Health care utilization by long-term survivors of blood or marrow transplantation-A Bone Marrow Transplant Survivor Study report.

BACKGROUND: Blood or marrow transplantation (BMT) survivors carry a high burden of morbidity, yet health care utilization by this vulnerable population remains understudied. Patterns and predictors of various domains of health care utilization in long-term BMT survivors were evaluated. METHODS: Study participants were drawn from the Bone Marrow Transplant Survivor Study (BMTSS). Patients transplanted between 1974 and 2014 at one of three transplant centers who had survived ≥2 years after BMT and were aged ≥18 years at the time of the study were included. A BMTSS survey served as the source of data for health care utilization, sociodemographics, and chronic health conditions. Domains of health care utilization in the 2 years preceding study participation included routine checkups, BMT-related visits, transplant/cancer center visits, emergency room (ER) visits, hospitalizations, and high health care utilization (≥7 physician visits during the 2 years before the study). Clinical characteristics and therapeutic exposures were abstracted from medical records. RESULTS: In this cohort of 3342 BMT survivors (52% allogeneic), the prevalence of health care utilization declined over time since BMT for both allogeneic and autologous BMT survivors, such that among those who had survived ≥20 years, only 49%-53% had undergone routine checkups, 37%-38% reported BMT-related visits, and 28%-29% reported transplant/cancer center visits. The presence of severe/life-threatening conditions and chronic graft-vs-host disease increased the odds of health care utilization across all domains. Lower education, lack of insurance, and Hispanic ethnicity were associated with a lower prevalence of routine checkups and/or transplant/cancer center visits. Lower income increased the odds of ER visits but reduced the odds of hospitalizations or high health care utilization. CONCLUSIONS: This study identified vulnerable populations of long-term BMT survivors who would benefit from specialized risk-based anticipatory care to reduce high health care utilization, ER visits, and hospitalizations.

Pharmacogenomic predictor of long-term residual chemotherapy-induced peripheral neuropathy in ovarian cancer survivors: A substudy of the GINECO Vivrovaire study.

BACKGROUND: Chemotherapy (CT) remains a backbone treatment of epithelial ovarian cancer (EOC) inducing persistent peripheral neuropathy (CIPN). Using a dedicated patient-reported outcome tool, this study investigated persistent CIPN and its pharmacogenetic predictors in a cohort of long-term EOC survivors. METHODS: Vivrovaire was a French multicenter cohort of patients with EOC free of disease 3 years after CT completion. Persistent CIPN was assessed using the FACT/GOG-Ntx4 self-questionnaire. The association of homozygous (hom) or heterozygous (het) single nucleotide polymorphisms (SNPs) in selected genes was evaluated. RESULTS: 130 patients were included with a median time from CT completion of 63 [35-180] months. The median CIPN score was 37 [18-44], with 35 (26.9%) patients reporting severe CIPN (<33). SNPs were identified as follows: CYP2C8 [hom, n = 32 (24.6%)/het, n = 99, (76.2%)]; CYP3A4 [hom, n = 0 (0%)/het, n = 8 (6.2%)], ERCC1 [hom, n = 21 (16.2%)/het, n = 57 (43.8%)], and XPC [hom, n = 45 (34.6%)/het, n = 66 (50.8%)]. In univariate analysis, the identification of ≥1 hom SNP was associated with a lower CIPN score (continuous variable; p = 0.045). Patients harboring hom or het CYP2C8_rs1934951 SNP reported more likely severe CIPN (threshold <33) score (OR 2.482; 95% CI [1.126-5.47], p = 0.024). In the multivariate analyses, age, interval from CT completion, type and number of CT courses were not significantly associated with CIPN score (OR 5.165, 95% CI [0.478-55.83], p = 0.176). CONCLUSIONS: Persistent CIPN is common among ovarian cancer long-term survivors. CYP2C8_rs1934951 SNP may be associated with severe residual CIPN in EOC survivors. More studies are warranted to identify predictive factors of CIPN.

Improving Care for People Aging with HIV: A Collaborative Quality Improvement Approach.

