Malignant Breast Tumors After Radiotherapy for a First Cancer During Childhood

Purpose 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. Patients and Methods 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). Results 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). Conclusion 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.

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Mantle irradiation alone for selected patients with laparotomy-staged IA to IIA Hodgkin's disease: preliminary results of a prospective trial.

Journal of Clinical Oncology ◽

10.1200/jco.1995.13.4.947 ◽

1995 ◽

Vol 13 (4) ◽

pp. 947-952 ◽

Cited By ~ 23

Author(s):

P M Mauch ◽

G P Canellos ◽

L N Shulman ◽

B Silver ◽

N J Tarbell ◽

...

Keyword(s):

Overall Survival ◽

Hodgkin's Disease ◽

Hodgkin’S Disease ◽

Prospective Trial ◽

Results Of Treatment ◽

Early Results ◽

Negative Laparotomy

PURPOSE To determine the feasibility of omitting prophylactic paraaortic irradiation in selected patients with laparotomy-staged (pathologically staged [PS]) IA to IIA Hodgkin's disease. PATIENTS AND METHODS We initiated a prospective single-arm trial in October 1988 to study the role of mantle irradiation alone in selected PS IA to IIA patients with Hodgkin's disease. A total of 37 patients have been entered onto this trial. Entrance criteria included nodular sclerosis (NS) or lymphocyte predominance (LP) histology, absence of B symptoms, disease limited above the carina, and a negative laparotomy. Results of treatment of 23 patients in the prospective trial, monitored off treatment for > or = 1 year, are presented. Twenty-three additional PS IA to IIA patients, treated with mantle irradiation alone from 1970 to 1987, were analyzed as a comparison group. The median follow-up durations were 32 and 113 months, respectively, for the two groups. RESULTS The 4-year actuarial rates of freedom from relapse and overall survival are 83% and 100%, respectively, for the prospective trial. The 10-year actuarial rates of freedom from relapse and overall survival are 83% and 89%, respectively, for retrospectively studied patients. There have been five recurrences among 46 patients who received mantle irradiation alone, all with a component of relapse below the diaphragm. CONCLUSION These early results support the use of mantle irradiation alone in selected PS IA to IIA patients with NS or LP histology. Relapses, although rare, have occurred predominantly below the diaphragm. This suggests the need for continued long-term surveillance of abdominal and pelvic nodes in this group of treated patients.

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Second Malignant Neoplasms Among Long-Term Survivors of Hodgkin’s Disease: A Population-Based Evaluation Over 25 Years

Journal of Clinical Oncology ◽

10.1200/jco.2002.09.038 ◽

2002 ◽

Vol 20 (16) ◽

pp. 3484-3494 ◽

Cited By ~ 383

Author(s):

Graça M. Dores ◽

Catherine Metayer ◽

Rochelle E. Curtis ◽

Charles F. Lynch ◽

E. Aileen Clarke ◽

...

Keyword(s):

Relative Risk ◽

Solid Tumors ◽

Hodgkin's Disease ◽

Hodgkin’S Disease ◽

Population Based ◽

Malignant Neoplasms ◽

Second Cancers ◽

Female Breast ◽

Long Term Survivors

PURPOSE: To quantify the relative and absolute excess risks (AER) of site-specific second cancers, in particular solid tumors, among long-term survivors of Hodgkin’s disease (HD) and to assess risks according to age at HD diagnosis, attained age, and time since initial treatment. PATIENTS AND METHODS: Data from 32,591 HD patients (1,111 25-year survivors) reported to 16 population-based cancer registries in North America and Europe (1935 to 1994) were analyzed. RESULTS: Two thousand one hundred fifty-three second cancers (observed-to-expected ratio [O/E] = 2.3; 95% confidence interval [CI] = 2.2 to 2.4), including 1,726 solid tumors (O/E = 2.0; 95% CI, 1.9 to 2.0) were reported. Cancers of the lung (observed [Obs] = 377; O/E = 2.9), digestive tract (Obs = 376; O/E = 1.7), and female breast (Obs = 234; O/E = 2.0) accounted for the largest number of subsequent malignancies. Twenty-five years after HD diagnosis, the actuarial risk of developing a solid tumor was 21.9%. The relative risk of solid neoplasms decreased with increasing age at HD diagnosis, however, patients aged 51 to 60 years at HD diagnosis sustained the highest cancer burden (AER = 79.2/10,000 patients/year). After a progressive rise in relative risk and AER of all solid tumors over time, there was an apparent downturn in risk at 25 years. Temporal trends and treatment group distribution for cancers of the esophagus, stomach, rectum, female breast, bladder, thyroid, and bone/connective tissue were suggestive of a radiogenic effect. CONCLUSION: Significantly increased risks of second cancers were observed in all HD age groups. Although significantly elevated risks of stomach, female breast, and uterine cervix cancers persisted for 25 years, an apparent decrease in relative risk and AER of solid tumors at other sites is suggested.

