoing work to maintain awareness for patients and primary care of the diagnosis and emergency pathways is essential to optimize outcomes.

Transforming growth factor ß repressor, SnoN, is overexpressed in human gastrointestinal stromal tumors.

PURPOSE: The transforming growth factor bgr; (TGF-ß)/ Smad pathway is implicated in the development of interstitial cells of Cajal. The aim of this study was to examine the role of this pathway in human gastrointestinal stromal tumors (GISTs). METHODS: The expression of TGF-ß receptor II (TßRII), phosphorylated Smad2 (p-Smad2), SnoN, p21(WAF17sol;CIP1) and p27(KIP1) was examined by immunohistochemistry in 30 hu-man GISTs in relation to prognostic factors. RESULTS: TßRII was expressed in 76.9% of the cases. All cases were positive for p-Smad2 and SnoN, with significantly higher expression levels in small intestinal compared to gastric GISTs. Downregulation of p21(WAF1/CIP1) and p27(KIP1) was found in 78.6% and 46.4% of the cases respectively, while cytoplasmic expression of p27(KIP1) was also noted in 50% of GISTs. CONCLUSIONS: TGF-ß/Smad pathway may contribute to GIST pathogenesis. SnoN overexpression and low levels of p21(WAF1)/CIP1 and p27(KIP1) may be of importance in GISTs.