Thankamma Ajithkumar

Management of solid tumours in organ-transplant recipients

Malignancy is a well-recognised complication of transplantation and can occur de novo, as a recurrence of a pre-existing malignancy, or from transmission of malignancy from the donor. Common de-novo malignancies are those of the skin and the lymphoreticular system. Various solid-organ cancers have also been reported in transplant recipients and each poses a unique management challenge in view of the unusual setting. We review solid-organ cancers in transplant recipients and their management, including surveillance and prevention.

Management of malignant ovarian germ cell tumors.

Malignant ovarian germ cell tumors are rare, highly curable cancers of young women. The majority of patients can be cured with either fertility-preserving surgery alone or a combination of surgery and chemotherapy. Relapses occur in 10% to 20% of patients, and the significant proportion of them can be salvaged with chemotherapy. There is no evidence that treatment for malignant ovarian germ cell tumors will adversely affect menstrual or reproductive functions, increase future pregnancy loss, or increase the risk of congenital malformations of the fetus. Late effects, such as secondary leukemia, from chemotherapy are reported but rare. Target Audience: Obstetricians & Gynecologists and Family Physicians. Learning Objective: After completing this CME activity, physicians should be better able to diagnose ovarian germ cell tumors, outline management of malignant ovarian germ cell tumors, and understand the impact of treatment on fertility and late effects.

Multidisciplinary management of malignant ovarian germ cell tumours

OBJECTIVES Malignant ovarian germ cell tumours (MOGCT) are rare cancers of young women. Limited prospective trials exist from which evidence-based management can be developed. This review summarizes the available literature concerning MOGT in order to provide the clinician with information relevant to their multidisciplinary management. METHODS MEDLINE was searched between 1966 and 2010 for all publications in English where the studied population included women diagnosed with malignant ovarian germ cell tumours. RESULTS The majority of patients can be cured with fertility-preserving surgery with or without combination chemotherapy. Long term survival approaches 100% in early stage disease and is approximately 75% in advanced stage disease. Most studies suggest that the treatment has little, if any, effect on future fertility and limited data suggest that there is no adverse effect on the future quality of life. CONCLUSION MOGCTs are rare tumours of young women the majority of which can be successfully treated with fertility-preserving surgery with or without chemotherapy with preservation of reproductive function. Minimisation of chemotherapy in good prognostic groups and improved treatment in resistant and relapsed MOGCT are important goals for the future. Further studies are needed to quantify the late adverse effects of treatment in long term survivors.

Anticancer chemotherapy in teenagers and young adults: managing long term side effects

#### What you need to know Cancer is the leading cause of disease related death in teenagers and young adults (TYAs) in Western countries.1 2 In the UK, cancer in TYAs accounts for 9% and 15% of all male and female deaths respectively, and its incidence has risen by 19% since the mid-1990s, leading to 2300 new cases a year between 2011 and 2013.1 In Japan it accounted for nearly 7000 deaths between 2000 and 2006.3 TYA cancer survivors are likely to live for many decades but are at risk of late effects of their treatment. This article provides information for generalists on late effects of anticancer chemotherapy (see infographic and supplementary table A) that may affect quality of life. Radiotherapy related effects are not discussed but are summarised elsewhere.4 There is no internationally accepted age definition for TYAs. In the UK, TYA age is 15-24 years, whereas the US National Cancer Institute defines adolescents and young adults as aged 15-39 years. In this review we use the UK definition of 15-24 years. #### Sources and selection criteria This article is an evidence based review of late effects of chemotherapy in teenagers and young adults (TYAs). Our review encompasses studies using all age ranges termed as TYA or adolescents and young adult (AYA). We searched PubMed and the Cochrane databases between 1990 and 2016 using the search terms “teenage and young …

Prevention of radiotherapy-induced neurocognitive dysfunction in survivors of paediatric brain tumours: the potential role of modern imaging and radiotherapy techniques

Neurocognitive dysfunction is the leading cause of reduced quality of life in long-term survivors of paediatric brain tumours. Radiotherapy is one of the main contributors to neurocognitive sequelae. Current approaches for prevention and reduction of neurocognitive dysfunction include avoidance of radiotherapy in young children and reduction of the radiotherapy dose and volume of brain irradiated. Substantial advances have been made in brain imaging, especially with functional imaging and fibre tracking with the use of diffusion tensor imaging. Radiotherapy techniques for photon therapy have also evolved, with widespread use of techniques such as image-guided radiotherapy, volumetric modulated arc therapy, helical tomotherapy, and adaptive radiotherapy. The number of proton beam and heavy ion therapy facilities is increasing worldwide and there is great enthusiasm for clinical use of advanced MRI-guided radiotherapy systems. Here, we review the potential role of modern imaging and innovative radiotherapy techniques in minimisation of neurocognitive sequelae in children with brain tumours, and discuss various strategies to integrate these advances to drive further research.

