Robert M. Weetman

Twenty years of follow-up among survivors of childhood and young adult acute myeloid leukemia: A report from the Childhood Cancer Survivor Study

Limited data exist on the comprehensive assessment of late medical and social effects experienced by survivors of childhood and young adult acute myeloid leukemia (AML).

Effect of nutrition staging on treatment delays and outcome in stage IV neuroblastoma

The effect of the state of nutrition of 18 children with Stage IV neuroblastoma at diagnosis and during initial therapy, was evaluated with respect to treatment delays, drug dosage alterations, tumor response, days to first event (relapse or death), and survival. All patients received similar therapy (CCSG protocol CCG 371). Based on nutrition staging at diagnosis, nine were classified as malnourished; four were randomized to receive total parenteral nutrition (TPN) and four peripheral parenteral nutrition plus enteral nutrition for 28 days (through 2 chemotherapy courses), and one died before randomization. Nine were nourished at diagnosis; seven received a comprehensive enteral nutrition program and two received TPN. By life‐table analysis, the duration of remission was significantly greater in the nourished than the malnourished (P < 0.01) and a trend towards improved survival was evident at one year (P = 0.08). The median length of survival for children nourished at diagnosis was approximately 12 months, whereas those malnourished had a median survival of only 5 months. Nine children remained nourished or were becoming renourished during the first 21 days of therapy, and one of these had treatment delays and decreased drug dosages. Seven were becoming malnourished or remained malnourished during this period and six had treatment delays (P < 0.01). These data support the idea that nutrition staging at diagnosis and during initial treatment should be an integral part of protocol design and initial evaluation of children with Stage IV neuroblastoma.

Treatment of Wilms tumor relapsing after initial treatment with vincristine, actinomycin D, and doxorubicin. A report from the national Wilms tumor study group

We evaluated the use of alternating cycles of cyclophosphamide/etoposide and carboplatin/etoposide in children entered on National Wilms Tumor Study (NWTS)‐5 who were diagnosed between August 1, 1995 and May 31, 2002 and who relapsed after chemotherapy with vincristine, actinomycin D, and doxorubicin (VAD) and radiation therapy (DD‐4A).

Treatment of Wilms tumor relapsing after initial treatment with vincristine and actinomycin D: A report from the National Wilms Tumor Study Group

NWTS‐5 was a multi‐institutional clinical trial for patients less than 16 years of age at diagnosis with specific renal neoplasms who were diagnosed between August 1, 1995 and May 31, 2002. A uniform approach to the treatment of patients with relapse was employed.

Latent onset of clinical pancreatitis in children receiving l‐asparaginase therapy

The pancreatic toxicity of L‐asparaginase manifested in 43 children (48 trials of therapy) is presented. Seven of the 43 children (16.2%) developed evidence of pancreatitis. Five of the 43 children developed transient hyperglycemia or diabetes mellitus (11.6%). Pancreatitis secondary to L‐asparaginase therapy has been reported to occur during administration of the drug. In contrast, 4 of our 7 patients with acute pancreatitis secondary to L‐asparaginase developed their disease 4 days to 10 weeks after therapy was stopped. Five of these 7 patients who developed pancreatitis were females greater than 9 years of age. Since estrogens potentiate activity of L‐asparaginase in vivo in animal studies, these data raise the question that pubertal females may be at greater risk of acquiring pancreatic toxicity from L‐asparaginase than their male counterparts.

Rhabdomyosarcoma in childhood: Analysis of survival in 98 cases

Ninety-eight infants and children with rhabdomyosarcoma were analyzed for age, stage, site, and therapy as they relate to survival. Age and sex were not factors. Survival was 91% (10/11) for Stage I, 86% (13/15) for Stage II, 35% (12/34) for Stage III, and 5.2% (2/38) for Stage IV. Overall survival was 37% (37/98); however, 75% had advanced disease at diagnosis. Primary tumor site was genitourinary (GU) (31), extremity (17), head-neck (14), trunk (14), orbit (8), paratesticular (4), retroperitoneal (3), paraspinal (3), buttocks (3), and perianal (1). Survival was favorable in orbital, paratesticular, and (GU) sites. Survival was 20% (9/45) before and 52% (28/53) after chemotherapy and irradiation. The only survivors had embryonal cell histology. Tumor stage and site are important prognostic indicators. Chemotherapy improves survival in Stage I (91%) and Stage II (86%) and shrinks bulky Stage III tumors allowing less radical procedures in selected sites (e.g., GU). Survival is poor in Stage III (35%) and dismal in Stage IV (5.2%) despite combined therapy. Relapse was fatal despite attempts at second-look resection, and altered chemotherapy and irradiation.

