Photon versus proton whole ventricular radiotherapy for non-germinomatous germ cell tumors: A report from the Children's Oncology Group.

PURPOSE: To determine if proton therapy reduces doses to cranial organs at risk (OARs) as compared to photon therapy in children with non-germinomatous germ cell tumors (NGGCT) receiving whole ventricular radiotherapy (WVRT). METHODS AND MATERIALS: Dosimetric data for patients with NGGCT prospectively enrolled in stratum 1 of the Children's Oncology Group study ACNS1123 who received 30.6 Gy WVRT were compared. Target segmentation was standardized using a contouring atlas. Doses to cranial OARs were compared between proton and photon treatments. Clinically relevant dose-volume parameters that were analyzed included mean dose and dose to 40% of the OAR volume (D40). RESULTS: Mean and D40 doses to the supratentorial brain, cerebellum, and bilateral temporal, parietal, and frontal lobes were statistically significantly lower amongst proton-treated patients, as compared to photon-treated patients. In a subgroup analysis of patients uniformly treated with a 3-mm planning target volume, patients who received proton therapy continued to have statistically significantly lower doses to brain OARs. CONCLUSIONS: Children treated with proton therapy for WVRT had lower doses to normal brain structures, when compared to those treated with photon therapy. Proton therapy should be considered for patients receiving WVRT for NGGCT.

Echocardiographic Detection of Cardiac Dysfunction in Childhood Cancer Survivors: How Long Is Screening Required?

BACKGROUND: Childhood cancer survivors treated with anthracycline chemotherapy are at an increased risk of long-term cardiac toxicity, and guidelines recommend that exposed survivors undergo echocardiography every 1-5 years. However, it is unclear whether survivors should undergo echocardiographic screening indefinitely, or if a period of echocardiographic stability indicates that screening is no longer necessary. The objective of this study was to evaluate the outcomes of echocardiographic screening to aid in the refinement of existing guidelines. METHODS: We retrospectively analyzed the results of echocardiographic screening in a cohort of adult survivors of childhood cancer treated with anthracyclines and/or cardiac radiation therapy. Interval regression analysis was performed to identify predictors of single-episode or sustained abnormal echocardiograms. RESULTS: The cohort constituted 333 survivors, with median follow-up time of 15.8 years post-treatment (range: 5.0-47.9), and median age at treatment of 8 years (range: 1.5-18). Forty-nine survivors had an abnormal echocardiogram (14.7%), and 29 (8.7%) had reproducible abnormal findings. An ongoing continual increase in the incidence of sustained echocardiographic abnormality was seen among patients treated with >250 mg/m(2) doxorubicin at age <5 years, reaching 43% by 20 years of therapy. In contrast, no sustained abnormal echocardiographic findings arose after 10 years of therapy in survivors treated with <250 mg/m(2) at age ≥5 years. CONCLUSIONS: Single-episode echocardiographic abnormalities are often not reproduced in subsequent evaluations. The duration of echocardiographic screening for childhood cancer survivors should be reassessed for patients who received lower doses of anthracycline after age 5.

Pilot Study of Waterpipe Tobacco Smoking Among US Muslim College Students.

Waterpipe smoking is common among the young in Muslim-majority countries despite recent Islamic rulings on tobacco. US Muslim college students, especially immigrants, may be at high risk for smoking, but information is lacking. In this pilot study, respondent-driven sampling was used to sample 156 Muslim college students. Waterpipe smoking was common (44.3%). Leading motivations to smoke were social and perceived low tobacco harm. Independent risk factors among the Muslim students were perception that friends and other students smoked, and ever drank alcohol. Personal belief that waterpipe smoking is prohibited in Islam was not significant. This pilot suggests that Muslim students are at high risk for waterpipe smoking and more definitive studies are needed.

Breast cancer detection among young survivors of pediatric Hodgkin lymphoma with screening magnetic resonance imaging.