Nearly 60% of people with HIV in New York State are over 50 years of age. After town halls and a statewide survey of long-term survivors, older people living with HIV, and their providers, the Quality of Care Program of the AIDS Institute in the New York State Department of Health developed a statewide quality improvement project that aimed to improve screening for functional impairments among people aging with HIV. Thirteen sites reported outcomes of a pilot project using a modification of the World Health Organization's Integrated Care of Older People (ICOPE) intrinsic capacity screen in small scale, short cycle tests of change. A total of 1,629 people were found to be eligible for screening, and of these, 638 people were screened. Both clinical and non-clinical sites were able to identify significant areas of need. Positive screens ranged from a low of 17% for the identification of hearing issues to 49% for vision concerns. Only 11% of people with memory or nutritional concerns were referred for services; hearing loss was the domain with the largest number of referrals, at 27%. Although in many cases, when referrals were not made, patients/clients were already under care for the identified functional deficit, in other cases no services were available for referral or patients/clients declined to use the offered service. Sites also responded to the findings of the screen by initiating process changes, and many reported continuing to screen for functional impairments after the close of the pilot. The modified ICOPE screen is still in use in sites throughout the state. This pilot demonstrated that a collaboration between people with lived HIV experience, the New York State Department of Health, clinicians, and service providers could result in improved quality of care for people aging with HIV.

Network visualization to interpret which healthcare services are central to people living with HIV.

AIM: To employ network analysis to identify the central healthcare service needs of people living with HIV (PLWH) for integrated care. DESIGN: Cross-sectional survey. METHODS: A list of healthcare services was identified through literature reviews, expert workshops and validity evaluations by PLWH. A total of 243 PLWH participated at five hospitals and self-reported their need for healthcare services on a four-point Likert scale. Centrality of healthcare service needs was analysed using network analysis. RESULTS: The mean score for 20 healthcare service needs was 3.53 out of 4. The highest scoring need, "Precaution for interaction between antiretroviral therapy and other drugs," received a rating of 3.73 but had a centrality of only 0.31. The most central node in the network of healthcare service needs, "Information and coping with opportunistic infections," had a strength centrality of 1.63 and showed significant relationships with "non-HIV-related medical services (e.g., health check-ups)" and "Regular dental services." The correlation stability coefficient, which quantifies the stability of centrality, was 0.44 with an acceptable value. CONCLUSIONS: The most central need was information on opportunistic infections that had connections with many nodes in network analysis. By interpreting the relationships between needs, healthcare providers can design interventions with an integrative perspective. IMPLICATIONS FOR PATIENT CARE: Network visualization provides dynamic relationships between needs that are unknown from the score scale by presenting them graphically and qualitatively. IMPACT: Using network analysis to interpret need assessment offers an integrated nursing perspective. Coping with opportunistic infection is central to connecting the chain of healthcare. This study highlights the multifaceted understanding of patients' needs that nurses gain when they conduct network analysis. REPORTING METHOD: We adhered to the STROBE checklist. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Deoxyhypusine hydroxylase: A novel therapeutic target differentially expressed in short-term vs long-term survivors of glioblastoma.

Glioblastoma (GB) is the most aggressive neoplasm of the brain. Poor prognosis is mainly attributed to tumor heterogeneity, invasiveness and drug resistance. Only a small fraction of GB patients survives longer than 24 months from the time of diagnosis (ie, long-term survivors [LTS]). In our study, we aimed to identify molecular markers associated with favorable GB prognosis as a basis to develop therapeutic applications to improve patients' outcome. We have recently assembled a proteogenomic dataset of 87 GB clinical samples of varying survival rates. Following RNA-seq and mass spectrometry (MS)-based proteomics analysis, we identified several differentially expressed genes and proteins, including some known cancer-related pathways and some less established that showed higher expression in short-term (<6 months) survivors (STS) compared to LTS. One such target found was deoxyhypusine hydroxylase (DOHH), which is known to be involved in the biosynthesis of hypusine, an unusual amino acid essential for the function of the eukaryotic translation initiation factor 5A (eIF5A), which promotes tumor growth. We consequently validated DOHH overexpression in STS samples by quantitative polymerase chain reaction (qPCR) and immunohistochemistry. We further showed robust inhibition of proliferation, migration and invasion of GB cells following silencing of DOHH with short hairpin RNA (shRNA) or inhibition of its activity with small molecules, ciclopirox and deferiprone. Moreover, DOHH silencing led to significant inhibition of tumor progression and prolonged survival in GB mouse models. Searching for a potential mechanism by which DOHH promotes tumor aggressiveness, we found that it supports the transition of GB cells to a more invasive phenotype via epithelial-mesenchymal transition (EMT)-related pathways.

