Long-term Late Effects Research Articles

Long-term late effects in older gastric cancer survivors: Survival analysis using Cox hazard regression model by retrospective electronic health records

PurposeBecause the population of older gastric cancer survivors (GCSs) is growing, understanding the long-term late effects experienced by these GCSs and their impact on survival outcomes is crucial for optimizing survivorship care. This study aims to identify and characterize these effects and investigate their association with survival outcomes.MethodsA retrospective analysis of electronic health records was conducted on 9,539 GCSs diagnosed between 2011 and 2017. The GCSs were divided into two age groups (< 65 and ≥ 65 years) and the long-term late effects were categorized by age using Cox proportional hazard models. The impact of clinical factors and age-specific late effects on survival was evaluated in the older GCSs.ResultsAmong the total GCSs, 37.6% were over and 62.4% were under 65 years of age. Significant differences between the age groups were observed in the cumulative hazard ratios (HRs) for iron and vitamin B12 levels and prognostic nutritional index (PNI) scores. In older GCSs, abnormal iron levels (HR 1.98, 95% CI 1.16–3.41, p = .013) and poor PNI scores (HR 1.59, 95% CI 1.03–2.47, p = .038) were associated with poorer survival outcomes. Additionally, being female was identified as a risk factor for lower survival rates (if male, HR 0.42, 95% CI 0.18–0.98, p = .045).ConclusionThis study highlights the typical long-term late effects experienced by older GCSs. By tailoring survivorship care to address nutritional-, age-, and gender-related factors, the overall survival and quality of life of older GCSs can be improved.

Multicenter Pilot Trial of Intrathecal Liposomal Cytarabine Combined with FAB Chemoimmunotherapy with Reduced Doxorubicin in CAYA with Mature De-Novo B-NHL

Background: Children, adolescents, and young adults (C-AYA) with newly diagnosed advanced Mature B Non-Hodgkin Lymphoma (MB-NHL), specifically Burkitt Lymphoma (BL) and Diffuse Large B Cell Lymphoma (DLBCL), have achieved ≥ 90% overall survival with multi-agent chemotherapy and intrathecal chemotherapy (IT) without central nervous system (CNS) radiation (Cairo et al., Blood 2007; Goldman/Cairo et al., BJH 2014; Frazier/Cairo, et al., BJH 2014; Minard-Colin, et al., NEJM 2020). Standard therapy includes short but intensive courses of multiagent chemotherapy including CNS-penetrating high dose methotrexate and cytarabine for CNS penetration as well as vincristine, prednisone, doxorubicin, and cyclophosphamide with or without etoposide. Patients also receive 9, 10 and 13 IT doses of intrathecal chemotherapy when treated according to FAB Group B, FAB Group C (CNS -) and FAB Group C (CNS +) protocols, respectively. While this approach has effectively eliminated need for CNS radiation for disease control, the need for sedation of patients during these procedures results in the need for repeated episodes of patient fasting, increased healthcare costs, and most importantly, general anesthesia is associated with long-term late effects in cognitive development (Banerjee et al., JAMA Oncol, 2019). Liposomal cytarabine (LC) is a formulation of cytarabine encapsulated in spherical multivesicular, biodegradable particles known as DepoCyt® which has a maximum-tolerated intrathecal dose of 35 mg in patients between the ages of 3 and 21 years (Bomgaars et al., JCO, 2004). This liposomal formulation has a half-life of 100-263 hours compared with only 3.4 hours of standard cytarabine. As an s-phase specific agent, prolonged exposure may increase its efficacy in controlling CNS disease while decreasing the total number of intraventricular doses required for treatment. Objective: To determine the safety and efficacy of reduction of IT therapy and substitution of LC within modified FAB group B and C backbones of systemic immunochemotherapy. Methods: LC was incorporated into the multiagent chemotherapy regimen in a unique manner to mitigate the risk of possible CNS toxicity. A total of 2 doses of LC were administered as part of the prophylaxis IT therapy for Group B and CNS negative group C patients. A total of 4 doses of LC were administered as part of the treatment of Group C CNS + patients (Table 1). The LC was given only in phases of therapy in which no systemic cytarabine was administered. When Methotrexate was given, the LC was only given after clearance. Dexamethasone replaced prednisone for all patients to mitigate potential CNS toxicities from LC. Results: This trial enrolled 33 patients with newly diagnosed MB-NHL (25 Group B, 8 Group C with 7 CNS+). Median age was 12 (Range 3-25). Males comprised 64% of patients and 52% had Burkitt Lymphoma/Leukemia. The CNS was involved in 21% of patients, and a total of 78 doses of LC was given. Twenty-six patients received 2 prophylactic doses (25 Group B and 1 Group C CNS negative). Six of seven CNS + patients received all 4 planned doses of LC. The median days from the start of the induction cycles until LC administration (post methotrexate clearance) was 3 days. Of the 33 patients, only 1 (3%) had a transient Grade 3 adverse event (facial nerve palsy). With dexamethasone prophylaxis, there were minimal adverse events and no toxic deaths reported. There were no other serious adverse events, such as seizure, headaches, nausea, vomiting, fever, somnolence, confusion, or asthenia that have been previously reported. The 2-year EFS and OS of LC when added to an FAB backbone for MB-NHL, was 94.5% and 97.2%, respectively (Figure 1). Conclusions: By utilizing dexamethasone prophylaxis and waiting for systemic methotrexate clearance, we were able to demonstrate that IT LC in C-AYAs with MB-NHL who received FAB chemoimmunotherapy with HD MTX was feasible, safe, and did not compromise event free and overall survival. We were also able to reduce the total number of IT injections without apparent compromise to CNS prophylaxis and treatment.

