Primary synovial sarcoma (SS) of the kidney is a rare neoplasm and its presenting features are similar to other common renal tumors, making early diagnosis difficult. To date, few cases have been reported in the literature. Primary renal SSs can exist in either a monophasic or a biphasic pattern, the former being more common and tending to have a better prognosis than the biphasic variant. Herein we describe a case of primary renal SS that was diagnosed based on histopathology and immunohistochemistry after radical nephrectomy. Fusion gene product analysis was also done by FISH and RT-PCR. Patient follow-up and literature review are presented, focused on systemic therapy. We highlight that these tumors should be correctly diagnosed as clinical results and specific treatment are distinct from primary epithelial renal cell carcinoma. Adjuvant chemotherapy should be tailored for each patient in the management of disease, although its role still remains unclear.
synovial sarcoma; kidney neoplasms; SYT-SSX fusion protein; chemotherapy
Both PCR and Hybrid Capture II (HCII) have been used for identifying cervical dysplasia; however, comparisons on the performance between these two tests show inconsistent results. We evaluated the performance of HCII and PCR MY09/11 in both screening and diagnostic populations in sub-sample of 1,675 non-pregnant women from a cohort in three clinical centers in the United States and Canada.
Sensitivity, specificity, positive predictive value, negative predictive value, and concordance between the two tests were calculated.
Specificity of HCII in detecting low-grade squamous intraepithelial lesion (LSIL) was higher in the screening group (88.7%; 95% CI: 86.2%–90.8%) compared to the diagnostic group (46.3%; 95% CI: 42.1%–50.6%); however, specificity of PCR was low in both the screening (32.8%; 95% CI: 29.6%–36.2%) and diagnostic (14.4%; 95% CI: 11.6%–17.6%) groups. There was comparable sensitivity by both tests in both groups to detect high-grade squamous intraepithelial lesion (HSIL); however, HCII was more specific (89.1%; 95% CI: 86.8%–91.0%; 66.2%; 95% CI: 62.0%–70.1%) than PCR (33.3%; 95% CI: 30.2%–36.5%; 17.9%; 95% CI: 14.8%–21.6%) in the screening and diagnostic groups, respectively. Overall agreement for HPV positivity was approximately 50% between HCII and PCR MY09/11; with more positive results coming from the PCR MY09/11.
In the current study, PCR MY09/11 was more sensitive but less specific than HCII in detecting LSIL, and HCII was more sensitive and specific in detecting HSIL than PCR in both screening and diagnostic groups.
comparison; test accuracy; hybrid capture II (HC II); polymerase chain reaction (PCR); cervical dysplasia
Acute myeloid leukemia (AML) represents a malignant accumulation of immature myeloid cells in the marrow, presenting with impaired hematopoiesis and its attendant complications, including bleeding, infection, and organ infiltration. Chromosomal abnormalities remain the most powerful predictors of AML prognosis and help to identify a subgroup with favorable prognosis. However, the majority of AML patients who are not in the favorable category succumb to the disease. Therefore, better efforts to identify those patients who may benefit from more aggressive and investigational therapeutic approaches are needed. Newer molecular markers aim at better characterizing the large group of intermediate-risk patients and to identify newer targets for therapy. A group that has seen little improvement over the years is the older AML group, usually defined as age ≥ 60. Efforts to develop less intensive but equally efficacious therapy for this vulnerable population are underway.
AML; management; prognosis
The purpose of the present retrospective study was to review outcome and patterns of failure of patients who were treated with radiotherapy for cervical lymph node metastases from an unknown primary site (CUP).
Patients and Methods
Between 2000 and 2009, 34 patients diagnosed with squamous cell CUP were admitted to radiotherapy in curative intent. In 26 of 34 patients (76%) neck dissection was performed prior to radiotherapy, extracapsular extension (ECE) was seen in 20 of 34 patients (59%). Target volumes included the bilateral neck and panpharyngeal mucosa. Concomitant chemotherapy was applied in 14 of 34 patients (41%).
