Rathke’s cleft cysts: review of natural history and surgical outcomes

Rathke’s cleft cysts (RCCs), also known as pars intermedia cysts, represent benign lesions formed from remnants of the embryologic Rathke’s pouch. Commonly asymptomatic, they are identified in nearly 1 in 6 healthy volunteers undergoing brain imaging. When symptomatic, they can cause headaches, endocrine dysfunction, and, rarely, visual disturbances. A systematic review of the published English literature was performed focusing on large modern case series of RCCs to describe their natural history, clinicopathologic features, radiographic features, and surgical outcomes, including rates of recurrence. The natural history of asymptomatic RCCs is one of slow growth, suggesting that observation through serial magnetic resonance imaging is appropriate for smaller asymptomatic RCCs. Symptomatic RCCs can be treated by surgical resection with low morbidity, usually through an endonasal transsphenoidal corridor using either a microscope or an endoscope. Surgical treatment frequently provides symptomatic relief of headaches and visual disturbances, and sometimes even improves endocrine dysfunction. Rates of recurrence after surgical treatment range from 16 to 18 % in large series, and higher rates of recurrence are associated with suprasellar location, inflammation and reactive squamous metaplasia in the cyst wall, superinfection of the cyst, and use of a fat graft into the cyst cavity.     

Barrett’s esophagus: Review of natural history and comparative efficacy of endoscopic and surgical therapies

Barrett's esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC). Progression to cancer typically occurs in a stepwise fashion through worsening dysplasia and ultimately, invasive neoplasia. Established EAC with deep involvement of the esophageal wall and/or metastatic disease is invariably associated with poor long-term survival rates. This guides the rationale of surveillance of Barrett’s in an attempt to treat lesions at an earlier, and potentially curative stage. The last two decades have seen a paradigm shift in management of Barrett’s with rapid expansion in the role of endoscopic eradication therapy (EET) for management of dysplastic and early neoplastic BE, and there have been substantial changes to international consensus guidelines for management of early BE based on evolving evidence. This review aims to assist the physician in the therapeutic decision-making process with patients by comprehensive review and summary of literature surrounding natural history of Barrett’s by histological stage, and the effectiveness of interventions in attenuating the risk posed by its natural history. Key findings were as follows. Non-dysplastic Barrett’s is associated with extremely low risk of progression, and interventions cannot be justified. The annual risk of cancer progression in low grade dysplasia is between 1%-3%; EET can be offered though evidence for its benefit remains confined to highly select settings. High-grade dysplasia progresses to cancer in 5%-10% per year; EET is similarly effective to and less morbid than surgery and should be routinely performed for this indication. Risk of nodal metastases in intramucosal cancer is 2%-4%, which is comparable to operative mortality rate, so EET is usually preferred. Submucosal cancer is associated with nodal metastases in 14%-41% hence surgery remains standard of care, except for select situations.     

Combining PARP inhibitors with radiation therapy for the treatment of glioblastoma: Is PTEN predictive of response?

Glioblastoma (GBM) is fatal. The standard radiotherapy and chemotherapy (temozolomide) followed by an adjuvant phase of temozolomide provide patients with, on average, a 2.5 months benefit. New treatments that can improve sensitivity to the standard treatment are urgently needed. Herein, we review the mechanisms and utility of poly (ADP-ribose) polymerase inhibitors in combination with radiation therapy as a treatment option for GBM patients and the role of phosphatase and tensin homologue mutations as a biomarker of response.     

Targeting ALK: a promising strategy for the treatment of non-small cell lung cancer, non-Hodgkin’s lymphoma, and neuroblastoma

Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor that affects a number of biological and biochemical functions through normal ligand-dependent signaling. It has oncogenic functions in a number of tumors including non-small cell lung cancer (NSCLC), anaplastic large cell lymphoma, and neuroblastoma when altered by translocation or amplification or mutation. On August 2011, a small molecule inhibitor against ALK, crizotinib, was approved for therapy against NSCLC with ALK translocations. As we determine the molecular heterogeneity of tumors, the potential of ALK as a relevant therapeutic target in a number of malignancies has become apparent. This review will discuss some of the tumor types with oncogenic ALK alterations. The activity and unique toxicities of crizotinib are described, along with potential mechanisms of resistance and new therapies beyond crizotinib.     

