Long-term Survivors Research Articles

Head and neck cancer survivors: Long-term nutrition impact symptoms, eating problems, and barriers to care impact psychosocial health.

12044 Background: Head and neck cancer (HNC) survivors experience significant long-term side effects of their treatment, and health-related quality-of-life (HRQoL) assessments of HNC survivors are still early in development. This survey captured long-term nutrition impact symptoms, eating problems, psychosocial impact, and barriers to accessing health care of HNC survivors. Methods: The Cancer Support Community (CSC) conducted an online survey with participants from CSC, Head and Neck Cancer Alliance, and Support for People with Oral and Head and Neck Cancer (SPOHNC). 172 “long-term survivors” (LTS), at least 2 years past initial diagnosis completed the survey. Most respondents were white (94%) & female (58%). The average age was 64. The most common treatments reported were radiation (93%), surgery (66%), and chemotherapy (59%). Results: Physical and psychosocial issues are prevalent and persistent among LTS. Almost all (99%) LTS reported experiencing eating problems since diagnosis, and 92% had symptoms persist into the last 7 days. Dry mouth (85% ever/68% in last week) and problems swallowing (82%/62%) were most common. Prevalence of side effects was independent of stage of cancer and time since initial diagnosis. 42% of LTS reported still not eating a solid food diet (30% “soft” food; 9% feeding tube; 4% liquid or pureed food). 63% ever used a feeding tube. For those no longer using a feeding tube, 71% used it for ≤6 months. Current users had feeding tubes for a median of 39 months. Weaning from a feeding tube was most likely before 14 months. 62% of LTS reported still feeling self-conscious when eating, 45% feeling embarrassed about their eating habits, 44% having their daily activities affected by eating problems, 37% said they avoid going out in public when it involves eating or drinking. Despite this, 27% reported never seeing a health care professional (HCP) or mental health professional (MHP) to manage their eating problems & psychosocial impact. Only 11% of LTS ever met with MHPs to address their distress. Female LTS of younger age and those with Medicare insurance were more likely to meet with HCPs (except dentists for Medicare recipients) and MHPs. Financial, transportation, & logistical concerns were top barriers to receiving care. 19% reported cost of care as a moderate to great barrier to cancer treatment. LTS reported difficulty paying for dental work (29%), supplemental nutrition drinks (11%), and other products to manage eating problems (9%). Conclusions: Although HNC’S are generally considered “curable,” the nature of the disease and the required aggressive treatment regimens leave LTS with a broad range of common physical and psychosocial issues that are rarely addressed. Survey data highlight almost universal, long-term persistence of eating and nutrition problems which cause significant psychosocial impact over LTS’s lifetime.

Risk of low bone mineral density in young pediatric cancer survivors with sarcopenia.

10070 Background: Required treatments to cure pediatric cancer at such a young age increase the risk of later health-related complications. Early exposure to DNA damaging agents, during a vital period of active skeletal growth, interferes with accrual of bone mass. Treatments not only impair bone health, but also affect skeletal muscle function and mass. Long-term pediatric cancer survivors present these limitations due to myofibrillary atrophy caused by degradation of myosin heavy chain and decrease in myosin synthesis death. Muscle weakness (both muscle strength deficits and low lean mass hereafter referred to as sarcopenia) and low areal bone mineral density (aBMD) have been observed to coexist in adult survivors of paediatric cancer. However, in young pediatric cancers survivors, associations between sarcopenia and low aBMD are not well described. Therefore, this study aimed to examine the risk of low aBMD in young pediatric cancer survivors with sarcopenia confirmed/probable, compared to not having sarcopenia. Methods: This cross-sectional study included 116 pediatric cancer survivors (12.1±3.3 years old; 42% female) enrolled on a randomized controlled trial designed to improve bone health (iBoneFIT project). Handgrip strength was used to assessed muscle strength. Dual-energy X-ray absorptiometry estimated aBMD (g/cm2) at the total body (less head), lumbar spine, total hip and femoral neck, and appendicular lean mass index (ALMI, kg/m2). Sarcopenia status was determined using age and sex specific international reference data from a healthy population. “No sarcopenia” was defined when muscle strength was >decile 2. “Sarcopenia probable” was defined when muscle strength was ≤decile 2 and ALMI Z-score was > -1.5 standard deviation (SD). “Sarcopenia confirmed” was defined when muscle strength was ≤decile 2 and ALMI Z-score ≤-1.5 SD. Logistic regression, adjusted for time from treatment completion and radiation exposure, was used to evaluate the risk of low aBMD (age-, sex- and race-specific aBMD Z-score < -1.0) by sarcopenia status. Results: More than one-third of survivors met criteria for sarcopenia confirmed (37.9%); 19.0% met criteria for sarcopenia probable. Survivors with sarcopenia confirmed had higher risk of low aBMD at the total body (odd ratio [OR]: 6.91, 95% confidence interval [CI]: 2.31-24.15), total hip (OR: 2.98, 95% CI: 1.02-9.54) and femoral neck (OR: 4.72, 95% CI: 1.72-14.19) than those without sarcopenia. Survivors with sarcopenia probable had higher risk of having low aBMD only at the total body (OR: 4.13, 95% CI: 1.04-17.60) than those without sarcopenia. Conclusions: Over one-third of young paediatric cancer survivors presented sarcopenia confirmed with higher risk of low aBMD. These findings suggest that interventions to mitigate osteosarcopenia in this population should be implemented at early stages after treatment completion.