Comparative analysis of deeply phenotyped GBM cohorts of 'short-term' and 'long-term' survivors.

BACKGROUND: Glioblastoma (GBM) is an aggressive brain cancer that typically results in death in the first 15 months after diagnosis. There have been limited advances in finding new treatments for GBM. In this study, we investigated molecular differences between patients with extremely short (≤ 9 months, Short term survivors, STS) and long survival (≥ 36 months, Long term survivors, LTS). METHODS: Patients were selected from an in-house cohort (GLIOTRAIN-cohort), using defined inclusion criteria (Karnofsky score > 70; age < 70 years old; Stupp protocol as first line treatment, IDH wild type), and a multi-omic analysis of LTS and STS GBM samples was performed. RESULTS: Transcriptomic analysis of tumour samples identified cilium gene signatures as enriched in LTS. Moreover, Immunohistochemical analysis confirmed the presence of cilia in the tumours of LTS. Notably, reverse phase protein array analysis (RPPA) demonstrated increased phosphorylated GAB1 (Y627), SRC (Y527), BCL2 (S70) and RAF (S338) protein expression in STS compared to LTS. Next, we identified 25 unique master regulators (MR) and 13 transcription factors (TFs) belonging to ontologies of integrin signalling and cell cycle to be upregulated in STS. CONCLUSION: Overall, comparison of STS and LTS GBM patients, identifies novel biomarkers and potential actionable therapeutic targets for the management of GBM.

On the parameter estimation of Box-Cox transformation cure model.

We propose an improved estimation method for the Box-Cox transformation (BCT) cure rate model parameters. Specifically, we propose a generic maximum likelihood estimation algorithm through a non-linear conjugate gradient (NCG) method with an efficient line search technique. We then apply the proposed NCG algorithm to BCT cure model. Through a detailed simulation study, we compare the model fitting results of the NCG algorithm with those obtained by the existing expectation maximization (EM) algorithm. First, we show that our proposed NCG algorithm allows simultaneous maximization of all model parameters unlike the EM algorithm when the likelihood surface is flat with respect to the BCT index parameter. Then, we show that the NCG algorithm results in smaller bias and noticeably smaller root mean square error of the estimates of the model parameters that are associated with the cure rate. This results in more accurate and precise inference on the cure rate. In addition, we show that when the sample size is large the NCG algorithm, which only needs the computation of the gradient and not the Hessian, takes less CPU time to produce the estimates. These advantages of the NCG algorithm allows us to conclude that the NCG method should be the preferred estimation method over the already existing EM algorithm in the context of BCT cure model. Finally, we apply the NCG algorithm to analyze a well-known melanoma data and show that it results in a better fit when compared to the EM algorithm.

A study of modifiable factors associated with health-related quality of life in long-term cervical cancer survivors.

INTRODUCTION: Health-related quality of life (HR-QoL) in cancer survivors is relevant for symptom relief and optimal care. The aim of this cross-sectional study of long-term cervical cancer survivors was two-fold: (a) To compare HR-QoL in long-term cervical cancer survivors with reference data; and (b) to identify modifiable factors significantly associated with low levels of generic cancer HR-QoL in long-term cervical cancer survivors using high HR-QoL as reference. MATERIAL AND METHODS: Women treated for cervical cancer from 2000 through 2007 who were cancer-free and alive in 2013 received a mailed questionnaire including scales for anxiety, depression, and HR-QoL. To obtain a homogeneous sample only women with FIGO stages 1 and 2 were included. The questionnaire included the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire.C-30 (EORTC QLQ C-30) for generic HR-QoL. Groups with high and low HR-QoL were defined by the median score on the general HR-QoL item. Between-group differences were examined with descriptive statistics. Logistic regression analyses examined independent variables associated with low generic HR-QoL. RESULTS: Complete C-30 scores were delivered by 472 long-term cervical cancer survivors. Median age at survey was 53 (interquartile range 14.9) years, and median time since diagnosis was 11 (interquartile range 3.9) years. The proportion of survivors with stage 1 disease was 83% and stage 2 was 17%. Mean generic HR-QoL scores showed minor differences between long-term cervical cancer survivors and reference data. In the multivariable analysis, only modifiable variables remained significantly associated with low generic HR-QoL namely self-rated health, probable depression, fatigue, and pain. In bivariate analyses other modifiable variables also showed significant associations with low generic HR-QoL like probable anxiety disorder, obesity, smoking, sleep disturbances, and bowel symptoms. CONCLUSIONS: Clinicians should be aware that generic HR-QoL in long-term cervical cancer survivors eventually may be improved by identification and treatment of modifiable factors through the whole follow-up period.

