Disease-free Survivors Research Articles

Multi-parametric atlas of the pre-metastatic liver for prediction of metastatic outcome in early-stage pancreatic cancer.

Metastasis occurs frequently after resection of pancreatic cancer (PaC). In this study, we hypothesized that multi-parametric analysis of pre-metastatic liver biopsies would classify patients according to their metastatic risk, timing and organ site. Liver biopsies obtained during pancreatectomy from 49 patients with localized PaC and 19 control patients with non-cancerous pancreatic lesions were analyzed, combining metabolomic, tissue and single-cell transcriptomics and multiplex imaging approaches. Patients were followed prospectively (median 3 years) and classified into four recurrence groups; early (<6 months after resection) or late (>6 months after resection) liver metastasis (LiM); extrahepatic metastasis (EHM); and disease-free survivors (no evidence of disease (NED)). Overall, PaC livers exhibited signs of augmented inflammation compared to controls. Enrichment of neutrophil extracellular traps (NETs), Ki-67 upregulation and decreased liver creatine significantly distinguished those with future metastasis from NED. Patients with future LiM were characterized by scant T cell lobular infiltration, less steatosis and higher levels of citrullinated H3 compared to patients who developed EHM, who had overexpression of interferon target genes (MX1 and NR1D1) and an increase of CD11B+ natural killer (NK) cells. Upregulation of sortilin-1 and prominent NETs, together with the lack of T cells and a reduction in CD11B+ NK cells, differentiated patients with early-onset LiM from those with late-onset LiM. Liver profiles of NED closely resembled those of controls. Using the above parameters, a machine-learning-based model was developed that successfully predicted the metastatic outcome at the time of surgery with 78% accuracy. Therefore, multi-parametric profiling of liver biopsies at the time of PaC diagnosis may determine metastatic risk and organotropism and guide clinical stratification for optimal treatment selection.

Reduced-Volume Irradiation of Uninvolved Neck in Patients With Nasopharyngeal Cancer: Updated Results From an Open-Label, Noninferiority, Multicenter, Randomized Phase III Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We previously reported comparable 3-year regional relapse-free survival (RRFS) using elective upper-neck irradiation (UNI) in N0-1 nasopharyngeal carcinoma (NPC) compared with standard whole-neck irradiation (WNI). Here, we present the prespecified 5-year overall survival (OS), RRFS, late toxicity, and additional analyses. In this randomized trial, patients received UNI (n = 224) or WNI (n = 222) for an uninvolved neck. After a median follow-up of 74 months, the UNI and WNI groups had similar 5-year OS (95.9% v 93.1%, hazard ratio [HR], 0.63 [95% CI, 0.30 to 1.35]; P = .24) and RRFS (95.0% v 94.9%, HR, 0.96 [95% CI, 0.43 to 2.13]; P = .91) rates. The 5-year disease-free survivors in the UNI group had a lower frequency of hypothyroidism (34% v 48%; P = .004), neck tissue damage (29% v 46%; P < .001), dysphagia (14% v 27%; P = .002), and lower-neck common carotid artery stenosis (15% v 26%; P = .043). The UNI group had higher postradiotherapy circulating lymphocyte counts than the WNI group (median: 400 cells/μL v 335 cells/μL, P = .007). In conclusion, these updated data confirmed that UNI of the uninvolved neck is a standard of care in N0-1 NPC, providing outstanding efficacy and reduced long-term toxicity, and might retain more immune function.

Early hematopoietic cell transplantation for familial hemophagocytic lymphohistiocytosis in a regional treatment network in Japan.

Familial hemophagocytic lymphohistiocytosis (FHLH) is a fatal hyperinflammation syndrome arising from the genetic defect of perforin-mediated cytolysis. Curative hematopoietic cell transplantation (HCT) is needed before development of central nervous system (CNS) disease. We studied treatment outcomes of 13 patients (FHLH2 n = 11, FHLH3 n = 2) consecutively diagnosed from 2011 to 2022 by flow cytometric screening for non-myeloablative HCT in a regional treatment network in Kyushu, Japan. One patient with a novel PRF1 variant escaped screening, but all patients with FHLH2 reached diagnosis and 8 of them received HCT until 3 and 9months of age, respectively. The earliest HCT was conducted 65days after birth. Three pretransplant deaths occurred in newborns with liver failure at diagnosis. Ten posttransplant patients have remained disease-free, 7 of whom had no neurological involvement. Time from first etoposide infusion to HCT was shorter in patients without CNS disease or bleeding than in patients with those factors (median [range] days: 62 [50-81] vs. 122 [89-209], p = 0.016). Six of 9 unrelated patients had a PRF1 c.1090_1091delCT variant. These results suggest that the critical times to start etoposide and HCT are within 3months after birth and during etoposide control, respectively. Newbornscreening may increase the percentage of disease-free survivors without complications.

