To report the Institut Gustave Roussy brachytherapy (BT) experience in the management of vulval and vaginal rhabdomyosarcoma with special emphasis on long-term outcome.
Between 1971 and 2005, the ...data concerning 39 girls who had undergone BT as a part of their treatment were retrospectively analyzed. Of the 39 girls, 20 had been treated before 1990, when the BT volume encompassed the initial tumor extension. After 1990, only residual disease was included in the BT volume. Side effects were classified using the Common Terminology Criteria for Adverse Events, version 3.0.
The median age was 16.3 months at diagnosis. Vaginal or vulvar rhabdomyosarcoma was diagnosed in 26 and 6 patients, respectively. The median follow-up was 8.4 years. The 5-year overall survival rate was 91%. Of the 39 patients, 6 developed a relapse. Of the 20 patients treated before 1990, 6 experienced Grade 1-2 renal/genitourinary function symptoms and 75% developed sequelae, in the form of vaginal or urethral sclerosis or stenosis. Four patients received follow-up treatment for psychological disorders. Of the 19 patients treated after 1990, 2 developed acute side effects, with maximal Grade 1-2 renal/genitourinary function symptoms, and 20% developed vaginal or urethral sclerosis or stenosis. Two cases of psychological disturbances were also documented.
Reducing the BT volume coverage, better indications for surgery, and more efficient chemotherapy, all combined within a multidisciplinary approach, tended to improve results in terms of both survival and long-term sequelae.
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GEOZS, IJS, NUK, OILJ, UL, UM, UPUK
To investigate the roles of radiation therapy and chemotherapy in the occurrence of subsequent leukemia after childhood cancer.
We analyzed data from a case-control study with 35 cases and 140 ...controls. The active bone marrow (ABM) was segmented into 19 compartments, and the radiation dose was estimated in each. The chemotherapy drug doses were also estimated to enable adjustments. Models capable of accounting for radiation dose heterogeneity were implemented for analysis.
Univariate analysis showed a significant trend in the increase of secondary leukemia risk with radiation dose, after accounting for dose heterogeneity (P=.046). This trend became nonsignificant after adjustment for doses of epipodophyllotoxins, alkylating agents, and platinum compounds and the first cancer on multivariate analysis (P=.388). The role of the radiation dose appeared to be dwarfed, mostly by the alkylating agents (odds ratio 6.9, 95% confidence interval 1.9-25.0). Among the patients who have received >16 Gy to the ABM, the radiogenic risk of secondary leukemia was about 4 times greater in the subgroup with no alkylating agents than in the subgroup receiving ≥10 g/m(2).
Notwithstanding the limitations resulting from the size of our study population and the quite systematic co-treatment with chemotherapy, the use of detailed information on the radiation dose distribution to ABM enabled consideration of the role of radiation therapy in secondary leukemia induction after childhood cancer.
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GEOZS, IJS, NUK, OILJ, UL, UM, UPUK
The presence of metastasis is a major prognostic factor in Ewing tumor (ET). The relapse pattern of patients with localized tumors has long indicated that cases with disseminated ET cells escape ...detection at diagnosis. ET cells are characterized by specific gene fusions that can be detected with high sensitivity and specificity by reverse transcriptase polymerase chain reaction (RT-PCR).
RT-PCR targeting EWS-FLI-1 or EWS-ERG transcripts was used to search for occult tumor cells in peripheral blood (PB) and bone marrow (BM) at diagnosis in 172 patients with ET, and the prognostic significance of this parameter was assessed.
As we suggested previously in a smaller series of patients, RT-PCR positivity of the BM was correlated with a high risk of adverse outcome in the overall study population (P =.007). More interestingly, among patients with otherwise localized tumors, BM micrometastasis also predicted significantly poorer disease-free survival rates (P =.043). The presence of circulating tumor cells (CTC) was more frequently observed in patients with large tumors (P =.006). CTC were associated with a poor outcome among patients with clinically localized disease (P =.045). Patients with clinically localized disease and peripheral occult tumor cells as evidenced by BM and/or PB RT-PCR positivity had axial or proximal tumors and experienced relapses at a systemic rather than at a local level.
Patients with localized ET and BM micrometastasis or CTC are comparable to patients with metastases in terms of the localization of the primary tumor, outcome, and relapse pattern.
To explore a strategy by which radiotherapy (RT) could be avoided in the treatment of young children with parameningeal rhabdomyosarcoma (PM RMS).
Fifty-nine children (median age, 2 years 3 months) ...with nonmetastatic cranial PM RMS were treated in the International Society of Pediatric Oncology MMT 89 and 95 trials between 1989 and 2003.
Five-year EFS and OS rates were 46% and 54%, respectively, for the whole group. No standard clinical or pathologic variables had prognostic impact. Fifty (85%) of 59 patients achieved complete local control either with (n = 28) or without (n = 22) RT administered as part of their primary treatment. Nine patients (15%) did not achieve local control (four of whom had had RT), and all died. Patients who received RT had a significantly superior 5-year EFS rate compared with patients who did not receive RT (59% v 28%, respectively). Twenty-three patients (48%) experienced relapse at a median interval of 15 months. Ultimately, only seven patients (12%) were cured without RT, although this represented 32% of those who achieved local control with initial chemotherapy.