A randomised controlled trial to improve the resilience of oesophageal cancer survivors in rural China: A study protocol.

AIM: To design a protocol based on the experiences of long-term survivors to facilitate resilience for oesophageal cancer patients in rural China. BACKGROUND: According to the latest Global Cancer Statistics Report, 604,000 new cases of oesophageal cancer were reported, of which over 60% of the disease burden is distributed in China. The incidence of oesophageal cancer in rural China (15.95/100,000) is twice as high as those in urban areas (7.59/100,000). To be sure, resilience can help patients better adapt to post-cancer life. But universal interventions involving improving the resilience of oesophageal cancer patients have much less been explored, especially for rural patients. METHODS: The two-arm, parallel design, non-blinded, randomised controlled trial will be implemented in 86 adults diagnosed with oesophageal cancer and will be randomly assigned to the control group or the intervention group via the blocked randomisation. The intervention group will undergo an intervention with one-on-one guidance from a nurse while viewing a CD of the experiences of long-term survivors with oesophageal cancer in rural areas. Every 2 weeks, a theme session will be introduced, and the entire intervention will continue for 12 weeks. Psychosocial variables (resilience, self-efficacy, coping mode and family support) will be surveyed at baseline, post-intervention and 3 months after the intervention. The paper complies with the Standard Protocol Items: Recommendations for Intervention Trials 2013 and Consolidated Standards of Reporting Trials guidelines for study protocols adapted for designing and reporting parallel group randomised trials. CONCLUSION: The intervention programme transitions from hospitalisation to discharge, which includes one-on-one interventions by medical personnel and a portable CD describing the experiences of long-term survivors with rural oesophageal cancer. Once the intervention's effectiveness is proven, this protocol will provide psychological support for massive oesophageal cancer patients. RELEVANCE TO CLINICAL PRACTICE: The intervention programme may be used as an auxiliary therapy to promote patients' postoperative psychological rehabilitation. This programme has the advantages of being cost-effective, flexible, accessible, and convenient and can be implemented without the limitation of time, place and clinical medical staff. TRIAL REGISTRATION: The Chinese Clinical Trial Registration number is ChiCTR2100050047. Registered on 16 August 2021.

Stories of a long life with HIV: A qualitative study of a narrative intervention.

BACKGROUND: The dominant story of HIV in Denmark portrays HIV as compatible with a nearly normal life. International research on the experiences of elderly people diagnosed with human immunodeficiency virus (HIV) in the 1980s to mid-1990s challenges this narrative. AIMS: To gain knowledge on the experiences of elderly long-term survivors of HIV in Denmark and to evaluate if a narrative intervention 'giving voice' to this specific group was experienced as improving their quality of life. METHODS: In collaboration with relevant stakeholders, we developed a narrative intervention at REHPA, the Danish Knowledge Centre for Rehabilitation and Palliative Care focusing on the experiences and stories of people having lived a long life with HIV. Nineteen women and men living with HIV were included in the study. The intervention's evaluation design was based on ethnographic fieldwork that included participant observation and focus group interviews. The qualitative data were analysed using thematic content analysis. RESULTS: The findings show that the dominant story on HIV does not adequately cover the experiences of elderly Danes who have lived a long life with HIV. The participants continue to suffer from late complications and physical, existential, emotional and social challenges. The narrative intervention helped improve how participants experienced their quality of life. CONCLUSION: Long-term elderly Danish survivors diagnosed with HIV in the 1980s to mid-1990s suffer from complex symptoms and problems related to living their lives with HIV and treatment. They found that telling and sharing their life stories with other people with HIV gave them a sense of coherence, meaning and direction in life. RELEVANCE: The study documents the experiences of a group of long-term survivors of HIV in Denmark, making it relevant for organisations supporting people with HIV and for health care professionals working with this group. Furthermore, the study adds to the knowledge base on the use of narrative methods in rehabilitation.