The impact of the HER2-low status on conditional survival in patients with breast cancer.

With recent advances in breast cancer (BC) treatment, the disease-free survival (DFS) of patients is increasing and the risk factors for recurrence and metastasis are changing. However, a dynamic approach to assessing the risk of recurrent metastasis in BC is currently lacking. This study aimed to develop a dynamically changing prediction model for recurrent metastases based on conditional survival (CS) analysis. Clinical and pathological data from patients with BC who underwent surgery at the Affiliated Hospital of Qingdao University between August 2011 and August 2022 were retrospectively analysed. The risk of recurrence and metastasis in patients with varying survival rates was calculated using CS analysis, and a risk prediction model was constructed. A total of 4244 patients were included in this study, with a median follow-up of 83.16 ± 31.59 months. Our findings suggested that the real-time DFS of patients increased over time, and the likelihood of DFS after surgery correlated with the number of years of prior survival. We explored different risk factors for recurrent metastasis in baseline patients, 3-year, and 5-year disease-free survivors, and found that low HER2 was a risk factor for subsequent recurrence in patients with 5-year DFS. Based on this, conditional nomograms were developed. The nomograms showed good predictive ability for recurrence and metastasis in patients with BC. Our study showed that the longer patients with BC remained disease-free, the greater their chances of remaining disease-free again. Predictive models for recurrence and metastasis risk based on CS analysis can help improve the confidence of patients fighting cancer and help doctors personalise treatment and follow-up plans.

Prevalence and factors of polypharmacy among disease-free survivors of adults after allogeneic hematopoietic cell transplantation

Prevalence and factors of polypharmacy among disease-free survivors of adults after allogeneic hematopoietic cell transplantation

Cancer-related fatigue: Towards a more targeted approach based on classification by biomarkers and psychological factors.

Cancer-related fatigue is a frequent, burdensome and often insufficiently treated symptom. A more targeted treatment of fatigue is urgently needed. Therefore, we examined biomarkers and clinical factors to identify fatigue subtypes with potentially different pathophysiologies. The study population comprised disease-free breast cancer survivors of a German population-based case-control study who were re-assessed on average 6 (FU1, n = 1871) and 11 years (FU2, n = 1295) after diagnosis. At FU1 and FU2, we assessed fatigue with the 20-item multidimensional Fatigue Assessment Questionnaire and further factors by structured telephone-interviews. Serum samples collected at FU1 were analyzed for IL-1ß, IL-2, IL-4, IL-6, IL-10, TNF-a, GM-CSF, IL-5, VEGF-A, SAA, CRP, VCAM-1, ICAM-1, leptin, adiponectin and resistin. Exploratory cluster analyses among survivors with fatigue at FU1 and no history of depression yielded three clusters (CL1, CL2 and CL3). CL1 (n = 195) on average had high levels of TNF-α, IL1-β, IL-6, resistin, VEGF-A and GM-CSF, and showed high BMI and pain levels. Fatigue in CL1 manifested rather in physical dimensions. Contrarily, CL2 (n = 78) was characterized by high leptin level and had highest cognitive fatigue. CL3 (n = 318) did not show any prominent characteristics. Fatigued survivors with a history of depression (n = 214) had significantly higher physical, emotional and cognitive fatigue and showed significantly less amelioration of fatigue from FU1 to FU2 than survivors without depression. In conclusion, from the broad phenotype "cancer-related fatigue" we were able to delineate subgroups characterized by biomarkers or history of depression. Future investigations may take these subtypes into account, ultimately enabling a better targeted therapy of fatigue.