BACKGROUND: Female survivors of pediatric Hodgkin lymphoma (HL) who have received chest radiotherapy are at increased risk of breast cancer. Guidelines for early breast cancer screening among these survivors are based on little data regarding clinical outcomes. This study reports outcomes of breast cancer screening with MRI and mammography (MMG) after childhood HL. METHODS: We evaluated the results of breast MRI and MMG screening among 96 female survivors of childhood HL treated with chest radiotherapy. Outcomes measured included imaging sensitivity and specificity, breast cancer characteristics, and incidence of additional imaging and breast biopsy. RESULTS: Median age at first screening was 30 years, and the median number of MRI screening rounds was 3. Ten breast cancers were detected in 9 women at a median age of 39 years (range, 24-43 years). Half were invasive and half were preinvasive. The median size of invasive tumors was 8 mm (range, 3-15 mm), and none had lymph node involvement. Sensitivity and specificity of the screening modalities were as follows: for MRI alone, 80% and 93.5%, respectively; MMG alone, 70% and 95%, respectively; both modalities combined, 100% and 88.6%, respectively. All invasive tumors were detected by MRI. Additional investigations were required in 52 patients, (54%), and 26 patients (27%) required breast biopsy, with 10 patients requiring more than 1 biopsy. CONCLUSIONS: Screening including breast MRI with MMG has high sensitivity and specificity in pediatric HL survivors, with breast cancers detected at an early stage, although it is associated with a substantial rate of additional investigations.

Paediatric radiation therapy without anaesthesia - Are the children moving?

PURPOSE: Children who require radiation therapy (RT) should ideally be treated awake, without anaesthesia, if possible. Audiovisual distraction is a known method to facilitate awake treatment, but its effectiveness at keeping children from moving during treatment is not known. The aim of this study was to evaluate intrafraction movement of children receiving RT while awake. METHODS: In this prospective study, we measured the intrafraction movement of children undergoing treatment with fractionated RT, using pre- and post-RT cone beam CT (CBCT) with image matching on bony anatomy. Study CBCTs were acquired at first fraction, weekly during RT, and at last fraction. The primary endpoint was the magnitude of vector change between the pre- and post-RT scans. Our hypothesis was that 90 % of CBCT acquisitions would have minimal movement, defined as <3 mm for head-and-neck (HN) treatments and <5 mm for non-HN treatments. RESULTS: A total of 65 children were enrolled and had evaluable data across 302 treatments with CBCT acquisitions. Median age was 11 years (range, 2-18; 1st and 3rd quartiles 7 and 14 years, respectively). Minimal movement was observed in 99.4 % of HN treatments and 97.2 % of non-HN treatments. The study hypothesis of >90 % of evaluations having minimal movement was met. Children who were age >11 years moved less at initial evaluation but tended to move more as a course of radiation progressed, as compared to children who were younger. CONCLUSION: Children receiving RT with audiovisual distraction while awake had small magnitudes of observed intrafraction movement, with minimal movement in >97 % of observed RT fractions. This study validates methods of anaesthesia avoidance using audiovisual distraction for selected children.

A Prospective Study of Machine Learning-Assisted Radiation Therapy Planning for Patients Receiving 54 Gy to the Brain.