Health-related quality of life outcomes after neoadjuvant chemoradiotherapy for rectal cancer in NRG Oncology/NSABP R-04.

BACKGROUND: There has been limited evaluation of health-related quality of life (HRQOL) in rectal cancer patients receiving neoadjuvant chemoradiotherapy. HRQOL outcomes in the National Surgical Adjuvant Breast and Bowel Project R-04 trial are examined in this article. METHODS: Between 2004 and 2010, R-04 patients were invited to enroll in the HRQOL substudy, with questionnaires administered before randomization, after completion of chemoradiotherapy, and 1-year after surgery. HRQOL measures included: Functional Assessment of Cancer Therapy for colorectal cancer (FACT-C); Short Form-36v.2 Vitality scale; a treatment-specific symptom scale; and the FACT neurotoxicity scale. A 5-year postsurgery assessment was added to the protocol in 2012. Mixed-effects models examined neoadjuvant therapy treatment effects in the 1-year sample and models that explored associations of host factors and treatment impact on 5-year HRQOL. RESULTS: A total of 1373 patients completed baseline HRQOL and at least one additional assessment. The average age was 58 years (range, 23-85 years), male (68%), and 59% Stage II. There were no statistically significant differences in HRQOL outcomes by treatment arm, but HRQOL worsened from baseline to postneoadjuvant chemoradiotherapy, with statistically significant effect sizes changes ranging from 0.6 (Vitality) to 0.9 (FACT-C Trial Outcome Index). Neurotoxicity was greater in the oxaliplatin-treated groups. Obese/overweight patients had statistically significantly worse FACT-C Trial Outcome Index scores than did underweight/normal weight groups. At 5 years, younger patients and those with normal baseline weight had statistically significantly better physical function scores and older patients had better mental health outcomes. CONCLUSIONS: HRQOL did not differ across the four R-04 treatment arms; however, host factors explained significant variation in posttreatment HRQOL. CLINICALTRIALS: gov: NCT00058474 (https://ClinicalTrials.gov/ct2/show/NCT00058474). LAY SUMMARY: This article reports on the health-related quality of life (HRQOL) outcomes of patients treated with four different chemotherapy regimens combined with radiation in rectal cancer patients before definitive surgical treatment. There were no significant differences in HRQOL by treatment regimen, but all patients experienced decreased vitality (energy) and physical functioning. By 1 year after treatment, most patients had returned to pretreatment vitality and physical functioning, with the exception of increased neurotoxicity. In a subsample of patients assessed at 5 years after surgery, physical function was better in those who at pretreatment were younger, normal weight, and had better performance status. Mental function was better in those who at pretreatment were older and had better performance status.

Adherence of long-term breast cancer survivors to follow-up care guidelines: a study based on real-world data from the SURBCAN cohort.

PURPOSE: To identify adherence to follow-up recommendations in long-term breast cancer survivors (LTBCS) of the SURBCAN cohort and to identify its determinants, using real-world data. METHODS: We conducted a retrospective study using electronic health records from 2012 to 2016 of women diagnosed with incident breast cancer in Spain between 2000 and 2006 and surviving at least 5 years. Adherence to basic follow-up recommendations, adherence according to risk of recurrence, and overall adherence were calculated based on attendance at medical appointments and imaging surveillance, by year of survivorship. Logistic regression models were fitted to depict the association between adherence and its determinants. RESULTS: A total of 2079 LTBCS were followed up for a median of 4.97 years. Of them, 23.6% had survived ≥ 10 years at baseline. We estimated that 79.5% of LTBCS were overall adherent to at least one visit and one imaging test. Adherence to recommendations decreased over time and no differences were found according to recurrence risk. Determinants of better overall adherence were diagnosis in middle age (50-69 years old), living in a more-deprived area, having fewer years of survival, receiving primary treatment, and being alive at the end of follow-up. CONCLUSION: We identified women apparently not complying with surveillance visits and tests. Special attention should be paid to the youngest and eldest women at diagnosis and to those with longer survival.

Change Toward Healthier Lifestyles Is Associated With Better Health-Related Quality of Life in Long-Term Colorectal Cancer Survivors.