Abstract 17170: Association of Plasma Homocysteine Levels in Cancer Survivors - Data From Framingham Heart Study Offspring Cohort

Introduction: Cancer survivors experience a high prevalence of vascular remodeling from their anti-cancer therapies, which can lead to arterial stiffness. High plasma homocysteine (Hcy) is associated with increased cardiovascular disease risk via its role in decreasing nitric oxide bioavailability and impairing vascular function. However, there is limited work on its role in cancer survivorship. We, therefore, hypothesized that survivors of breast, gastrointestinal, and prostate cancer with elevated plasma Hcy values have higher arterial stiffness and lower endothelial function compared to those with low plasma Hcy. Methods: We evaluated cardiovascular disease-free cancer survivors in the Framingham Heart Study Offspring Cohort (n=196, 66±8 years old, 55.1% women, 26.4±1.2 years from cancer diagnosis, Range: [23.8 - 29.6 years]) with plasma Hcy measurements. The cohort median plasma Hcy was used to define low (&lt;8.16 μmol/L) and high Hcy (≥8.16 μmol/L) groups. Arterial stiffness was assessed via carotid-femoral pulse wave velocity (cfPWV). Peripheral vascular endothelial function was assessed via endothelium-dependent brachial artery flow-mediated dilation (FMD). Differences in cfPWV, FMD, and cardiovascular risk factors were assessed via independent sample t-test or chi-square test. Differences in cfPWV and FMD were further assessed via one-way ANCOVA with age, sex, and cardiovascular medications included as covariates. Results: cfPWV was significantly higher in the high Hcy (9.9±1.5m/s) vs. low Hcy group (8.5±1.9m/s, p=0.005); however, there were no differences in FMD between groups (2.4±1.7 vs. 2.7±2.0%, p=0.42). After controlling for our covariates, cfPWV was still significantly higher in the high Hcy group (Mean[95% CI]): (9.8[9.0-10.61]) compared to the low Hcy group (8.5[8-9.1]) (p=0.015). Conclusions: Our findings suggest an association between elevated Hcy and an increase in arterial stiffness in cancer survivors. This supports the potential adverse consequences of vascular stiffening following cancer diagnosis and treatment which could have long-term cardiovascular health implications.

Severity of Chronic Graft-versus-Host Disease and Late Effects Following Allogeneic Hematopoietic Cell Transplantation for Adults with Hematologic Malignancy

The study aimed to determine the association of chronic graft-versus-host disease (cGVHD) diagnosis and severity with the development of subsequent neoplasms (SN) and nonmalignant late effects (NM-LE) in 2-year disease-free adult survivors following hematopoietic cell transplantation (HCT) for a hematologic malignancy. To do so, we conducted a retrospective analysis of 3884 survivors of HCT for hematologic malignancy in the Center of International Blood and Marrow Transplant Research database. We conducted a landmark analysis at the 2-year post-transplantation date, comparing first SN and NM-LE in survivors with and without cGVHD. The cumulative incidence (CuI) of SN and NM-LE were estimated through 10 years post-HCT in both groups, with death or disease relapse as a competing risk. Cox proportional hazards models were used to evaluate the associations of cGVHD and its related characteristics with the development of SN and NM-LE. The estimated 10-year CuI of SN in patients with GVHD (n=2669) and patients without cGVHD (n=1215) was 15% (95% confidence interval [CI], 14% to 17%) versus 9% (7.2% to 11%) (P < .001). cGVHD by 2 years post-HCT was independently associated with SN (hazard ratio [HR], 1.94; 95% CI, 1.53 to 2.46; P < .0001) with a standardized incidence ratio of 3.2 (95% CI, 2.9 to 3.5; P < .0001). Increasing severity of cGVHD was associated with an increased risk of SN. The estimated 10-year CuI of first NM-LE in patients with and without cGVHD was 28 (95% CI, 26% to 30%) versus 13% (95% CI, 11% to 15%) (P < .001). cGVHD by 2 years post-HCT was independently associated with NM-LE (HR, 2.23; 95% CI, 1.81 to 2.76; P < .0001). Multivariate analysis of cGVHD-related factors showed that increasing severity of cGVHD, extensive grade, having both mucocutaneous and visceral involvement, and receiving cGVHD treatment for >12 months were associated with the greatest magnitude of risk for NM-LE. cGVHD was closely associated with both SN and NM-LE in adult survivors of HCT for hematologic malignancy. Patients identified as having more severe involvement and both mucocutaneous and visceral organ involvement may warrant enhanced monitoring and screening for SNs and NM-LEs. However, caution is warranted when interpreting these results, as patients with cGVHD may have more vigilant post-transplantation health care and surveillance for late effects.

Emotional Distress in Portuguese Cancer Patients: The Use of the Emotion Thermometers (ET) Screening Tool.

