Diminished ovarian reserve in adolescent cancer survivors treated with heavy metal chemotherapy

The extent to which heavy metal chemotherapy results in treatment-related ovarian damage is controversial. Anti-Mullerian hormone (AMH) levels measured more than 1 year after cancer therapy completion were abstracted from the medical records of 39 female survivors of childhood cancer aged 11 years and older, whose only gonadotoxic exposure was heavy metal chemotherapy. One-fifth of survivors who received cisplatin had AMH levels indicative of diminished ovarian reserve at last measurement. There was an observed clustering of low AMH in patients diagnosed in the peripubertal age range (i.e., 10–12 years). These findings may support a small, but present, risk of gonadal damage after heavy metal chemotherapy.     

The risk of cancer in twins: a report from the childhood cancer survivor study

BACKGROUND: Twin concordance studies help evaluate the contribution of genetic factors in childhood cancers, but previous reports have primarily focused on leukemia because of the rarity of other malignancies. In the current report, a large cohort of childhood cancer survivors was used to: (1) describe twin concordance patterns for a range of cancers, (2) calculate the standardized incidence rates of cancers in twins, and (3) describe clinical features and outcomes of concordant twins. PROCEDURE: Cancer family history was obtained on the 211 twins participating in the Childhood Cancer Survivor Study (CCSS) (14,352 participants surviving > or =5 years after a malignancy diagnosed at <21 years during January 1, 1970-December 31, 1986) to calculate probandwise twin concordance rates and standardized incidence ratios (SIRs) using Surveillance, Epidemiology, and End-Results data. RESULTS: Seven monozygotic twin pairs were concordant for cancer (six for leukemia, one for non-Hodgkin lymphoma), yielding probandwise concordance rates of 9.5%, 20.7%, and 20.0% for all cancer, leukemia, and non-Hodgkin lymphoma (NHL), respectively. No concordance was observed among dizygotic twins or for dissimilar cancers. The SIR in monozygotic twins was 23.3 (95% CI = 11.1-48.9) for all cancer, 112.4 (95% CI = 50.5-250.1) for leukemia, and 40.5 (5.7-287.5) for NHL. Concordant twins were similar in age at diagnosis and vital status. CONCLUSIONS: Twin concordance for cancer is largely restricted to monozygotic twins and hematological malignancies, consistent with in utero malignancy transmission demonstrated by others. Our data support clinical monitoring of the twins of cases with hematological malignancies, and does not contribute evidence for genetic factors in other cancers.     

Psychological distress in long-term survivors of solid tumors diagnosed in childhood: a report from the childhood cancer survivor study

PURPOSE: To evaluate and compare psychological distress in long-term survivors of solid tumors diagnosed in childhood and their siblings, and to identify significant correlates of psychological distress. PROCEDURE: Adult survivors (2,778) of solid tumors diagnosed in childhood and 2,925 siblings completed a long-term follow-up questionnaire assessing symptoms associated with depression, somatization, and anxiety, as well as demographic, health, and medical information. RESULTS: Overall, a large majority of siblings and survivors reported few, if any, symptoms of psychological distress. In the aggregate, solid tumor cancer survivors reported significantly higher levels of global distress as measured by the Brief Symptom Inventory (BSI-18), as well as higher levels of somatization and anxiety, when compared to siblings. However, when compared to population norms, both survivors and siblings reported lower levels of global and dimensional distress. Female gender, lower educational and income attainment, perceived poor health status and reports of current health problems all were associated with reporting psychological distress symptoms for both survivors and siblings. Among survivors, having a limb amputation was associated with reporting fewer symptoms of global and dimensional distress. CONCLUSION: Poor health status, low levels of income, education, and employment appear to be predictors of distress for survivors of solid tumors. Thus, interventions that promote health and facilitate educational advancement, income attainment and social interaction to minimize isolation and maximize social support may reduce psychological distress and promote quality of life for childhood cancer survivors.     

Long-term medical effects of childhood and adolescent rhabdomyosarcoma: a report from the childhood cancer survivor study