BACKGROUND: Little is known about how changes in a constellation of lifestyle factors affect health-related quality of life (HRQoL) in colorectal cancer (CRC) survivors. Our study aimed to investigate the association between changes in healthy lifestyle and HRQoL over time in survivors of stage I-IV CRC. METHODS: We included 2,283 long-term (≥5 years postdiagnosis) survivors. A healthy lifestyle score (HLS) comprising smoking, alcohol consumption, diet, physical activity, and body fatness was derived at diagnosis and 5-year follow-up (5YFU) and categorized as low, moderate, or high. We assessed HRQoL with the EORTC Quality of Life Questionnaire-Core 30 at 5YFU and 10-year follow-up. We used multivariable linear regression and linear mixed models to explore associations between changes in HLS and HRQoL over follow-up. RESULTS: A low baseline HLS was associated with poorer functioning and global health/QoL and a higher symptom burden at 5YFU compared with a high baseline HLS. An improved HLS from baseline to 5YFU was associated with better functioning, higher global health/QoL, and fewer symptoms at 5YFU than a maintained-high HLS. In longitudinal analyses, improved HLS was associated with better functioning at follow-up. Survivors with a maintained-high or an improved HLS reported generally less fatigue, pain, and dyspnea at follow-ups compared with survivors with a maintained-low or decreased HLS. CONCLUSIONS: Change toward a healthier lifestyle since diagnosis was associated with better HRQoL in long-term CRC survivors. Our results support the importance of maintaining and/or promoting a healthier lifestyle among CRC survivors postdiagnosis.

Long term survivors of stereotactic radiosurgery for brain metastases: do distant brain failures reach a plateau and what factors are associated with a brain metastasis velocity of zero?

PURPOSE: Life expectancy continues to increase for patients with brain metastases treated with stereotactic radiosurgery (SRS). The present study sought to retrospectively analyze brain metastasis patients who have survived 2 years or more, and assess for what factors may predict for a final brain metastasis velocity (BMV) of zero. METHODS: This was a single-institution retrospective study of 300 patients treated with SRS from 2001 to 2019 for brain metastases who survived greater than 2 years after first SRS. Final BMV is calculated by summing all metastases through the observed time divided by the total time in years. A BMV of zero is defined as at least 2 years of imaging follow-up without distant brain failure (DBF). RESULTS: Median age at first SRS is 61 (IQR: 53, 70). Kaplan-Meier estimated median overall survival is 4.9 years and time to DBF is 1.5 years (95% CI 1.2, 2.0). Twenty-eight (9.3%) patients underwent subsequent WBRT. One hundred and one (33.7%) patients never had any further brain metastases (BMV = 0) at a median follow-up time of 3.3 years. Median BMV is 0.4 (IQR: 0, 1.4). Distant brain failures reach a plateau at 4 years where the cumulative incidence of DBF is 82%. 70% of first time DBFs have occurred by 2 years. Factors significantly associated with a BMV of zero include fewer brain metastases at first SRS (HR 1.1; p = 0.0004) and Caucasian race (HR 1.5; p = 0.03). CONCLUSION: Approximately one third of brain metastasis patients who live beyond 2 years after initial SRS have a BMV of zero. DBFs appear to reach a plateau at 4 years. Factors significantly associated with a BMV of zero include Caucasian race and having had a single brain metastasis at first SRS.

A two-way flexible generalized gamma transformation cure rate model.

We propose a two-way flexible cure rate model. The first flexibility is provided by considering a family of Box-Cox transformation cure models that include the commonly used cure models as special cases. The second flexibility is provided by proposing the wider class of generalized gamma distributions to model the associated lifetime. The advantage of this two-way flexibility is that it allows us to carry out tests of hypotheses to select an adequate cure model (within the family of Box-Cox transformation cure models) and a suitable lifetime distribution (within the wider class of generalized gamma distributions) that jointly provides the best fit to a given data. First, we study the maximum likelihood estimation of the generalized gamma Box-Cox transformation (GGBCT) model parameters. Then, we use the flexibility of our proposed model to carry out power studies to demonstrate the power of likelihood ratio test in rejecting mis-specified models. Furthermore, we study the bias and efficiency of the estimators of the cure rates under model mis-specification. Our findings strongly suggest the importance of selecting a correct lifetime distribution and a correct cure rate model, which can be achieved through the proposed two-way flexible model. Finally, we illustrate the applicability of our proposed model using a data from a breast cancer study and show that our model provides a better fit than the existing semiparametric Box-Cox transformation cure model with piecewise exponential approximation to the lifetime distribution.