Psychoneurological symptoms, inflammatory biomarkers and gut microbiome richness and diversity in individuals receiving hematopoietic cell transplantation (HCT).

e24053 Background: Hematopoietic Stem Cell Transplantation (HCT) is a potentially curative treatment for certain hematologic cancers. Although survival rates are markedly higher than in the past, there are a growing number of long-term HCT survivors who are at risk for short and long-term sequela, which can negatively affect quality of life. Psychoneurological (PN) symptoms are common occurrences associated with heightened inflammation in other cancers and chronic conditions. Emerging research links the gut microbiota to inflammatory biomarkers and suggests that gut-microbiota-brain crosstalk impacts the severity of psychoneurological symptoms among HCT recipients. Methods: This longitudinal descriptive study investigated the relationship among a cluster of PN symptoms (pain, fatigue, and depression), inflammatory biomarkers (IL-6, IL-10, C-reactive protein (CRP), and microbiota diversity measures (Shannon and Chao Beta diversity indexes) in 55 individuals receiving HCT for a hematologic malignancy. The time periods examined covered pre-transplant, 30-days, and 100-days following transplant. The PN symptoms were collected through self-reported questionnaires via computer with assistance from study staff, along with blood samples and stool specimens obtained at each study visit. Inflammatory marker values were log-transformed when used as dependent variables. Gut microbiota samples were analyzed using 16S ribosomal gene (V4 region) amplicons using Illumina MiSeq. Data analysis was performed using SAS 9.4, with PROC MIXED used for the mixed model analyses. Results: The analysis characterized mean changes in microbiota diversity over time for both Shannon and Chao indexes. IL6 levels were consistent over time, with an inverse association with Chao but not Shannon index. IL10 and CRP levels changed over time, but without associations with either Shannon or Chao. Pain severity and interference changed over time, but with no associations with inflammatory markers or gut microbiome beta diversity. Fatigue severity and interference changed over time and were positively associated with IL10. Depression did not change over time and was not associated with inflammatory markers or diversity. Conclusions: This study provides preliminary information related to associations between PN symptoms, inflammatory markers, and selected measures of gut microbiome diversity in HCT recipients. Further research is needed to explore and validate these findings to examine the implications for microbiota diversity on inflammatory factors and PN symptoms. Clinical trial information: NCT02398708 .

Late mortality and chronic health conditions in long-term survivors of nasopharyngeal cancers: The 20-year follow-up of territory-wide Hong Kong Nasopharyngeal Cancer Survivor Study (HKNPCSS).