Despite concerns about the late effects of its use in young children, cure of PM RMS remains unlikely without systematic use of RT. The accurate prediction of the small subset of patients who achieve local control without RT and who do not experience relapse would provide an opportunity for a minority of patients to avoid RT.
Abstract Purpose This study aimed at comparing gonadal toxicity of ifosfamide versus cyclophosphamide received during childhood. Methods The evaluation was based on basal FSH measurement. LH and ...testosterone were also measured in most of the patients. One hundred patients had received ifosfamide and 59 had received cyclophosphamide. Results Median age at treatment was 11.2 years. The median interval since treatment was 10.7 years (range 4.1–20.2) and median age at evaluation was 21.4 years (17.5–36.1). The median dose of ifosfamide and of cyclophosphamide was 54 g/m2 (18–114) and 8.3 g/m2 (4.6–22), respectively. All but two males had normal testosterone levels. FSH was abnormal in 28/59 patients (47.5%) after receiving cyclophosphamide and was within the normal range in 94/100 patients (94%) after receiving ifosfamide. Conclusions These results show that ifosfamide is associated with a lower risk of gonadal damage than cyclophosphamide. The risk of abnormal FSH increased with the cumulative dose of cyclophosphamide.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
After successful treatment of cancers in childhood, the occurrence of second malignant neoplasm (SMN) came to the fore. Few studies have considered the relationship between the radiation dose ...received and the risk of developing an SMN. To take into account the heterogeneity of the dose distribution so as to evaluate the overall risk of an SMN after a childhood cancer, we therefore focused on the integral dose restricted to the irradiated fields.
The study was performed in a cohort of 4,401 patients who were 3-year survivors of all types of childhood cancer treated between 1947 and 1986 in France and Great Britain. For each patient, the integral dose was estimated for the volume inside the beam edges.
We found a significant dose-response relationship between the overall risk of an SMN and the estimated integral dose. The excess relative risk for each incremental unit of the integral dose was only 0.008 in a linear model and 0.017 when a negative exponential term was considered, when adjusted for chemotherapy. The risk of SMN occurrence was 2.6 times higher in the case of irradiation. However among patients who had received radiotherapy, only those who had received the highest integral dose actually had a higher risk.
The integral dose in our study cannot be considered as a good predictor of later risks. However other studies with the same study design are obviously needed to evaluate the use of the integral dose as a tool for decision making concerning different radiotherapy techniques.
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GEOZS, IJS, NUK, OILJ, UL, UM, UPUK
To assess the specific role of treatment and type of first cancer (FC) in the risk of long-term subsequent breast cancer (BC) among childhood cancer survivors.
In a cohort of 1,814 3-year female ...survivors treated between 1946 and 1986 in eight French and English centers, data on chemotherapy and radiotherapy were collected. Individual estimation of radiation dose to each breast was performed for the 1,258 patients treated by external radiotherapy; mean dose to breast was 5.06 Gy (range, 0.0 to 88.0 Gy) delivered in 20 fractions (mean).
Mean follow-up was 16 years; 16 patients developed a clinical BC, 13 after radiotherapy. The cumulative incidence of BC was 2.8% (95% CI, 1.0% to 4.5%) 30 years after the FC and 5.1% (95% CI, 2.1% to 8.2%) at the age of 40 years. The annual excess incidence increased as age increased, whereas the standardized incidence ratio decreased. On average, each Gray unit received by any breast increased the excess relative risk of BC by 0.13 (< 0.0 to 0.75). After stratification on castration and attained age, and adjusting for radiation dose, FC type, and chemotherapy, a higher risk of a subsequent BC was associated with Hodgkin's disease (relative risk, 7.0; 95% CI, 1.4 to 30.9).
The reported high risk of BC after childhood Hodgkin's disease treatment seems to be due not only to a higher radiation dose to the breasts, but also to a specific susceptibility.
The temporal pattern in mortality from late second malignant neoplasms in solid childhood cancer survivors, according to the type of treatment, has not been investigated in detail.
We studied 4,230 ...5-year survivors of solid childhood cancer diagnosed between 1942 and 1986 in France and the United Kingdom. Complete clinical, chemotherapy, and radiotherapy data were recorded and the integral radiation dose was estimated for 2,701 of the 2,948 patients who had received radiotherapy.
After a median follow-up of 28 years, 134 fatal events were due to second malignancies, compared with the 13.3 expected from the general France-UK population rates. The standardized mortality ratio was of a similar magnitude after radiotherapy alone and chemotherapy alone and higher after both treatments. The standardized mortality ratio decreased with follow-up, whereas the absolute excess risk increased significantly over a period of at least 25 years after the first cancer. This temporal pattern was similar after chemotherapy alone, radiotherapy alone, or both treatments. We observed a similar long-term temporal pattern among survivors who had died of a second malignant neoplasm of the gastrointestinal tract and breast. Survivors who had received a higher integral radiation dose during radiotherapy were at a particularly high risk, as well as those who had received alkylating agents and epipodophyllotoxins.
Five-year survivors of childhood cancer run a high long-term mortality risk for all types of second malignant neoplasms whatever the treatment received and require careful long-term screening well beyond 25 years after the diagnosis.
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