Is there a general autoantibody signature for cancer?

BackgroundThere is longstanding evidence for the diagnostic potential of single autoantibodies for cancer and other diseases and more recently for the potential of complex autoantibody signatures. Here we address the question whether cancer specific signatures exist.MethodsWe analysed our autoantibody screening data both newly and previously generated using a single array platform with 1827 identified immunogenic clones. These clones were tested for their reactivity against a total of 428 human sera including 191 sera of patients with different cancer entities, 60 sera of healthy individuals and 177 sera of patients with non-cancer diseases by using bioinformatics approaches.ResultsPrincipal Component Analysis and hierarchical clustering revealed significant differences between the three cohorts. Evaluating the autoantibody reactivities in the three groups using Support Vector Machines, we were able to separate cancer sera from normal sera with an accuracy of 94.08%. A pathway analysis that was based on antigens with an increased reactivity in patients’ sera as compared to controls indicated glycolysis as central pathway. The separation between cancer and non-cancer disease sera was possible with an accuracy of only 69.58%, which is still significantly higher than by random classification.ConclusionAs for single autoantigens, we show that proteins that are frequently reactive with cancer sera are also frequently reactive with non-cancer sera. While these results underline the potential of autoantibody signatures for cancer diagnosis, they also caution to premature claim specificity of a signature.     

Is there a role for nontraditional resection of early gastric cancer?

Current trends in the treatment of gastric cancer indicate the emergence of a more sophisticated approach, with tailored therapy applied to individual cases. Treatment includes a broader spectrum of therapeutic options (Fig. 3), including EMR, laparoscopic or laparoscopy-assisted surgery, modified radical surgery, and typical radical surgery with lymph node dissections. Precise characterization of the lesions, especially the depth of invasion in the gastric wall, its size, histology and whether there is ulceration, is the key to successful treatment of N0 mucosal cancer. Micrometastasis and metastasis at the molecular level are issues that require further investigation. Laparoscopic surgery may be more widely accepted. The limitations of nodal dissection based on the concept of a sentinel node should be carefully evaluated in future studies. [figure: see text] Many treatment options, ranging from minimally invasive surgery to D2 node dissection, are available to the surgical oncologist who is treating EGC. As more information is gathered, surgeons will be better able to select patients who are good candidates for minimal surgical procedures.     

Is there a role for chemotherapy in prostate cancer?

There is evidence from randomised-controlled trials that patients with symptomatic hormone-refractory prostate cancer may experience palliative benefit from chemotherapy with mitoxantrone and prednisone. This treatment is well tolerated, even by elderly patients, although the cumulative dose of mitoxantrone is limited by cardiotoxicity. Treatment with docetaxel or paclitaxel, with or without estramustine, appears to convey higher rates of prostate-specific antigen response in phase II trials, but is more toxic. Large phase III trials comparing docetaxel with mitoxantrone have completed accrual. There is no role for chemotherapy in earlier stages of disease except in the context of a well-designed clinical trial.     

Is there a need for axillary dissection in breast cancer?

The involvement of axillary nodes remains a significant prognostic factor in breast cancer. However, management has changed from complete surgical staging to sentinel lymph node biopsies. Although little controversy exists regarding patients with negative sentinel lymph node biopsies, some remains regarding what to do with patients with small volume of axillary disease. This article focuses on the examination of recent evidence in management of the axilla. It focuses on both the prognostic and therapeutic information gleaned from isolated tumor cells and micrometastatic disease and on the use of completion axillary lymph node dissections or axillary radiation in preventing regional recurrence.     

Is there a role for intraperitoneal chemotherapy in the management of ovarian cancer?

Phase I and II clinical trial data have demonstrated the safety, pharmacokinetic advantage, and potential for enhanced cytotoxicity associated with the intraperitoneal administration of antineoplastic agents in the management of ovarian cancer. In two randomized phase III studies comparing the intraperitoneal and intravenous administration of cisplatin (Platinol) as initial therapy for small-volume residual advanced ovarian cancer, intraperitoneal delivery of the agent produced superior progression-free and overall survival. Reluctance to employ intraperitoneal cisplatin in the standard management of ovarian cancer appears to be related to the added time, effort, and potential morbidity associated with the approach, as well as a general preference for the less toxic, less complicated carboplatin (Paraplatin)-based regimen. However, existing data support the use of this unique method of drug delivery in carefully selected patients outside of the clinical trial setting.     

Loco-regional treatment in metastatic breast cancer patients: Is there a survival benefit?

