Reviews & Analysis

The aberrant tumour vasculature and the associated angiogenic factors have been implicated in tumour immune evasion and progression. Herein, the authors provide their perspectives on how normalization of the tumour microenvironment using antiangiogenic agents could potentially increase the effectiveness of immunotherapies and improve the outcomes of patients with cancer. The authors also highlight important considerations for future research in this area.

Precision cancer medicine has the potential to dramatically improve the outcomes of patients with cancer; however, despite the precise nature of the therapies involved, generating reliable evidence of efficacy is often challenging. In this Perspective, the authors describe the challenges and potential solutions that might address the need for evidence in precision cancer medicine.

Accurate detection and monitoring of treatment responses is an essential element of the management of patients with lymphoma. In this Perspectives, the authors describe the evolution of lymphoma staging criteria and highlight unaddressed questions, which, if answered, will substantially improve the management of patients with lymphoma.

Precision medicine has dramatically changed the landscape of drug development in oncology, but this paradigm shift remains to be adopted in early phase clinical trials of molecularly targeted agents and immunotherapeutic agents in children with cancer. The authors, members of the Innovative Therapies for Children with Cancer (ITCC) Consortium, describe trial design strategies to enable drugs with promising activity to progress rapidly to randomized studies and, therefore, substantially accelerate drug development for children and adolescents with cancer.

The costs of both newly approved, and established anticancer drugs have risen dramatically in the past decade, to the point where the costs of such treatments are becoming unsustainable. In this perspective, the authors outline the extent of this problem, and how it is likely to continue, while also suggesting measures that could be taken in future to address these rising costs.

The expansion of research and development of anticancer drugs in China has resulted in considerable delays in the approval of both clinical trials of novel agents, and the marketing approval of these agents once tested. In this Perspective, the authors describe the measures taken by the Chinese FDA to address these challenges in a rapidly developing research environment.

Clinical trial design has dramatically evolved with the advent of precision medicine. As a result, expedited drug-approval decisions have been made on the basis of evidence obtained in uncontrolled clinical trials. Herein, Saad et al. discuss the need to conduct randomized controlled trials at all phases of drug development in oncology, and present strategies to facilitate a seamless transition between phases of drug and/or biomarker development.

Assessment of tumour burden has become an integral part of most oncology clinical trials, and enables the evaluation of the activity and efficacy of new cancer therapeutics in solid tumours. Although RECIST was developed to assess treatment activity in early phase II trials with tumour response as the primary end point, it is now applied across the spectrum from early phase I trials through to confirmatory phase III trials. Several questions regarding the role of RECIST in the rapidly changing landscape of oncology therapeutics, and the challenges faced in its evaluation, are highlighted.

A multidisciplinary approach is essential for the optimization of patient care in oncology, especially in the current landscape, in which standard-of-care approaches to cancer treatment are evolving towards highly targeted treatments, precise image guidance and personalized cancer therapy. Herein, the authors discuss current career development pathways for oncologists, suggesting strategies to improve clinical training and research, with specific emphasis on the involvement of trainees in multidisciplinary teams.

Autophagy is fundamental to cellular homeostasis and also has a central role in the development and progression of cancer. However, autophagy is also required for optimal immune system function, including the development of an anticancer immune response. In this Perspective, the authors present the available preclinical and clinical evidence that autophagy might enhance the effectiveness of both immunogenic chemotherapy and radiotherapy, as opposed to the general view of inhibition of autophagy as an antitumour strategy.

The presence ofde novoresistance or the development of acquired resistance in cancer cells has limited the use of targeted agents. Combinations of targeted treatments can circumvent some mechanisms of resistance to yield clinical benefit. The authors explore the challenges in identifying the best drug combinations and the best combination strategies, as well as the complexities of delivering these treatments to patients.

Unwarranted variations, which cannot be attributed to patients' underlying illnesses or comorbidities, medical needs, or the dictates of evidence-based medicine, can account for substantial variations in patient outcomes. In this Perspectives, the authors describe possible approaches intended to address these variations in the context of colorectal cancer care.

Comparisons of patients' and clinicians' reports of adverse effects during clinical trials frequently reveal underreporting by clinicians and a discord between the severities of the adverse effects experienced by patients and estimates from clinicians. Despite this situation, few trials include patient-reported outcome measures (PROMs). In this Perspectives, the authors compare and discuss the use of such measures in clinical trials in men with prostate cancer over the past 5 years, highlighting a need for greater use of PROMs.

The use of multigene panels for the assessment of cancer susceptibility is expanding rapidly in clinical practice. The appropriate management of individuals harbouring moderate-penetrance genetic variants in individuals referred for clinical testing is unclear. The authors of this Perspectives article provide a framework for clinical decision-making pending the development of a sufficient evidence base to document the clinical utility of the interventions for individuals with inherited moderate-penetrance gene mutations associated with an increased risk of cancer.

The Internet is a valuable tool that continues to revolutionize many aspects of our lives. Herein, the current trends in the use of online resources in oncology are described, using the findings from the National Cancer Institute's Health Information National Trends Survey (HINTS) as a foundation. Future opportunities and challenges relating to the use of the Internet to improve cancer prevention and care are discussed.

Telomerase reverse transcriptase (TERT) is expressed constitutively in tumour cells throughout the evolution of many cancers; therefore, this potential tumour self-antigen has been an important target for anticancer vaccines over the past 10 years, but only modest benefits from this approach have been observed in clinical trials. In this Perspectives, Maurizio Zanetti reviews these studies, and highlights advances in our knowledge that warrant further development and refinement of TERT immunotherapy.

Patients with advanced cancer often have no access to potentially effective targeted drugs, despite expressing a known biomarker of a marketed drug. However, if the agent is not licensed for that particular malignancy, the only solution is to prescribe the drug off-label or not at all. Tumour molecular profiling can exacerbate this dilemma. The authors of this Perspectives discuss the French AcSé Programme that aims to provide access to molecular testing and the option to receive targeted drugs outside of planned or approved marketing indications in a manner that is safe and further builds on the evidence-base for the use of such agents.

Substantial interest exists in the effects of immunotherapy; however, radiation therapy also has the potential to stimulate an antitumour immune response. In this Perspectives, the authors describe the rationale for combining immunotherapy with stereotactic ablative radiotherapy based on the available clinical data, and provide recommendations for the future testing of approaches using this combination of treatments.

The general effectiveness of radiotherapy has improved over time, owing to improvements in technology which have enabled, among others, image-guided and intensity-modulated approaches to be used. In this Perspectives article, the authors describe how these advances can be best implemented for treatment of squamous-cell carcinoma of the anus.

Reporting of toxic adverse effects of anticancer treatments by clinicians generally results in the underreporting of these toxicities. Patient-reported outcomes, which fully reflect the experiences of patients receiving treatment, offer an alternative to reporting of toxicities by clinicians. In this Perspective, the authors describe the barriers and challenges to routine integration of patient-reported outcomes into clinical trials, and describe the PRO–CTCAE, which is designed to help circumvent some of these challenges.