Active Breathing Control for Hodgkin’s Disease in Childhood and Adolescence: Feasibility, Advantages, and Limits

PURPOSE To assess the risk of subsequent malignant neoplasms among Hodgkin's disease patients diagnosed before 20 years of age in the five Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden). PATIENTS AND METHODS There were 1,641 Hodgkin's disease patients identified through the national cancer registries since the 1940s or 1950s. The patients were monitored for 17,000 person-years until the end of 1991. Expected figures were derived from the age-specific incidence rates in each country and standardized incidence ratios (SIR) were calculated. RESULTS A total of 62 subsequent neoplasms were diagnosed (SIR, 7.7; 95% confidence interval [CI], 5.9 to 9.9). The overall cumulative risk of subsequent neoplasms was 1.9% at the 10-year follow-up point, 6.9% at 20 years, and 18% at 30 years. There were 26 subsequent neoplasms among males (SIR, 6.5; 95% CI, 4.3 to 9.6) and 36 among females (SIR, 8.9; 95% CI, 6.2 to 12), of which 16 were breast cancers (SIR, 17; 95% CI, 9.9 to 28). High risks were seen for thyroid cancer (SIR, 33; 95% CI, 15 to 62), for secondary leukemia (SIR, 17; 95% CI, 6.9 to 35), and for non-Hodgkin's lymphoma (SIR, 15; 95% CI, 4.9 to 35). The relative risk increased from 3.3 (95% CI, 1.2 to 7.1) for Hodgkin's disease patients diagnosed in the 1940s and 1950s to 15 (95% CI, 7.4 to 27) in the 1980s. The highest risk of secondary leukemia (SIR, 68; 95% CI, 18 to 174) was seen among those diagnosed with Hodgkin's disease in the 1980s. CONCLUSION Patients who survive Hodgkin's disease at a young age are at very high relative risk of subsequent malignant neoplasms throughout their lives. In particular, the high relative risk of breast cancer following Hodgkin's disease in the teenage years calls for enhanced activity for early diagnosis.

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Second Cancers Among Long-Term Survivors of Hodgkin’s Disease Diagnosed in Childhood and Adolescence

Journal of Clinical Oncology ◽

10.1200/jco.2000.18.12.2435 ◽

2000 ◽

Vol 18 (12) ◽

pp. 2435-2443 ◽

Cited By ~ 255

Author(s):

Catherine Metayer ◽

Charles F. Lynch ◽

E. Aileen Clarke ◽

Bengt Glimelius ◽

Hans Storm ◽

...

Keyword(s):

Solid Tumors ◽

Late Effects ◽

Hodgkin's Disease ◽

Hodgkin’S Disease ◽

Cumulative Risk ◽

Childhood And Adolescence ◽

Acute Leukemias ◽

Second Cancers ◽

Long Term Survivors

PURPOSE: To quantify the risk of second cancers among long-term survivors of Hodgkin’s disease (HD) diagnosed before 21 years of age and to explore sex-, age-, and site-related differences. PATIENTS AND METHODS: We analyzed data from 5,925 pediatric HD patients, including 2,646 10-year and 755 20-year survivors, who were reported to 16 population-based cancer registries in North America and Europe between 1935 and 1994. RESULTS: A total of 157 solid tumors (observed/expected ratio [O/E] = 7.0; 95% confidence interval [CI], 5.9 to 8.2.) and 26 acute leukemias (O/E = 27.4; 95% CI, 17.9 to 40.2) were reported. Risk of solid tumors remained significantly increased among 20-year survivors (O/E = 6.6, observed [O] = 40, cumulative risk = 6.5%) and persisted for 25 years (O/E = 4.6, O = 15, cumulative risk = 11.7%). Temporal trends for cancers of thyroid, female breast, bone/connective tissue, stomach, and esophagus were consistent with the late effects of radiotherapy. Greater than 50-fold increased risks were observed for tumors of the thyroid and respiratory tract (one lung and one pleura) among children treated before age 10. At older ages (10 to 16 years), the largest number of second cancers occurred in the digestive tract (O/E = 19.3) and breast (O/E = 22.9). Risk of solid tumors increased with decreasing age at HD on a relative but not absolute scale. CONCLUSION: Children and adolescents treated for HD experience significantly increased risks of second cancers at various sites for 2 to 3 decades. Although our results reflect the late effects of past therapeutic modalities, they underscore the importance of lifelong follow-up of pediatric HD patients given early, more aggressive treatments.

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Subsequent malignancies in children and adolescents after treatment for Hodgkin's disease.

Journal of Clinical Oncology ◽

10.1200/jco.1995.13.3.603 ◽

1995 ◽

Vol 13 (3) ◽

pp. 603-609 ◽

Cited By ~ 98

Author(s):

O Beaty ◽

M M Hudson ◽

C Greenwald ◽

X Luo ◽

L Fang ◽

...

