Spontaneous regression of metastatic melanoma – Clinical evidence of the abscopal effect

Introduction

Metastatic melanoma is poorly understood. Regression of primary lesions has been associated with poor prognosis, but spontaneous regression of all metastatic disease is clearly beneficial. A patient's own immune responses occasionally appear to stimulate spontaneous regression of metastatic disease in melanoma.

Patients and methods

We present six interesting cases of complete or nearly complete spontaneous regression of metastatic melanoma, suggest possible causes and review the literature.

Results and conclusions

These cases show clear radiological, pathological or clinical evidence of spontaneous regression of metastatic melanoma. This remains a poorly understood phenomena warranting further investigation and may prove useful in the development of immune mediated solutions.     

Clinical Trials with Retrovirus Mediated Gene Therapy – what Have we Learned?

Retrovirus (RV) has been one of the earliest recombinant vectors to be investigated in the context of cancer gene therapy. Experiments in cell culture and in animal brain tumor models have demonstrated the feasibility of RV mediated gene transduction and killing of glioma cells by toxicity generating transgenes. Phase I and II clinical studies in patients with recurrent malignant glioma have shown a favorable safety profile and some efficacy of RV mediated gene therapy. On the other hand, a prospective randomized phase III clinical study of RV gene therapy in primary malignant glioma failed to demonstrate significant extension of the progression-free or overall survival times in RV treated patients. The failure of this RV gene therapy study may be due to the low tumor cell transduction rate observed in vivo. The biological effects of the treatment may also heavily depend on the choice of transgene/prodrug system and on the vector delivery methods. Retrovirus clinical trials in malignant glioma have nevertheless produced a substantial amount of data and have contributed toward the identification of serious shortcomings of the non-replicating virus vector gene therapy strategy. Novel types of therapeutic virus vector systems are currently being designed and new clinical protocols are being created based on the lessons learned from the RV gene therapy trials in patients with malignant brain tumors.     

Proton Beam Therapy – the Challenges of Delivering High-quality Evidence of Clinical Benefit

The use of proton beam therapy (PBT) offers the opportunity to improve greater conformality of radiotherapy treatment delivery in some patients. However, it is associated with a high capital cost and the need to build new dedicated facilities. We discuss how the global radiotherapy community can respond to the challenge of producing high-quality evidence of clinical benefit from PBT in adult patients. In the UK, the National Cancer Research Institute-funded Clinical and Radiotherapy Translational group has established the PBT Clinical Trial Strategy Group. An eight-point framework is described that can assist the development and delivery of high-quality clinical trials.     

Turn Off the IDO: Will Clinical Trials Be Successful?

Summary: Indoleamine 2,3-dioxygenase (IDO) is overexpressed in many human cancers and is believed to play a role in tumor immune evasion, but a requirement for IDO in tumor progression has not been formally shown. The study by Smith and colleagues in this issue of Cancer Discovery provides genetic evidence for the importance of IDO in tumorigenesis, which supports the use of IDO inhibitors in clinical trials in humans. Cancer Discov; 2(8); 673-5. ?2012 AACR.     

What Is the Role of Radiotherapy in Malignant Pleural Mesothelioma?

Objective.

A review of the evidence supporting the use of radiotherapy in patients with mesothelioma was performed.

Methods.

Relevant publications were searched for on Medline.

Results.

In a Medline search on radiotherapy and mesothelioma, 611 hits were obtained. A limited number of prospective phase II trials of radiotherapy as part of trimodality protocols for early disease and in the palliation of pain were found, along with three small randomized controlled trials of port-site prophylaxis.

Conclusion.

No randomized data exist to support the use of radiotherapy after radical surgery, although there are a large number of publications describing its use as an integral part of therapy, including seven phase II studies. One ongoing trial is randomizing patients to radiotherapy or not after extrapleural pneumonectomy. None of these studies provided any assessment of radiotherapy independent of the other modalities investigated, nor did any formally assess intensity-modulated radiotherapy. There have been several reports of excessive toxicity with this technique, and its use should be limited to phase I studies until the basis of this toxicity is better understood. Three trials have looked at port-site prophylaxis, one supporting its use and two showing no evidence of benefit. Two studies addressed pain control prospectively, one showing definite but short-lived benefits.

Implications.

Radiotherapy is widely used in treating mesothelioma with little supporting evidence. More randomized trials are required to justify this use in all three common settings for its use.     

Complying with the European Clinical Trials directive while surviving the administrative pressure – An alternative approach to toxicity registration in a cancer trial

The European Clinical Trials Directive of 2004 has increased the amount of paper work and reduced the number of initiated clinical trials. Particularly multinational trials have been delayed. To meet this challenge we developed a novel, simplified, fast and easy strategy for on-line toxicity registration for patients treated according to the Nordic/Baltic acute lymphoblastic leukaemia protocol, NOPHO ALL 2008, for children and young adults, including three randomisations. We used a risk-assessment based approach, avoiding reporting of expected adverse events and instead concentrating on 20 well-known serious, but rarer events with focus on changes in therapy introduced in the treatment protocol. This toxicity registration strategy was approved by the relevant regulatory authorities in all seven countries involved, as compliant within the EU directive of 2004. The centre compliance to registration was excellent with 98.9% of all patients being registered within 5 weeks from the requested quarterly registration. Currently, four toxicities (thrombosis, fungal infections, pancreatitis and allergic reactions) have been chosen for further detailed exploration due to the cumulative fraction of patients with positive registrations exceeding 5%.This toxicity registration offers real-time toxicity profiles of the total study cohort and provides early warnings of specific toxicities that require further investigation.     