Cancer patients may experience significant distress. The "Emotion Thermometers" (ETs) are a short visual analogue scale used to screen patients for psychosocial risk. This study aimed to assess emotional distress in a large sample of cancer patients attending psychological services at an non-governmental organization (NGO), and to explore factors that may contribute to it. The ETs were answered by 899 cancer patients. They were, on average, 59.9 years old, the majority were female, had breast cancer, were under treatment or were disease-free survivors, and reported high levels of emotional distress, above the cut-off (≥5). A Generalized Linear Model was used to measure the association between the level of distress, age, gender, disease phase and 33 items of the problem list. Four items-sadness, depression, sleep and breathing-were found to be significantly related to a higher level of distress. Additionally, women and patients who were in the palliative phase also had significantly higher levels of distress. The results confirm the need for early emotional screening in cancer patients, as well as attending to the characteristics of each patient. Additionally, they highlight the utility of the ETs for the clinical practice, allowing to optimize the referral to specialized psychosocial services.

Survival and late mortality among patients who survived disease-free for 2 years after stem cell transplantation.

Most events that limit life expectancy after allogeneic haematopoietic stem cell transplantation (allo-HSCT) occur within the first 2 years; however, treatment outcomes in long-term survivors who survive for at least 2 years post-HSCT without relapse are yet to be elucidated. To explore the life expectancy trends and late complications and to assess the main mortality-related factors, we investigated the characteristics of patients who received allo-HSCT for haematological malignancies from 2007 to 2019 in our centre and survived in remission for 2 years. A cohort of 831 patients was enrolled; of these, 508 received grafts from haploidentical-related donors (61.1%). The estimated overall survival rate at 10 years was 91.9% (95% confidence interval [CI], 89.8-93.5), which was affected by prior grade III-IV acute graft-versus-host disease (GVHD) (hazard ratio [HR], 2.98; 95% CI, 1.47-6.03; p = 0.002) and severe chronic GVHD (HR, 3.60; 95% CI, 1.93-6.71; p < 0.001). The probability of late relapse and non-relapse mortality at 10 years was 8.7% (95% CI, 6.9-10.8) and 3.6% (95% CI, 2.5-5.1) respectively. The top cause of late mortality was relapsed (49.0%). Projected long-term survival in 2-year disease-free survivors following allo-HSCT was excellent. Strategies should be implemented to minimise the late death-specific hazards in recipients.

Experiences with pain management for survivors of complex cancers: Focus on opioids and cannabis.

12118 Background: Survivors of complex cancers often experience pain. Clinical practice guidelines for pain management in cancer survivors cautiously recommend opioids and cannabis for subgroups with certain pain phenotypes, despite limited evidence regarding benefits and harms in survivor populations. We aimed to better understand pain management for these survivors, focusing on attitudes toward, and experiences with, opioids and cannabis. Methods: We conducted 7 90-minute focus groups with 26 disease-free survivors of head and neck and lung cancer who still experience cancer-related pain. Multiple coders conducted thematic analyses to identify themes regarding 1) experiences with post-treatment pain and pain management and 2) utilization, benefits, and harms of post-treatment cannabis and opioids. Results: Survivors (7-35 months from treatment completion) experienced post-treatment physical and psychological pain that affected multiple aspects of their daily life. Since treatment completion, 69% used opioids previously and 8% currently using. Fifty-four percent had used any cannabis product since treatment completion, and 35% currently use cannabis. While some survivors experienced no pain management challenges, others enumerated various difficulties, including fears of addiction to opioids or cannabis, perceived stigma around both products, and access challenges around provider attitudes, cost and insurance coverage, and legality. Survivors reported that providers did not know how to advise about cannabis; for example: “When I talked [to providers] about marijuana they didn’t want to talk about it. They couldn’t recommend it because there’s no clinical data.” Opioids were often perceived as critical to pain management but came with unpleasant side effects. Cannabis was effective at reducing both pain and anxiety for many, but not all, survivors. For some, cannabis reduced anxiety, which in turn reduced pain: “It just keeps my mind occupied enough where I’m not thinking of pain.” Reducing anxiety also helped some survivors eat: “I have a lot of anxiety around eating because I have a fear of choking, so sometimes it helps that.” Survivors described a balance of benefits and harms of opioids and cannabis; for example: “Where [the doctor has] me now...if I go down any lower, it's not going to work. If I go up any higher, I'm going to be not able to function.” Conclusions: Post-treatment survivors of complex cancers continue to experience cancer-related pain, both psychological and physical, for which both opioids and cannabis present a complex set of harms and benefits that vary across survivors. Providers who care for cancer survivors should be aware of the interplay between psychological and physical pain, patient concerns and stigma around opioids and cannabis, and nuances of the harms, benefits, and access issues regarding these treatments.