Oral chronic GVHD after allogeneic stem cell transplantation without total body irradiation performed at a young age.

PURPOSE: Long-term survivors (LTSs) of allogeneic hematopoietic stem cell transplantation (allo-HCT) may experience oral long-term effects like chronic graft-versus-host disease (oral cGVHD). The aim of this study was to investigate oral cGVHD in patients treated at a young age (< 30 years) more than 5 years after allo-HCT without total body irradiation (TBI). METHODS: All 94 participants went through a semi-structured interview, and an oral examination. Diagnosis of oral cGVHD was based on the "National Institutes of Health (NIH) cGVHD diagnosis and staging consensus criteria" from 2014. RESULTS: Mean age at transplantation was 17.5 years (range 0.4-29.9 years), and mean time since transplantation was 16.7 years (range 6-26 years). Oral cGVHD was diagnosed in 26 (28%) of 94 LTSs. Of which 20 (21.5%) showed lichen planus-like (LPL) changes, and additionally six (6.5%) also fulfilled the diagnostic criteria of oral cGVHD since they had one or more distinctive signs and symptoms of oral cGVHD combined with definite cGVHD in another organ. No LTSs reported oral cGVHD (NIH) grade 3. There was a significant association between cGVHD in the oral cavity and cGVHD in another organ (77% vs 29%, p < 0.001). Out of 72 LTSs, who answered the questions regarding taste disturbances, 16 (22%) reported dysgeusia. No LTSs developed secondary malignancies in the oral cavity during follow-up time. CONCLUSION: Oral long-term effects, such as oral cGVHD, may persist for many years after allo-HCT without TBI-conditioning in patients treated at a young age.

Symptom burden, psychological distress, and health-related quality of life in cancer survivors with pelvic late radiation tissue injuries.

PURPOSE: Curative radiotherapy for cancer may lead to severe late radiation tissue injuries (LRTIs). However, limited knowledge exists about pelvic cancer survivors' LRTI symptoms, distress, and health-related quality of life (HRQOL). We sought to assess the symptom burden, distress, and HRQOL in survivors with established pelvic LRTIs compared to norm populations and to investigate the relation between these factors. METHODS: Cancer survivors referred for treatment of established pelvic LRTIs were recruited nationwide. LTRIs were assessed with the Expanded Prostate Cancer Index Composite (EPIC), psychological distress was assessed with the General Health Questionnaire (GHQ-12), and HRQOL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORCT-QLQ-C30). RESULTS: A total of 107 participants (mean age 64, 53% men) were included. Compared to norms, participants reported more urinary (mean 68.7 vs. 89.5; p = 0.00; d = 1.4) and bowel symptoms (mean 62.5 vs. 92.4; p = 0.00; d = 2.7), increased psychological distress (mean 13.4 vs. 10.3; p = 0.00; d = 0.6), and overall poorer HRQOL (mean 54.9 vs. 71.2; p = 0.00; d = 0.7). Higher symptom burden and higher levels of psychological distress were associated with lower HRQOL (r2 = 46%), but psychological distress did not moderate the influence of symptoms on HRQOL. CONCLUSION: Cancer survivors with established pelvic LRTIs are highly burdened compared to norms. The association of the LRTI-related symptom burden with HRQOL is independent of the level of psychological distress. Both coping and treatment interventions are crucial to promoting long-term health and HRQOL. TRIAL REGISTRATION: NCT03570229.

Outcomes of long-term nivolumab and subsequent chemotherapy in Japanese patients with head and neck cancer: 2-year follow-up from a multicenter real-world study.