Progress in the Management of Malignant Pleural Mesothelioma in 2017

Malignant pleural mesothelioma (MPM) is an uncommon, almost universally fatal, asbestos-induced malignancy. New and effective strategies for diagnosis, prognostication, and treatment are urgently needed. Herein we review the advances in MPM achieved in 2017. Whereas recent epidemiological data demonstrated that the incidence of MPM-related death continued to increase in United States between 2009 and 2015, new insight into the molecular pathogenesis and the immunological tumor microenvironment of MPM, for example, regarding the role of BRCA1 associated protein 1 and the expression programmed death receptor ligand 1, are highlighting new potential therapeutic strategies. Furthermore, there continues to be an ever-expanding number of clinical studies investigating systemic therapies for MPM. These trials are primarily focused on immunotherapy using immune checkpoint inhibitors alone or in combination with other immunotherapies and nonimmunotherapies. In addition, other promising targeted therapies, including pegylated adenosine deiminase (ADI-PEG20), which focuses on argininosuccinate synthase 1–deficient tumors, and tazemetostat, an enhancer of zeste 2 polycomb repressive complex 2 subunit inhibitor of BRCA1 associated protein 1 gene (BAP1)-deficient tumors, are currently being explored.     

Clinical Review of Iressa for the Treatment of NSCLC

Following development of basic science and the advancement of tumor molecular biology, molecular-target therapy has evolved as a new field for cancer treatment. The agents used act at specific target points such as receptors, kinases and signal transduction systems which are related to tumor growth. These actions result in inhibting proliferation, metastasis, vascularization, and promoting tumor apoptosis. Iressa （gefitinib） which is used for the treatment of NSCLC is a small molecular weight agent acting by inhibition of epidermal growth factor receptor-tyrosine kinase. Iressa was the first approved agent for target therapy for the treatment of NSCLC. This article focuses on the results from clinical trials and the potential of Iressa for the treatment of NSCLC.     

Does Participation in Clinical Trials Influence the Implementation of New Techniques? A Look at Changing Techniques in Breast Radiotherapy in the UK

AimsTo examine the effect of UK breast radiotherapy trials on the adoption of new radiotherapy techniques over the last 15 years.Materials and methodsThe data were taken from questionnaires returned to the national radiotherapy quality assurance team for each of the major trials (START, Supremo, FAST, IMPORT) with additional information sought from heads of radiotherapy physics departments where needed.ResultsThe peak years for the introduction of three-dimensional radiotherapy corresponded to the opening of new trials requiring these techniques. Some non-trial centres had still not implemented three-dimensional techniques for breast cancer patients at the time the most recent questionnaire was completed (2009).ConclusionClinical trials provide the framework and impetus for introducing more accurate radiotherapy for UK women with early breast cancer.     

Clinical Characteristics and Prognosis of Patients With Advanced Non–Small-cell Lung Cancer Who Are Ineligible for Clinical Trials

Background

Most patients with non–small-cell lung cancer (NSCLC) are ineligible for clinical trials. However, few studies have reported on the profiles and treatment outcomes for these patients. Therefore, we investigated the characteristics, outcomes, and survival of patients with advanced NSCLC who were ineligible for clinical trials.

The Overview of the Chinese Journal of Clinical Onclolgy

CJCO is produced six times a year and publishes original work, reviews, articles of interest and letters under a broad scope of     

Racial and Ethnic Composition of Cancer Clinical Drug Trials: How Diverse Are We?

Many approved drugs demonstrate different pharmacokinetics, pharmacodynamics, and/or safety across racial and ethnic groups. The primary objective of the current study was to summarize the racial and ethnic makeup of cancer clinical drug trials using cancer drugs approved by the U.S. Food and Drug Administration (FDA) between January 1, 2010, and July 31, 2016. In clinical studies used for FDA approvals, 82.3% of participants identified as white, 10.2% as Asian, 2.3% as black, and 4.7% as Hispanic. Black participants made up 7.7% of U.S. and Canadian cancer clinical drug trials and 2.6% of global cancer clinical drug trials while Asian participants made up 13.5% of global cancer clinical drug trials but only 1.8% of U.S. and Canadian cancer clinical drug trials. The current study indicates that although cancer clinical drug trials have become more inclusive of Asian participants, other racial and ethnic minority groups remain under‐represented. This may result in an inadequate understanding of drug safety and efficacy in many racial and ethnic populations.     

Angiosarcoma of the Breast – specific findings of MRI

We present a case of low-grade angiosarcoma of the breast. A 26-year old woman presented with a lump in the left breast. An elastic hard and ill-defined tumor, 80 x 50 mm in size, was palpated in the upper region of her left breast. Mammography showed a dense lesion with poorly defined border. Ultrasonography showed a hyper-and hypo-echoic lesion with an unclear border, but no definite tumor. Fine needle aspiration cytology showed no evidence of malignancy. Therefore, she was followed with a diagnosis of mastopathy. Six months later, the lump got enlarged. A contrast-enhanced MRI of the breast was performed. It showed a 100 x 60 mm enhancing vascular mass. Most parts of the tumor enhanced remarkably at the early phase, and prolonged enhancement was recognized at the late phase. Core needle biopsy was performed, and a possible angiosarcoma was diagnosed. It is not easy to diagnose the mammary angiosarcoma. MRI may contribute to the accurate diagnosis and play an important role regarding this entity.