Patient-Reported Outcomes in Long-Term Survivors of Autologous Hematopoietic Cell Transplantation for Hodgkin and Non-Hodgkin Lymphoma: Secondary Analysis from Two Multi-Center Randomized Controlled Trials of Hematopoietic Cell Transplant Survivorship Interventions

Background: Autologous hematopoietic cell transplantation (AHCT) recipients with Hodgkin's and Non-Hodgkin's lymphoma (HL and NHL) who survive progression-free for ≥2years can expect a 5-year overall survival rate of 90% (Myers et al, Cancer, 2018). However, patient-reported outcomes (PROs) in long-term lymphoma survivors after AHCT have not been well described. We present secondary analyses from a combined baseline dataset from two multi-center randomized clinical trials of HCT survivorship interventions, enrolling at 18 US transplant centers, including a large cohort of 1-10-year lymphoma AHCT survivors. Our objectives were to describe health-related quality of life (HRQoL) and cancer and treatment-related distress (CTXD), and to examine their associations with available clinical and sociodemographic correlates. Methods: Cross-sectional data at the time of study enrollment were pooled from two trials: SCP (Survivorship Care Plan; NCT02200133) and INSPIRE (INternet Survivorship Program with Information and REsources; NCT01602211). The SCP study enrolled patients (N=456) who were in a stable remission 1-5 years after transplant and the INSPIRE study enrolled survivors (N=1177) who were 2-10 years post-transplant, between 2003-2014. This analysis was restricted to AHCT recipients with diagnosis of HL or NHL. Our objectives were to describe HRQoL and cancer related distress (CTXD), and to examine their association with available baseline correlates. HRQoL was assessed using SF-12 v2 (12-item short survey form) and described as physical component summary (PCS) and mental component summary (MCS) T-scores (higher scores indicated better functioning). Comparisons between SF-12 scores and age-matched population norm (mean score 50, standard deviation [SD] 10) were analyzed using paired t-tests. Distress was assessed using the CTXD instrument, which reports mean scores from 0 to 3, with higher scores indicating greater distress. Based on prior receiver operating characteristic analysis, CTXD score >1.1 was considered clinically significant. Multivariate linear regression models were performed to evaluate the association of PCS score, MCS score, and CTXD with the following variables: diagnosis (HL vs. NHL), sex, race/ethnicity, number of HCT, use of total body irradiation (TBI) for AHCT, subsequent allogeneic transplant, age at time of enrollment, and time since AHCT. Results: Of 522 HL and NHL AHCT recipients, 60% were male, 94% were Caucasian, 94 (18%) had HL, 428 (82%) had NHL; 26 (5%) received >1 HCT, including 16 (4%) who received a subsequent allogeneic HCT. 8% patients received TBI-based conditioning regimens. Median age at index AHCT was 55 (range: 17-80) years, and median time from AHCT to study entry was 5 (range: 2-11) years. The mean [±SD] PCS T-score in the study population (48.96 [±10.59]) was slightly lower than the population norm (50 [±10]) (p=0.03). Mean [±SD] MCS T-scores were not significantly different between patients (50.75 [±10.40]) and general population (50 [±10]) (p=0.16) (Figure 1). The mean CTXD score was 0.79 (±0.59), with 135 (26%) patients reporting clinically significant distress (mean score ≥ 1.1). Among CTXD domains, "health burden” and "uncertainty” accounted for the highest burden of clinically significant distress, with 42% and 35% of patients reporting distress in these domains, respectively (Figure 2). On multivariable analysis, older age at study entry was associated with higher MCS score (estimated slope: 1.3 [95% CI: 0.5-2.2]; p=0.002), although there was no association of age with PCS score or CTXD. We did not observe associations of other variables and PCS score, MCS score, or CTXD. Conclusions: Patients with HL and NHL who are long-term disease-free survivors of AHCT have lower physical HRQoL compared to general population, although the difference is not clinically meaningful. Mental HRQoL in HL and NHL AHCT survivors is similar to general population. Older age is associated with higher mental HRQoL. Approximately a quarter of patients report clinically significant cancer and treatment-related distress. Survivorship programs should continue to screen for, and address concerns regarding HRQoL and distress. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The impact of APOE and smoking history on cognitive function in older, long-term breast cancer survivors.