After a median follow-up of 45 months for the entire group, 2 of 34 patients (6%) presented with an isolated regional recurrence, another 2 of 34 patients (6%) developed both local and distant recurrence, and 6 of 34 patients (18%) had distant failure only. Estimated overall survival after 2- and 5 -years was 78% and 63%. All patients with N1 or N2a disease (n=6) were disease free after 5 years. ECE, concomitant chemotherapy and involvement of neck levels 4 and 5 were associated with worse overall survival on univariate analysis.
Radiotherapy of the panpharynx and bilateral neck leads to excellent local control while distant metastases are the most frequent site of failure and prognostically limiting. Therefore intensified concomitant or sequential systemic therapies should be evaluated in future trials.
radiotherapy; CUP; unknown primary site; patterns of failure
The objective of this study was to evaluate some of the mechanisms involved in the activation of the immune system in patients with advanced-stage cancer (n = 7) who received an autologous dendritic cell vaccine. We examined the immune response mediated by macrophages (CD14+), natural killer cells (CD56+), and B lymphocytes (CD19+) by flow cytometry and assessed the expression of Th1 (IFN-γ, TNF-α, IL-2, and IL-12), Th2 (IL-4), and Treg (TGF-β) cytokines by flow cytometry and an enzyme-linked immunosorbent assay. The CD14+ TNF-α+ population was significantly increased (P < 0.04) when patients received the vaccine; IL-2 expression in both NK cells and in B lymphocytes was increased after a transient initial increase showed a nearly significant decrease (P < 0.07 and P < 0.06 respectively), whereas the CD19+ and CD56+ populations did not show significant changes. Dendritic cell-based immunotherapy led to increased secretion of IFN-γ and IL-12 and reduced secretion of TGF-β. In conclusion, it is likely that the autologous dendritic cell vaccine stimulated the immune cells from the peripheral blood of patients with cancer and generally increased the production of Th1 cytokines, which are related to immunomodulatory responses against cancer.
immune response; cancer; dendritic cells; immunotherapy
Primary malignant lymphoma of the breast is a rare tumor, defined as a tumor localized in the breast with or without axillary lymph-node metastases. Such a tumor is mainly found in female patients and located more frequently in the right breast. It is difficult to make primary breast lymphoma (PBL) diagnosis before operation, and PBL diagnosis is mainly based on pathological biopsy and immunohistochemical staining. In this paper, the cases of three patients who had PBL, and who were treated for it at the Institute for Oncology and Radiology of Serbia between 2008 and 2012, are reviewed and discussed. These cases of PBL had no recorded reoccurrence of the disease and were originally treated by surgery, radiotherapy R-CHOP, and/or chemotherapy. While there is no consensus to the question of how to best treat PBL (ie, with chemotherapy, radiotherapy, or combined therapy), it is hoped that this review will offer insight into successful treatment procedures for tumors of this category.
breast lymphoma; extranodal non-hodgkin lymphoma; breast cancer
Cervical cancer is still a major contributor to cancer-related mortality amongst women living in poor, rural communities of developing countries. The objective of this study is to establish the clinical presentation of cervical cancer and the management challenges encountered in Abakaliki, southeast Nigeria, with a view to finding intervention strategies. This study is a retrospective descriptive assessment of cases of clinically diagnosed cervical cancer managed at a state teaching hospital over six years. Of 76 cases managed, 61 (80.3%) cases notes were available for study. The mean age and parity of patients were 53.8 years and 6.8 years, respectively. The majority (75.4%) were illiterate. All had been married, but 42.6% were widowed. The main occupations were farming or petty trading. One patient (1.6%) had had a single Pap smear in her life. The major presenting complaints were abnormal vaginal bleeding (86.9%), offensive vaginal discharge (41.0%), and weight loss. Twenty patients (32.8%) were lost to follow-up prior to staging. Of the remaining 41 patients, 16 (39.0%) had stage III disease and 17.1% stage IV. Fifteen patients (24.6%) with late stage disease accepted referral, and were referred for radiotherapy. Those who declined were discharged home on request, though 4 (9.8%) died in the hospital. There was no feedback from referred patients confirming that they went and benefitted from the referral. The presentation followed known trends. Illiteracy, poverty, early marriages, high parity, widowhood, non-use of screening methods, late presentation, non-acceptance of referral, and lack of communication after referral were some of the major challenges encountered. These underscore the needs for health education and awareness creation, women educational and economic empowerment, legislation against early marriages and in protection of widows, and creation of a well-staffed and well-equipped dedicated gynecologic oncology unit to forestall further referral.