Recent advances in the diagnosis and therapy of richter’s syndrome

Richter’s syndrome (RS) denotes the development of aggressive lymphoma that arises in patients with chronic lymphocytic leukemia (CLL). Presenting features typically include a rapid clinical deterioration with fever in the absence of infection, progressive lymph node enlargement, and an elevation in serum LDH. Diagnostic biopsy of affected sites usually reveals large cell lymphomas; however, Hodgkin variant cases have been described. Richter’s transformation occurs in approx 5% of CLL patients and may be associated with infection with Epstein-Barr virus (EBV). Chromosome 11 and 14 abnormalities have also been described as well as tumor suppressor gene defects involving p53, p21, and p27. Treatment options for these patients are limited and include combination chemotherapy with or without the addition of monoclonal antibodies and stem cell transplantation. Response to therapy is variable and generally short-lived. Median survival is usually in the order of 5–8 mo. More effective management for RS is needed as well as prognostic models that will identify CLL patients at risk of transformation. This review will address the current status of RS and deal with the pathophysiology, diagnostic approach, and treatment of this challenging disease.     

Second malignancies after treatment for Ewing’s sarcoma: a report of the CESS-studies

Purpose: During recent years, more intensified systemic and local treatment regimens have increased the 5-year survival figures in localized Ewing’s sarcoma to more than 60%. There is, however, concern about the risk of second malignancies (SM) in long-term survivors. We have analyzed the second malignancies in patients treated in the German Ewing’s Sarcoma Studies CESS 81 and CESS 86.Materials and Methods: From January 1981 through June 1991, 674 patients were registered in the two sequential multicentric Ewing’s sarcoma trials CESS 81 (recruitment period 1981–1985) and CESS 86 (1986–1991). The systemic treatment in both studies consisted of a four-drug-regimen (VACA = vincristine, actinomycin D, cyclophosphamide, and adriamycin; or VAIA = vincristine, actinomycin D, ifosfamide, and adriamycin) and a total number of four courses, each lasting nine weeks, was recommended by the protocol. Local therapy in curative patients was either complete surgery (n = 162), surgery plus postoperative radiotherapy with 36–46Gy (n = 274), or definitive radiotherapy with 46–60Gy (n = 212). The median follow-up at the time of this analysis was 5.1 years, the maximum follow-up 16.5 years.Results: The overall survival of all patients including metastatic patients was 55% after 5 years, 48% after 10 years, and 37% after 15 years. Eight out of 674 patients (1.2%) developed a SM. Five of these were acute myelogenic leukemias (n = 4) or MDS (n = 1), and three were sarcomas. The interval between diagnosis of Ewing’s sarcoma and the diagnosis of the SM was 17–78 months for the four AMLs, 96 months for the MDS and 82–136 months for the three sarcomas. The cumulative risk of an SM was 0.7% after 5 years, 2.9% after 10 years, and 4.7% after 15 years. Out of five patients with AML/MDS, three died of rapid AML-progression, and two are living with disease. Local therapy (surgery vs. surgery plus postoperative irradiation vs. definitive radiotherapy) had no impact on the frequency of AML/MDS, but local therapy did influence the risk of secondary sarcomas. All three patients with secondary sarcomas had received radiotherapy; however, all three sarcomas were salvaged by subsequent treatment and are in clincal remission with a follow-up of 1 month, 4.3 years, and 7.5 years after the diagnosis of the secondary sarcoma. Thus far, SM contributed to less than 1% (3/328) of all deaths in the CESS-studies.Conclusions: The risk of leukemia after treatment for Ewing’s sarcoma is probably in the range of 2%. The risk of solid tumors also seems to be low within the first 10 years after treatment and remains in the range of 5% after 15 years. In the CESS-studies, less than 1% of all deaths within the first 10 years after diagnosis were caused by SM. Effective salvage therapy for secondary sarcomas is feasible.     

RETRACTED ARTICLE: Applications of radiotherapy and radiosurgery in the management of pediatric Cushing’s disease: a review of the literature and our experience

Surgical extirpation of pituitary adenomas is considered the mainstay of therapy in pediatric patients with Cushing's disease. However, a small subset of patients will require adjuvant therapy either due to tumor invasiveness, or disease recurrence. Conventional radiation therapy (or radiotherapy) delivers ionizing radiation to control hormonally active cells in fractionated doses (spread out over time) in order to give normal cells time to recover, while radiosurgery involves focusing a high dose of radiation structures in a single treatment session to the adenoma while generally sparing the normal gland and surrounding of any substantial amount of radiation. This paper reviews the effectiveness of radiation in the treatment of pediatric Cushing's disease.     

Paget’s disease of the vulva: a clinicopathologic institutional review

Background

The aim of this study was to assess the clinicopathologic characteristics of patients with Paget??s disease of the vulva who were treated by our gynecologic oncology service between 1985 and 2010.

Methods

Vulvar Paget??s disease patient demographics, pathologic diagnosis, treatment and follow-up data were reviewed over a 25-year period.