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Long-Term Survival and Competing Causes of Death in Patients With Early-Stage Hodgkin’s Disease Treated at Age 50 or Younger

Journal of Clinical Oncology ◽

10.1200/jco.2002.08.021 ◽

2002 ◽

Vol 20 (8) ◽

pp. 2101-2108 ◽

Cited By ~ 301

Author(s):

Andrea K. Ng ◽

M. Patricia Bernardo ◽

Edie Weller ◽

Kendall H. Backstrand ◽

Barbara Silver ◽

...

Keyword(s):

Relative Risk ◽

Hodgkin's Disease ◽

Excess Mortality ◽

Early Stage ◽

Hodgkin’S Disease ◽

Term Survival ◽

Long Term Survival ◽

Favorable Prognosis

PURPOSE: To analyze the long-term survival and the pattern and timing of excess mortality in patients with early-stage Hodgkin’s disease. PATIENTS AND METHODS: Between 1969 and 1997, 1,080 patients age 50 or younger were treated for clinical stage IA to IIB Hodgkin’s disease. Overall survival was determined, and prognostic factors were assessed. Relative risk and absolute excess risk (AR) of mortality were calculated for the entire cohort and by prognostic groups (on the basis of B symptoms, mediastinal status, and number of sites, modified from the European Organization for Research and Treatment of Cancer). RESULTS: The median follow-up was 12 years. The 15- and 20-year Kaplan-Meier survival estimates were 84% and 78%, respectively. Cox proportional hazards models showed that number of involved sites (P = .006), mediastinal status (P = .02), and histology (P = .02) were independent predictors of death from all causes. The AR of mortality in patients with a favorable prognosis increased over time, whereas for those with an unfavorable prognosis, the AR peaked in the first 5 years, predominantly from Hodgkin’s disease. The relative risk of mortality from all causes, causes other than Hodgkin’s disease, second tumors, and cardiac disease remained significantly elevated more than 20 years after treatment. CONCLUSION: Patients treated for early-stage Hodgkin’s disease have a sustained excess mortality risk despite good control of the disease. Treatment reduction efforts in patients with early-stage, favorable-prognosis disease should continue, but for patients with an unfavorable prognosis, modified treatment may not be advisable. The excess mortality noted beyond two decades underscores the importance of long-term follow-up care in patients treated for Hodgkin’s disease.

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Long-Term Depletion of Naive T Cells in Patients Treated for Hodgkin's Disease

Blood ◽

10.1182/blood.v90.9.3662 ◽

1997 ◽

Vol 90 (9) ◽

pp. 3662-3672 ◽

Cited By ~ 49

Author(s):

Nobukazu Watanabe ◽

Stephen C. De Rosa ◽

Anthony Cmelak ◽

Richard Hoppe ◽

Leonore A. Herzenberg ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Hodgkin's Disease ◽

Hodgkin’S Disease ◽

Cell Subset ◽

T Cell Subsets ◽

Naive T Cells ◽

Naïve T Cells ◽

Cell Counts

Abstract We investigated the representation of T cells in patients who had been treated for Hodgkin's disease (HD). We found a marked depletion in both CD4 and CD8 naive T-cell counts that persists up to 30 years after completion of treatment. In contrast, CD4 and CD8 memory T-cell subsets recovered to normal or above normal levels by 5 years posttreatment. Thus, the previously-reported long-term deficit in total CD4 T-cell counts after treatment for HD is due to specific depletion of naive T cells. Similarly, total CD8 T-cell counts return to normal by 5 years only because CD8 memory T cells expand to higher than normal levels. These findings suggest that the treatment (mediastinal irradiation) results in a longterm dysregulation of T-cell subset homeostasis. The profound depletion of naive T cells may explain the altered T-cell function in treated patients, including the poor response to immunization after treatment for HD. Further, in some individuals, we identified expansions of unusual subsets expressing low levels of CD8. Eight-color fluorescence-activated cell sorting analyses showed that these cells largely express CD8αα homodimers and CD57, consistent with the phenotype of potentially extrathymically derived T cells. In addition, these cells, both CD4+ and CD4−, are probably cytotoxic lymphocytes, as they express high levels of intracellular perforin. In adults treated for HD, an increased activity of extrathymic T-cell differentiation may partially compensate for the loss of thymic-derived T cells.

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