This study aims to determine whether older breast cancer survivors score lower on neuropsychological tests compared to matched non-cancer controls and to test the hypotheses that survivors who were APOE ε4 carriers would have the lowest cognitive performance but that smoking history would decrease the negative effect of ε4 on cognition. Female breast cancer survivors who had been diagnosed and treated at age 60 or older and were 5-15-year survivors (N = 328) and age and education matched non-cancer controls (N = 162) were assessed at enrollment and at 8-, 16-, and 24-month follow-ups with standard neuropsychological and psychological assessments. Blood for APOE genotyping was collected, and smoking history was assessed at enrollment. Participants were purposely recruited so that approximately 50% had a history of treatment with chemotherapy or no chemotherapy and approximately 50% had a smoking history. After adjusting for age, cognitive reserve, depression, and fatigue, breast cancer survivors scored significantly lower on all domains of cognitive function. A significant two-way interaction demonstrated that the negative effect of ε4 on cognitive performance was stronger among survivors. A significant three-way interaction supported the hypothesis that smoking history had a protective effect on cognitive function in ε4 carriers that was more pronounced in the controls than the survivors. The results support the long-term cognitive impact of breast cancer diagnosis and treatments on older, disease-free survivors, particularly for ε4 carriers. The results also emphasize the importance of assessing smoking history when examining APOE and cognition and are an example of the complex interactions of age, genetics, health behaviors, and disease history in determining cognitive function. These results help explain why only a subset of breast cancer survivors appear to be vulnerable to cognitive problems.

Recurrence Patterns and Survival Outcomes after Multidisciplinary Treatment of Pancreatic Cancer

INTRODUCTION: The aim of this retrospective study was to determine whether change in neoadjuvant therapy affected patterns of recurrence after operation among patients with pancreatic ductal adenocarcinoma (PDAC) throughout the past 2 decades. METHODS: Patients who received any neoadjuvant therapy followed by pancreatectomy for PDAC at our institution from 1998 to 2018 were identified. Treatment strategy, recurrence site and timing, and survival outcomes were compared between time periods (1998 to 2004, 2005 to 2011, 2012 to 2018). RESULTS: We included 728 patients (205, 251, and 272 patients, respectively). The proportion of patients with borderline resectable or locally advanced tumor increased over time (11%, 30%, and 42%). Chemotherapy use increased over time (37%, 67%, 75%); ~90% received a gemcitabine-based non–nab-paclitaxel regimen in the first 2 periods, and 55% received FOLFIRINOX and 25% received gemcitabine/nab-paclitaxel in the 3rd period. (Chemo)radiation therapy use decreased (95%, 82%, 81%) and overall survival (OS) improved (median 24, 28, 31 months) over time. Despite similar incidence of recurrence across periods (66% to 69%), when the 3rd period was compared with other periods, conditional risk of recurrence (recurrence among disease-free survivors yearly) appeared to be shifted from the first to second and third years and was uncommon (<5%) after the 3rd year (Figure). Treatment in the 3rd period was independently associated with improved OS (hazard ratio [HR] 0.67; p = 0.008) and OS after recurrence (HR 0.63; p = 0.003).FigureCONCLUSION: Despite increase in borderline resectable and locally advanced cases, OS improved over time. Despite stable recurrence patterns overall, conditional risk of recurrence changed over time, which should be considered in postoperative surveillance plans.

Quality of life in cancer survivorship: Sociodemographic and disease-related moderators.

To identify high-risk survivors in order to provide appropriate care. To analyse the quality of life (QOL) of cancer survivors using an instrument designed specifically for this population and considering different sociodemographic and disease-related characteristics as possible modulating variables. The Quality of Life in Adult Cancer Survivors (QLACS) was filled out by a large and heterogeneous sample of disease-free post-treatment Spanish cancer survivors (N = 1862). QLACS scores were comparable to those obtained in other studies and indicative of worse QOL as a function of shorter elapsed time since the end of primary treatment. The best QOL was shown by prostate, and the worst by hematologic cancer survivors. Both systemic treatments (chemotherapy and hormone therapy) and the combination of radiotherapy and chemotherapy were associated with worse QOL. Likewise, younger age, female sex, unemployment status and not having a stable partner were associated with worse QOL. Greater understanding of the QOL experienced by the already large and continuously growing population of cancer survivors is relevant for guiding both clinical practice and health policy. In addition, knowing the risk factors associated with worse QOL facilitates the development of targeted prevention programmes for those survivors who need it the most.