PURPOSE: The capacity for machine learning (ML) to facilitate radiation therapy (RT) planning for primary brain tumors has not been described. We evaluated ML-assisted RT planning with regard to clinical acceptability, dosimetric outcomes, and planning efficiency for adults and children with primary brain tumors. METHODS AND MATERIALS: In this prospective study, children and adults receiving 54 Gy fractionated RT for a primary brain tumor were enrolled. For each patient, one ML-assisted RT plan was created and compared with 1 or 2 plans created using standard ("manual") planning procedures. Plans were evaluated by the treating oncologist, who was blinded to the method of plan creation. The primary endpoint was the proportion of ML plans that were clinically acceptable for treatment. Secondary endpoints included the frequency with which ML plans were selected as preferable for treatment, and dosimetric differences between ML and manual plans. RESULTS: A total of 116 manual plans and 61 ML plans were evaluated across 61 patients. Ninety-four percent of ML plans and 93% of manual plans were judged to be clinically acceptable (P = 1.0). Overall, the quality of ML plans was similar to manual plans. ML plans comprised 34.5% of all plans evaluated and were selected for treatment in 36.1% of cases (P = .82). Similar tumor target coverage was achieved between both planning methods. Normal brain (brain minus planning target volume) received an average of 1 Gy less mean dose with ML plans (compared with manual plans, P < .001). ML plans required an average of 45.8 minutes less time to create, compared with manual plans (P < .001). CONCLUSIONS: ML-assisted automated planning creates high-quality plans for patients with brain tumors, including children. Plans created with ML assistance delivered slightly less dose to normal brain tissues and can be designed in less time.

Respondent-driven sampling of Muslim undergraduate U.S. college students and alcohol use: pilot study.

PURPOSE: Prevention of alcohol abuse requires information about all demographic groups. However, little is known about drinking among people affiliated with proscriptive religions due to omission of religious affiliation in many surveys and challenges sampling them. Our objective was to pilot a sampling technique frequently used in the HIV literature, respondent-driven sampling, to assess potential association of alcohol use with religiosity, personal proscriptive belief, and social influences among Muslim U.S. college students. METHODS: Self-identified Muslim undergraduate students (N = 156) at one urban commuter university completed a web-based survey. RESULTS: Prevalence adjusted for sampling was 9.1 % (95 % CI: 0.2-17.1 %) with in-group recruitment of 0.36 for drinkers and 0.43 for abstainers. In unadjusted analyses, students who were lifetime abstainers were more likely than drinkers to hold personal proscriptive belief and strongly agree with a measure of private religiosity. There was no difference on public religiosity measures between groups. Lifelong abstainers were more likely to report fewer students, fewer Muslim students, and fewer of their friends drank alcohol. They also were more likely to report that they attended high school with more Muslims and currently live in neighborhoods with more Muslims. CONCLUSIONS: In this pilot study, lifetime abstinence was associated with high private religiosity, personal proscriptive religious beliefs, and more proscriptive social influences. The findings suggest that respondent-driven sampling may be feasible in recruiting Muslim students. However, validation against other sampling techniques is needed.

Validation of the new IDF-DAR risk assessment tool for Ramadan fasting in patients with diabetes.

BACKGROUND: A new IDF-DAR (International Diabetes Federation - Diabetes and Ramadan Alliance) risk stratification tool was published in 2021 to better stratify the risk of Ramadan fasting in people with diabetes. METHODS: We performed a prospective, survey-based study before and after Ramadan 1442/2021 to explore the ability of the new IDF-DAR risk stratification tool to predict the probability of fasting and the risk of complications from fasting in people with diabetes. RESULTS: A pre-Ramadan assessment was completed for 659 patients who intended to fast in Ramadan; 647(98.2%) answered the post-Ramadan follow-up questionnaire. Mean age was 53.5 years and 47.9% were females. 603(91.5%) had type 2 diabetes while 56(8.5%) had type 1 diabetes. Using the IDF-DAR risk criteria at the pre-Ramadan assessment, 339(51.4%) were categorized as low-risk (score <3), 173(26.3%) as moderate-risk (score 3.5-6) and 147(22.3%) as high-risk (score >6). 94.3%, 81.1% and 76.9% patients fasted the full 30 days in the low, moderate and high risk groups respectively (p < 0.0001). Any hypoglycaemia was reported in the low, moderate and high risk groups by 6.3%, 21.9% and 35.0% respectively while severe hypoglycaemia was reported by 3(2.1%) patients in the high, 3(1.8%) in the moderate and none(0%) in the low risk groups. Hyperglycaemia (>250 mg/dL) was reported in the low, moderate and high risk groups by 2.7%, 13.0% and 23.8% respectively. CONCLUSION: The new IDF-DAR risk assessment tool appears to reliably predict both the ability to fast during Ramadan as well as the likelihood of getting hypoglycaemia or hyperglycaemia.

