The Pediatric Oncology unit of Istituto Nazionale Tumori, Milan
The Pediatric Oncology unit of Istituto Nazionale Tumori (INT) in Milan conducts clinical and research projects on pediatric cancers. With 23 inpatients and 12 outpatients beds, the unit has always been tailored to the treatment of children with solid tumors (265 newly diagnosed patients treated in 2010), while it has been cooperating closely with the pediatric hemato-oncology center at San Gerardo Hospital in Monza since the 1980s, where it refers children with leukemia. and includes a pediatric surgery subunit. The INT’s pediatric oncology unit is part of the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP), the network of Italian pediatric oncology centers founded in the late 1970s to promote multicenter clinical trials and research.
Unlike other Italian pediatric oncology centers at children’s hospitals, or forming part of pediatric departments in general hospitals, our unit is the only pediatric oncology unit in Italy within a large cancer hospital. As well as attracting large numbers of patients over the years, this has facilitated close cooperation with the INT divisions dedicated to adult cancers, enabling us to gain particular experience of certain tumor types (e.g. bone and soft tissue sarcomas) across the pediatric and adult age groups, or adult-type tumors occurring in children (melanoma, carcinomas), or pediatric-type tumors (e.g. rhabdomyosarcoma, medulloblastoma) occurring in adults. For many years now there has been no upper age limit for admitting patients with pediatric cancers to our pediatric unit: a large number of adolescents, and also patients up to 25 or even 30 years old with pediatric tumors, have consequently been referred to our unit.
The pattern of patients’ age: the first focus on adolescents
Between 1985 and 2010, the INT’s pediatric oncology unit treated 4,110 patients: 880 were between 15 and 19 years old, while 206 were over twenty; 26% of all treated cases were more than 15 years old.
Figure 1. Proportions of adolescents/young adults and children treated at the INT’s pediatric oncology unit (A: years 1985-2010, B: 1985-2000, C: 2001-2010), and comparison with the proportions of patients with solid tumors treated at AIEOP centers (D), and the cases expected to occur in Italy judging from incidence rates drawn from population-based cancer registries (E).
The picture that emerges confirms that the INT’s pediatric oncology unit focuses much more on adolescents than the other AIEOP centers. It is also noteworthy that the proportion of adolescents seen at the INT has increased in the last decade.
Figure 2. Tumor types seen at the INT’s pediatric oncology unit (1985-2010) and age-related different patterns of cancer. Central nervous system tumors were the most frequent among the 0-14 year-olds, whereas soft tissue and bone sarcomas became predominant among the >15 year-olds. Legend: CNS - central nervous system; STS – soft tissue sarcomas; NBL – neuroblastoma; NHL – non-Hodgkin’s lymphoma; EW – Ewing’s sarcoma; OS – osteosarcoma, WT – Wilms’ tumor; rare – rare tumors; HD – Hodgkin’s’ disease
As another example of how the INT’s pediatric oncology unit focuses on adolescents, Figure 3 shows the cases registered by Italian AIEOP centers in the European pediatric Soft Tissue Sarcoma (EpSSG) database from 2005 to June 2011. One in three of all Italian cases were referred to our center and the median age of the patients recruited was 14.5 years for the INT’s cases and 6 years for all the other Italian centers. The age-related pattern of patient referral depended on the type of unit: in Padova (where the unit is part of a general hospital), the median age of the cases registered was 10 years and patients were evenly distributed between sarcoma types; at two pediatric hospitals (the Gaslini Hospital in Genova and the Ospedale Pediatrico Bambino Gesù in Rome), the median age of patients was 4 years, with a preponderance of rhabdomyosarcoma cases. At the other end of the spectrum, there is the Youth Area Project at the Centro di Riferimento Oncologico (CRO) in Aviano, which is not a pediatric unit but is nonetheless officially affiliated to the AIEOP because it has all the facilities needed to treat adolescents. The Aviano center is dedicated to 14-24 year-olds, but was only able to register 9 patients in the EpSSG database. These figures demonstrate that a particular focus on adolescents has been a feature of our unit for many years, long before any formal youth project was developed.
