The osteolytic nature of bone metastasis results from a tumor-driven increased bone resorption. Bone remodeling is orchestrated by the molecular triad RANK-RANKL-OPG. This process is dysregulated in bone metastases, mostly via induction of RANKL by tumor-derived factors. These factors increase expression of RANKL, which induce osteoclast formation, function, and survival, thereby increasing bone resorption. RANK is unexpectedly expressed by cancer cells, and the activation of RANKL-RANK pathway correlates with an increased invasive phenotype. To investigate the interaction between RANK expression in human breast and prostate cancer cells and their pro-metastatic phenotype we analyzed the activation of RANKL-RANK pathway and its effects on cell migration, invasion, gene expression in vitro, and osteolysis-inducing ability in vivo. RANKL activates kinase signaling pathways, stimulates cell migration, increases cell invasion, and up-regulates MMP-1 expression. In vivo, MMP-1 knockdown resulted in smaller x-ray osteolytic lesions and osteoclastogenesis, and decreased tumor burden. Therefore, RANKL inhibition in bone metastatic disease may decrease the levels of the osteoclastogenesis inducer MMP-1, contributing to a better clinical outcome.

Background:

Prognostic factors for progression-free survival (PFS), overall survival (OS), and long-term OS (30 months) were investigated in sunitinib-treated patients with metastatic renal cell carcinoma (RCC).

Methods:

Data were pooled from 1059 patients in six trials. Baseline variables, including ethnicity, were analysed for prognostic significance by Cox proportional-hazards model.

Results:

Median PFS and OS were 9.7 and 23.4 months, respectively. Multivariate analysis of PFS and OS identified independent predictors, including ethnic origin, Eastern Cooperative Oncology Group performance status, time from diagnosis to treatment, prior cytokine use, haemoglobin, lactate dehydrogenase, corrected calcium, neutrophils, platelets, and bone metastases (OS only). Characteristics of long-term survivors (n=215, 20%) differed from those of non-long-term survivors; independent predictors of long-term OS included ethnic origin, bone metastases, and corrected calcium. There were no differences in PFS (10.5 vs 7.2 months; P=0.1006) or OS (23.8 vs 21.4 months; P=0.2135) in white vs Asian patients; however, there were significant differences in PFS (10.5 vs 5.7 months; P<0.001) and OS (23.8 vs 17.4 months; P=0.0319) in white vs non-white, non-Asian patients.

Conclusion:

These analyses identified risk factors to survival with sunitinib, including potential ethnic-based differences, and validated risk factors previously reported in advanced RCC.British Journal of Cancer advance online publication, 21 May 2013; doi:10.1038/bjc.2013.236 www.bjcancer.com.

Radiation recall phenomenon is a tissue reaction that develops throughout a previously irradiated area, precipitated by the administration of certain drugs. Radiation recall is uncommon and easily neglected by physicians; hence, this phenomenon is underreported in literature. This manuscript reports two cases of radiation recall. First, a 44-year-old man with nasopharyngeal carcinoma was treated with radiotherapy in 2010 and subsequently developed multi-site bone metastases. A few days after the docetaxel-based chemotherapy, erythema and papules manifested dermatitis, as well as swallowing pain due to pharyngeal mucositis, developed on the head and neck that strictly corresponded to the previously irradiated areas. Second, a 19-year-old man with recurrent nasal NK/T cell lymphoma initially underwent radiotherapy followed by chemotherapy after five weeks. Erythema and edema appeared only at the irradiated skin. Both cases were considered chemotherapeutic agents that incurred radiation recall reactions. Clinicians should be knowledgeable of and pay attention to such rare phenomenon.

This work summarizes the clinical features and treatment of 10 AIDS patients with malignant lymphoma.A total of 10 AIDS patients with malignant lymphoma seen in Beijing Ditan Hospital since 2009 were enrolled. Clinical manifestations, pathological examinations, immunity levels, Epstein-Barr virus antibody examinations, complications, treatments, and outcomes were retrospectively analyzed.The main clinical manifestations of these patients included intermittent fever in 2 cases, neck masses and fever in 3 cases, auxiliary lymph node enlargement in 2 cases, and abdominal pain and bloating with fever in 3 cases. Up to 7 patients were pathologically diagnosed with diffuse large B cell lymphoma (DLBCL), and 3 patients were pathologically diagnosed with Burkitt's lymphoma. Up to 8 patients had CD4 cell counts below 200/µL, and 2 patients had a level of more than 200/µL. Up to 7 patients were negative for EBV-IgM antibodies and 3 patients were not examined. Six patients underwent different chemotherapy and their prognoses were different. One patient with Burkitt's lymphoma alternatively took CODOXM and IVAC for 3 turns after VP chemotherapy; 1 patient with liver metastasis took R-CHOP 5 times, then changed therapy regimen to R-MINE and MINE. One patient with adrenal DLBCL took CHOP 6 times. Three patients with DLBCL took CHOP 1 or 2 times. Four patients gave up treatment. Various infections and side effects occurred, including bone marrow suppression, gastrointestinal bleeding, and renal dysfunction during chemotherapy. Six patients took HAART, and 4 did not. Six patients died, whereas 3 patients got improved; and 1 patient was discharged.AIDS patients with malignant lymphoma had various clinical manifestations, were immunocompromised, and had multiple metastases when they were admitted; they were already in the interim or late stage of lymphoma. Chemotherapy was not effective, and additional complications occurred. HAART failed to improve patient prognosis, and the overall prognosis was poor.

