The Ottawa clinical fear of recurrence instruments: A screener, self-report, and clinical interview.

OBJECTIVE: Clinical fear of cancer recurrence (FCR) was recently defined by a group of experts during a Delphi study. Five criteria were agreed upon, namely: (a) high levels of preoccupation, (b) high levels of worry, (c) that are persistent, (d) hypervigilance and hypersensitivity to physical sensations that e) may result in functional impairment. No existing instruments comprehensively capture all these criteria for clinical FCR. METHODS: To remedy this gap, a set of three patient-reported outcome instruments including a one-item screener, self-report questionnaire, and semi-structured clinical interview, named the Ottawa Clinical Fear of Recurrence instruments, were developed. To do so, the research team first conducted a literature review of potential items. Additional FCR experts discussed the content of the screener and interview. The self-report's items were assessed for content validity by the same expert panel using Likert ratings and the Content Validity Index to narrow down the number of items. The three instruments were piloted with a group of cancer survivors to assess face validity following the European Organization for Research and Treatment of Cancer recommendations. RESULTS: The literature review and content validity assessment led to a final draft pre-pilot of 23 potential items for the self-report questionnaire. The instruments were piloted. Pilot study participants suggested changing wording and response options (particularly for the self-report) for greater clarity. CONCLUSIONS: Based on the feedback received, minor modifications were made, mostly for the self-report. In general, content and face validity for the three instruments were good for both experts and cancer survivors.

When Lightning Strikes Twice: Routes to Second Malignancies in Young Patients.

SUMMARY: Given the rarity of cancer in childhood, it should be even more uncommon for pediatric cancer survivors to develop a second, independent malignancy, yet they incur a greatly elevated risk after initial remission. In this issue of Cancer Discovery, Sánchez-Guixé and colleagues unpick the origins of second tumours in four children, and the potential role platinum-based chemotherapy may play in subsequent tumorigenesis. See related article by Sánchez-Guixé et al., p. 953 (8).

Shifting Gears: Transitioning Healthy Lifestyle Education Into Early Post-Treatment Survivorship.

During cancer treatment, oncology nurses emphasize patient and family education about coping strategies to manage adverse events such as gastrointestinal effects and fatigue. However, information about how to return to health.

Closing the Gaps: Addressing the Unmet Needs of Cancer Survivors.

Moving Beyond Cancer to Wellness is a patient- and caregiver-focused educational outreach event with an inspirational message and lectures that address common concerns among cancer survivors. This event is open to the communi.

Measures of financial toxicity in cancer survivors: a systematic review.

PURPOSE: Comprehensive cancer-related financial toxicity (FT) measures as a multidimensional construct are lacking. The aims of this systematic review were to (1) identify full measures designed explicitly for assessing FT and evaluate their psychometric properties (content validity, structural validity, reliability, and other measurement properties) using Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN), and (2) provide an analysis of the domains of FT covered in these measures. METHODS: MEDLINE, CINAHL, Web of Science, and Cochrane CENTRAL were searched for quantitative studies published from January 2000 to July 2023 that reported psychometric properties of FT measures in cancer survivors. The psychometric properties of FT measures and study risk of bias were analysed using COSMIN. Each FT measure was compared against the six domains of FT recommended by Witte and colleagues. Results were synthesized narratively. The detailed search strategies are available in Table S1. RESULTS: Six FT tools including the COST-FACIT, PROFFIT, FIT, SFDQ, HARDS, and ENRICh-Spanish were identified. The COST-FACIT measure had good measurement properties. No measure reached an excellent level for overall quality but was mostly rated as sufficient. The SFDQ, HARDS, and ENRICh-Spanish were the most comprehensive in the inclusion of the six domains of FT. CONCLUSION: This review emphasizes the need for validated multidimensional FT measures that can be applied across various cancer types, healthcare settings, and cultural backgrounds. Furthermore, a need to develop practical screening tools with high predictive ability for FT is highly important, considering the significant consequences of FT. Addressing these gaps in future research will further enhance the understanding of FT.