The INT Youth Project
Despite the appeal of an initial proposal to create a new unit specifically for AYA patients, it was soon clear that such a scheme was unfeasible for administrative, logistic and economic reasons. Hence the idea to develop a Youth Project within our pediatric oncology unit, based on our experience with AYA patients, in the conviction that adolescent patients may benefit from our multidisciplinary team (typical of the pediatric oncology setting), where pediatric oncologists team up with surgeons, radiotherapists, nutritionists, infectious disease experts, neurologists and endocrinologists, as well as with psychologists and social workers. In fact, numerous published studies have reported significantly better outcomes for adolescent patients with various tumors treated at pediatric cancer centers than for similar cases admitted to adult facilities. In addition, developing such a project as an offshoot of our existing activities was far more straightforward (and feasible) than setting up a separate AYA unit, with new professional figures, new accountabilities, new spaces.
The INT’s pediatric oncology unit thus officially launched its Youth Project in 2011, focusing on adolescents (over 15 years old) and young adults (up to 25 years old) with pediatric tumors. Patients in this age range are admitted to our inpatient and outpatient wards and managed by the same staff as our children, though they may also have access to particular services (regarding their psychosocial support, fertility preserving measures, and their access to care after completing their cancer therapy). Since our unit was originally designed for children (so there are cartoons on the walls, for instance, and clowns working with the children), one of the main aims of the Youth Project is to help the older patients feel more at home in the hospital by providing dedicated, adequately equipped multifunctional rooms and various activities and events.
Psychological support: For many years, we have known that proper management of adolescents with cancer also demands a medical staff with particular skills to cope with the complex psychological world of teenagers and the dramatic psychological impact of a cancer diagnosed at this age. Providing psychological support was consequently considered a fundamental aspect of our Youth Project. We are convinced that an important initial psychological management effort must involve the whole medical team (doctors and nursing staff, as well as social workers and teachers) in providing emotional support for adolescents faced with the anguish associated with a diagnosis of cancer and the prospect of therapies, and also to identify cases needing specialist counseling. The unit’s staff also receive specific training on these issues at meetings and courses. Clinical psychology specialists represent the second level of intervention and three such specialists are permanent staff members routinely available on a daily basis and working in close cooperation with the other members of staff to establish a genuine, ongoing relationship with patients. One of our clinical psychologists is dedicated specifically to adolescent patients and meets all new cases when they are admitted to the unit.
Fertility and sexuality: Preserving fertility is a major issue for AYA patients needing radiation to the gonads and chemotherapy regimens containing alkylating agents. Cooperation with gynecology departments at other hospitals in Milan enables a sperm cryopreservation service to be routinely offered to men at risk of temporary or permanent azoospermia before they undergo cytotoxic therapy, and, more recently, cryopreservation of oocytes. It is very important to tell patients about the risks to their fertility and the psychologist is usually involved in doing so, because potential damage to their reproductive capacity can have a devastating impact on young people. Another major issue concerns the possible impact of cancer on an individual’s psychosexual identity, maturation, and sexual function,30 and this is another area of intervention for our psychologists.
Social support and school: Schooling activities are fundamental in reducing teenagers’ maladaptive reactions to their disease and avoiding the negative impact in their future social life of losing a year at school. Three levels of intervention are organized: a) efforts to enable patients to attend their own school regularly, whenever possible; b) a hospital-based school for when patients are admitted to hospital or obliged to stay far away from their homes for lengthy periods, e.g. patients coming from outside the area to receive radiotherapy; and c) a “home schooling” program for patients unable to attend school. Four teachers (including a high-school teacher) and 5 educators are part of the unit’s team and cooperate directly with patients’ own school teachers. When dealing with young adults, the unit’s team may also need to address problems relating to a patient’s job and our social workers have a major part to play. The unit’s staff includes one social worker, who welcome all inpatients or outpatients and their families when they first come to the unit. For adolescents, the initial talk with the social worker is often the first step they take to reorganize their lives around the new needs stemming from the diagnosis of their tumor. Social worker has an essential role in helping families in various ways: they provide information on social and economic support opportunities, helping to deal with the related paperwork; they arrange for hospitality for families coming from other regions; and they provide support for foreign patients.