Development and Validation of Risk Prediction Models for Coronary Heart Disease and Heart Failure After Treatment for Hodgkin Lymphoma.

PURPOSE: Previous efforts to predict absolute risk of treatment-related cardiovascular diseases (CVDs) have mostly focused on childhood cancer survivors. We aimed to develop prediction models for risk of coronary heart disease (CHD) and heart failure (HF) for survivors of adolescent/adult Hodgkin lymphoma (HL). METHODS: For model development, we used a multicenter cohort including 1,433 5-year HL survivors treated between 1965 and 2000 and age 18-50 years at HL diagnosis, with complete data on administered chemotherapy regimens, radiotherapy volumes and doses, and cardiovascular follow-up. Using cause-specific hazard models, covariate-adjusted cumulative incidences for CHD and HF were estimated in the presence of competing risks of death because of other causes than CHD and HF. Age at HL diagnosis, sex, smoking status, radiotherapy, and anthracycline treatment were included as predictors. External validation for the CHD model was performed using a Canadian cohort of 708 HL survivors treated between 1988 and 2004 and age 18-50 years at HL diagnosis. RESULTS: After a median follow-up of 24 years, 341 survivors had developed CHD and 102 had HF. We were able to predict CHD and HF risk at 20 and 30 years after treatment with moderate to good overall calibration and moderate discrimination (areas under the curve: 0.68-0.74), which was confirmed by external validation for the CHD model (areas under the curve: 0.73-0.74). On the basis of our model including prescribed mediastinal radiation dose, 30-year risks ranged from 4% to 78% for CHD and 3% to 46% for HF, depending on risk factors. CONCLUSION: We developed and validated prediction models for CHD and HF with good overall calibration and moderate discrimination. These models can be used to identify HL survivors who might benefit from targeted screening for CVD and early treatment for CVD risk factors.

A pilot study of machine-learning based automated planning for primary brain tumours.

PURPOSE: High-quality radiotherapy (RT) planning for children and young adults with primary brain tumours is essential to minimize the risk of late treatment effects. The feasibility of using automated machine-learning (ML) to aid RT planning in this population has not previously been studied. METHODS AND MATERIALS: We developed a ML model that identifies learned relationships between image features and expected dose in a training set of 95 patients with a primary brain tumour treated with focal radiotherapy to a dose of 54 Gy in 30 fractions. This ML method was then used to create predicted dose distributions for 15 previously-treated brain tumour patients across two institutions, as a testing set. Dosimetry to target volumes and organs-at-risk (OARs) were compared between the clinically-delivered (human-generated) plans versus the ML plans. RESULTS: The ML method was able to create deliverable plans in all 15 patients in the testing set. All ML plans were generated within 30 min of initiating planning. Planning target volume coverage with 95% of the prescription dose was attained in all plans. OAR doses were similar across most structures evaluated; mean doses to brain and left temporal lobe were lower in ML plans than manual plans (mean difference to left temporal, - 2.3 Gy, p = 0.006; mean differences to brain, - 1.3 Gy, p = 0.017), whereas mean doses to right cochlea and lenses were higher in ML plans (+ 1.6-2.2 Gy, p < 0.05 for each). CONCLUSIONS: Use of an automated ML method to aid RT planning for children and young adults with primary brain tumours is dosimetrically feasible and can be successfully used to create high-quality 54 Gy RT plans. Further evaluation after clinical implementation is planned.

Hearing Loss After Radiation and Chemotherapy for CNS and Head-and-Neck Tumors in Children.

