Outcomes: Epidemiology / Late Effects
Late Effects of Treatment for Cancer
As a result of improvements in diagnosis,
staging and treatment an increasing number of patients can expect
to enjoy prolonged survival following treatment for cancer.
Consequently, the late effects of treatment on endocrine, cardiac
and pulmonary function, fertility, risk of second cancers and
psycho-social morbidity are of increasing importance and warrant
further study.
Late effects of cancer treatment affect the physical
functioning and the resultant quality of life of thousands of
cancer survivors in the UK, and millions worldwide. It is becoming
increasingly recognised that survivors of cancer may still
experience treatment-related health problems many years after
treatment has finished.
Two of our research areas within late effects are
described below:
Late Effects Treatment
Programme
In Manchester we have had a particular interest in the
impact of treatment on endocrine function and fertility and were
the first group to describe temporary resumption of ovarian
function following re-implantation of autologous ovarian tissue
harvested and cryopreserved before the start of sterilising
chemotherapy. We have also performed experiments investigating the
risk of disease transmission following ovarian tissue
reimplantation and have described the ultra-structural changes
associated with cryopreservation in these tissues.
We have described a method for isolating and
cryopreserving human spermatogonial stem cells and are completing a
study in which these cells were transplanted into the human testes
following sterilising chemotherapy. Reproductive outcome following
semen cryopreservation has also been evaluated and published and we
have investigated reasons for non-utilisation of these
gametes.
In addition we would wish to study second cancers, both in terms
of conveying information to individual patients and modifying
behaviour (particularly smoking), better understanding the risk of
this complication of treatment and its early detection. We already
have a large database and are collaborating with the Cochrane
Organisation and Professor Tony Swerdlow at the Institute of Cancer
Research in large epidemiological studies. In addition a joint
project has been established with Dr Paul Lorigan in which
serum/plasma from patients with early stage lung cancer, advanced
stage lung cancer and unaffected individuals is being stored for
proteomic analysis.
It is hoped this might provide a signature sufficiently
sensitive/specific for prompting a screening CT scan in
appropriately high risk populations (such as smokers treated with
chemotherapy and thoracic radiotherapy for Hodgkin lymphoma).
Finally we are interested in the psycho-social impact of
treatment on careers, relationships, earning potential, ambitions
and mental illness and are hoping to obtain funding for a PhD
studentship in this area.
The late effects treatment programme is led by Professor John
Radford. Access to patients for this research programme would be
through a new late effects clinic that is currently being
established in conjunction with our lymphoma nurse clinician and a
lymphoma clinical nurse specialist
Outcome Measures Group
The aims of the outcome measures (OM) group are to develop
robust clinical tools to record and score acute and late effects of
cancer treatments, specifically those involving radiation, and to
investigate management, prediction and prevention strategies. The
OM Group produced user-friendly questionnaires, which have provided
a practical approach for obtaining reliable and consistent
treatment effects data. The OM Group is now concentrating on
refining the questionnaires, and validating them in upcoming
national/international clinical trials. A major aim is to identify
questions that accurately measure late radiation toxicity, and omit
those questions which are non-discriminatory or superfluous. The
group has prospectively collected LENT data on patients who
received radical radiotherapy for gynaecological, prostate and head
and neck cancers. These data will be analysed using multivariate
principal components and factor analyses. Such refinement of the
questionnaires will help develop them into a tool which is
practical for routine clinical use
A study looking at an electronic version of the toxicity
questionnaires to see if this improves the assessment and recording
of treatment effects has started accrual. The common terminology
criteria for adverse events (CTCAE) gynaecological questionnaire is
to be used in a Coordinated Research Project sponsored by the
International Atomic Energy Agency to add comprehensive treatment
morbidity assessment onto an international cervix cancer trial
(Brazil, S.Africa and India). Questionnaires have been translated
into Portuguese, Hindi, Marathi and Afrikaans.
The late effects on normal tissues (LENT) - Subjective,
Objective, Management and Analytic (SOMA) scales were published in
1995 by joint effort of the EORTC and RTOG to attempt to produce a
universal scoring system for measuring and recording radiation
treatment effects. For further information on the LENT SOMA scales,
including access to the
questionnaires produced by the OM group, please click here.
The OM group is led by Dr Susan Davidson. This work is supported
by Jacqueline Routledge, research nurse.
