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 role for intravenous iron therapy in patients undergoing colorectal cancer resection?

Evaluation of: Titos-Arcos JC, Soria-Aledo V, Carrillo-Alcaraz A, Ventura-López M, Palacios-Muñoz S, Pellicer-Franco E. Is intravenous iron useful for reducing transfusions in surgically treated colorectal cancer patients? World J. Surg. 36(8), 1893–1897 (2012).

Worldwide, colorectal cancer (CRC) is one of the most common forms of malignancy and is increasing in incidence in many regions. At diagnosis, approximately 40% of patients with CRC are anemic, a figure that increases over the course of a patient’s treatment due to many factors, including ongoing hemorrhage. Preoperative anemia is therefore associated with increased allogenic red blood cell transfusion (ARBT) rates. In the context of CRC, perioperative ARBT has been linked with adverse postoperative outcomes, including higher morbidity, mortality and cancer recurrence rates. Therefore, strategies to potentially reduce the need for ARBT have been the focus of several recent studies. We critically evaluate a recent paper that explores intravenous iron III sucrose as a treatment option for the management of postoperative anemia in CRC patients. This study is a retrospective, observational case-controlled study that was designed to evaluate whether the use of postoperative intravenous iron reduces the incidence of ARBT following CRC resection.     

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 role for a specialized follow-up clinic for survivors of pediatric cancer?

Due to advances in chemotherapy and supportive care, greater than 70% of patients with childhood cancer will survive 5 years. However, there are long-term physiological and psychological sequelae of these treatments that may not manifest until pediatric survivors are into adulthood. Various studies done in the long-term pediatric survivors have noted that they are at increased risk for poor health and for chronic health problems. One complicating factor in treating these patients for their health problems is that many childhood cancer survivors are unaware of their past medical history and what their past cancer treatment entailed. There are also a number of barriers to medical care in survivors of childhood cancer which include inadequate insurance coverage for many and lack of knowledge of long-term effects physicians. As pediatric cancer survivors age they usually transition to community physicians. This paper proposes different models for follow-up clinics for survivors of pediatric cancers so childhood cancer survivors are not be subjected to cost ineffective or excessive evaluations but rather medical screening tests that are risk and guidelines that are set forth by experts.     

Is adjuvant chemotherapy necessary for early gastric cancer?

Objective:To quantify the potential benefit of adjuvant chemotherapy (ACT) with respect to survival, and to identify factors for predicting prognoses in early gastric cancer patients.Methods:Patients with pT1 gastric cancer (GC) who underwent radical resection with D2 lymphadenectomy were retrospectively analyzed. Based on lymph node metastasis (LNM) status and treatment regimens, patients were classified into groups, and clinicopathological variables, overall survival (OS), and disease-specific survival (DSS) were compared.Results:Of 1,050 enrolled patients, 151 patients (14.4%) had a positive LNM status. Submucosal invasion, undifferentiated state, tumor size > 2 cm, ulceration, and lymphovascular invasion were independent risk factors for LNM using multivariate analyses. The 5-year OS of all patients was 96.4%. HER2 positive, perineural invasion, and LNM were independent factors for worse survival. Patients with pT1N3 GC had a worse 5-year OS and DSS than pT1N0, pT1N1, and pT1N2 patients (P < 0.001). The 5-year OS and DSS for pT1N1 patients showed no significant difference between ACT and surgery only patients. For pT1N2 patients, the 5-year OS and DSS showed no significant difference between S-1 and Xelox treatments. For pT1N3 patients, 7 (36.8%) received S-1, while 12 (63.2%) received Xelox treatment. Patients receiving Xelox treatment showed a better 5-year OS (75.0% vs. 14.3%) and DSS (81.8% vs. 20.0%) than patients receiving S-1 (P < 0.05).Conclusions:Curative surgery only was adequate for patients with pT1N0 and pT1N1. Xelox showed no survival benefits for pT1N2 patients. Therefore, S-1 is the optimal choice for pT1N2 patients, when considering adverse effects. Xelox is recommended for pT1N3 patients.     

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.     

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.     

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 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.     

Second malignancy after gastrectomy for early gastric cancer-is there any evidence that adjuvant chemotherapy for early gastric cancer causes a second malignancy ?

The common causes of post-operative death in early gastric cancer are other diseases and second malignancy. In Japan, adjuvant chemotherapy using oral administration of 5-fluorouracil is widely accepted in spite of no statistical evidence until the presentation by Kinoshita in 2005. In 1999, Fujimoto mentioned that adjuvant chemotherapy and chemo-immune-therapy cause a second malignancy. Adjuvant chemotherapy was once the standard treatment for early gastric cancer patients. So, we investigated the relation between adjuvant chemotherapy and second malignancy for early gastric cancer patients. As a result, adjuvant chemotherapy using 5-fluorouracil(Tegafur)did was not cause second malignancy under multivariate analysis. The most important factor in second malignancy with post-operative early gastric cancer patients was heredity(cancer within first-degree relatives). From this point of view, early gastric patients after gastrectomy and endoscopic treatment are necessary in regular examinations to detect other organ cancers and remnant gastric cancer, especially in patients with hereditary factors.     

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.     

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 specialized geriatric centers in treating geriatric cancer patients?

As the population with colorectal cancer ages, the tailored approach required to manage older patients becomes all the more important for all providers and institutions treating colorectal cancer to adopt and improve the outcomes and well-being of this important and increasingly prevalent population. Joint guidelines from the American College of Surgeons and American Geriatric Association should be followed. Older cancer patients undergoing colorectal cancer surgery should be referred to centers with expertise in minimally invasive surgery. Likewise, older rectal cancer patients should be referred to centers with expertise in treating rectal cancer.