cervical cancer; late presentation; cancer-related deaths; management challenges; referral
Metastatic melanoma remains a difficult disease to treat, and long term survivors are rare. Over the past few years, however, breakthroughs in both immunotherapy as well as targeted agents have had a tremendous impact on patients diagnosed with this disease. This review summarizes recent advances in systemic therapies for melanoma, including immune modulators directed against cytotoxic T lymphocyte associated antigen-4 (CTLA-4) and programmed death-1 (PD-1), as well as a number of targeted agents. These approaches hold great promise as the landscape of therapeutic options for advanced melanoma continues to evolve.
metastatic melanoma; therapy; ipilimumab; PD-1; BRAF; MEK; KIT
Glioblastoma (GBM) or grade IV glioma is the most common primary brain tumor in adults. Standard treatment median overall survival (OS) is only 14–15 months and less than 10% of patients will survive 5 years after diagnosis. There is no standard treatment in recurrent GBM and OS ranges from 3 to 9 months. GBM is 1 of the most vascularized human tumors and GBM cells produce vascular endothelial growth factor (VEGF). Bevacizumab, a humanized monoclonal antibody against VEGF, has demonstrated activity in vitro and in phase II trials in relapse, as well as in 1 phase III trial as first line therapy. Bevacizumab also improves quality of life for patients suffering GBM. This paper reviews the mechanism of action of bevacizumab, its metabolism and pharmacokinetic profile. It summarizes the clinical studies in recurrent and newly diagnosed GBM, its potential side effects and complications and its place in therapy.
glioblastoma; bevacizumab; VGEF; chemotherapy; antiangiogenesis
Gain-of-function mutations in oncogenes and loss-of-function mutations in tumor suppressor genes (TSG) lead to cancer. In most human cancers, these mutations occur in somatic tissues. However, hereditary forms of cancer exist for which individuals are heterozygous for a germline mutation in a TSG locus at birth. The second allele is frequently inactivated by gene deletion, point mutation, or promoter methylation in classical TSGs that meet Knudson’s two-hit hypothesis. Conversely, the second allele remains as wild-type, even in tumors in which the gene is haplo-insufficient for tumor suppression. This article highlights the importance of PTEN, APC, and other tumor suppressors for counteracting aberrant PI3K, β-catenin, and other oncogenic signaling pathways. We discuss the use of gene-engineered mouse models (GEMM) of human cancer focusing on Pten and Apc knockout mice that recapitulate key genetic events involved in initiation and progression of human neoplasia. Finally, the therapeutic potential of targeting these tumor suppressor and oncogene signaling networks is discussed.
tumor suppressor gene; mouse model; PTEN; AKT; APC; ATM; CHK2; VHL
Hepatocellular carcinoma (HCC) is the most common liver cancer and the third leading cause of cancer death. It has been a major worldwide health problem with more new cases being diagnosed each year. The current available therapies for patients with advanced HCC are extremely limited. Therefore, it is of great clinical interests to develop more effective therapies for systemic treatment of advanced HCC. Several promising target-based drugs have been tested in a number of clinical trials. One breakthrough of these efforts is the approved clinical use of sorafenib in patients with advanced HCC. Targeted therapies are becoming an attractive option for the treatment of advanced HCC. In this review, we summarize the most recent progress in clinical targeted treatments of advanced HCC.