Results

The vulvar Paget??s disease patients were primarily (62.5%) treated with a partial simple vulvectomy. Three patients had a history of malignancy, although none of them was intercurrent. Eleven patients had microscopically positive margins, 5 of whom developed progressive disease. Conversely, 5 patients had negative margins, of whom 4 had recurrent disease. There was a significant relationship between the presence of invasive disease and patient progression-free interval (PFI) (p = 0.007), but margin status and lesion size did not correlate with PFI (p > 0.05). Median patient PFI and follow-up was 30 and 53 months, respectively.

Conclusions

We found a significant relationship between the presence of invasive disease and patient PFI in vulvar Paget??s disease although the presence of microscopic positive margins and lesion size were not prognostic indicators. In patients with high risk factors, prolonged surveillance should be considered an essential component of optimal patient management.     

Radiation therapy for older adults with glioblastoma: radical treatment,palliative treatment,or no treatment at all?

The incidence of glioblastoma in older adults has increased over the last few decades. Current treatment includes surgery, radiotherapy, and chemotherapy, but optimal disease management remains a matter of debate. Both standard (60 Gy in 30 daily fractions) and hypofractionated radiotherapy (30–40 Gy in 10–15 daily fractions) have been employed with a similar survival benefit. Recent randomized studies indicate that chemotherapy with the alkylating agent temozolomide is a safe and effective therapeutic option for patients aged 60 years or older with newly diagnosed glioblastoma, suggesting that it should be a sufficient treatment for patients presenting with a methylated O6-methylguanine-DNA methyltransferase (MGMT) promoter gene. The addition of concomitant temozolomide chemotherapy, adjuvant temozolomide chemotherapy, or both to postoperative radiotherapy, which is the standard treatment for adults with glioblastoma, has been associated with a survival benefit for older patients with a good performance status; however, aggressive treatment in this population may be associated with a high risk of neurological toxicity and deterioration of quality of life. Survival stratification according to age, MGMT promoter methylation status, and neurological status may be useful for clinical decision making and designing randomized trials for adequately evaluating the optimal combination of radiotherapy and chemotherapy for older patients with glioblastoma.     

Pomalidomide for the treatment of relapsed–refractory multiple myeloma: a review of biological and clinical data

Despite the improvements thanks to the introduction of proteasome inhibitors and immunomodulatory drugs (IMiDs), nearly all myeloma patients eventually become refractory to these drugs. Consequently, the outcome of these patients is very poor. Pomalidomide is a new IMiD with a similar structure to the commonly used IMiD thalidomide and lenalidomide. Pomalidomide exhibited more potent anti-myeloma activity and a similar favorable safety profile compared with thalidomide and lenalidomide. In Phase I–II studies pomalidomide plus low-dose dexamethasone demonstrated activity in myeloma patients refractory to both bortezomib and IMiDs. Based on the results of a Phase III trial, the FDA and EMA agencies granted accelerated approval to pomalidomide, which is now considered a new effective strategy for relapsed and/or refractory myeloma patients. Very promising results were obtained when pomalidomide-dexamethasone was used in combination with other compounds. This review provides updated information about pharmacokinetics, mechanism of action, resistance, clinical efficacy and safety of pomalidomide.     

Dose–response relationship for fractionated irradiation in the treatment of spinal meningeal melanocytomas: a review of the literature

Summary Complete resection (CTR) of meningeal melanocytomas results in better outcome than incomplete resection (ITR). After ITR, outcome is improved by radiotherapy. CTR is less frequent with spinal melanocytomas than with cerebral melanocytomas. This study of 49 spinal melanocytoma patients was performed to define an appropriate radiation dose after ITR. All reported spinal melanocytoma cases were reviewed for extent of surgery, radiotherapy (total dose, dose per fraction), and outcome. CTR was compared to ITR for local control (LC) and overall survival (OS). ITR alone was compared to ITR plus radiotherapy (ITR + RT). In the ITR + RT group, doses of 50–52.2 Gy (1.8–2.0 Gy per fraction) were compared to doses < 50 Gy (30–45 Gy). The 5-year LC was 78% after CTR alone vs. 22% after ITR alone (P < 0.001). Five year OS was 83 and 40% (P = 0.011) respectively. ITR + RT was superior to ITR for LC (59% vs. 22%, P = 0.029) and OS (85% vs. 40%, P = 0.10). In the ITR + RT group, 50–52.2 Gy resulted in better LC than 30–45 Gy (100% vs. 33%; P = 0.042), but not in significantly better OS (100% vs. 77%, P = 0.33). CTR was associated with better significantly outcome than ITR. After ITR, the outcome was significantly improved by radiotherapy, 50–52.2 Gy was significantly superior to 30–45 Gy. To reduce the risk of radiation myelopathy, 50.4 Gy (1.8 Gy per fraction) appears appropriate for most patients. The recurrence rates after CTR would mandate the use of post-operative radiotherapy in all spinal meningeal melanocytoma cases. Our results should be confirmed in a larger series of patients when available.     