Spaces: Since the “medical” spaces used for adolescent inpatients and outpatients at our pediatric oncology unit have remained the same as for children, the Youth Project has focused on providing tailored “recreational” spaces by converting three rooms previously used for other purposes (two laboratories and a nurses’ locker room):
• one is now a 30 m2 multifunctional room for socializing and recreation with couches, TVs, computers and Internet connections, musical instruments, a library with books, magazines, and DVDs, a radio, and a corner for face make-up;
• one is a 20 m2 classroom with computers, a quiet room where adolescents can go to study (alone or with a teacher) or to read;
• finally, a 30 m2 gym will be built on the same floor as the inpatients ward, with an exercise bike, a rowing machine, treadmill and various other equipment. A personal trainer with specific skills in physiotherapy and the management of disabled patients will be periodically available to assist patients at the gym.
These spaces have been devised as places where adolescent and young adult patients can take some time off and not be disturbed, where they can interact with their peers and organize their own activities; these areas will be accessible only to 15-25 year-old patients (and possibly to their friends), not to parents or younger patients.
Activities: Various activities, events and courses (e.g. arts, music, photography, make-up, new technologies) for adolescent and young adult patients (“Magic Time”) have been planned. In particular, with the collaboration of various professionals who work with the patients, we have started with the project of a stylist collection made by teenagers, with its own brand (B.LIVE), a planned fashion parade, and a photographic book.
Philanthropic financial support: The limited budget of hospital administrations has often been seen as the main obstacle to the development of any new scheme. Our project was created as an offshoot of the pediatric oncology unit partly to avoid additional costs for the INT. We are striving to the show the community and the mass media the potential indirect benefits of our program (new services, patient satisfaction, better enrollment in clinical trials) because other sources of funds have been needed to prepare the spaces dedicated to the project. A charity called the Associazione Bianca Garavaglia (ABG) has been supporting our unit for 25 years and recently adopted the Youth Project as its main objective. Like other charities elsewhere, the ABG has made an important contribution not only to covering the costs, but also to stimulating new ideas and actions. More recently, the ABG has been helped by another partner, the Near/Magica Cleme Foundation, which focuses particularly on organizing activities and events.
Access to care after cancer therapy: The issue of access to appropriate medical care for teenagers and young adults who have successfully completed their cancer therapy is a major challenge for a dedicated AYA program. Most of these patients require careful long-term monitoring because of the risks of relapse and sequelae, but competent and appropriate psychosocial follow-up is needed as well, partly to identify unexpressed needs and any psychopathological consequences of their cancer’s diagnosis and treatment, which can significantly affect these patients’ future life, and partly to help adolescents cured of cancer to arrive at an independent adulthood. Various models have been suggested for an adolescent’s access to care after cancer therapy and the transition from a child-oriented to an adult-oriented healthcare system has sometimes reportedly been traumatic for patients. For many years, our unit has adopted flexible models that are adapted to patients’ different ongoing needs in the light of their prior clinical history. Long-term survivors continue to be managed by the physicians who first treated them and, although two permanent members of staff are especially dedicated to this service, all clinicians are involved in the follow-up. Visits are scheduled according to the characteristics of each patient’s tumor and its treatment, and are generally protracted up to the tenth year after completing the cancer treatment, irrespective of the patient’s age. Financial support to cover travelling expenses may be available for needy families. Afterwards, follow-up is tailored to the different situations based on at least three possible options:
• yearly contact by phone for “low-risk” cases: i.e. patients who were not heavily treated (no radiation or alkylating agents), or who carry no risk of functional sequelae;
• in selected cases, when a specific expertise is required (i.e. melanoma patients are probably more adequately monitored by dermatologists), a transfer to INT departments for adults is proposed (single-site switch model), although the link with the pediatric staff is maintained in order to update the pediatric oncology database and support the patient’s transition;
• for “high-risk” patients there are dedicated programs, e.g. physical, neurological and psychological rehabilitation programs for survivors of brain tumors, accurate cardiologic monitoring for patients treated with anthracyclines, endocrine function monitoring, early breast screening after radiotherapy to the chest wall (and, more in general, for radiation-induced second neoplasms).