"Being ill was the easy part": exploring cancer survivors' reactions to perceived challenges in engaging with primary healthcare.

PURPOSE: Cancer survivors experience barriers to primary healthcare (PHC) services. The aim was to explore reactions to and opinions about perceived challenges associated with PHC access and quality among cancer survivors in Sweden, including how they have acted to adapt to challenges. METHODS: Five semi-structured focus group interviews were conducted with cancer survivors (n = 20) from Skåne, Sweden, diagnosed with breast, prostate, lung, or colorectal cancer or malignant melanoma. Focus groups were mixed in regard to diagnosis. Data were analysed using a descriptive template analysis approach. RESULTS: In light of perceived challenges associated with access to adequate PHC, participants experienced that they had been forced to work hard to achieve functioning PHC contacts. The demands for self-sufficiency were associated with negative feelings such as loneliness and worry. Participants believed that cancer survivors who lack the ability to express themselves, or sufficient drive, risk missing out on necessary care due to the necessity of being an active patient. CONCLUSIONS: The findings highlight negative patient experiences. They have implications for the organization of care for cancer survivors as they indicate a need for more efficient post-treatment coordination between cancer specialist care and PHC providers, as well as increased support for patients leaving primary cancer treatment.

Effects of the "AI-TA" Mobile App With Intelligent Design on Psychological and Related Symptoms of Young Survivors of Breast Cancer: Randomized Controlled Trial.

BACKGROUND: Young women often face substantial psychological challenges in the initial years following cancer diagnosis, leading to a comparatively lower quality of life than older survivors. While mobile apps have emerged as potential interventions, their effectiveness remains inconclusive due to the diversity in intervention types and variation in follow-up periods. Furthermore, there is a particular dearth of evidence regarding the efficacy of these apps' intelligent features in addressing psychological distress with these apps. OBJECTIVE: This study aims to evaluate the effectiveness of a mobile app with intelligent design called "AI-TA" on cancer-related psychological health and ongoing symptoms with a randomized controlled design. METHODS: Women aged 18 to 45 years diagnosed with breast cancer were randomly assigned to the intervention or control group. The intervention was AI-TA, which included 2-way web-based follow-up every 2 weeks. Both intention-to-treat (ITT) and per-protocol (PP) analyses employed repeated measurement analysis of variance. The participants' background features, primary outcomes (psychological distress and frequency, self-efficacy, and social support), and secondary outcomes (quality of life) were measured using multiple instruments at 3 time points (baseline, 1-month intervention, and 3-month intervention). RESULTS: A total of 124 participants were randomly allocated to the control group (n=62, 50%) or intervention group (n=62, 50%). In total, 92.7% (115/124) of the participants completed the intervention. Significant improvements in psychological symptoms (Memorial Symptom Assessment Scale-Short Form) were observed in the ITT group from baseline to 1-month intervention relative to the control group (ITT vs control: 1.17 vs 1.23; P<.001), which persisted at 3-month follow-up (ITT vs control: 0.68 vs 0.91; P<.001). Both the ITT and PP groups exhibited greater improvements in self-efficacy (Cancer Behavior Inventory-Brief Version) than the control group at 1-month (ITT vs PP vs control: 82.83 vs 77.12 vs 65.35; P<.001) and 3-month intervention (ITT vs PP vs control: 92.83 vs 89.30 vs 85.65; P<.001). However, the change in social support (Social Support Rating Scale) did not increase significantly until 3-month intervention (ITT vs control: 50.09 vs 45.10; P=.002) (PP vs control: 49.78 vs 45.10; P<.001). All groups also experienced beneficial effects on quality of life (Functional Assessment of Cancer Therapy-Breast), which persisted at 3-month follow-up (P<.001). CONCLUSIONS: The intelligent mobile app AI-TA incorporating intelligent design shows promise for reducing psychological and cancer-related symptoms among young survivors of breast cancer. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200058823; https://www.chictr.org.cn/showproj.html?proj=151195.