PURPOSE: Hearing loss (HL) is a serious secondary effect of treatment for CNS and head-and-neck tumors in children. The goal of this study was to evaluate incidence and risk factors for HL in patients with multiple ototoxic exposures. PATIENTS AND METHODS: We evaluated 340 ears from 171 patients with CNS or head-and-neck tumors treated with radiation, with or without chemotherapy, who had longitudinal audiologic evaluation. International Society of Pediatric Oncology-Boston grades were assigned to 2,420 hearing assessments. Multivariable weighted ordinal logistic regression was fitted to evaluate the effect of clinicopathologic features on HL. RESULTS: Mean cochlea dose (odds ratio [OR] 1.04 per Gy, P < .001), time since radiotherapy (RT; OR 1.21 per year, P < .001), cisplatin dose (OR 1.48 per 100 mg/m2, P < .001), and carboplatin dose (OR 1.41 per 1,000 mg/m2, P = .002) were associated with increasing International Society of Pediatric Oncology-Boston grade of HL. There was no synergistic effect of RT and cisplatin (interaction term, P = .53) or RT and carboplatin (interaction term, P = .85). Cumulative incidence of high-frequency HL (> 4 kHz) was 50% or greater at 5 years after RT if mean cochlea dose was > 30 Gy, while incidence of HL across all frequencies continued to increase beyond 5 years after RT. CONCLUSION: Children treated with radiation and chemotherapy experience a high incidence of HL over time, with associations found between more severe HL and cisplatin or carboplatin dose as well as mean cochlea dose. Mean cochlea dose of ≤ 30 Gy is proposed as a goal to reduce the risk of HL; a lower threshold (20-25 Gy) may be considered in patients receiving platinum chemotherapy to reduce cumulative HL burden.

Alcohol use among U.S. Muslim college students: risk and protective factors.

Drinking behavior among Muslim college students in the United States is unknown. To obtain estimates and examine risk factors, the authors conducted secondary data analysis of the public access database from the 2001 Harvard School of Public Health College Alcohol Study. Two variables were associated with drinking-religious activities, which were protective against drinking, and parental approval of drinking, which was a risk factor for drinking. Although American Muslim students had a low rate of drinking in the past year (46.6%) compared to their U.S. college counterparts, they had a higher rate of alcohol consumption compared to their counterparts in predominately Muslim countries.

Dose-response relationships for radiation-related heart disease: Impact of uncertainties in cardiac dose reconstruction.

BACKGROUND AND PURPOSE: Radiation-related heart disease (RRHD) can occur many decades after thoracic radiotherapy for Hodgkin lymphoma (HL) or childhood cancer (CC). To quantify the likely risk of RRHD for patients treated today, dose-response relationships derived from patients treated in previous decades are used. Publications presenting these dose-response relationships usually include estimates of uncertainties in the risks but ignore the effect of uncertainties in the reconstructed cardiac doses. MATERIALS/METHODS: We assessed the systematic and random uncertainties in the reconstructed doses for published dose-response relationships for RRHD risk in survivors of HL or CC. Using the same reconstruction methods as were used in the original publications, we reconstructed mean heart doses and, wherever possible, mean left-ventricular doses for an independent case-series of test patients. These patients had known, CT-based, cardiac doses which were compared with the reconstructed doses to estimate the magnitude of the uncertainties and their effect on the dose-response relationships. RESULTS: For all five reconstruction methods the relationship between reconstructed and CT-based doses was linear. For all but the simplest reconstruction method, the dose uncertainties were moderate, the effect of the systematic uncertainty on the dose-response relationships was less than 10%, and the effects of random uncertainty were small except at the highest doses. CONCLUSIONS: These results increase confidence in the published dose-response relationships for the risk of RRHD in HL and CC survivors. This may encourage doctors to use these dose-response relationships when estimating individualised risks for patients-an important aspect of personalising radiotherapy treatments today.

Cost-Effectiveness of Colonoscopy-Based Colorectal Cancer Screening in Childhood Cancer Survivors.