Keyword(s):

Radiation Therapy ◽

Solid Tumors ◽

Hodgkin's Disease ◽

Hodgkin’S Disease ◽

Late Complication ◽

Cumulative Risk ◽

Childhood And Adolescence ◽

Second Malignancies ◽

Multiagent Chemotherapy

PURPOSE We assessed the cumulative risk of malignancies following treatment for Hodgkin's disease in childhood and adolescence and investigated related patient and treatment characteristics. PATIENTS AND METHODS Medical records of 499 Hodgkin's disease patients treated between 1962 and 1993 were reviewed. There were 385 adolescents (> or = 10 years of age at diagnosis) and 114 preadolescents (< 10 years). Most patients (n = 346) were treated with radiation plus multiagent chemotherapy, while 30 received only chemotherapy and 123 only radiation therapy. Radiation doses ranged from 20 to 42 Gy. RESULTS At a median follow-up duration of 9 years (range, 0.1 to 27.4), 25 patients have had second malignancies: 19 solid tumors, four acute nonlymphoblastic leukemias (ANLLs), 1 non-Hodgkin's lymphoma (NHL), and one chronic myeloid leukemia (CML). Three patients have had a third malignancy. The estimated cumulative risk of second malignancies increased from 1.5% at 5 years to 7.7% at 15 years. All but two of the patients with second malignancies were > or = 10 years of age at initial diagnosis, which reflects the higher risk among patients treated for Hodgkin's disease as adolescents (P = .01). Second malignancies were more common among female patients (P = .0002), even when those breast cancer were excluded (P = .007), and in those treated for recurrent Hodgkin's disease (P = .02). Patients with ANLL/NHL were older at diagnosis of Hodgkin's disease than those with solid tumors, (median age, 18.3 v 13.8 years; P = .04). There was no difference between groups treated with radiation therapy alone, chemotherapy alone, or radiation plus multiagent chemotherapy. CONCLUSION Adolescents treated for Hodgkin's disease are at greater at risk of second malignancies than younger patients. Overall, adolescent females treated for recurrent Hodgkin's disease appear to be at greatest risk, while preadolescents appear to be protected from this late complication.

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The effect of mediastinal irradiation on cardiac function of patients treated during childhood and adolescence for Hodgkin's disease.

Journal of Clinical Oncology ◽

10.1200/jco.1987.5.2.239 ◽

1987 ◽

Vol 5 (2) ◽

pp. 239-245 ◽

Cited By ~ 69

Author(s):

D M Green ◽

R L Gingell ◽

J Pearce ◽

A M Panahon ◽

J Ghoorah

Keyword(s):

Cardiac Dysfunction ◽

Hodgkin's Disease ◽

Hodgkin’S Disease ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Childhood And Adolescence ◽

Ventricular Ejection Fraction ◽

Cardiothoracic Ratio ◽

Mediastinal Irradiation ◽

Pericardial Thickening

To determine the frequency of cardiac dysfunction in patients treated during childhood or adolescence with mediastinal irradiation for Hodgkin's disease (HD), 28 patients underwent cardiac evaluation 19 to 182 months (median, 90 months) after the completion of radiation therapy. No patient had symptoms of cardiac disease. All were normotensive. All patients had a normal cardiothoracic ratio. There were no abnormalities of voltage or rhythm in the ECGs. The left ventricular end diastolic volume was increased in 19.2% of patients, none of whom had evidence of impaired left ventricular function. The left ventricular ejection fraction (LVEF) was increased in 15.3% of patients. No patient had a decreased LVEF. Pericardial thickening was demonstrated on echocardiograms from 12 of 28 patients (42.9%). Thickening was more frequent among those patients observed for 72 or more months (47.1%; eight of 17) than among those with shorter periods of follow-up (36.4%; four of 11). This study demonstrates that cardiac dysfunction is an infrequent sequela of mediastinal irradiation following treatment using an equally weighted, anterior-posterior technique. Longitudinal study of these patients will be necessary to determine the clinical significance and evolution of the occult pericardial thickening that was identified.

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Cardiac disease following treatment of Hodgkin's disease in children and adolescents.