CAR T-cell therapy for glioblastoma: ready for the next round of clinical testing?

Introduction: The outcome for patients with glioblastoma (GBM) remains poor, and there is an urgent need to develop novel therapeutic approaches. T cells genetically modified with chimeric antigen receptors (CARs) hold the promise to improve outcomes since they recognize and kill cells through different mechanisms than conventional therapeutics.

Areas covered: This article reviews CAR design, tumor associated antigens expressed by GBMs that can be targeted with CAR T cells, preclinical and clinical studies conducted with CAR T cells, and genetic approaches to enhance their effector function.

Expert commentary: While preclinical studies have highlighted the potent anti-GBM activity of CAR T cells, the initial foray of CAR T-cell therapies into the clinic resulted only in limited benefits for GBM patients. Additional genetic modification of CAR T cells has resulted in a significant increase in their anti-GBM activity in preclinical models. We are optimistic that clinical testing of these enhanced CAR T cells will be safe and result in improved anti-glioma activity in GBM patients.     

Current concepts in the treatment of Ewing’s sarcoma

Current concepts in the treatment of patients with Ewing’s sarcoma are presented focusing on the role of chemotherapy, radiation therapy and surgical resection. Particular attention is given to current methods of limb salvage. Problem areas, including the pelvis, proximal femur and spine, are discussed.     

Evaluation of the efficacy and usability of NCI’s Facing Forward booklet in the cancer community setting

Introduction

The NCI developed the print-based educational brochure, Facing Forward, to fill a gap in helping cancer patients meet the challenges of transitioning from active treatment to survivorship; however, little research has been conducted on its efficacy.

Purpose

The aims of this study were to evaluate the efficacy of Facing Forward in promoting the uptake of recommended behaviors (e.g., ways to manage physical changes) and to explore its usability.

Methods

At the last treatment appointment, early-stage breast, prostate, colorectal, and thoracic cancer patients (N?=?340) recruited from community clinical oncology practices and an academic medical center completed a baseline assessment and were randomized to receive either Facing Forward (n?=?175) or an attention control booklet about the NCI’s Cancer Information Service (n?=?165). Patients completed follow-up assessments at 8 weeks and 6 months post-baseline.

Results

The reported uptake of recommended stress management behaviors was greater among intervention than control participants at both 8 weeks post-baseline (p?=?0.016) and 6 months post-baseline (p?=?0.017). At 8 weeks post-baseline, the intervention control group difference was greater among African-American than Caucasian participants (p?<?0.03) and significant only among the former (p?<?0.003); attendance at a cancer support group was also greater among the intervention than control group participants (p?<?0.02). There were no significant intervention control group differences in the reported uptake of recommended behaviors in three other categories (p?>?0.025). Intervention participants rated Facing Forward as understandable and helpful and indicated a high level of intention to try the behaviors recommended.

Conclusions

Facing Forward can enhance early-stage survivors’ reported ability to manage stress and increase support group use during the reentry period.

Implications for Cancer Survivors

Facing Forward can help survivors meet the challenges of the reentry period.     

Non-visible asymptomatic haematuria: a review of the guidelines from the urologist’s perspective

Introduction: Non-visible hematuria, also referred to as ‘microscopic hematuria’ or ‘dipstick positive hematuria’ is a common reason for urology referrals with prevalence rates that range from 13% to 20%. The main concern for investigating non-visible hematuria, especially in the absence of lower urinary tract symptoms, is its potential relation to urinary tract malignancy, which however does not exceed 5%.

The pathway of investigation of non-visible hematuria is impeded by the lack of clarity over definitions, diagnosis and specialist referral criteria. Towards that goal guidelines have been introduced by different societies. In this review we aim to discuss differences in current guideline regarding the investigation, management and follow up of non-visible hematuria.

Areas covered: Guidelines, recommendations, algorithms and original articles on hematuria published in the English literature were retrieved using the following PubMed search terms ‘microscopic hematuria’, ‘dipstick hematuria’, ‘non-visible hematuria’ and ‘guidelines’.

Expert commentary: Available guidelines for investigation of microscopic hematuria actually differ both in the extent and the intensity of the proposed imaging and invasive tests. There is evidence that guidelines are not adhered to and this reflects the necessity for introducing selection criteria and maybe variable levels of investigation for microscopic hematuria depending on the individual patient.