BACKGROUND: Childhood cancer survivors (CCS) are at increased risk of developing colorectal cancer (CRC) compared to the general population, especially those previously exposed to abdominal or pelvic radiation therapy (APRT). However, the benefits and costs of CRC screening in CCS are unclear. In this study, we evaluated the cost-effectiveness of early-initiated colonoscopy screening in CCS. METHODS: We adjusted a previously validated model of CRC screening in the US population (MISCAN-Colon) to reflect CRC and other-cause mortality risk in CCS. We evaluated 91 colonoscopy screening strategies varying in screening interval, age to start, and age to stop screening for all CCS combined and for those treated with or without APRT. Primary outcomes were CRC deaths averted (compared to no screening) and incremental cost-effectiveness ratios (ICERs). A willingness-to-pay threshold of $100 000 per life-years gained (LYG) was used to determine the optimal screening strategy. RESULTS: Compared to no screening, the US Preventive Services Task Force's average risk screening schedule prevented up to 73.2% of CRC deaths in CCS. The optimal strategy of screening every 10 years from age 40 to 60 years averted 79.2% of deaths, with ICER of $67 000/LYG. Among CCS treated with APRT, colonoscopy every 10 years from age 35 to 65 years was optimal (CRC deaths averted: 82.3%; ICER: $92 000/LYG), whereas among those not previously treated with APRT, screening from age 45 to 55 years every 10 years was optimal (CRC deaths averted: 72.7%; ICER: $57 000/LYG). CONCLUSIONS: Early initiation of colonoscopy screening for CCS is cost-effective, especially among those treated with APRT.

Meningioma Screening With MRI in Childhood Leukemia Survivors Treated With Cranial Radiation.

PURPOSE: Radiation-induced meningioma is a known late effect of cranial radiation therapy. Cranial magnetic resonance imaging (MRI) can detect small meningiomas, but its potential value as a screening tool is unknown. METHODS AND MATERIALS: MRI was used to screen asymptomatic survivors of childhood acute lymphoblastic leukemia (ALL) treated with cranial radiation therapy ≥10 years previously. The incidence of radiation-induced meningioma and outcomes of this group were compared with a historical cohort of survivors with the same exposure who underwent imaging only to investigate clinical signs or symptoms. RESULTS: One hundred seventy-six childhood leukemia survivors were included in this study: 70 in the screening group and 106 unscreened. Screening MRI was performed a median of 25 years after radiation therapy and detected meningioma in 15 (21.4%). In the unscreened group, 17 patients (16.0%) had neurologic symptoms leading to an MRI a median interval of 24 years after radiation therapy, 9 of whom (8.5%) were diagnosed with meningioma. There was no significant difference between screened versus unscreened patients in the size of meningioma (mean diameter, 1.6 cm vs 2.6 cm; P = .13), meningioma incidence (7.4% vs 4.0% at 25 years; P = .19), or extent of resection. Three patients had persistent neurologic symptoms in the unscreened group versus none among screened patients (P = .28). CONCLUSIONS: Screening MRI was able to detect small meningiomas that were not clinically apparent; however, we could not demonstrate a significant improvement in the chance of total resection or a significant decrease in morbidity. A larger sample could clarify potential reduction in neurologic sequelae associated with screening.

Salvage Treatment and Survival for Relapsed Follicular Lymphoma Following Primary Radiation Therapy: A Collaborative Study on Behalf of ILROG.