The Italian AIEOP Committee on Adolescents
In the light of other research, the AIEOP investigated how many 15-19 year-olds were treated at pediatric oncology units, as compared with the numbers expected to be seen in Italy judging from incidence rates drawn from population-based cancer registries. It became clear that the AIEOP was failing to enroll adolescents in its trials: the ratio of observed to expected cases was only 0.10 for adolescents, as opposed to 0.77 for children up to 14 years old. An AIEOP Committee on Adolescents was consequently founded to explore the reasons why adolescents were under-represented in AIEOP clinical trials and to seek to improve this situation. This Committee was coordinated by our unit. First, we conducted a survey to assess the Italian pediatric oncology units’ adoption of inflexible upper age limits, finding that many centers set upper limits of 16, 15, or even 14 years of age, thus barring the way for adolescents to be admitted to AIEOP centers. The Committee’s actions are now focusing on various issues:
• increasing the number of adolescents referred to pediatric oncology units: an official document has been written to send to AIEOP centers with a view to removing administrative barriers and raising upper age limits for patient admission;
• improving awareness: a press release has been launched on adolescent access to care, a brief documentary video has been uploaded on YouTube, and various conferences have been organized; a document to send to the Ministry of Health, universities and hospitals has been prepared;
• addressing specific issues: links have been established with other AIEOP working groups to define adolescent-specific aims in their protocols, and adolescent-focused biological studies have been planned;
• cooperation with adult medical oncologists: cooperative schemes with adult cancer units have been developed because it has become clear that raising the upper age limits for pediatric centers and protocols can only really help if groups of adult patients are involved as well (to give an example, a protocol for treating adult RMS according to a pediatric-like strategy has recently been arranged in cooperation with the Italian Sarcoma Group).
- Ferrari A, Bleyer A. Participation of adolescents with cancer in clinical trials. Cancer Treat Rev 2007; 33: 603-608.
2. Ferrari A, et al. Starting an AYA program: some success stories and some obstacles to overcome. J Clin Oncol 2010; 28:4850-4857.
3. Gatta G, et al. Survival of European children and young adults with cancer diagnosed 1995-2002. Eur J Cancer 2009;45:992-1005
4. Ferrari A, et al. Adolescents with cancer in Italy: entry into the national cooperative paediatric oncology group AIEOP trials. Eur J Cancer 2009; 45:328-334.
5. Ferrari A, et al. Upper age limits for accessing pediatric oncology centers in Italy: a barrier preventing adolescents with cancer from entering national cooperative AIEOP trials. Pediatr Hematol Oncol 2012 ; 29:55-61
6. Ferrari A, et al. Rhabdomyosarcoma in adults. A retrospective analysis of 171 patients treated at a single institution. Cancer 2003;98(3):571-580
7. Collini P, et al. Papillary thyroid carcinoma of childhood and adolescence. A 30-year monoinstitutional series of the Istituto Nazionale Tumori of Milan. Pediatr Blood Cancer, 46(3):300-306, 2006.
8. Ferrari A, et al. Does melanoma behave better in younger children than in adults? A retrospective study on 33 cases of childhood melanoma from a single institution. Pediatrics 2005;115:649-654.
9. Ferrari A, et al. Colorectal carcinoma in children and adolescents: the experience of the Istituto Nazionale Tumori of Milan, Italy. Pediatr Blood Cancer 2008; 50:588-593.
10. Spreafico F, et al Survival of adults treated for medulloblastoma using paediatric protocols. Eur J Cancer 2005; 41:1304-1310.
11. Terenziani M, et al. Adult Wilms' tumor: a monoinstitutional experience and a review of the literature. Cancer 2004; 101:289-293.
12. Clerici CA, et al. Psychological referral and consultation for adolescents and young adults with cancer treated at a pediatric oncology unit. Pediatr Blood Cancer 2008; 51:105-109.
13. Ferrari A, et al. Symptom interval in children and adolescents with soft tissue sarcomas. Cancer 2010;116: 177-183
14. Clerici CA, et al. Videos on rhabdomyosarcoma on YouTube: an example of the availability of information on pediatric tumors on the web. J Pediatr Hematol Oncol, J Ped Hematol Oncol, 34(8):e329-31, 2012
15. Ferrari A, et al. Two cases of adolescents with paratesticular rhabdomyosarcoma inadequately treated: the problem of referral. J Adolesc Young Adult Oncol 2011;1:152-154.
16. Ferrari A, et al. The challenge of access to care for soft tissue sarcomas bridging pediatric and adult age: the Italian pediatric oncology view. Expert Rev Anticancer Ther. 2012;12:243-254.
17. Ferrari A, et al. The Youth Project at the Istituto Nazionale Tumori in Milan. Tumori 98(4):399-407, 2012