Journal of Clinical Oncology ◽

10.1200/jco.1993.11.7.1208 ◽

1993 ◽

Vol 11 (7) ◽

pp. 1208-1215 ◽

Cited By ~ 347

Author(s):

S L Hancock ◽

S S Donaldson ◽

R T Hoppe

Keyword(s):

Children And Adolescents ◽

Cardiac Disease ◽

Hodgkin's Disease ◽

Hodgkin’S Disease ◽

Combined Treatment ◽

Childhood And Adolescence ◽

Neoplastic Disease ◽

Cardiac Diseases ◽

Risk Of Death ◽

Mediastinal Radiation

PURPOSE Cardiac disease is second only to neoplastic disease as a cause of death after treatment for Hodgkin's disease. This study evaluates the risks of cardiac disease following treatment of Hodgkin's disease during childhood and adolescence. PATIENTS AND METHODS We reviewed records of 635 patients treated for Hodgkin's disease before 21 years of age at Stanford University between 1961 and 1991. Mean age was 15.4 years; mean follow-up duration was 10.3 years, representing 6,564 person-years of observation. Relative risks (RRs) of death from cardiac diseases were calculated by comparison with age-, sex-, and race-matched general population rates from United States decennial life-tables. RESULTS Twelve patients have died of cardiac disease (RR, 29.6; 95% confidence interval [CI], 16.0 to 49.3), including seven deaths from acute myocardial infarction ([AMI] RR, 41.5; 95% CI, 18.1 to 82.1), three from valvular heart disease, and two from radiation pericarditis/pancarditis. Thus far, the risk of AMI death was comparable after radiation alone (RO) or after chemotherapy and radiation (CM) (RO-AMI RR, 52.2; 95% CI, 21.1 to 108.7; CM-AMI RR, 21.1; 95% CI, 0.0 to 104.4; P = .6). The risk for other cardiac death (CD) tended to be higher after combined treatment (RO-non-AMI RR, 7.4; 95% CI, 0.0 to 36.5; CM-non-AMI RR, 45.8; 95% CI, 14.4 to 110.6; P = .1). Deaths occurred 3 to 22 years after patients received 42 to 45 Gy to the mediastinum between 9 and 20 years of age. There have been no deaths among patients treated to lower mediastinal radiation doses or without mediastinal radiation. There are no clear trends in the latency of risk. One hundred six nonfatal abnormalities have also been diagnosed. CONCLUSION Mediastinal radiation of 40 to 45 Gy increases the risk of death from coronary artery and other cardiac diseases. The risk increases within 5 years of irradiation. These observations support combined-modality, low-dose irradiation regimens in children and adolescents and suggest the need for careful cardiac screening of treated patients.

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Hodgkin's disease in childhood and adolescence: results of chemotherapy-radiotherapy in clinical stages IA-IIB.

Journal of Clinical Oncology ◽

10.1200/jco.1985.3.11.1495 ◽

1985 ◽

Vol 3 (11) ◽

pp. 1495-1502 ◽

Cited By ~ 22

Author(s):

P Cramer ◽

J M Andrieu

Keyword(s):

Complete Remission ◽

Hodgkin's Disease ◽

Bone Growth ◽

Hodgkin’S Disease ◽

Clinical Stage ◽

Childhood And Adolescence ◽

Growth Defects ◽

Clinical Stages ◽

Mediastinal Involvement ◽

Number Of Cycles

From April 1972 to May 1980, 72 children and adolescents (aged 5 to 19 years old, median 16) with Hodgkin's disease, clinical stages IA-IIB (IA, 18; II2A, two areas involved on the same side of the diaphragm, 23; II3+A, three areas or more, 16; IIB, 15) were prospectively treated in two successive clinical trials (H 72 and H 77). Clinical stages IA and II2A received three courses of mechlorethamine, Oncovin, procarbazine, and prednisone (MOPP) and supradiaphragmatic radiotherapy (40 Gy), and no laparotomy was performed. Clinical stages II3+A and IIB received either six cycles of MOPP (H 72), three cycles of MOPP, or three cycles of CCNU, vinblastine, procarbazine, and prednisone (CVPP) (H 77) and subsequently had a laparotomy followed by supradiaphragmatic radiotherapy and a lumboaortic field if results of laparotomy were positive. Patients without evidence of mediastinal involvement did not have mediastinal radiotherapy. At the completion of therapy, the disease in 70 of 72 patients was in complete remission (one failure, one death during treatment). Eight patients relapsed (in situ, 1; marginal, 1; nonirradiated subdiaphragmatic area, 6) after three to 57 months of complete remission (median 20 months); one patient died after relapse. There were three deaths after complete remission of the disease (infection, two; acute nonlymphocytic leukemia [ANLL], one). As of June 1984 the median follow-up was 82 months (range, 49 to 145 months), the actuarial probabilities for survival and freedom from relapse for all patients being 91.6% and 87.6%, respectively. There was no statistical difference according to clinical stage, age (greater than 15 or less than 15 years), sex, or number of cycles of chemotherapy (six or three). Bone growth defects related to radiotherapy were reduced particularly in the 29 patients who did not receive mediastinal radiotherapy. None of these patients had a mediastinal relapse. Azoospermia was the rule for the male patients studied, but young girls and young women retained reproductive integrity.

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