PURPOSE: We previously reported that ∼30% of patients with localized follicular lymphoma (FL) staged by 18F-fluorodeoxyglucose positron emission tomography-computed tomography receiving primary radiation therapy (RT) will relapse within 5 years. We sought to report outcomes for those who relapsed. METHODS AND MATERIALS: We conducted a multicenter, retrospective study of patients aged ≥18 years who received RT ≥ 24 Gy for stage I to II, grade 1 to 3A FL, staged with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography. Observation was defined as >6 months without treatment from relapse. Overall survival (OS) and freedom from progression (FFP) were estimated with Kaplan-Meier analysis and univariable and multivariable analyses with Cox regression. RESULTS: Of 512 patients with median follow-up of 52 months, 149 (29.1%) developed recurrent lymphoma at a median of 23 months (range, 1-143) after primary RT. Median follow-up was 33 months after relapse. Three-year OS was 91.4% after recurrence. OS was significantly worse for those with relapse ≤12 months from date of diagnosis versus all others-88.7% versus 97.6%, respectively (P = .01)-and remained significantly worse on multivariable analyses (follicular lymphoma international prognostic index-adjusted hazard ratio, 3.61; P = .009). Histology at relapse included 93 indolent (grade 1-3A), 3 FL grade 3B/not otherwise specified, and 18 diffuse large B-cell lymphoma; 35 patients did not undergo biopsy. Of those with follow-up ≥3 months who underwent biopsy (n = 74) or had presumed (n = 23) indolent recurrence, 58 patients (59.8%) were observed, 19 (19.6%) had systemic therapy, 16 (16.5%) had RT, and 4 (4.1%) had systemic therapy + RT. For patients with indolent recurrences that were observed, 3-year FFP or freedom from treatment was 56.6% (median, 48 months). For all patients with biopsied/presumed indolent recurrence receiving salvage treatment (n = 59, including 20 initially observed) 3-year FFP was 73.9%. CONCLUSIONS: Prognosis for patients with relapsed FL after primary radiation therapy is excellent, supporting the role of primary radiation in the management of early stage disease. Patients with localized FL treated with primary RT who experience early relapse (<12 months) have inferior survival compared with those with longer disease-free interval.

Late Cardiac Toxicity After Mediastinal Radiation Therapy for Hodgkin Lymphoma: Contributions of Coronary Artery and Whole Heart Dose-Volume Variables to Risk Prediction.

PURPOSE: Mediastinal radiation therapy (RT) for Hodgkin lymphoma (HL) is associated with late cardiotoxicity, but there are limited data to indicate which dosimetric parameters are most valuable for predicting this risk. This study investigated which whole heart dosimetric measurements provide the most information regarding late cardiotoxicity, and whether coronary artery dosimetry was more predictive of this outcome than whole heart dosimetry. METHODS AND MATERIALS: A random sample of 125 HL patients treated with mediastinal RT was selected, and 3-dimensional cardiac dose-volume data were generated from historical plans using validated methods. Cardiac events were determined by linking patients to population-based datasets of inpatient and same-day hospitalizations and same-day procedures. Variables collected for the whole heart and 3 coronary arteries included the following: Dmean, Dmax, Dmin, dose homogeneity, V5, V10, V20, and V30. Multivariable competing risk regression models were generated for the whole heart and coronary arteries. RESULTS: There were 44 cardiac events documented, of which 70% were ischemic. The best multivariable model included the following covariates: whole heart Dmean (hazard ratio [HR] 1.09, P=.0083), dose homogeneity (HR 0.94, P=.0034), male sex (HR 2.31, P=.014), and age (HR 1.03, P=.0049). When any adverse cardiac event was the outcome, models using coronary artery variables did not perform better than models using whole heart variables. However, in a subanalysis of ischemic cardiac events only, the model using coronary artery variables was superior to the whole heart model and included the following covariates: age (HR 1.05, P<.001), volume of left anterior descending artery receiving 5 Gy (HR 0.98, P=.003), and volume of left circumflex artery receiving 20 Gy (HR 1.03, P<.001). CONCLUSION: In addition to higher mean heart dose, increasing inhomogeneity in cardiac dose was associated with a greater risk of late cardiac effects. When all types of cardiotoxicity were evaluated, the whole heart variable model outperformed the coronary artery models. However, when events were limited to ischemic cardiotoxicity, the coronary artery-based model was superior.