Associations between patient-reported late effects and systemic cytokines in long-term survivors of head and neck cancer treated with radiotherapy

PurposeHead and neck cancer (HNC) treatment may lead to late effects and impaired health-related quality of life of survivors. Knowledge on long-term late effects after radiotherapy (RT) and potential underlying biological mechanisms is lacking. We assessed the prevalence of xerostomia, dysphagia, and chronic fatigue (CF) in HNC survivors ≥ 5 years post-RT, and examined associations between pro-inflammatory cytokines and late effects.MethodsIn a cross-sectional study, 263 HNC survivors treated between 2007 and 2013 were enrolled. They completed validated questionnaires assessing xerostomia and dysphagia (the EORTC QLQ-H&N35), and CF (the Fatigue Questionnaire), and underwent blood sampling and clinical examination. Pro-inflammatory cytokines were analyzed in 262 survivors and 100 healthy age- and gender-matched controls.ResultsMedian time since treatment was 8.5 years. The proportions of survivors reporting xerostomia, dysphagia, and CF were 58%, 31%, and 33%, respectively, with a preponderance of females. We found no significant associations between IL-6, IL-8, IP-10, TARC, TNF, or ENA-78 and the three late effects. The odds of having elevated levels of IL-6 and IP-10 were significantly higher in the survivors compared to the controls.ConclusionsMore than one-third of long-term HNC survivors experienced xerostomia, dysphagia, and CF. Persistent inflammation, with elevated systemic cytokines, was not associated with these late effects, although HNC survivors had higher levels of some cytokines than the controls.Implications for Cancer SurvivorsThis study provides new knowledge on late effects that can serve as grounds for informing patients with HNC about risk of late effects more than 5 years after RT.

Side Effects 15 Years After Lymph Node Irradiation in Breast Cancer: Randomized EORTC Trial 22922/10925.