Clinical and sociodemographic determinants of disease-specific health-related quality of life in long-term breast cancer survivors

PurposeIt is important to monitor disease-specific health-related quality of life (HRQoL) in breast cancer (BC) survivors to identify potential unmet supportive care needs. However, previous studies were characterized by small samples of mostly short-term survivors and were limited to certain age ranges, stages and/or treatments.MethodsWe used data from 3045 long-term BC survivors (5–15 years post-diagnosis) recruited in a German multi-regional population-based study. We assessed disease-specific HRQoL with the EORTC QLQ-BR23, scoring from 0 to 100. Differences in functioning and symptoms according to age at survey, self-reported treatments, stage, and disease status (disease-free vs. active disease) were assessed with multiple regression. Active disease was defined as any self-report of recurrence, metastasis or second primary cancer after the index cancer.ResultsOlder BC survivors reported a higher body image and a better future perspective, but lower sexual functioning. Survivors aged 30–49 years who had breast-conserving therapy or mastectomy with breast reconstruction reported a better body image compared to those who had mastectomy only. We also found differences in symptoms according to treatments in some age groups. Stage at diagnosis was not associated with HRQoL overall and in most age subgroups. Disease-free BC survivors aged 30–79 years reported a better future perspective and less systemic therapy side effects than those with active disease.ConclusionSeveral treatment-associated symptoms and functioning detriments were found 5–15 years after diagnosis. The results emphasize the need of a comprehensive, individualized survivorship care, recognizing differential needs of long-term BC survivors according to age, treatment modalities, and disease status.

Association of Chronic Graft-versus-Host Disease with Late Effects following Allogeneic Hematopoietic Cell Transplantation for Children with Hematologic Malignancy

Chronic graft-versus-host disease (cGVHD) occurs in up to 25% of children following allogeneic hematopoietic cell transplantation (HCT) and continues to be a major cause of late morbidity and poor quality of life among long-term survivors of pediatric HCT. Late effects (LEs) of HCT are well documented in this population, and cGVHD has been identified as a risk factor for subsequent neoplasms (SNs) and several nonmalignant LEs (NM-LEs); however, the reported correlation between cGVHD and LEs varies among studies. We compared LEs occurring ≥2 years following childhood HCT for a hematologic malignancy in 2-year disease-free survivors with and without cGVHD and further evaluated the association of cGVHD features on the development of LEs. This systematic retrospective analysis used data from the Center of International Blood and Marrow Transplant Research (CIBMTR) on a large, representative cohort of 1260 survivors of pediatric HCT for hematologic malignancy to compare first malignant LEs and NM-LEs in those with a diagnosis of cGVHD and those who never developed cGVHD. The cumulative incidences of any first LE, SN, and NM-LE were estimated at 10 years after HCT, with death as a competing risk for patients with cGVHD versus no cGVHD. Cox proportional hazards models were used to evaluate the impact of cGVHD and its related characteristics on the development of first LEs. The estimated 10-year cumulative incidence of any LE in patients with and without cGVHD was 43% (95% CI, 38% to 48.2%) versus 32% (95% confidence interval [CI], 28.5% to 36.3%) (P < .001), respectively. The development of cGVHD by 2 years post-HCT was independently associated with any LE (hazard ratio [HR], 1.38; 95% CI, 1.13 to 1.68; P=.001) and NM-LE (HR, 1.37; 95% CI, 1.10 to 1.70; P=.006), but not SN (HR, 1.30; 95% CI, .73 to 2.31; P=.38). cGVHD-related factors linked with the development of an NM-LE included having extensive grade cGVHD (HR, 1.60; 95% CI, 1.23 to 2.08; P=.0005), severe cGVHD (HR, 2.25; 95% CI, 1.60 to 3.17; P < .0001), interrupted onset type (HR, 1.57; 95% CI, 1.21 to 2.05; P=.0008), and both mucocutaneous and visceral organ involvement (HR, 1.59; 95% CI, 1.24 to 2.03; P=.0002). No significant association between cGVHD-specific variables and SN was identified. Finally, the duration of cGVHD treatment of cGVHD with systemic immunosuppression was not significantly associated with SNs or NM-LEs. cGVHD was more closely associated with NM-LEs than with SNs among survivors of pediatric HCT for hematologic malignancy. In this analysis, the development of SNs was strongly associated with the use of myeloablative total body irradiation. cGVHD-related characteristics consistent with a state of greater immune dysregulation were more closely linked to NM-LEs.