targeted therapy; hepatocellular carcinoma (HCC); sorafenib; tumor inhibitor; signaling pathway
The aim of the study was to seek evidence for the production of IL-12 by CD4+ T lymphocytes in in vitro and ex vivo trials. We performed in vitro trials with spleen cells from mice subjected to carcinogenesis, as well as ex vivo trials with cells obtained from the peripheral blood of healthy individuals and cancer patients. We were able to verify a significantly increased expression of IL-12 in CD4+ T lymphocytes from mice and patients with tumors, compared to controls. Follow-up studies are needed to clarify whether this difference is related to being in a chronic disease state or whether it is an attempt by the immune system to produce an anti-tumor response, since T lymphocytes from healthy donors were not able to produce IL-12 when in contact with polyclonal stimuli. We concluded that, in cancer, T helper cells are capable of synthesizing IL-12, raising the question of whether we are faced with another profile, Th12.
cancer; immune response; T lymphocyte; interleukin 12
Recent years have seen a dramatic change in the approach towards diagnosing and treating Multiple Myeloma. Newer and more target specific approach to treatment has prolonged the survival for patients with multiple myeloma. The proteasome inhibitors make an important class of anti-myeloma drugs that disrupts the proteolytic machinery of the tumor cells preferentially, enhancing their susceptibility to apoptosis. Bortezomib, in particular has shown significant clinical efficacy in myeloma treatment. It is the most commonly used proteasome inhibitor and has been tested to be effective in prolonging the overall survival in several trials. Its combinations with cyclophosphamide and dexamethasone are the treatment of choice for standard risk patients following the mSMART guidelines. The success with its lower dosage in elderly and its proven efficacious subcutaneous usage makes Bortezomib a useful agent for maximizing patient compliance and minimizing therapy related toxicity and costs. This review discusses several trials where Bortezomib has been used as a single/combination agent for front-line treatment of multiple myeloma.
multiple myeloma; Bortezomib; first-line; efficacy; clinical outcomes
Trastuzumab, a humanized mouse monoclonal antibody directed against HER2 (Human Epidermal Growth Factor Receptor 2), is currently a keystone in the treatment of breast cancer. Meanwhile, trastuzumab has been validated for use in other types of cancer too. But the data on HER2 expression in colorectal cancer are ambiguous, with reported overexpression of HER2 varying between zero and 84%. In this review these studies are evaluated and compared. It shows that many factors influence the determination of HER2-expression, especially of the intracellular fraction of HER2. It is concluded that although membranous overexpression of HER2 is low in colorectal cancer with only 5% of all patients being positive, a significant proportion of the patients (30%) shows cytoplasmic HER2 overexpression. The clinical impact of enhanced intracellular HER2 is not known, because the nature and origin have not completely been revealed yet. Enlightening this process could be a stepping stone towards targeting of intracellular HER2 as a treatment option.
HER2; ErbB2; Her2/neu; colorectal cancer; survival; membranous; cytoplasmic; immunohistochemistry; tissue microarray; biomarker; trastuzumab; herceptin
Amrubicin hydrochloride (AMR) is a key agent for lung cancer. NADPH quinone oxidoreductase 1 (NQO1) metabolizes the quinone structures contained in both amrubicin (AMR) and amrubicinol (AMR-OH). We hypothesized that NQO1 C609T polymorphism may affect AMR-related pharmacokinetics and clinical outcomes.
Patients received AMR doses of 30 or 40 mg/m2/day on days 1–3. Plasma sampling was performed 24 hours after the first and third AMR injections. Concentrations of AMR and AMR-OH were determined by HPLC and the NQO1 C609T polymorphism was assayed by RT-PCR.
A total of 35 patients were enrolled. At a dose of 40 mg/m2, the T/T genotype exhibited a tendency toward a relationship with decrease concentrations of AMR-OH on days 2 and 4. The genotype also showed a significant decrease of hematological toxicities (P < 0.05).