Uncertainty about the benefit-risk ratio of regional lymph node irradiation led to varying clinical protocols. We investigated long-term late side effects after internal mammary and medial supraclavicular (IM-MS) lymph node irradiation to improve shared decision making. The multicenter European Organization for Research and Treatment of Cancer trial (ClinicalTrials.gov, NCT00002851) randomly assigned stage I-III breast cancer patients with involved axillary nodes and/or a medially located primary tumor. We analyzed late side effects both longitudinally at every follow-up and cross-sectionally at 5-year intervals. All statistical tests were 2-sided. Between 1996 and 2004, 46 departments from 13 countries accrued 4004 patients. Median follow-up was 15.7 years. Longitudinal follow-up data showed cumulative incidence rates at 15 years of 2.9% (95% confidence interval [CI] = 2.2% to 3.8%) vs 5.7% (95% CI = 4.7% to 6.9%) (P < .001) for lung fibrosis, 1.1% (95% CI = 0.7% to 1.7%) vs 1.9% (95% CI = 1.3% to 2.6%) (P = .07) for cardiac fibrosis, and 9.4% (95% CI = 8.0% to 10.8%) vs 11.1% (95% CI = 9.6% to 12.7%) (P = .04) for any cardiac disease when treated without or with IM-MS lymph node irradiation. There was no evidence for differences between left- and right-sided breast cancer (Wald χ2 test of treatment by breast side interaction, P = .33 and P = .35, for cardiac fibrosis and for any cardiac disease, respectively). The cumulative incidence probabilities of cross-sectionally reported side effects with a score of 2 or greater at 15 years were 0.1% (95% CI = 0.0% to 0.5%) vs 0.8% (95% CI = 0.4% to 1.4%) for pulmonary (P = .02), 1.8% (95% CI = 1.1% to 2.8%) vs 2.6% (95% CI = 1.8% to 3.7%) for cardiac (P = .15), and 0.0% (95% CI not evaluated) vs 0.1% (95% CI = 0.0% to 0.4%) for esophageal (P = .16), respectively. No difference was observed in the incidence of second malignancies, contralateral breast cancer, or cardiovascular deaths. The incidence of late pulmonary side effects was statistically significantly higher after IM-MS lymph node irradiation, as were some of the cardiac events, without a difference between left- and right-sided treatments. Absolute rates and differences were very low, without increased non-breast cancer-related mortality, even before introducing heart-sparing techniques.

Cohort profile: an observational longitudinal data collection of health aspects in a cohort of female cancer survivors with a history of pelvic radiotherapy—a population-based cohort in the western region of Sweden

PurposeThe study ‘Health among women after pelvic radiotherapy’ was conducted in response to the need for more advanced and longitudinal data concerning long-term radiotherapy-induced late effects and chronic states among...

Effect of race/ethnicity on long-term cytopenias and major infections in adolescent young adult breast cancer survivors.

11568 Background: Many Adolescent and Young Adult (AYA) Breast Cancer (BC) patients receive chemotherapy as part of their initial treatment. Long-term bone marrow suppression is a potential complication, but no studies have evaluated the impact of race/ethnicity on the development in AYA BC survivors. Methods: Female patients ages 15-39 diagnosed with BC during 1996-2012 and surviving ≥ 2 years were obtained from the California Cancer Registry and linked to statewide hospitalization data. We estimated the cumulative incidence of developing anemia, leukopenia, or major infection/sepsis (≥ 2 years after diagnosis), accounting for death as a competing risk, and examined the impact of race/ethnicity using multivariable Cox proportional hazards regression. Results: Of 14,729 patients, 48.8% were non-Hispanic white, 8.3% non-Hispanic black, 25.5% Hispanic, and 16.5% Asian/Pacific Islander. At diagnosis, 95.5% had local or regional disease (27.7% stage I, 49.4% stage II), and were mostly treated with surgery (96.2%) and chemotherapy (74.3%). The 10-year cumulative incidence of anemia (16.8% vs 11.7%), leukopenia (4.6% vs 2.1%), and major infection/sepsis (13.2% vs 7.9%) was greater following initial treatment with chemotherapy (p &lt; 0.0001 for all vs no chemotherapy). In multivariable analyses controlling for sociodemographic factors, baseline comorbidities, treatment and stage, Blacks had the highest risk (vs. non-Hispanic whites) of medical late effects, including anemia [HR: 1.62, CI 1.41-1.86], leukopenia (HR: 1.53, CI 1.17-2.00), and major infection/sepsis (HR: 1.36, CI 1.16-1.60). Similarly, Hispanic and Asian/Pacific Islanders had a higher risk of developing anemia (HR: 1.16, CI 1.04-1.29; HR: 1.17, CI 1.03-1.33) and trended toward developing more leukopenia (HR: 1.24, CI 1.00-1.54; HR: 1.25, CI 0.98-1.61). Conclusions: AYAs of Black, Hispanic, and Asian/Pacific Islander race/ethnicity are at an increased risk of anemia and leukopenia after chemotherapy compared with non-Hispanic Whites. With improvements in prognostic testing resulting in potential decreased chemotherapy usage, there may be a decrease in long-term late effects for these young cancer survivors.