BACKGROUND: This study was conducted to evaluate the incidence of adverse medical conditions and to assess the risk of developing these conditions in a cohort of long-term survivors of rhabdomyosarcoma (RMS) diagnosed before age 21. PROCEDURE: Using data from the Childhood Cancer Survivor Study (CCSS), we evaluated the incidence of self-reported adverse medical conditions for 606 RMS survivors and 3,701 siblings of cancer survivors. Cancer and treatment data abstracted from medical records were used to evaluate the effects of primary tumor site and combined modality therapy on the risk of developing sequelae in survivors. RESULTS: The relative risk (RR) for developing sequelae among survivors compared with siblings was greatest within 5 years after diagnosis. RR was elevated more than 5 years after diagnosis for several conditions (RR, 95% CI) as follows: eye impairment (cataract: 7.4, 2.9-18.9; visual disturbances: 3.2, 2.0-5.1; very dry eyes: 2.0, 1.2-3.3), endocrine impairment (growth hormone deficiency: 83.9, 33.0-213.6; hypothyroidism: 6.9, 4.1-11.3; need for medications to induce puberty: 90.4, 30.2-270.5), cardiopulmonary impairment (congestive heart failure: 43.0, 12.7-145.5; angina-like symptoms: 2.0, 1.3-2.9), neurosensory impairment (legal blindness: 9.8, 4.8-20.0; abnormal sensations: 1.5, 1.0-2.2), and neuromotor impairment (repeated seizures: 2.3, 1.2-4.4; motor problems: 3.7, 2.2-6.4; problems chewing or swallowing: 3.8, 1.9-7.5). CONCLUSIONS: Survivors are at risk for developing sequelae many years after their initial diagnosis and treatment. Continued medical surveillance is necessary to ensure the long-term health and well-being of RMS survivors.     

Orthotopic ovarian transplant--review and three surgical techniques

Transplantation of organs is a rapidly expanding faculty of medicine. While the solid organ transplantation has grown by leaps and bounds, ovarian transplantation is still in its infancy. Although recent interest has been generated for preservation of fertility in cancer therapy patients, other indications have emerged. Ovarian dysgenesis with missing normal ovarian complement and premature ovarian failure has come in the forefront. Three cases of orthotopic ovarian transplant with different surgical techniques have been described along with a brief overview.     

Impact of ovarian transposition before pelvic irradiation on ovarian function among long‐term survivors of childhood Hodgkin lymphoma: A report from the St. Jude Lifetime Cohort Study

1 Background

We reviewed the effect of ovarian transposition (OT) on ovarian function among long‐term survivors of childhood Hodgkin lymphoma (HL) treated with pelvic radiotherapy.

2 Procedure

Female participants (age 18+ years) with HL in the St. Jude Lifetime Cohort Study (SJLIFE) were clinically evaluated for premature ovarian insufficiency (POI) 10 or more years after pelvic radiotherapy. Reproductive history including age at menopause and pregnancy/live births was available on all patients.

3 Results

Of 127 eligible females with HL, 90 (80%) participated in SJLIFE, including 49 who underwent OT before pelvic radiotherapy. Median age at STLIFE evaluation was 38 years (range 25–60). In a multiple regression adjusted for age at diagnosis, pelvic radiotherapy doses > 1,500 cGy (hazard ratio [HR] = 25.2, 95% confidence interval [CI] = 3.1–207.3; P = 0.0027) and cumulative cyclophosphamide equivalent doses of alkylating agents > 12,000 mg/m² (HR = 11.2, 95% CI = 3.4–36.8; P < 0.0001) were significantly associated with POI. There was no significant association between OT and occurrence of POI (HR = 0.6, 95% CI = 0.2–1.9; P = 0.41).

4 Conclusions

OT did not appear to modify risk of POI in this historic cohort of long‐term survivors of HL treated with gonadotoxic therapy. Modern fertility preservation modalities, such as mature oocyte cryopreservation, should be offered to at‐risk patients whenever feasible.     

Should ovarian cryopreservation be offered to girls with cancer

Current therapy of childhood cancer makes long-term survival a realistic outcome for most patients. However, some treatment regimens entail a significant risk of infertility. No established method for preservation of female fertility is currently available. Ovarian cryopreservation is an experimental technology that is being offered with increasing frequency to women undergoing cancer therapy. It has not yet been reported in children and adolescent girls. The aim of this review is to stimulate discussion on the possibility of performing ovarian cryopreservation in pre-menarcheal girls in advance of therapies that may induce ovarian failure. We present a multi-disciplinary discussion of the risks and benefits associated with the procedure and propose guidelines for its implementation. We propose that all girls about to receive treatment that has a high risk for infertility be offered consultation about the possibility of ovarian cryopreservation.     

Adverse childhood experiences and resilience in childhood and adolescent and young adult cancer patients

Childhood and adolescent and young adult (AYA) cancer survivors experience poor health outcomes in adulthood. Adverse childhood experiences (ACEs) also portend poor health outcomes for the general population. Resilience can mitigate effects of ACEs. We examined the feasibility of assessing ACEs and resilience in childhood and AYA cancer patients. We also described occurrences of ACEs, resilience, and poor health outcomes. Of 52 participants, most rated their study experience favorably, with privacy in answering sensitive questions. Half reported ACEs, and those with ACEs had lower resilience; X²(3, N = 52) = 9.4, p = .02. Further investigations of ACEs and resilience in larger cohorts are warranted to delineate associations with long-term health outcomes.