What proportion of patients with stage 3 ovarian cancer are potentially cured following intraperitoneal chemotherapy? Analysis of the long term (≥10 years) survivors in NRG/GOG randomized clinical trials of intraperitoneal and intravenous chemotherapy in stage III ovarian cancer

ObjectivePatients with advanced epithelial ovarian cancer (EOC) alive without progression at a landmark time-point of 10 years from diagnosis are likely cured. We report the proportion of patients with Stage III EOC who were long-term disease-free survivors (LTDFS≥10 years) following either intraperitoneal (IP) or intravenous (IV) chemotherapy as well as the predictors of LTDFS. MethodsData from 3 mature NRG/GOG trials (104, 114, 172) were analyzed and included demographics, clinicopathologic details, route of administration, and survival outcomes of patients living ≥10 years assessed according to the Kaplan-Meier method. Cox regression survival analysis was performed to evaluate independent prognostic predictors of LTDFS. ResultsOf 1174 patients randomized, 10-year overall survival (OS) was 26% (95% CI, 23–28%) and LTDFS ≥10 years was 18% (95% CI, 16–20%). Patients with LTDFS ≥10 years had a median age of 54.6 years (p < 0.001). Younger age (p < 0.001) was the only independent prognostic factor for LTDFS≥10 years on multivariate Cox analysis. ConclusionsApproximately 18% of patients were LTDFS ≥10 years. They form the tail end of the survival curve and are likely cured. Our results provide a comparative benchmark to evaluate the impact of PARP inhibitors in 1st line maintenance trials on survival outcomes.

Late effects, long‐term problems and unmet needs of cancer survivors

Great efforts are being made in cancer treatment, with impressive improvement in survival. The situation concerning research and care for long-term problems and late effects in the growing population of cancer survivors, however, is unsatisfactory. Therefore, in the FiX survey 1348 disease-free survivors about 4 years after diagnosis of different cancer types were asked to rate existing burdens and support received for them along a list of 36 potential problems. Health-related quality of life (HRQoL) was assessed with the EORTC QLQ-C30. Determinants of burdens were explored using logistic regression analysis. While cancer survivors' global HRQoL, physical and role function ratings were comparable or better than age- and sex-matched reference values of the general population, emotional and cognitive function was worse, especially among women (P< .01). Most frequently reported problems with at least moderate burden were loss of physical performance (36.3%), fatigue (35.1%), sexual problems (34.7%), sleep problems (34.1%), arthralgia (33.8%), anxiety (28.0%), neuropathy (25.6%), memory problems (23.0%) and concentration problems (21.9%). Burdened survivors often rated received support as poor, especially regarding support for problems that physicians might consider medically nonthreatening, or for which no effective pharmacologic or medical treatment is known. Determinants for burden included higher age, female gender, having ever received chemotherapy and overweight/obesity. In conclusion, a significant number of cancer survivors suffer from long-term or late effects and have unmet care needs. Awareness of health care professionals should be increased for these issues. The results of our study can contribute to the development of targeted survivorship plans.

Examination of risk factors for discontinuation of follow-up care in patients with head and neck cancer.

Little research has examined discontinuation of follow-up care in patients with head and neck cancer. This exploratory study sought to examine key demographic, disease, and behavioral factors as possible correlates of discontinuation (N=512). Cross-sectional study examined correlates of discontinuation of follow-up care within 1 year. The primary outcome was defined as a disease-free survivor not returning to cancer clinic for two consecutive follow-up appointments within the first year of care and not reentering oncologic care at any point thereafter. Demographic, disease, and behavioral factors were examined using multivariable logistic regression. One hundred twenty-six (24.6%) patients discontinued by 12-month follow-up. Being unmarried (OR=1.28, 95% CI=1.01-1.63, p=0.041) and having elevated depressive symptomatology (OR=1.04, 95% CI=1.01-1.07, p=0.034) were significantly associated with discontinuation. Receipt of a single (vs. multimodal) treatment approached significance (OR=1.71, 95% CI=0.96-3.07, p=0.071). Approximately one quarter of patients disengaged from important follow-up care within 1 year. Lack of social support, depressive symptomatology, and single treatment modality may be important correlates of discontinuation of care in patients with head and neck cancer. Additional studies of this outcome are needed. Improved understanding of correlates associated with discontinuation could facilitate the identification of at-risk patients and further development of interventions to keep patients engaged at a crucial time in the survivorship care trajectory.