Long-term follow-up of intensive chemotherapy followed by reduced-dose and reduced-field irradiation for intracranial germ cell tumor.

OBJECTIVE The authors analyzed the efficacy of intensive chemotherapy followed by reduced-dose and reduced-field irradiation for intracranial germ cell tumors (GCTs) and evaluated the long-term late effects caused by chemoradiotherapy (CRT). METHODS The authors performed a retrospective study. The subjects were 24 patients who received CRT between April 1994 and April 2015. After surgery, intensive chemotherapy followed by reduced-dose and reduced-field irradiation was administered. For those with pure germinoma, who comprised the “good prognosis” group, five courses of conventional-dose chemotherapy (CDC) were administered, and radiotherapy (24 Gy) was applied to the whole ventricle. For all others, defined as the “intermediate and poor prognosis” group, two or three courses of CDC and high-dose chemotherapy were administered with peripheral blood stem cell transplantation and radiotherapy (24–30 Gy) applied to the whole ventricle or a larger field with or without local boost irradiation (20 Gy), which was applied as needed. RESULTS The median period of follow-up was 112.5 months (range 28–261 months), and the 5-/10-year overall and progression-free survival rates were 100%/83.5% and 91.3%/86.5%, respectively. The 5-/10-year overall survival rates determined based on the histological subtypes were 100%/100% for pure germinoma and 93.8%/78.7% for others, respectively. The late toxicities were as follows: endocrine disorder (33% in pure germinoma, 56% in others), involuntary movements (17% in pure germinoma, 39% in others), ear and labyrinth disorders (17% in pure germinoma, 33% in others), and psychiatric disorders (0% in pure germinoma, 33% in others). Nineteen of 24 patients underwent MRI (T2*- or susceptibility-weighted imaging) after radiotherapy, and 16 (84%) of those 19 patients had microbleeds detected, while 2 (10.5%) had radiation-induced cavernous vascular malformations detected. CONCLUSIONS Intensive chemotherapy followed by reduced-dose and reduced-field irradiation for intracranial GCTs had the same outcome as that reported in the literature, but late adverse effects after treatment were observed. Almost all of the complications were relatively mild but had the potential to lead to psychiatric disorders and intracranial hemorrhaging. ABBREVIATIONS AFP = alpha-fetoprotein; CDC = conventional-dose chemotherapy; CMB = cerebral microbleed; CRT = chemoradiotherapy; CSI = craniospinal irradiation; EP = etoposide and cisplatin; GCT = germ cell tumor; HCG = human chorionic gonadotropin; HDC = high-dose chemotherapy; ICE = ifosfamide, cisplatin, and etoposide; NGGCT = nongerminomatous GCT; OS = overall survival; PBSCT = peripheral blood stem cell transplantation; PFS = progression-free survival; RICM = radiation-induced cavernous malformation; STGC = syncytiotrophoblastic giant cell; SWI = susceptibility-weighted imaging.

Late Effects of Therapy in Childhood Acute Lymphoblastic Leukemia Survivors

Over the last 50 years, the survival rates in children with acute lymphoblastic leukemia (ALL) have increased remarkably. The optimal use of antileukemic agents in cooperative group protocols, central nervous system-directed treatment, improvements in supportive care, and recognition of biological, clinical, and treatment response characteristics that predict patients with a higher or a lower risk of treatment failure have improved 5-year event-free survival rates, reaching more than 85%, and 5-year overall survival rates, reaching more than 90%. Consequently, it has become increasingly important to characterize the occurrence of long-term late effects. ALL treatments have been associated with increased risks for adverse outcomes such as late mortality, secondary malignancies, and neurological, cardiac, endocrine, and social/psychological disorders. In recent decades, cooperative groups in Europe and in the United States have provided essential information about the long-term effects of ALL therapy, giving recommendations for screening as well as facilitating new approaches for reducing late-term morbidity and mortality. Current frontline protocols continue to examine ways to lower the intensity and amount of therapy to reduce late effects, whereas survivorship studies attempt to predict such adverse effects precisely and develop targeted prevention and treatment strategies.