Anti-Müllerian hormone screening to assess ovarian reserve among female survivors of childhood cancer.

PURPOSE: Anti-Müllerian hormone (AMH) is an indicator of oocyte reserve in healthy females. The role of AMH testing in oncology remains investigational, although its sensitivity and stability over the menstrual cycle make it an attractive screening test for fertility assessment among female cancer survivors. We measured AMH level in survivors of childhood cancer and evaluated its association with treatment and patient factors. METHODS: Participants were adult female survivors of childhood malignancy treated with chemotherapy. Serum AMH was measured at a random day of the menstrual cycle. Multivariate analysis was used to evaluate the association between AMH level, alkylating agent exposure using the cyclophosphamide equivalent dose (CED), and other covariates. RESULTS: Sixty-six females with a median attained age of 23.3 years were eligible for analysis. Median AMH was 25.5 pM (range 0.5-108.0), at a median time of 11.5 years (range 1.4-25.1) since cancer diagnosis. Twenty-three patients (34.8%) had low AMH, including a significant proportion that reported normal menstrual cycles. Compared to ALL survivors, sarcoma survivors had significantly lower AMH levels. Among alkylating agents evaluated, procarbazine had the greatest adverse effect on AMH. In multivariate analysis, higher CED (p = 0.001), older age at diagnosis (p < 0.001), and use of oral contraceptive pills (p = 0.04) remained significantly associated with lower AMH. CONCLUSIONS: Random AMH can reveal evidence of oocyte depletion among female survivors reporting normal cycles, although low AMH should be interpreted cautiously among those taking oral contraception. Age at exposure and CED can aid identification of those more likely to have low AMH, although CED may underestimate the effect of procarbazine on oocyte reserve. IMPLICATIONS FOR CANCER SURVIVORS: Measurement of AMH can reveal apparent depletion of ovarian reserve in female childhood cancer survivors reporting normal menstrual cycles. Sarcoma survivors and those exposed to procarbazine may benefit from targeted AMH evaluation in an outpatient setting, and thereby allow appropriate fertility counseling before the onset of premature ovarian failure. The cyclophosphamide equivalent dose may facilitate comparison of the potential effect of different regimens on fertility.

Fertility among female hodgkin lymphoma survivors attempting pregnancy following ABVD chemotherapy.

Although ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy is infrequently associated with premature amenorrhea, little is known about the success rate of women attempting pregnancy following ABVD. In the present study females treated for HL with ABVD chemotherapy without pelvic radiation therapy (RT) and who were alive without relapse > or =3 years after treatment were identified from a clinical database and screened for inclusion. Using a standardized questionnaire, we determined the pregnancy rate (i.e. time-to-pregnancy, TTP) among survivors who had become pregnant, tried to become pregnant, or who had been sexually active for over 2 months without using contraception at any time following ABVD. The cumulative incidence of pregnancy was calculated using the Kaplan-Meier method. Cox proportional hazards models were constructed to compare the pregnancy rate among HL survivors to that reported by friend or sibling controls. Thirty-six female HL survivors, who had attempted pregnancy after ABVD treatment, and 29 controls, completed the survey. Eighteen patients (50%) received 2-4 cycles of ABVD, 16 (44%) received 4-6 cycles, and 2 (6%) received >6 cycles. The median TTP among both HL survivors and controls was 2.0 months. The 12-month pregnancy rates were 70% and 75%, respectively. The fertility ratio (FR) for HL survivors versus controls was 0.94 (95%CI = 0.53-1.66; p = 0.84) after adjusting for age and frequency of intercourse (where FR < 1 indicates subfertility). Age at treatment and the number of cycles of chemotherapy were not associated with pregnancy rate among HL survivors. Female HL patients who had survived without recurrence > or =3 years and who had attempted pregnancy after ABVD did not experience significant sub-fertility.