Donor-derived urologic cancers after renal transplantation: A retrospective non-randomized scientific analysis.

BACKGROUND: Malignancies in the urinary tract and the kidney graft are quite common after kidney transplantation. In some selected cases tumours develop from donor-derived tissue. OBJECTIVES: We hypothesised that there is a clinical value to investigate donor/recipient origin in urologic malignancies in renal transplant recipients. METHODS: In this retrospective study, including patients transplanted between the years 1969 and 2014 at Uppsala University Hospital, Sweden, 11 patients with malignancies in urinary tract and 4 patients with malignancies in kidney transplants were investigated. Donor/recipient origin of tumour tissue was analysed by polymerase chain reaction (PCR) of human leucocyte antigen (HLA) genotypes or by fluorescence in situ hybridization (FISH analysis) of sex chromosomes. HLA genotype and sex chromosomes of the tumour were compared to the known HLA genotype and sex chromosomes of recipient and donor. RESULTS: Three of ten cancers in the urinary tract and three of four cancers in the kidney transplants were donor-derived. CONCLUSIONS: We suggest that urologic malignancies in renal transplant recipients can be investigated for transplant origin. In addition to conventional therapy the allograft immune response against these tumours can be valuable to treat donor-derived cancers.

Intratumoral immunostimulatory AdCD40L gene therapy in patients with advanced solid tumors.

AdCD40L is a replication-deficient virus carrying the gene for CD40 ligand which has previously been evaluated in patients with urothelial cancer and malignant melanoma. Herein, we present the results of repeated intratumoral injections of AdCD40L in seven patients with metastatic solid cancer. One patient who developed urothelial cancer derived from a renal transplant was treated with repeated injections of AdCD40L alone. The remaining patients suffered from cholangiocarcinoma, kidney, breast, rectal, or ovarian cancer and received AdCD40L repeatedly (4x) in combination with cyclophosphamide. The treatment was safe and generally well-tolerated. Two patients had clinical benefit of the treatment and one of them was accepted for re-treatment. Circulating proinflammatory cytokines were commonly increased after treatment, but save for TNFα, significances were not reached which could be due to the low number of patients. Similar to earlier findings in AdCD40L-treated melanoma patients, IL8 plasma levels were high in the present study. In conclusion, gene therapy by repeated intratumoral AdCD40L injections alone, or in combination with cyclophosphamide, is feasible and safe in patients with solid cancers. The potential of intratumoral CD40L gene transfer as treatment of cancer was illustrated by the clinical improvement in two out of seven patients.

Relative and absolute cancer risks among Nordic kidney transplant recipients-a population-based study.

Kidney transplant recipients (KTRs) have an increased cancer risk compared to the general population, but absolute risks that better reflect the clinical impact of cancer are seldom estimated. All KTRs in Sweden, Norway, Denmark, and Finland, with a first transplantation between 1995 and 2011, were identified through national registries. Post-transplantation cancer occurrence was assessed through linkage with cancer registries. We estimated standardized incidence ratios (SIR), absolute excess risks (AER), and cumulative incidence of cancer in the presence of competing risks. Overall, 12 984 KTRs developed 2215 cancers. The incidence rate of cancer overall was threefold increased (SIR 3.3, 95% confidence interval [CI]: 3.2-3.4). The AER of any cancer was 1560 cases (95% CI: 1468-1656) per 100 000 person-years. The highest AERs were observed for nonmelanoma skin cancer (838, 95% CI: 778-901), non-Hodgkin lymphoma (145, 95% CI: 119-174), lung cancer (126, 95% CI: 98.2-149), and kidney cancer (122, 95% CI: 98.0-149). The five- and ten-year cumulative incidence of any cancer was 8.1% (95% CI: 7.6-8.6%) and 16.8% (95% CI: 16.0-17.6%), respectively. Excess cancer risks were observed among Nordic KTRs for a wide range of cancers. Overall, 1 in 6 patients developed cancer within ten years, supporting extensive post-transplantation cancer vigilance.

High Posttransplant Cancer Incidence in Renal Transplanted Patients With Pretransplant Cancer.