A number of studies have recently demonstrated a survival benefit in stage IV breast cancer patients following surgical resection of the primary tumor. Here, we investigate the relationship between loco-regional treatment and survival in patients with metastatic breast cancer and evaluate the impact of different loco-regional treatments. We conducted a systematic review of the literature using PubMed to analyze studies with the following criteria: Type of loco-regional treatment (surgery alone or combined with radiation, radiotherapy), overall survival, progression-free survival, selection factors for local treatment, and complication rates. Thirteen studies evaluated the effect of loco-regional treatment on overall survival with overall median survival increasing from a range of 12.6–28.3 months among patients without surgery to a range of 25–42 months among patients with surgery. In addition, six studies reported a 3-year survival benefit of 28–95% and 17–79% in women with and without loco-regional therapy respectively. Two studies did not find any improvement in overall survival. One study found an improvement in 5-year breast cancer-specific survival of 27% with negative surgical margins versus 12% with no surgery. Three studies reported an advantage in progression-free survival in the treatment group compared with the non-treatment group. Loco-regional treatment for breast cancer patients with distant metastases at diagnosis is an important issue because of possible improvement of survival or disease-free survival. The possibility of surgery and/or radiotherapy following induction chemotherapy should be weighed and left to individual practice. Participation in randomized controlled trials should be encouraged.     

Is there still a place for docetaxel rechallenge in prostate cancer?

Three-weekly docetaxel plus prednisone is the standard first-line cytotoxic treatment for patients with metastatic castrate-resistant prostate cancer (mCRPC). Today, several new treatment options are available for patients with tumor progression after first-line docetaxel: Abiraterone, enzalutamide, cabazitaxel, sipuleucel-T immunotherapy, and the radionuclide radium-223. However, despite the evolving scenario in CRPC treatment, the optimal sequencing of the innovative therapies remains unclear. The reintroduction of docetaxel at the occurrence of disease progression after a drug holiday (docetaxel rechallenge) was often proposed, and this chemotherapeutic agent showed to maintain antitumor activity in mCRPC patients. Docetaxel rechallenge may still constitute a valid treatment option mainly for patients with favorable response to first-line docetaxel, at least > 3 mo progression-free interval, age less than 75 years, good performance status, and acceptable docetaxel toxicity. The risk of cumulative toxicity must be evaluated, since sensory neuropathy, nail disorders and fatigue might occur on docetaxel rechallenge.     

Is there a role for Notch signalling in human breast cancer?

Aberrant Notch signalling has been observed in several human cancers, including acute T-cell lymphoblastic leukaemia and cervical cancer, and is strongly implicated in tumourigenesis. Unregulated Notch signalling in the mouse mammary gland leads to tumour formation. These results raise the possibility that Notch signalling might play a role in human breast cancer. There are currently few reports that address this question directly and this appears to be an area worthy of further investigation.     

Is there a role for second-line chemotherapy in advanced gastric cancer?

Gastric cancer remains one of the most common forms of cancer worldwide. Unfortunately, most patients will present with advanced-stage disease, and will therefore need palliative chemotherapy. Some chemotherapy regimens have been well established as first-line therapy, and have been shown to increase survival; however, almost all patients with metastatic gastric cancer will develop progressive disease after first-line therapy. With the availability of several active chemotherapy drugs, many patients who retain a good performance status after the initial treatment remain good candidates for additional therapy; however, no standard approach for second-line therapy exists. Many small, phase 2 trials have been done and the findings are variable. No data from randomised-controlled trials suggest a benefit of second-line chemotherapy compared with supportive care alone. We review the published data concerning the use of chemotherapy in the second-line setting for the treatment of advanced gastric cancer.     

Is there a use for tailored print communications in cancer risk communication?

The manner of presentation of cancer risk information is critical to its understanding and acceptance by the individual recipient. Optimal communication of cancer risk information must effectively translate the technical meaning and subtleties of risk and its associated factors to a conceptual level understandable by the recipient. Tailored print communications (TPCs) may be an appropriate medium for cancer risk communication (CRC). TPCs are more refined than targeted communication materials. They are print materials created especially for an individual on the basis of knowledge about that person. The goal is to provide individually relevant and appropriate information. This review examines the nature of TPCs, assesses the use and potential of TPCs for the purpose of CRC, and highlights new directions in CRC. Articles dealing with TPCs were located by searching the MEDLINE(R) and PsychInfo(R) databases and seeking in-press articles. TPCs were identified for several areas of CRC, including dietary change, smoking cessation, mammography use, hormone replacement therapy, health risk appraisal, and genetic susceptibility to cancer. Although TPCs have been used in a number of different behavioral areas, they have not yet achieved their potential for CRC. The use of TPCs in the communication of cancer risk shows great promise, however, particularly as knowledge evolves regarding both the nature of risk and the most effective tailoring of health communication messages.     