Evaluation of racial disparities in pediatric optic pathway glioma incidence: Results from the Surveillance, Epidemiology, and End Results Program, 2000–2014

BackgroundRacial predilection to pediatric cancer exists; however optic pathway glioma (OPG) risk differences by race/ethnicity are undefined. We estimated differences in OPG incidence across racial/ethnic groups in a multi-state cancer surveillance registry in the United States. MethodsOPG data were obtained from the Surveillance, Epidemiology, and End Results (SEER-18) Program, 2000–2014. Race/ethnicity was categorized as: White; Black; Asian; Other; and Latino/a (“Spanish-Hispanic-Latino”). Latino/a included all races, while all other categories excluded those identified as Latino/a. Age-adjusted incidence rates and rate ratios (IRR) with 95% confidence intervals (CIs) were generated in SEER-STAT (v8.3.4). ResultsData on 709 OPG cases ages 0–19 were abstracted from SEER-18. Minority children experienced lower age-adjusted OPG incidence rates compared to White children (IRRBlack = 0.38, 95% CI: 0.28–0.50; IRRAsian = 0.41, 95% CI: 0.29–0.58; and IRRLatino/a = 0.39, 95% CI: 0.32–0.48). In subgroup analyses among the highest risk age categories (0–4, 5–9), minority children experienced lower incidence rates compared to White children. Specific patterns for Latinos/as also emerged. Latino/a children ages 0–4 experienced the lowest incidence rates of all racial/ethnic groups compared to Whites (0.24 per 100,000 person-years versus 0.66 per 100,000 person-years, respectively), whereas among those ages 5–9, Black and Asian children experienced the lowest incidence rates (0.08 per 100,000 person-years each). ConclusionsIncidence of OPGs was highest among White children. This study represents one of the largest to assess differences in OPG susceptibility by race/ethnicity. These findings may inform future studies that seek to evaluate modifying factors for this pediatric tumor including tumorigenesis, treatment, outcome, and long-term late effects.

Optimal local control and tolerability of three-dimensional conformal radiation therapy in prostate cancer: a single institutional experience of dose escalation in 125 patients.

To evaluate long-term late side effects, clinical and biochemical relapse in non-metastatic prostate cancer patients treated with dose escalation, from 74 to 78 Gy, by means of three dimensional conformal radiation therapy. Clinical data of 125 patients with prostate cancer who underwent three-dimensional conformal radiation therapy were retrospectively evaluated. All patients were stratified, according to the NCCN classification, in low, intermediate and high risk, and all of them showed histologically proven adenocarcinoma stage T1-T3 with at least 2 years of follow-up. Late toxicity was analyzed using a modified Radiation Therapy Oncology Group toxicity scale. With a median of follow-up of 48 months, grade ≥2 late genitourinary toxicity was reported in 18% and grade ≥2 gastrointestinal toxicity was detected in 12%. The PSA relapse rate was 20% in the high-risk group, 7% in the intermediate-risk group, and 3% in the low-risk group. Late side effects and tumor control in patients with non-metastatic prostate cancer in dose escalation from 74 to 78 Gy was acceptable. Three-dimensional conformal radiation therapy still represents a valid therapeutic option for departments where intensity-modulated radiation therapy or image-guided radiation therapy is still not available.

Dosimetric Comparison of Intensity-Modulated Radiation Therapy via Breath Hold Technique and Proton Therapy With or Without Breath Hold for Mediastinal Lymphoma