BACKGROUND: Patients with previous cancer have increasingly been accepted for renal transplantation. Posttransplant cancer risk and survival rates of these patients are unknown. Our objective was to assess the risk of posttransplant cancer in this patient group. METHODS: In this retrospective, nested case-control study, we assessed the outcome of all (n = 95) renal transplanted patients with pretransplant cancer diagnoses in the Uppsala-Örebro region, Sweden. The control group was obtained from the Collaborative Transplant Study registry and included European patients without pretransplant cancer. The other control group comprised the entire renal transplanted population in Uppsala. Development of recurrent cancer, de novo cancer, and patient survival were determined. RESULTS: Patients with pretransplant cancer showed higher incidence of posttransplant cancers and shorter survival compared with the control groups (P < 0.001). No obvious pattern in malignant diagnoses was observed. Death-censored graft survival was unaffected. CONCLUSIONS: Despite previously adequate cancer treatments and favorable prognoses, almost half of the patients experienced a posttransplant cancer. These observations do not justify abstaining from transplanting all patients with previous malignancies, because more than 50% of the patients survive 10 years posttransplantation. A careful oncological surveillance pretransplant as well as posttransplant is recommended.

Malignancies in transplanted patients: Multidisciplinary evaluation and switch to mTOR inhibitors after kidney transplantation - experiences from a prospective, clinical, observational study.

Background Solid organ transplant recipients are at increased risk of developing malignancies. The objective of this prospective, observational, one-armed study was to study the feasibility to add a mammalian target of rapamycin (mTOR) inhibitor to the immunosuppressive regimen in transplanted patients with post-transplant malignancies. During the trial the need to improve identification of post-transplant malignancies and to reassure adequate oncological treatment of these patients became evident. Multidisciplinary team (MDT) evaluation of oncological and immunosuppressive treatments was implemented for all patients with malignancies after renal or combined renal and pancreas transplantation because of the trial. Material and methods At Uppsala University Hospital, Sweden, a MDT consisting of transplant surgeons, nephrologists, oncologists and dermatologists evaluated 120 renal or combined renal and pancreas-transplanted recipients diagnosed with malignancies from September 2006 to July 2012. To identify all malignancies, the population was linked to the Regional Tumor Registry (RTR). We recorded to which extent a switch to mTOR inhibitors was possible and how often the originally planned oncological managements were adjusted. All patients were followed for three years. (ClinicalTrials.gov: NCT02241564). Results In 76 of 120 patients (63%) a switch to mTOR inhibitors was possible. Immunosuppression was interrupted in seven patients (6%), reduced in three patients (2%) and remained unchanged in 34 of 120 patients (28%). Identification of post-transplant malignancies increased significantly after linkage to RTR (p = 0.015). The initially recommended oncological treatment was adjusted in 23 of 44 patients (52%) with solid or hematological malignancies; 36 of these patients (82%) were treated according to national guidelines. Conclusion In two thirds of the patients the immunosuppressive treatment could be changed to an mTOR inhibitor with anti-tumor effects in transplanted patients with post-transplant malignancies. The use of regional tumor registers considerably improved the identification of patients with post-transplant malignancies indicating that post-transplant malignancies might be timely underreported in transplant registers.

Regional differences in breast cancer survival despite common guidelines.

PURPOSE: Despite a uniform regional breast cancer care program, breast cancer survival differs within regions. We therefore examined breast cancer survival in relation to differences in diagnostic activity, tumor characteristics, and treatment in seven Swedish counties within a single health care region. METHODS: We conducted a population-based observational study using a clinical breast cancer register in one Swedish health care region. Eligible women (n = 7,656) ages 40 to 69 years diagnosed with primary breast cancer between 1992 and 2002 were followed up until 2003. The 7-year relative survival ratio was used to estimate breast cancer survival. Excess mortality was modeled using Poisson regression to study differences in survival between counties. RESULTS: The 7-year relative survival for breast cancer patients was significantly lower (up to 7% in absolute risk difference) in one county (county A) compared with the others. This difference existed only among women diagnosed before 1998, ages 50 to 59 years, and was strongest among stage II breast cancer patients. Adjustment for amount of diagnostic activity eliminated the survival differences among the counties. The amount of diagnostic activity was also lower in county A during the same time period. After county A, during 1997-1998, began to adhere strictly to the regional breast cancer care program, neither any survival differences nor diagnostic activity differences were observed. INTERPRETATIONS: Markers of diagnostic activity explained survival differences within our region, and the underlying mechanisms may be several. Low diagnostic activity may entail later diagnosis or inadequate characterization of the tumor and thereby missed treatment opportunities. Strengthening of multidisciplinary management of breast cancer can improve survival.