Quality of life in chordoma survivors: results from the Chordoma Foundation Survivorship Survey.

OBJECTIVE: Chordomas are rare malignant bone tumors whose location in the skull base or spine, invasive surgical treatment, and accompanying adjuvant radiotherapy may all lead patients to experience poor quality of life (QOL). Limited research has been conducted on specific demographic and clinical factors associated with decreased QOL in chordoma survivors. Thus, the aim of the present study was to investigate several potential variables and their impact on specific QOL domains in these patients as well the frequencies of specific QOL challenges within these domains. METHODS: The Chordoma Foundation (CF) Survivorship Survey was electronically distributed to chordoma survivors subscribed to the CF Chordoma Connections forum. Survey questions assessed QOL in three domains: physical, emotional/cognitive, and social. The degree of impairment was assessed by grouping the participants into high- and low-challenge groups designated by having ≥ 5 or < 5 symptoms or challenges within a given QOL domain. Bivariate analysis of demographic and clinical characteristics between these groups was conducted using Fisher's exact test and the Mann-Whitney U-test. RESULTS: A total of 665 chordoma survivors at least partially completed the survey. On bivariate analysis, female sex was significantly associated with increased odds of significant emotional (p = 0.001) and social (p = 0.019) QOL burden. Younger survivors (age < 65 years) were significantly more likely to experience significant physical (p < 0.0001), emotional (p < 0.0001), and social (p < 0.0001) QOL burden. Skull base chordoma survivors had significantly higher emotional/cognitive QOL burden than spinal chordoma survivors (p = 0.022), while the converse was true for social QOL challenges (p = 0.0048). Survivors currently in treatment were significantly more likely to experience significant physical QOL challenges compared with survivors who completed their treatment > 10 years ago (p = 0.0074). Fear of cancer recurrence (FCR) was the most commonly reported emotional/cognitive QOL challenge (49.6%). Only 41% of the participants reported having their needs met for their physical QOL challenges as well as 25% for emotional/cognitive and 18% for social. CONCLUSIONS: The authors' findings suggest that younger survivors, female survivors, and survivors currently undergoing treatment for chordoma are at high risk for adverse QOL outcomes. Additionally, although nearly half of the participants reported a FCR, very few reported having adequate emotional/cognitive care. These findings may be useful in identifying specific groups of chordoma survivors vulnerable to QOL challenges and bring to light the need to expand care to meet the QOL needs for these patients.

The association between serum methylmalonic acid, cobalamin-related biomarkers, and long-term mortality risk in cancer survivors: a prospective cohort study.

BACKGROUND: Elevated serum methylmalonic acid (MMA), a marker of cobalamin (vitamin B12) deficiency, has been linked to cancer progression. However, the impact of MMA or cobalamin on mortality risk in cancer survivors remains unknown. OBJECTIVES: To explore the relationship between MMA, serum, dietary, and supplement of cobalamin, MMA metabolism-related genes, and poor prognosis in adult cancer survivors. METHODS: We analyzed data from 1988 cancer survivors aged ≥20 y. Patients were selected from the National Health and Nutrition Examination Survey and followed up until December 31, 2019. Weighted Cox proportional hazard regression was used to estimate hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) for mortality risk assessment. Genomic analysis identified MMA metabolism-related genes linked to early death in a 33-cancer-type cohort from The Cancer Genome Atlas. RESULTS: Among 1988 participants, 872 deaths occurred over a 10-year follow-up. Higher serum MMA levels were significantly linked to increased long-term mortality risk (tertile 3 compared with tertile 1: adjusted HR: 1.37; 95% CI: 1.11, 1.70; P-trend < 0.001). No associations were found between serum, dietary, and supplement of cobalamin and cancer survivor mortality (each P-trend > 0.143). However, MMA-associated mortality was notable in patients without deficiency. When combining cobalamin and MMA categories, multivariate-adjusted HR (95% CI) for all-cause mortality was 2.06 (95% CI: 1.60, 2.65) in participants with >250 nmol/L and cobalamin >295.1 pmol/L compared with those with MMA ≤250 nmol/L and cobalamin >295.1 pmol/L. Moreover, reduced transcriptional levels of MMA metabolism-related genes, indicating decreased mitochondrial MMA metabolism capability, are linked to an unfavorable prognosis in certain cancer types. CONCLUSIONS: Serum MMA was associated with long-term mortality risk in adult cancer survivors, which was more significant among individuals with higher levels of serum cobalamin. These findings suggest that mortality related to MMA was attributed to the insufficient flux of MMA metabolism, not cobalamin deficiency.