BACKGROUND: We have previously reported the effectiveness and safety of nivolumab in patients with head and neck cancer (HNC) in real-world clinical practice in Japan. Here, we report long-term outcomes from this study in the overall population and subgroups stratified by subsequent chemotherapy. METHODS: In this multicenter, retrospective observational study, Japanese patients with recurrent or metastatic (R/M) HNC receiving nivolumab were followed up for 2 years. Effectiveness endpoints included overall survival (OS), OS rate, progression-free survival (PFS), and PFS rate. Safety endpoints included the incidence of immune-related adverse events (irAEs). RESULTS: Overall, 256 patients received a median of 6.0 doses (range: 1-52) of nivolumab over a median duration of 72.5 days (range: 1-736). Median OS was 9.5 months [95% confidence interval (CI) 8.2-12.0] and median PFS was 2.1 months (95% CI 1.8-2.7). A significant difference between 2-year survivors (n = 62) and non-2-year survivors was observed by median age (P = 0.0227) and ECOG PS (P = 0.0001). Of 95 patients who received subsequent chemotherapy, 54.7% received paclitaxel ± cetuximab. The median OS and PFS from the start of paclitaxel ± cetuximab were 6.9 months (95% CI 5.9-11.9) and 3.5 months (95% CI 2.3-5.5), respectively. IrAEs were reported in 17.2% of patients. Endocrine (7.0%) and lung (4.3%) disorders were the most common irAEs; kidney disorder (n = 1) was newly identified in this follow-up analysis. CONCLUSIONS: Results demonstrated the long-term effectiveness of nivolumab and potential effectiveness of subsequent chemotherapy in patients with R/M HNC in the real-world setting. Safety was consistent with that over the 1-year follow-up.

Implementation of the frailty assessment to improve liver transplant outcomes.

The majority of patients undergoing Orthotopic Liver Transplantation (OLT) have increased in age, therefore chronological age may have become an unreliable parameter for supporting clinical decisions. The age-related deficit accumulation model measuring frailty proposed by Rockwood et al., may propose an alternative in providing an estimate of an individual's biological age. No Frailty Index (FI) tailored specifically for OLT patients exists to date. Forty-three consecutive OLT patients with ≥ 20 years of survival with a functioning graft were included in our study. The FI was computed taking to account 39 items (FI-39), meeting the standard criteria for internal validation. Endpoints were polypharmacy, and recent Emergency Room admission. The mean age of our population was 69 (sd 9) years. The mean FI-39 was 0.23 (sd 0.1). The FI-39 was associated with polypharmacy [odds ratio (OR) 1.13; Confidence interval (95%CI) 1.03-1.24; p = 0.01], and recent Emergency Room admission [beta coefficient + 1.98; 95%CI + 0.26, + 3.70; p = 0.03], independent for age and sex. This study demonstrates that an FI can be derived from data collected during routine clinical follow-up and allows for improved differentiation related to the OLT clinical complexity in OLT patients, independent of chronological age. This may lead to the adoption of FI-39 to improve personalized OLT patient care.

Kidney Function after Treatment for Childhood Cancer: A Report from the St. Jude Lifetime Cohort Study.

BACKGROUND: Survivors of childhood cancer may be at increased risk for treatment-related kidney dysfunction. Although associations with acute kidney toxicity are well described, evidence informing late kidney sequelae is less robust. METHODS: To define the prevalence of and risk factors for impaired kidney function among adult survivors of childhood cancer who had been diagnosed ≥10 years earlier, we evaluated kidney function (eGFR and proteinuria). We abstracted information from medical records about exposure to chemotherapeutic agents, surgery, and radiation treatment and evaluated the latter as the percentage of the total kidney volume treated with ≥5 Gy (V5), ≥10 Gy (V10), ≥15 Gy (V15), and ≥20 Gy (V20). We also used multivariable logistic regression models to assess demographic and clinical factors associated with impaired kidney function and Elastic Net to perform model selection for outcomes of kidney function. RESULTS: Of the 2753 survivors, 51.3% were men, and 82.5% were non-Hispanic White. Median age at diagnosis was 7.3 years (interquartile range [IQR], 3.3-13.2), and mean age was 31.4 years (IQR, 25.8-37.8) at evaluation. Time from diagnosis was 23.2 years (IQR, 17.6-29.7). Approximately 2.1% had stages 3-5 CKD. Older age at evaluation; grade ≥2 hypertension; increasing cumulative dose of ifosfamide, cisplatin, or carboplatin; treatment ever with a calcineurin inhibitor; and volume of kidney irradiated to ≥5 or ≥10 Gy increased the odds for stages 3-5 CKD. Nephrectomy was significantly associated with stages 3-5 CKD in models for V15 or V20. CONCLUSIONS: We found that 2.1% of our cohort of childhood cancer survivors had stages 3-5 CKD. These data may inform screening guidelines and new protocol development.