Treating patients affected with mediastinal lymphoma with radiation therapy (RT) has been associated with long-term late side effects. Deep inspiration breath-hold (BH) can result in significant dosimetric benefits to the heart and lung. We hypothesized that RT to the mediastinum with intensity modulated radiation therapy (IMRT) would be comparable to proton-free breathing (P-FB) plans but inferior to theoretical proton breath-hold (P-BH) plans in regards to dosimetry of organs at risk (OAR). Ten patients (including 5 females) that received mediastinal involved site RT with “butterfly” IMRT-BH and had 4D-CT treatment planning scans available were included. Female patients were positioned on a 15 degree inclined board for breast sparing. The Eclipse Treatment Planning System was used to generate two additional plans per patient (P-FB and P-BH), optimized to deliver 30.6 Gy or CGE in 17 fractions. We calculated total volume, mean dose, V30, V25, V15 and V5 for OAR including heart, left ventricle (LV), coronary arteries, lungs, and breasts. Comparisons were made using a non-parametric two tailed paired t test with a significant P value of < 0.05. All plans had to have comparable coverage of the PTV. Heart dose was not significantly different comparing IMRT-BH to P-FB, while P-BH significantly improved high and low doses to the heart (Table 1). There was a significant lower LV mean dose in favor of P-BH compared to IMRT-BH (1.0 Gy versus 3.3 Gy; P = 0.01). P-BH resulted in lower lung high and low doses compared to IMRT-BH and P-FB. Although lung V5 was significantly higher with IMRT-BH compared to both P-FB and P-BH, IMRT-BH significantly lowered the V30 and V25 (Table 1). In all plans, there were no statistically significant differences in mean dose, V30, V25, V15 or V5 for the left main/left anterior descending artery, right coronary artery, and bilateral breasts. Owing to its physical properties, proton RT can be advantageous for the treatment of lymphoma patients receiving RT to the mediastinum contingent on using deep inspiration BH technique; IMRT-BH was able to achieve comparable doses to the heart, breasts, and coronary arteries compared with P-FB plans.Tabled 1Abstract 130; Table 1OrganIMRT-BHP-FBP valueIMRT-BH vs. P-FBP-BHP valueIMRT-BH vs. P-BHP valueP-FB vs. P-BHLung Volume (cc)4369.62438.4.001 Mean Dose (Gy)861.9753.6.03664.7<.001.008 V306.810.8<.0018.7.004.001 V2513.916.2.00813.3.18.001 V2019.319.5.8616.4.001.001 V1524.523.4.4520.4.001.008 V540.533.8.00731.0<.001.03Heart Volume (cc)625.2653.1.23 Mean Dose (Gy)9.67.6.077.0.001.37 V3016.016.6.7415.0.43.32 V2521.719.9.5118.1.03.31 V1527.123.9.3522.1.02.35 V536.928.9.1026.8.004.36 Open table in a new tab

Hematopoietic stem cell transplantation for children with multiple sclerosis and neuromyelitis optica: Long-term outcomes and late effects

Hematopoietic stem cell transplantation for children with multiple sclerosis and neuromyelitis optica: Long-term outcomes and late effects

Adolescent and young adult (AYA) lymphoma survivors report lower health-related quality of life compared to a normative population: results from the PROFILES registry

Background: Trying to simultaneously achieve developmental milestones and cope with a life-threatening disease may place adolescents and young adults (AYAs) at risk for impaired health-related quality of life (HRQoL) later in life. The aim of this study was to examine differences in HRQoL between AYA lymphoma survivors and a normative population and to determine sociodemographic, clinical and long-term symptom-related factors associated with HRQoL.Material and methods: This study was part of a longitudinal, population-based survey among lymphoma survivors diagnosed between 1999 and 2012. The AYA survivor sample (18–39 years at time diagnosis) was compared to a sex- and age-matched normative population on HRQoL (EORTC-QLQ-C30) and psychological distress (HADS). Multiple linear regression analyses were conducted to determine factors associated with HRQoL among survivors.Results: One hundred and ninety-eight AYA lymphoma survivors (58%) responded to the study invitation. Compared to an age- and sex-matched normative population (N = 380), significantly and clinically relevant poorer HRQoL was observed for AYA lymphoma survivors in seven specific domains of HRQoL: physical, role, cognitive, emotional, social functioning, fatigue and financial difficulties (all p < 0.05). In addition, AYA lymphoma survivors less often had a spouse/partner and more often had a lower educational level compared to the normative population. Linear regression analyses showed that being unemployed, female gender, having one or more comorbid conditions, high levels of fatigue and psychological distress were most strongly associated with HRQoL.Conclusions: These findings identify specific domains of life in which cancer has a significant and long-term impact for AYA lymphoma survivors. Future investigations are needed to identify and test administrations and timing of psychosocial support interventions having potential to reduce long-term late effects in specific HRQoL domains and promote function and adaptability after cancer treatment.