Longitudinal associations of diurnal rest-activity rhythms with fatigue, insomnia, and health-related quality of life in survivors of colorectal cancer up to 5 years post-treatment.

BACKGROUND: There is a growing population of survivors of colorectal cancer (CRC). Fatigue and insomnia are common symptoms after CRC, negatively influencing health-related quality of life (HRQoL). Besides increasing physical activity and decreasing sedentary behavior, the timing and patterns of physical activity and rest over the 24-h day (i.e. diurnal rest-activity rhythms) could also play a role in alleviating these symptoms and improving HRQoL. We investigated longitudinal associations of the diurnal rest-activity rhythm (RAR) with fatigue, insomnia, and HRQoL in survivors of CRC. METHODS: In a prospective cohort study among survivors of stage I-III CRC, 5 repeated measurements were performed from 6 weeks up to 5 years post-treatment. Parameters of RAR, including mesor, amplitude, acrophase, circadian quotient, dichotomy index, and 24-h autocorrelation coefficient, were assessed by a custom MATLAB program using data from tri-axial accelerometers worn on the upper thigh for 7 consecutive days. Fatigue, insomnia, and HRQoL were measured by validated questionnaires. Confounder-adjusted linear mixed models were applied to analyze longitudinal associations of RAR with fatigue, insomnia, and HRQoL from 6 weeks until 5 years post-treatment. Additionally, intra-individual and inter-individual associations over time were separated. RESULTS: Data were available from 289 survivors of CRC. All RAR parameters except for 24-h autocorrelation increased from 6 weeks to 6 months post-treatment, after which they remained relatively stable. A higher mesor, amplitude, circadian quotient, dichotomy index, and 24-h autocorrelation were statistically significantly associated with less fatigue and better HRQoL over time. A higher amplitude and circadian quotient were associated with lower insomnia. Most of these associations appeared driven by both within-person changes over time and between-person differences in RAR parameters. No significant associations were observed for acrophase. CONCLUSIONS: In the first five years after CRC treatment, adhering to a generally more active (mesor) and consistent (24-h autocorrelation) RAR, with a pronounced peak activity (amplitude) and a marked difference between daytime and nighttime activity (dichotomy index) was found to be associated with lower fatigue, lower insomnia, and a better HRQoL. Future intervention studies are needed to investigate if restoring RAR among survivors of CRC could help to alleviate symptoms of fatigue and insomnia while enhancing their HRQoL. TRIAL REGISTRATION: EnCoRe study NL6904 ( https://www.onderzoekmetmensen.nl/ ).

E-PROOF: E-intervention for protein intake and resistance training to optimize function: A study protocol.

BACKGROUND: Accounting for more than 60% of cancer survivors, older (≥65 years) cancer survivors have a 2- to 5-fold risk of physical function impairment, compared to cancer-free peers. One strategy to improve physical function is dietary and resistance training interventions, which improve muscle strength and mass by stimulating muscle protein synthesis. The E-PROOF (E-intervention for Protein Intake and Resistance Training to Optimize Function) study will examine the feasibility, acceptability, and preliminary efficacy of a 12-week randomized controlled trial of an online, tailored nutritional and resistance training education and counseling intervention to improve physical function and associated health outcomes (muscle strength, health-related quality of life (HRQoL), self-efficacy, and weight management). METHODS: In this study, 70 older cancer survivors will be randomized to one of two groups: experimental (receiving remote behavioral counseling and evidence-based education and resources), and control (general survivorship education). We will examine the intervention effects on physical function, muscle strength, HRQoL, self-efficacy, weight, and waist circumference during a 12-week period between the experimental and control groups. Three months following the end of the intervention, we will conduct a follow-up assessment to measure physical function, muscle strength, and HRQoL. SIGNIFICANCE AND IMPACT: This study is the first synchronous, online protein-focused diet and resistance training intervention among older cancer survivors. This novel study advances science by promoting independent health behaviors among older cancer survivors to improve health outcomes, and provide foundational knowledge to further address this growing problem on a wider scale through online platforms.