NQO1 C609T polymorphism had a tendency of correlation with the plasma concentrations of AMR-OH, and thereby had significant correlations with hematologic toxicities.
NQO1; amrubicin; lung cancer; SNP; hematological toxicity
This multicenter phase II study determined the efficacy and safety of new daily oral S-1 and weekly irinotecan (CPT-11) combination schedule in patients with previously untreated advanced or recurrent colorectal cancer.
Patients and methods:
Patients received first-line chemotherapy comprising S-1 80 mg/m2/day given on days 3 to 7, 10 to 14, and 17 to 21 and 60 mg/m2 CPT-11 administered intravenously on days 1, 8, and 15 of a 28-day cycle.
A total of 45 eligible patients were enrolled in this study. The overall response rate was 48.9%. Median progression-free survival and median overall survival was 8.1 months and 20.9 months, respectively. The rates of grade 3 or 4 toxicity were as follows: neutropenia, 8.9%; anemia, 4.4%; anorexia, 6.7%; and diarrhea, 6.7%.
This new S-1 and irinotecan combination schedule appeared to be an effective, well-tolerated, and convenient regimen in patients with advanced colorectal cancer as compared with conventional regimens such as FOLFIRI and IRIS.
advanced colorectal carcinoma; first-line chemotherapy; irinotecan; multicenter phase II study; metronomic chemotherapy; S-1
Juxtacortical chondrosarcoma is a rare primary malignant cartilaginous tumor accounting for 0.2% of all bone tumors. Wide surgical resection is the treatment of choice for juxtacortical chondrosarcomas. Accurate preoperative diagnosis is important in ensuring appropriate management, staging, and treatment of the patient. A combination of radiographs, three-dimensional imaging with computerized tomography (CT) scan and magnetic resonance imaging (MRI) can typically allow accurate diagnosis of juxtacortical chondrosarcomas. Bone scan and chest x-ray or CT chest scans are indicated for appropriate staging of the patient. Pet scan, ultrasound, bone scan, etc. are not typically needed for the diagnosis. Certainly, pulmonary imaging and bone scan are required for staging and could be commented upon.
primary; periosteal; clavicular; juxtacortical chondrosarcoma
Prostate cancer (PC) is one of the most common cancers and is a leading cause of death. Its initial growth is dependent on androgens; most patients show an initial response to hormonal therapy but will experience disease progression when PC becomes resistant to castration. In 2004, two key randomized controlled trials demonstrated a benefit for docetaxel-based regimens in the treatment of men with castration-resistant prostate cancer (CRPC). Cabazitaxel (XRP6258, TXD258, and RPR116258A), a tubulin-binding taxane drug as potent as docetaxel in cell lines, was the first treatment able to prolong survival for metastatic CRPC in the post-docetaxel setting. This review describes pharmacologic parameters of this agent followed by a review of clinical trials involving cabazitaxel. Other available treatments and the place of cabazitaxel in metastatic CRPC setting are discussed.
cabazitaxel; prostate cancer; castrate resistant; chemotherapy; taxane
In the past decade, molecular-targeted drugs have been focused upon for the treatment of cancer. In 2002, gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor became available in Japan for the treatment of non-small cell lung cancer (NSCLC). Over 80% of selected patients, such as EGFR mutation-positive patients, respond to gefitinib treatment; however, most patients develop acquired resistance to gefitinib within a few years. Recently, many studies have been performed to determine precisely how to select patients who will respond to gefitinib, the best timing for its administration, and how to avoid the development of acquired resistance as well as adverse drug effects. This article reviews the use of gefitinib for the treatment of NSCLC from a pharmaceutical viewpoint.
gefitinib; EGFR; KRAS; NSCLC; lung cancer
To detect relative frequency of anaplastic lymphoma kinase (ALK-1) gene abnormality in diffuse large cell lymphoma (DLCL) using fluorescence in situ hybridization (FISH), and correlate its presence with clinicopathological features which may be useful for choice of therapy and predict survival in newly diagnosed cases.
