As cure rates for childhood cancers continue to rise, increasing numbers of childhood cancer survivors will be entering adulthood and will require close follow-up for late effects of their therapy. One particular group warranting close evaluation are survivors of bone tumours because of the nature of treatment, which often includes intensive chemotherapy, surgery and, at times, radiation therapy. As reviewed by Langeveld, several studies have already highlighted problems encountered by adult survivors of paediatric bone tumours (Langeveld et al, 2002
). Late effects relating to chemotherapy and irradiation (e.g. infertility, cardiomyopathy) are varied and have been the subject of extensive research (Bhatia et al, 2003
). Late effects relating to surgical local control of paediatric lower extremity bone tumours have been less thoroughly explored (Nagarajan et al, 2002
). Local control procedures include amputation and limb-sparing procedures (e.g. the use of radiation, arthrodesis, endoprosthesis, allograft bone, etc.). The decision to perform a limb-sparing surgery is based on the ability to achieve an equivalent oncologic result and a comparable or better functional result compared to amputation (Yaw, 1999
Amputation was standard treatment prior to the development of radiological and surgical techniques that have made limb-sparing surgery the more frequent treatment choice (Provisor et al, 1997
; Bacci et al, 1998
; Bielack et al, 2002
). The preference for limb-sparing surgery to treat paediatric lower extremity bone tumours had been the subject of debate and warranted careful evaluation in the past. The issues surrounding the debate have been succinctly described in four questions (Simon, 1991
): (1) will survival be the same? (2) how do the immediate and delayed morbidities (complications) compare? (3) how does function compare? and (4) does limb-sparing surgery impart improved psychosocial/quality of life outcomes? Regarding the first question, survival and local recurrence rates between amputation and limb-sparing surgery have not been found to be significantly different when adequate margins are achieved and adjuvant chemotherapy is used (Simon et al, 1986
; Sluga et al, 1999
; Bacci et al, 2000
; Bielack et al, 2002
). When considering short- and long-term complications, several studies have shown that there are more complications following limb-sparing surgery (Ruggieri et al, 1993
; Rougraff et al, 1994
; Lindner et al, 1999
; Nagarajan et al, 2002
). Of note, with new techniques and materials being developed for limb-sparig surgeries, long-term outcomes need to be continually evaluated.
In contrast, the last two questions have not been extensively studied, which is the basis for the current investigations. Overall, a trend toward an improvement of function has been reported for limb-sparing approaches. No differences in quality of life have thus far been shown between amputation and limb-sparing operative procedures. However, it is important to note that despite a number of authors addressing these outcomes, the overall conclusions have limitations because of the differing methodologic approaches and assessment tools used, small sample sizes, short follow-up, and limited study of adult survivors of childhood cancer (Nagarajan et al, 2002
). The most common instrument that has been used for functional assessment has been the Musculoskeletal Tumour Society survey, which relies on the subjective ratings given by the administering clinician with no other objective measure of function. This has been questioned as to whether this is an accurate reflection of function (Marchese et al, 2004
) and whether other more global functional assessments with QOL measures (TESS and QOL-CS) are needed to better represent the clinical status.
Children with lower extremely bone tumours have unique characteristics with implications for functional and quality-of-life outcomes. The emotional maturity of patients at the time of diagnosis can influence their ability to accept the loss of limb due to cancer (Kagan, 1976
; Ettinger and Heiney, 1993
; Felder-Puig et al, 1998
). Skeletal maturity is another important determinant of functional and QOL outcomes in children with lower extremity bone sarcomas because of its importance in determining the type of local surgical control (amputation/rotationplasty/expanding prosthesis) and the associated risk of complications. Those who are skeletally immature and have substantial growth potential at diagnosis are often treated with limb-sparing surgery, which requires removal of a skeletal growth plate. Such patients often need multiple subsequent surgeries to accommodate growth of the unaffected limb. Moreover, children have a substantial lifespan ahead of them following successful treatment of their malignancy and this may increase the potential risk of further reconstructive procedures and complications.
With the establishment of the CCSS to facilitate the investigation of late effects among long-term survivors of childhood cancer, we were able to examine some of these key issues. The current study represents the largest series of adult survivors of paediatric lower extremity bone tumours thus far evaluated for function and QOL. However, some limitations must be considered in the interpretation of the results of this study. These include the inability to further classify the procedures that nonamputees (e.g. allograft vs. endoprosthesis) and amputees (above the knee vs below the knee amputation) received and the fact that this study provides information regarding treatments performed between 1970 and 1986, which are likely quite different from today's surgical treatments. However, this study does provide an excellent assessment of the outcomes of amputees, which would be difficult to examine today given the infrequency with which amputations are performed for paediatric lower extremity bone tumours. An additional shortcoming of the study relates to the length of time from diagnosis (median 21 years) to current assessment, which precludes the examination of outcomes within 10 years of diagnosis. It is in this time frame that differences between groups may be substantial and may be masked or lost by longer follow-up. Other issues involved the assessment of subsequent surgeries or complications. Since the assessment of surgeries was restricted to the initial treating institution and complications were not specifically noted, the accurate enumeration of subsequent surgeries and complications is not possible. Further limitation of the study includes ascertainment bias since the cohort includes only those who have agreed to participate in the CCSS. This may underestimate deficits by excluding those who are having more difficulty adjusting and are unable or unwilling to participate.
We found no major differences in function and quality of life between those who had an amputation and those treated with limb-sparing surgery. Additionally, our assessment of the large population of patients who underwent amputation provides clear indication that amputees do well long-term. Thus, when an amputation is clinically indicated, patients, families and clincians can assume that long-term amputees have no different function and QOL compared to those without an amputation. One may attribute the lack of reported differences between amputees and nonamputees to ‘adjustment and accommodation’ to their current condition, rather than having comparable physical ability such as range of motion and strength. To determine actual physical ability, via clinical examination, in a cohort as large as this and as far from diagnosis would be very difficult to accomplish. Additionally, one may argue that ‘actual’ physical ability is only a component of overall perceived physical function, which is influenced by other individualised factors including self-image, motivation and social support (Neugebauer, 2000
Females reported significantly lower function and QOL, but did not report more disability. Survivors with a lower educational attainment also appeared to have lower function and QOL scores and a significantly increased likelihood of self-reported disability. In the author's prior study of psychosocial outcomes (Nagarajan et al, 2003
) in this group of survivors, female survivors were less likely to be employed and those with a higher educational attainment were more likely to ever been employed or married or ever have insurance. Female gender-related deficiencies may be related to differences in coping styles (Znajda et al, 1999
) and other gender-specific issues and the benefit of higher educational attainment may suggest more available opportunities or better social support. In the current study, those who were younger in age at completion of the questionnaire were less likely to have lower TESS and QOL-CS scores and significantly less likely to consider themselves disabled. This is most likely due to issues related to normal aging.
Further follow-up of this cohort, including reassessment to observe any changes in scores and perceived disability over time, is clearly warranted. It will also be important to prospectively investigate post-1986 populations of paediatric lower extremity bone tumour survivors in order to see how current surgical techniques affect function and quality of life. These prospective studies must encompass long-term assessments and integrate uniform methods of recording complications associated with the surgical procedures, as well as uniform collection of function and QOL data. Such an approach will aid paediatric oncologists and orthopaedic surgeons by providing insight into disease control, functional outcomes, and quality of life. We hope that this research study will help provide patients and families with needed information on anticipated long-term outcomes and on how to maximise function and quality of life as these paediatric patients grow into adulthood.