Psychosocial experiences regarding potential fertility loss and pregnancy failure after treatment in cancer survivors of reproductive age to identify psychosocial care needs: a systematic review.

PURPOSE: The challenges of fertility loss owing to cancer treatment persist long after treatment. However, psychosocial care for fertility among cancer survivors who have completed cancer treatment is insufficient. This systematic review examined psychosocial experiences related to the potential loss of fertility and unsuccessful pregnancy after treatment in cancer survivors of reproductive age to identify psychosocial care needs. METHODS: A systematic review was conducted using the online databases PubMed, Cochrane Library, PsycINFO, CINAHL, and Ichushi-Web between August and December 2022 to identify studies that addressed psychosocial experiences after fertility loss or failure to conceive among young cancer survivors. Study quality was assessed using the Mixed Methods Appraisal Tool. RESULTS: Forty studies were included, revealing psychosocial experiences across five categories: subjective fear of (potential) fertility loss, impact on romantic relationships, alternative methods for family building, reliance on social support, and specialized care. Only one study addressed the psychosocial aspects after complete loss of fertility in young cancer survivors. CONCLUSIONS: The possibility and uncertainty of fertility loss led to stress and depression, loss of identity, decreased opportunities to meet a new partner, and damaged relationships established before diagnosis. The needs encompass fertility preservation, sexuality, approaches to building a family, partner communication, and other diverse needs.

A caregivers' perspective on social reintegration and stigma of childhood cancer survivors in Kenya.

OBJECTIVES: Childhood cancer survivors' social reintegration may be hampered in low and middle-income countries. The nature and extent of social challenges and prejudices that survivors encounter in such settings are largely unknown. This study explores caregivers' perspectives on social reintegration and stigmatization of Kenyan childhood cancer survivors. METHODS: Caretakers of childhood cancer survivors (<18 years) were interviewed using mixed-methods questionnaires during home or clinic visits between 2021 and 2022. Stigma was assessed with an adjusted Social Impact Scale and risk factors were investigated. RESULTS: Caretakers of 54 survivors (median age 11 years) were interviewed. Families' income (93%) decreased since start of treatment. Caretakers (44%) often lost their jobs. Financial struggles (88%) were a burden that provoked conflicts within communities (31%). School fees for siblings became unaffordable (52%). Families received negative responses (26%) and were left or avoided (13%) by community members after cancer disclosure. Survivors and families were discriminated against because the child was perceived fragile, and cancer was considered fatal, contagious, or witchcraft. Survivors repeated school levels (58%) and were excluded from school activities (19%) or bullied (13%). Performance limitations of daily activities (p = 0.019), male sex (p = 0.032), solid tumors (p = 0.056) and a short time since treatment completion (p = 0.047) were associated with increased stigma. Caretakers recommended educational programs in schools and communities to raise awareness about cancer treatment and curability. CONCLUSIONS: Childhood cancer survivors and their families experienced difficulties with re-entry and stigmatization in society. Increasing cancer and survivorship awareness in schools and communities should facilitate social reintegration and prevent stigmatization.

Missingness mechanisms and generalizability of patient reported outcome measures in colorectal cancer survivors - assessing the reasonableness of the "missing completely at random" assumption.