Patients and methods
A prospective study was done between March 2004 and October 2009. Fifty patients newly diagnosed with DLCL were enrolled into the study. Immunophenotyping was done and detection of ALK-1 gene abnormalities were carried out by immunohistochemically (IHC) and FISH. Patients that proved to be ALK-1 positive were treated with standard cyclophosphamide –hydroxy-daunorubicin- oncovin-prednisone (CHOP) protocol.
All ALK +ve patients achieved complete remission (CR) vs. 93.5% CR and 6.5% partial remission (PR) for ALK −ve patients respectively. Disease free survival (DFS) at 24 months was 81.8% in the CHOP-14 group (ALK-1−) vs. 100% for the CHOP-21 group (ALK-1+). Overall survival (OS) at 30 months was 80.4% in the CHOP-14 group vs. 100% for the CHOP-21 group.
ALK-1; FISH; IHC; ALCL
Pancreatic neuroendocrine tumors (PNETs) are becoming increasingly common, with the majority of patients presenting with either lymph node involvement or metastatic disease, thus requiring systemic therapy. Targeted therapy is a type of medication that blocks the growth of cancer cells by interfering with specific targeted molecules needed for carcinogenesis and tumor growth rather than by simply interfering with rapidly dividing cells (eg, with traditional chemotherapy). In this review article, pharmacologic inhibition of multiple targets including vascular endothelial growth factor receptor (VEGF-R), platelet-derived growth factor receptor (PDGF-R), stem cell factor receptor (c-KIT-R), FML-like tyrosine kinase-3 receptor (FLT3-R), colony stimulating factor 1 receptor (CSF1-R), and glial cell-line derived neurotrophic factor receptor (RET-R) with sunitinib in patients with unresectable PNETs is discussed. Phase III data indicate that additional treatment with sunitinib can improve prognosis in these patients.
sunitinib; pancreatic neuroendocrine tumors; everolimus
Paravertebral titanium rod migration represents an unusual and potentially fatal complication of vertebral stabilization surgical procedures. This condition, which requires a prompt and rapid diagnosis, is often mistaken for other more common diseases, or scotomized. We present a case of a 69 years old female affected by a non-Hodgkin lymphoma with evidence of migration of both rods five years after the posterior stabilization procedure for a pathological L3 fracture. Unusual clinical onset was represented by a left S1 radiculopathy without other symptoms. For several months, the symptoms were attributed to a possible radicular infiltration by the lymphoma. We conclude that paravertebral rod migration could happen not only within the spinal canal, but could also rarely damage blood vessels or parenchymal organs. This is generally a long-term complication, probably due to an insufficient fixation. Strict long-term follow-up monitoring is mandatory since this unusual complication can mimic other more common pathological conditions.
primary bone lymphoma; spine stabilization; hardware failure; misdiagnosed clinical picture
Large randomized trials demonstrated a benefit of adjuvant chemotherapy after resection of the primary colon cancer. It improves overall survival and reduces the risk of death, by 5% in UICC (Union Internationale Contre le Cancer) stage II and approximately 15%–20% in stage III. Fluoropyrimidines have been the standard drugs for the treatment of colon cancer since large randomized controlled trials demonstrated their efficacy and safety in treating patients suffering from this disease. Capecitabine is an orally administered fluoropyrimidine, which is preferably activated in tumor tissue to the active moiety 5-fluorouracil (5FU) and is cytotoxic through inhibition of DNA synthesis. It has proven equivalent efficacy and tolerability despite a changed toxicity profile compared to 5FU with less myelosuppression but more hand-and-foot syndrome. Capecitabine is well tolerated in elderly patients. The oral route of administration avoids frequent clinical visits as well as insertion of central venous catheters. The impact of the particular drug features on daily clinical practice is discussed in this review.
colon cancer; localized; stage III; capecitabine