Is there a role for chemosensitivity tests in head and neck cancer?

Despite many advances in predictive testing of human malignancies, we are far from using it routinely in clinical practice. Investigating the responsiveness of solid tumors to cytostatic drugs is particularly challenging. Nevertheless, for head and neck cancer, chemosensitivity testing is an increasingly attractive option, since chemotherapy has proven to have curative potential in the therapy of head and neck cancer, in particular in combination with radiation. The significant need for predictive methods to identify patients responsive to therapy, first of all in organ preservation programs, which is an alternative to first-line surgery, had recently renewed the discussion on a possible role of chemosensitivity testing in head and neck cancer. In this review, we discuss the current state of chemosensitivity testing in head and neck cancer. Recent methodological developments, in particular elimination of photochemical artifacts and inclusion of stromal cell response studies, may soon augment the value of ex vivo chemosensitivity testing for the management of head and neck cancer.     

Vitamin D in esophageal cancer: Is there a role for chemoprevention?

Vitamin D has emerged as a promising anti-cancer agent due to its diverse biological effects on tumor differentiation, apoptosis and suppression of cellular proliferation. Current evidence suggests a protective role of vitamin D in colon cancer. The effect of vitamin D on esophageal cancer remains controversial. Multiple studies investigated the association between vitamin D and esophageal cancer, employing different modes of assessment of vitamin D status such as serum 25-hydroxyvitamin D levels, vitamin D dietary intake or exposure to ultraviolet B (UVB) radiation. Genetic variations of the vitamin D receptor (VDR) gene and VDR expression in esophageal specimens have also been investigated. Ecological studies evaluating exposure to UVB radiation yielded an inverse correlation with esophageal cancer. When vitamin D dietary intake was assessed, direct association with esophageal cancer was observed. However, circulating 25-hydroxyvitamin D concentrations showed inconsistent results. In this review article, we present a detailed summary of the current data on the effects of vitamin D on various histological subtypes of esophageal cancer and their precursor lesions. Well-powered prospective studies with accurate measurement of vitamin D status are needed before chemoprevention with vitamin D is recommended, as current evidence does not support a chemopreventive role of vitamin D against esophageal cancer. Future studies looking at the incidence of esophageal cancer in patients with pre-cancerous lesions (Barrett's esophagus and squamous cell dysplasia) receiving vitamin D supplementation are needed.     

Is there a role for short-term hormone use in the treatment of nonmetastatic prostate cancer?

We reviewed our institution's experience treating patients with prostate cancer with 3-dimensional conformal radiation therapy (3DCRT) and short-term adjuvant hormonal therapy to determine biochemical no evidence of disease (bNED) and clinical outcome compared with patients treated with 3DCRT alone. Between 4/1/89 and 11/30/94, 558 patients with clinically localized prostate cancer received treatment at Fox Chase Cancer Center (Philadelphia, Pa.); 484 patients were treated with 3DCRT alone (Group I); 74 patients were treated with 3DCRT and hormones (Group II). Five-year actuarial rates of bNED control, distant metastasis-free survival (DMFS), cause-specific survival (CSS), and overall survival (OS) were calculated for pretreatment PSA, Gleason score, T stage, use of hormones, treatment field size, age, and dose. A matched case/control analysis was performed to further evaluate the effect of hormones on treatment with 3DCRT. Median follow-up was 47 months (range: 2-97 months). The 5-year actuarial rates of bNED control, DMFS, CSS, and OS were 66%, 93%, 98%, and 86%, respectively, for Group I patients and 68%, 93%, 98%, and 89%, respectively, for Group II patients. Multivariate analysis demonstrated that hormone use was an independent predictor of bNED control only. A significant difference in bNED control was observed between Group I and II (43% vs. 71%) using the matched case/control analysis (P = 0.02). A trend towards significance was observed for different rates of DMFS between Group I and II (79% vs. 94%, P = 0.09). Patients with clinically localized prostate cancer with poor prognostic features (pretreatment PSA > or = 10 ng/ml, Gleason score > or = 7, and/or T2c or greater palpation stage) show improved rates of bNED control and a trend towards improved DMFS when treated with 3DCRT and short-term adjuvant hormones compared with 3DCRT alone. Long-term observation will be necessary to see if improvements in bNED control will translate into improvements in overall survival.