BACKGROUND: Patient-Reported Outcome Measures (PROM) provide important information, however, missing PROM data threaten the interpretability and generalizability of findings by introducing potential bias. This study aims to provide insight into missingness mechanisms and inform future researchers on generalizability and possible methodological solutions to overcome missing PROM data problems during data collection and statistical analyses. METHODS: We identified 10,236 colorectal cancer survivors (CRCs) above 18y, diagnosed between 2014 and 2018 through the Danish Clinical Registries. We invited a random 20% (2,097) to participate in a national survey in May 2023. We distributed reminder e-mails at day 10 and day 20, and compared Initial Responders (response day 0-9), Subsequent Responders (response day 10-28) and Non-responders (no response after 28 days) in demographic and cancer-related characteristics and PROM-scores using linear regression. RESULTS: Of the 2,097 CRCs, 1,188 responded (57%). Of these, 142 (7%) were excluded leaving 1,955 eligible CRCs. 628 (32%) were categorized as initial responders, 418 (21%) as subsequent responders, and 909 (47%) as non-responders. Differences in demographic and cancer-related characteristics between the three groups were minor and PROM-scores only marginally differed between initial and subsequent responders. CONCLUSION: In this study of long-term colorectal cancer survivors, we showed that initial responders, subsequent responders, and non-responders exhibit comparable demographic and cancer-related characteristics. Among respondents, Patient-Reported Outcome Measures were also similar, indicating generalizability. Assuming Patient-Reported Outcome Measures of subsequent responders represent answers by the non-responders (would they be available), it may be reasonable to judge the missingness mechanism as Missing Completely At Random.

Adding COVID to cancer: does cancer status influence COVID-19 infection preventive behaviors?

Introduction: A better understanding of how to promote disease mitigation and prevention behaviors among vulnerable populations, such as cancer survivors, is needed. This study aimed to determine patterns of and factors associated with COVID-19-related preventive behaviors among cancer survivors and assess whether the COVID-19 preventive behaviors of cancer survivors differ from the general population. Methods: In June 2020, an online survey of adults (N = 897) assessed predictors of COVID-19-related preventive behaviors, including socio-demographics, COVID-19 beliefs and perceptions (Health Belief Model [HBM] variables), and cancer statuses (cancer survivors currently in treatment, cancer survivors not currently in treatment, and individuals with no history of cancer). An average score of respondent engagement in eight preventive behaviors was calculated. Differences in HBM variables and preventive behaviors by cancer status were assessed using ANCOVAs. Hierarchical multiple regression analyzed associations among socio-demographics, HBM constructs, cancer statuses, and engagement in COVID-19 preventive behaviors. Results: Participants reported engaging in 3.5 (SD = 0.6) preventive behaviors. Cancer survivors not in treatment engaged in preventive behaviors significantly less than the comparison group. In the final adjusted model, after adding COVID-19 beliefs and perceptions, cancer status was no longer significant. All HBM constructs except perceived susceptibility were significant predictors of preventive behaviors. Conclusions: COVID-19 beliefs and perceptions were more robust predictors preventive behaviors than cancer status. Nonetheless, public health organizations and practitioners should communicate the risk and severity of infection among cancer survivors and emphasize the need to engage in protective behaviors for COVID-19 and other infectious diseases with this vulnerable population.

Qualitative exploration of sexual dysfunction and associated coping strategies among Iranian prostate cancer survivors.

OBJECTIVE: Our understanding of the experiences of prostate cancer survivors regarding their sexual life and related issues remains limited. Therefore, this study aimed to explore sexual dysfunction and associated coping strategies among Iranian prostate cancer survivors. METHODS: A qualitative study was undertaken. Participants were 15 Iranian prostate cancer survivors chosen using purposeful sampling. Data collection involved conducting in-depth semi-structured interviews, followed by the utilization of the conventional qualitative content analysis method for data analysis. RESULTS: Three themes were developed: (a) suspension of sexual life-treatment for prostate cancer significantly impacted participants' sexual lives; (b) emotional resilience and psychological coping strategies-various psychological strategies were used to tackle sexual dysfunction; (c) efforts to regain sexual function-several strategies were applied to enhance sexual performance. CONCLUSION: Our study findings provide insights into the experiences of prostate cancer survivors and subsequent shifts in their sexual dynamics and coping with the disease. Healthcare providers should actively identify patients' concerns and develop culturally tailored care strategies to address sexual challenges and improve coping among prostate cancer survivors.