Papillary thyroid carcinoma is the most common differentiated type of thyroid malignancy. It is largely a loco-regional disease with a high tendency to metastasize to regional cervical lymph nodes. Distant hematogenous metastases are very rare and primarily include lungs and bones. Distant bone metastases are present in approximately 1.7% of patients with differentiated thyroid malignancy. Sternum, ribs, and spine are the most frequent sites of osseous metastases. Up to our knowledge, we report the first occurrence of an extra nodal metastasis of papillary thyroid carcinoma to a femoral bone presenting as a pathological fracture in a 21-year-old 37-week primigravida. We report this case because of its unusual site of metastasis and atypical presentation during pregnancy. Moreover, we briefly elaborate on the management of such uncommon cases.

Background.

Surgical treatment of malignant pelvic bone tumors can be very challenging. The objective of this retrospective study was to evaluate the oncological as well as the clinical and functional outcome after limb salvage surgery and biological reconstruction. Methods. The files of 27 patients with malignant pelvic bone tumors, who underwent surgical resection at our department between 2000 and 2011, were retrospectively analyzed (9 Ewing's sarcoma, 8 chondrosarcoma, 4 osteosarcoma, 1 synovial sarcoma, 1 malignant fibrous histiocytoma, and 4 carcinoma metastases).

Results.

After internal hemipelvectomy reconstruction was performed by hip transposition (n = 16), using autologous nonvascularised fibular graft (n = 5) or autologous iliac crest bone graft (n = 2). In one patient a proximal femor prothetis and in three patients a total hip prosthesis was implanted at the time of resection. The median follow-up was 33 months. Two- and five-year disease-specific survival rates of all patients were 86.1% and 57.7%, respectively. The mean functional MSTS score was 16.5 (~55%) for all patients.

Conclusion.

On the basis of the oncological as well as the clinical and functional outcome, biological reconstruction after internal hemipelvectomy seems to be a reliable technique for treating patients with a malignant pelvic bone tumor.

A 58-year-old female patient, diagnosed with adenocarcinoma of the lung, underwent percutaneous vertebroplasty at the L4 vertebral body due to painful spinal metastases. Because of deep venous thrombosis of the left femoral and iliac veins, an inferior vena cava filter had been placed before vertebroplasty. Bone cement migrated into the venous bloodstream and then was being trapped within the previously placed filter. This case illustrates that caval filter could capture the bone cement and prevent it from migrating to the pulmonary circulation.

BACKGROUND:

The Follicle Stimulating Hormone receptor (FSHR) is expressed by the vascular endothelium in a wide range of human tumors. It was not determined however if FSHR is present in metastases which are responsible for the terminal illness.

METHODS:

We used immunohistochemistry based on a highly FSHR-specific monoclonal antibody to detect FSHR in cancer metastases from 6 major tumor types (lung, breast, prostate, colon, kidney, and leiomyosarcoma ) to 6 frequent locations (bone, liver, lymph node, brain, lung, and pleura) of 209 patients.

RESULTS:

In 166 patients examined (79%), FSHR was expressed by blood vessels associated with metastatic tissue. FSHR-positive vessels were present in the interior of the tumors and some few millimeters outside, in the normally appearing tissue. In the interior of the metastases, the density of the FSHR-positive vessels was constant up to 7 mm, the maximum depth available in the analyzed sections. No significant differences were noticed between the density of FSHR-positive vessels inside vs. outside tumors for metastases from lung, breast, colon, and kidney cancers. In contrast, for prostate cancer metastases, the density of FSHR-positive vessels was about 3-fold higher at the exterior of the tumor compared to the interior. Among brain metastases, the density of FSHR-positive vessels was highest in lung and kidney cancer, and lowest in prostate and colon cancer. In metastases of breast cancer to the lung pleura, the percentage of blood vessels expressing FSHR was positively correlated with the progesterone receptor level, but not with either HER-2 or estrogen receptors. In normal tissues corresponding to the host organs for the analyzed metastases, obtained from patients not known to have cancer, FSHR staining was absent, with the exception of approx. 1% of the vessels in non tumoral temporal lobe epilepsy samples.

CONCLUSION:

FSHR is expressed by the endothelium of blood vessels in the majority of metastatic tumors.

Prostate cancer is a leading cause of cancer death, frequently associated with widespread bone metastases. We report two cases of hypocalcemia following the first dose of denosumab in metastatic hormone refractory prostate cancer, the first case requiring 26days of intravenous calcium therapy. This is the first report of prolonged hypocalcemia following denosumab in a patient with normal renal function.