Metastatic neuroblastoma: Factors influencing survival

Ninety of 142 patients (63%) with neuroblastoma had metastatic disease at the time of diagnosis. Seventy-four (52%) patients had stage IV disease and 16 (11%) had stage IV-S. Survival in stage IV-S was 75% (12/16). Four deaths occurred in infants under 6 wk of age, three of whom had bone marrow involvement. Deaths were related to respiratory insufficiency and sepsis rather than progression of disease. All patients over 6 wk of age survived with resection of primary tumor and skin metastases. Survivors had slow, spontaneous regression of tumor over a 6–15 mo period regardless of treatment. Bone marrow involvement with tumor reduces the otherwise favorable outlook for patients with stage IV-S disease. This suggests that patients with bone marrow metastases be excluded from stage IV-S classification. Of 74 patients with stage IV disease, 49 were boys and 25 were girls, with a mean age of 37 mo. Site of primary tumor was adrenal in 40 patients, paraspinal in 27, and mediastinal in seven. Prior to 1965, the mean survival was 3 mo. Since that time, with chemotherapy programs, the mean survival is 20 mo with 18% of patients surviving more than 2 yr. While there is little objective evidence that chemotherapy increases the cure rate, it can reduce tumor size, cause histologic maturation of tumor, and result in considerable palliation. There are six survivors (8%) disease-free longer than 2 yr. Two were under 13 mo of age and three over 6 yr. All had delayed primary or second-look tumor resections, and five had bone marrow involvement, but only two had bone cortex metastases. These observations suggest that resection of bulk tumor and histologic evidence of tumor maturation, particularly in patients with only bone marrow involvement, may result in an occasional survival. These data further suggest a modification in the staging of metastatic cases into three groups: stage IV-M, bone marrow involvement only; stage IV-B, metastatic disease including bone cortex; and stage IV-S, metastatic disease involving liver and skin only.

Long-term outcomes for infants with very low risk wilms tumor treated with surgery alone in national wilms tumor study-5

Objective:To determine the event-free survival (EFS) and overall survival (OS) of children with very low risk Wilms tumor (VLRWT) treated with surgery only. Background:Previous studies suggested that postoperative chemotherapy had not improved the prognosis of children with VLRWT. A total of 77 children <24 months of age with small (<550 g) Stage I favorable histology Wilms tumors were treated with surgery only. This study was closed based on stopping rules to ensure that the 2-year EFS was ≥90%. Methods:A total of 77 children were assessed for EFS and OS. Of these patients, 21 enrolled at the time of closure were recalled, treated with dactinomycin and vincristine (regimen EE4A), and censored for analysis thereafter. About 111 children subsequently treated with EE4A were available for comparison. Results:Median follow-up of surviving patients was 8.2 years for surgery only (range, 1.9–11.8 years) and 5.2 years for the EE4A group (range, 1.6–8.9 years). The estimated 5-year EFS for surgery only was 84% (95% confidence interval [CI]: 73%, 91%); for the EE4A patients it was 97% (95% CI: 92%, 99%, P = 0.002). One death was observed in each treatment group. The estimated 5-year OS was 98% (95% CI: 87%, 99%) for surgery only and 99% (95% CI: 94%, 99%) for EE4A (P = 0.70). Conclusion:The surgery-only EFS was lower than anticipated but, coupled with a much higher than anticipated salvage rate of the chemotherapy naive patients whose disease recurred, led to an observed long-term OS equivalent to that seen with 2-drug chemotherapy. This approach to the treatment of patients with VLRWT eliminates the toxic side-effects of chemotherapy for a large majority of patients. A follow-up study is underway to confirm these findings.

Short- and long-term effectiveness of enteral and parenteral nutrition in reversing or preventing protein-energy malnutrition in advanced neuroblastoma a prospective randomized study

The effectiveness of enteral and parenteral nutrition regimens in preventing or reversing protein–energy malnutrition (PEM) and in preventing treatment delays was evaluated in 32 children receiving treatment for newly diagnosed Stage III (3 patients) and IV (29 patients) neuroblastoma. Ten of 18 malnourished patients were randomized to central parenteral nutrition (CPN) and 8 to peripheral parenteral nutrition (PPN) plus enteral nutrition for 4 weeks and then received enteral nutrition (EN: intense nutrition counselling, oral foods and supplements) for weeks 5 through 10. Ten of 14 nourished patients received EN and 4 CPN for 4 weeks and EN thereafter. Dietary, anthropometric and biochemical measurements were determined for weeks 0, 1, 2, 3, 4, 7, and 10 for 24 patients who completed the protocols. In malnourished patients, both CPN (seven patients) and PPN (seven patients) were effective in reversing PEM in the first 4 weeks; thereafter, EN effectively maintained nutritional gains in both groups. In nourished patients, EN (seven patients) was not as effective as CPN (three patients) in preventing PEM during the first 4 weeks; afterwards, EN maintained gains in the CPN group but did not promote needed increases in weight nor fat reserves in the EN group. Patients supported by parenteral nutrition (PN, weeks 1–4) had fewer treatment delays (2/17, 12%) than EN patients (4/7, 57%, P <0.05). These data indicate that PN reverses or prevents PEM and prevents treatment delays during the first 4 weeks of intense oncologic treatment and provides nutritional benefits which can be maintained with EN thereafter.

Nutritional Support of Children with Neoplastic Diseases

There are numerous factors promoting the development of PEM in the child with cancer. Some of these factors are related to the tumor, many to the treatment itself, and some to failure of recognition of PEM. Not all children with cancer are at great risk for the development of PEM. These patients must be monitored and supported with comprehensive enteral programs. Children who have developed or are at risk for PEM must be identified and supported with CPN or PPN plus CEN during early intensive periods of treatment and during the later phases of abdominal radiotherapy, operative resection of tumor, or relapse. The decision to institute CPN must be based not only on the childs current nutritional status but also on the nature of the therapy he or she is soon to receive and the likelihood that he or she will be able to maintain an adequate intake during that therapy. Realistic goals must be set for nutritional support. The value of nutritional intervention lies in its ability to correct or prevent the development of adverse effects related to PEM. This support is hoped to contribute to improved tolerance of therapy, increased energy to complete normal day-to-day activities, and an improved sense of well-being for the child. If these goals have been accomplished, then the nutritional therapy has been successful.