Treatment of choice for patients with EGFR mutation-positive non-small cell lung carcinoma presenting with choroidal metastases: radiotherapy or TKIs?

INTRODUCTION It is not uncommon for patients with non-small cell lung cancer (NSCLC) to develop choroidal metastases (CM). External beam radiotherapy (EBRT) has traditionally been considered the treatment of choice for CM as it offers high response rates and quick relief of symptoms. However, new targeted treatments can offer an effective, alternative treatment strategy for patients harbouring specific genetic abnormalities. CASE STUDY We present the case of a patient presenting with a symptomatic metastasis to the choroid from an epidermal growth factor receptor (EGFR) mutation-positive NSCLC and exhibiting an excellent clinical and radiological response to the tyrosine kinase inhibitor (TKI) gefitinib. DISCUSSION A review of the literature reveals 6 more reported cases of patients with NSCLC successfully treated with an EGFR-TKI (gefitinib or erlotinib). There are no prospective or retrospective studies comparing EBRT with EGFR-TKIs for the treatment of CM in patients with EGFR mutation-positive NSCLC. All available data suggest that in EGFR mutation-positive NSCLC patients, EGFR-TKIs can offer response rates, time to response, and duration of response equivalent to that seen with EBRT. In addition, EGFR-TKIs can promise a more favourable ophthalmic toxicity profile compared with EBRT. CONCLUSION We conclude that initial treatment with an EGFR-TKI is a reasonable option for patients presenting with EGFR mutation-positive NSCLC and a CM. EBRT can be reserved for those who either do not respond to treatment with an EGFR-TKI or have recurrence after initial therapy.

SIOPE – Brain tumor group consensus guideline on craniospinal target volume delineation for high-precision radiotherapy

OBJECTIVE To develop a consensus guideline for craniospinal target volume (TV) delineation in children and young adults participating in SIOPE studies in the era of high-precision radiotherapy. METHODS AND MATERIALS During four consensus meetings (Cambridge, Essen, Liverpool, and Marseille), conventional field-based TV has been translated into image-guided high-precision craniospinal TV by a group of expert paediatric radiation oncologists and enhanced by MRI images of liquor distribution. RESULTS The CTVcranial should include the whole brain, cribriform plate, most inferior part of the temporal lobes, and the pituitary fossa. If the full length of both optic nerves is not included, the dose received by different volumes of optic nerve should be recorded to correlate with future patterns of relapse (no consensus). The CTVcranial should be modified to include the dural cuffs of cranial nerves as they pass through the skull base foramina. Attempts to spare the cochlea by excluding CSF within the internal auditory canal should be avoided. The CTVspinal should include the entire subarachnoid space, including nerve roots laterally. The lower limit of the spinal CTV is at the lower limit of the thecal sac, best visible on MRI scan. There is no need to include sacral root canals in the spinal CTV. CONCLUSION This consensus guideline has the potential to improve consistency of craniospinal TV delineation in an era of high-precision radiotherapy. This proposal will be incorporated in the RTQA guidelines of future SIOPE-BTG trials using CSI.

Uncommon low-grade brain tumors

The 2016 World Health Organization (WHO) classification of primary central nervous system (CNS) tumors includes numerous uncommon (representing ≤1% of tumors) low-grade (grades I-II) brain neoplasms with varying clinical behaviors and outcomes. Generally, gross tumor or maximal safe resection is the primary treatment. Adjuvant treatments, though their exact role is unknown, may be considered individually based on pathological subtypes and a proper assessment of risks and benefits. Targetable mutations such as BRAF (proto-oncogene B-Raf), TRAIL (tumor necrosis factor apoptosis inducing ligand), and PDGFR (platelet derived growth factor receptor) have promising roles in future management.