Endocrine and Metabolic Disorders in Children with Cancer Treatment

Background: Survivors of childhood malignancy are at risk of long-term late effects. One of the most commonly involved systems in this effect is endocrine system. Appropriate timely recognition and treatment of late complications including endocrine complication is essential for the continuing health and improvement in quality of life in cancer survivors. Objectives: Therefore, this study has been conducted to investigate the aforementioned complications resulting from the treatment of the common malignancies in children in Iran. Patients and Methods: We performed a cross sectional study for evaluation of endocrine complication in cancer survivors who had finished their cancer treatment and come for followed up in oncology clinic of children medical center. Results: Demographic data, treatment modality, and endocrine late effect recorded and analyzed. There were 96 survivors with median age of 13.8 ± 5.8 years (range 3 - 31 years). The median follow up time was 2.7 years (range 1 - 10 years). Hyperinsulinemia was the most common late effect. Other complication was dyslipidemia, overweight, obesity, osteopenia, hypothyroidism, diabetes mellitus and osteoporosis respectively. Conclusions: Our study has demonstrated a significant prevalence of endocrine complication after childhood cancer therapy and a long term follow-up program for survivors of childhood cancer is therefore needed.

Abstract 3431: What are the greatest challenges of rectal cancer survivors? Results of a population-based survey

Abstract Purpose: Rectal cancer (RC) survivors with and without permanent ostomy have similar health-related quality of life outcomes, though these may be driven by different factors. Identifying patient-centered concerns among survivors with different surgical reconstructions can guide treatment decision-making and optimize survivorship care. Methods: We mailed a survey to long-term (≥5 years post-diagnosis) RC survivors enrolled in Kaiser Permanente (Northern California and Oregon/Southwest Washington). Participants with anastomosis, temporary ostomy, and permanent ostomy were asked an open-ended question about the “greatest challenge” they experienced related to their cancer surgery. Using a grounded theory approach, we identified all topics in the responses of 440 participants who wrote an answer (76% of 577 respondents). These topics were collapsed into codes and organized into domains. Responses were assigned as many codes as were applicable and double-coded by pairs of researchers who met to resolve any discrepancies. We used Bonferroni-adjusted chi-squares to test differences in the proportion of respondents within each surgical group who mentioned challenges in each domain. Results: Greatest challenge responses were provided by 241 participants with anastomosis, 54 with temporary ostomy, and 145 with permanent ostomy. Respondents were more educated but otherwise they resembled non-respondents demographically and clinically. Respondents described seven challenge domains: 1) bowel dysfunction; 2) bowel self-care; 3) post-operative recovery; 4) complications and late-effects; 5) negative psychosocial impacts; 6) comorbidities and aging (unrelated to RC); and 7) negative health care experiences. The most commonly reported problems in each group were bowel dysfunction, negative psychosocial impacts, complications and late effects, and bowel self-care. Anastomosis and temporary ostomy groups provided similar response profiles, but there were some significant differences in the proportion of respondents in each group who mentioned challenges for each domain. Respondents with permanent ostomy were less likely to mention challenges with bowel management than either respondents with temporary ostomy (p = .0024) or anastomosis (p = .0003). Respondents with temporary ostomy reported more complications and late effects than those with permanent ostomy (p = .0009). Respondents with anastomosis were less likely to report negative psychosocial impacts than those with permanent ostomy (p = .0003). Conclusions: We identified enduring concerns for long-term RC survivors that should be prioritized in survivorship care. Patients choosing among surgical options should know that long-term bowel dysfunction, complications, and late effects are more common concerns for patients without permanent ostomy. In contrast, patients with permanent ostomy report the most negative psychosocial impacts. Citation Format: Robert S. Krouse, Joanna E. Bulkley, Andrea Altschuler, Christopher S. Wendel, Marcia Grant, Mark C. Hornbrook, Virginia Sun, Carmit K. McMullen. What are the greatest challenges of rectal cancer survivors? Results of a population-based survey. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3431. doi:10.1158/1538-7445.AM2015-3431

Developing NaviCanPlan: A Mobile Web Resource Locator for Cancer Providers and Survivors.