Radiation Dose-Volume-Response Relationships for Adverse Events in Childhood Cancer Survivors: Introduction to the Scientific Issues in PENTEC.

At its very core, radiation oncology involves a trade-off between the benefits and risks of exposing tumors and normal tissue to relatively high doses of ionizing radiation. This trade-off is particularly critical in childhood cancer survivors (CCS), in whom both benefits and risks can be hugely consequential due to the long life expectancy if the primary cancer is controlled. Estimating the normal tissue-related risks of a specific radiation therapy plan in an individual patient relies on predictive mathematical modeling of empirical data on adverse events. The Pediatric Normal-Tissue Effects in the Clinic (PENTEC) collaborative network was formed to summarize and, when possible, to synthesize dose-volume-response relationships for a range of adverse events incident in CCS based on the literature. Normal-tissue clinical radiation biology in children is particularly challenging for many reasons: (1) Childhood malignancies are relatively uncommon-constituting approximately 1% of new incident cancers in the United States-and biologically heterogeneous, leading to many small series in the literature and large variability within and between series. This creates challenges in synthesizing data across series. (2) CCS are at an elevated risk for a range of adverse health events that are not specific to radiation therapy. Thus, excess relative or absolute risk compared with a reference population becomes the appropriate metric. (3) Various study designs and quantities to express risk are found in the literature, and these are summarized. (4) Adverse effects in CCS often occur 30, 50, or more years after therapy. This limits the information content of series with even very extended follow-up, and lifetime risk estimates are typically extrapolations that become dependent on the mathematical model used. (5) The long latent period means that retrospective dosimetry is required, as individual computed tomography-based radiation therapy plans gradually became available after 1980. (6) Many individual patient-level factors affect outcomes, including age at exposure, attained age, lifestyle exposures, health behaviors, other treatment modalities, dose, fractionation, and dose distribution. (7) Prospective databases with individual patient-level data and radiation dosimetry are being built and will facilitate advances in dose-volume-response modeling. We discuss these challenges and attempts to overcome them in the setting of PENTEC.

Reporting Standards for Complication Studies of Radiation Therapy for Pediatric Cancer: Lessons From PENTEC.

The major aim of Pediatric Normal Tissue Effects in the Clinic (PENTEC) was to synthesize quantitative published dose/-volume/toxicity data in pediatric radiation therapy. Such systematic reviews are often challenging because of the lack of standardization and difficulty of reporting outcomes, clinical factors, and treatment details in journal articles. This has clinical consequences: optimization of treatment plans must balance between the risks of toxicity and local failure; counseling patients and their parents requires knowledge of the excess risks encountered after a specific treatment. Studies addressing outcomes after pediatric radiation therapy are particularly challenging because: (a) survivors may live for decades after treatment, and the latency time to toxicity can be very long; (b) children's maturation can be affected by radiation, depending on the developmental status of the organs involved at time of treatment; and (c) treatment regimens frequently involve chemotherapies, possibly modifying and adding to the toxicity of radiation. Here we discuss: basic reporting strategies to account for the actuarial nature of the complications; the reporting of modeling of abnormal development; and the need for standardized, comprehensively reported data sets and multivariate models (ie, accounting for the simultaneous effects of radiation dose, age, developmental status at time of treatment, and chemotherapy dose). We encourage the use of tools that facilitate comprehensive reporting, for example, electronic supplements for journal articles. Finally, we stress the need for clinicians to be able to trust artificial intelligence models of outcome of radiation therapy, which requires transparency, rigor, reproducibility, and comprehensive reporting. Adopting the reporting methods discussed here and in the individual PENTEC articles will increase the clinical and scientific usefulness of individual reports and associated pooled analyses.