As of January, 2012, an estimated 13.7 million persons are living as cancer survivors. This population is expected to grow to nearly 18 million by 2022. While their treatment may be considered successful, many cancer survivors experience long-term physical, emotional, and psychosocial late effects of treatment. Our focus was on community-based cancer care-both rural and urban-as almost 90% of cancer care occurs in community settings, where a full complement of supportive healthcare professionals may not be available. This study describes the results of stakeholder engagement and the feedback processes used to create NaviCanPlan, a mobile web resource locator designed to educate and inform both providers and survivors in finding health-related services, often in noncancer center settings. Individual interviews with survivors and providers regarding resource needs to address a variety of physical and psychosocial late effects were supplemented with site visits, web-based polling, and webinars discussions. Overall, the results indicated a need for a programmatic approach to providing education about community, medical, and nonmedical resources for providers and survivors. Design and content criteria for a web-based mobile resource locator were defined, articulated, and implemented.

Interstitial Brachytherapy for Childhood Soft Tissue Sarcomas: Long-Term Disease Outcome and Late Effects

Interstitial Brachytherapy for Childhood Soft Tissue Sarcomas: Long-Term Disease Outcome and Late Effects

Long-term positive and negative psychological late effects for parents of childhood cancer survivors: a systematic review.

Increasing survival rates in childhood cancer have yielded a growing population of parents of childhood cancer survivors (CCSs). This systematic review compiles the literature on positive and negative long-term psychological late effects for parents of CCSs, reported at least five years after the child's diagnosis and/or two years after the end of the child's treatment. Systematic searches were made in the databases CINAHL, EMBASE, PsycINFO, and PubMed. Fifteen studies, published between 1988 and 2010, from 12 projects were included. Thirteen studies used quantitative methodology, one quantitative and qualitative methodology, and one qualitative methodology. A total of 1045 parents participated in the reviewed studies. Mean scores were within normal ranges for general psychological distress, coping, and family functioning. However, a substantial subgroup reported a clinical level of general psychological distress, and 21–44% reported a severe level of posttraumatic stress symptoms. Worry, disease-related thoughts and feelings, marital strains, as well as posttraumatic growth was reported. Several factors were associated with the long-term late effects, such as parents' maladaptive coping during earlier stages of the childs disease trajectory and children's current poor adjustment. Quality assessments of reviewed studies and clinical implications of findings are discussed and recommendations for future research are presented.

Optimal Local Control and Tolerability of Three-Dimensional Conformal Radiation Therapy in Prostate Cancer: A Single Institutional Experience of Dose Escalation in 125 Patients

To evaluate long-term late side effects, clinical and biochemical relapse in non-metastatic prostate cancer patients treated with dose escalation, from 74 to 78 Gy, by means of three dimensional conformal radiation therapy. Clinical data of 125 patients with prostate cancer who underwent three-dimensional conformal radiation therapy were retrospectively evaluated. All patients were stratified, according to the NCCN classification, in low, intermediate and high risk, and all of them showed histologically proven adenocarcinoma stage T1-T3 with at least 2 years of follow-up. Late toxicity was analyzed using a modified Radiation Therapy Oncology Group toxicity scale. With a median of follow-up of 48 months, grade ≥2 late genitourinary toxicity was reported in 18% and grade ≥2 gastrointestinal toxicity was detected in 12%. The PSA relapse rate was 20% in the high-risk group, 7% in the intermediate-risk group, and 3% in the low-risk group. Late side effects and tumor control in patients with non-metastatic prostate cancer in dose escalation from 74 to 78 Gy was acceptable. Three-dimensional conformal radiation therapy still represents a valid therapeutic option for departments where intensity-modulated radiation therapy or image-guided radiation therapy is still not available.

Préservation de la fertilité chez les enfants et adolescents traités pour un cancer

Given the excellent survival rate of children and teenagers treated for cancer, careful should be given in order to minimize long-term late effects of treatments and to improve quality of life. In this regard, fertility preservation is particularly important. Age, sex and concomitant therapies have an impact on the level of risk of hypofertility, with a stronger risk for chemotherapeutic regimens including alkylating agents, and gonads or hypothalamo-pituitary axis radiotherapy. Assessment of gonadotoxic impact of treatment strategy and fertility preservation techniques are crucial for limiting late effects. The objective of this literature review is to develop guidance for pediatric oncologists and hematologists relative to fertility preservation methods, in children and teenagers receiving gonadotoxic treatment. Specific follow-up after treatment is also proposed.