12045 Background: The survival rate of patients with nasopharyngeal cancer (NPC) has significantly improved in the last decade. However, there are only a few studies that have quantified the long-term morbidity and mortality that follow NPC treatment. This study aims to analyze the chronic health conditions, all-cause mortality, and cause-specific mortality among NPC survivors. Methods: The Hong Kong NPC Survivor Study (HKNPCSS) is a retrospective cohort study conducted across all six oncology centers in Hong Kong. It included longitudinal follow-up of 5-year survivors diagnosed with NPC between 1997 to 2015. We compared the standardized mortality ratio (SMRs) of 7893 survivors to a matched population in terms of age, sex, and calendar year. We also calculated the frequencies of chronic conditions of 7893 survivors and 23679 healthy individuals with matched age, sex, and date of cohort entry. Chronic health conditions were classified using the Common Terminology Criteria for Adverse Events. Cox proportional hazard models were used to estimate hazard ratios (HRs) for chronic health conditions. Results: The mean age of NPC survivors was 49.1 years, while healthy individuals had a mean age of 50.5 years. Among the 7893 NPC survivors, the 20-year cumulative all-cause mortality was 34.0% (95% CI, 29.1%-38.9%), with 1668 (59.9%) of 2785 deaths attributed to health-related causes. The SMR for NPC survivors compared to the general population was 3.81 (95% CI, 3.67-3.95), with the highest SMRs observed for pulmonary (SMR: 6.18, 95% CI, 5.73-6.64) and cardiovascular (SMR: 2.12, 95% CI, 1.90-2.36) causes. Among the survivors, 59.2% (n=4674) had severe, life-threatening, or fatal (grade 3-5) health conditions, with a 20-year cumulative incidence of 59.0% (95% CI, 56.4%-61.5%). The adjusted hazard ratio (HR) of grade 3-5 chronic condition in NPC survivors, compared to healthy cohorts, was 7.02 (95% CI, 6.64-7.42). Gastrointestinal (HR: 20.7), hearing, visual, and nasal (HR: 15.4), and neurological (HR: 8.39) conditions had the highest risks. Intensity modulated radiotherapy (IMRT), compared to non-IMRT, was associated with reduced risks of all-cause mortality (HR: 0.83, 95% CI, 0.74-0.91) and a trend towards reduced grade 3-5 chronic health conditions (HR: 0.89, 95% CI, 0.75-1.05). Conclusions: Even 20 years after diagnosis, NPC survivors still face increased risks of late mortality and morbidity. The findings emphasize the need for a comprehensive survivorship program to improve outcomes for NPC survivors.

Survey of long term survivors of oral cancer: Looking beyond cancer biology.

6087 Background: While surgery is the main stay of treatment for early stage oral cancers, advanced stages require adjuvant treatments in the form of radiotherapy or concurrent radiotherapy. Yet, the effectiveness of these interventions is not solely determined by clinical measures but also by personal factors such as individual motivation, support from loved ones, and financial security. These aspects might explain the survival rate variations among patients who, despite having similar prognostic categories and stages of disease, show differing outcomes. The role of social determinants in influencing patient survival, apart from the acknowledged impact of disease biology, is not well understood. Methods: All treatment-naive oral cavity cancer patients who underwent definitive treatment during 2014 to 2018 at our institute and are alive for more than five years were selected for this study. A custom investigator-administered questionnaire was developed and it had 32 questions under six domains- personal, habit history, financial, social, functional, and emotional. The study was approved by the institutional ethics committee. Of the 1787 potential participants, we found that 219 had expired, only 442 patients agreed to answer the questionnaire, while 45 refused to participate. The rest of the patients were not reachable telephonically. Results: This survey had 442 patients, of which 90% were males, with a mean age of 52.1 years. The most common site of the presentation was buccal mucosa (60%), and 59% presented in the locally advanced stage. Post-operatively, 71% received adjuvant therapy. All patients were motivated to undergo the radical treatments and had their family support. However, post-treatment, about 10% of individuals experienced a change in marital status. Financial constraints did affect 20% of patients during and after treatment, and more than 70% had their out-of-pocket expenditure above 50% of the total cost. While 80% did not have trouble attending social functions, 46% reported trouble eating socially. However, this was more common for patients who received adjuvant treatment (p < 0.001). About 21% reported shoulder dysfunction and body discomfort. However, no statistically significant associations could be drawn for any of the domains of the questionnaire when compared to patients between the early and late stages. Shoulder discomfort was experienced more by patients who were treated for tongue cancer (p-value 0.010). Conclusions: The results of this study shed light on the challenges faced by long-term survivors of oral cancer following radical treatment regimens. More than half of patients reported that out-of-pocket expenses constituted more than half of their total treatment costs. A notable minority of people suffer from shoulder dysfunction, suggesting there is a clear opportunity for advancements in reconstruction and rehabilitation.

Causes of death and patterns of metastatic disease at the end of life for patients with advanced melanoma in the immunotherapy era.

e21522 Background: Despite the drastic improvement in survival of patients with metastatic melanoma from immune checkpoint inhibitors (ICIs), almost half of patients still die from their disease. Factors surrounding death including mechanisms of death, sites of disease, and settings of death remain poorly described. A better understanding of these factors is paramount to optimize management for these patients. Methods: A retrospective observational cohort study was performed for patients age > 18 who died after treatment for advanced melanoma with anti-PD1 therapy or ipilimumab + nivolumab (Ipi/Nivo) at Yale Cancer Center (YCC) between 1/2009 and 6/2023. Primary outcome was cause of death. Statistical analyses were performed with Stata SE, version 15.0 (StataCorp, College Station, TX). This study was approved by the Yale Institutional Review Board (Protocol #2000034631). Results: Overall, 287 patients with melanoma who received ICIs were documented to be deceased; 183 met inclusion criteria. Median time from metastatic diagnosis to death was 16.1 mos (range 0.3 to 135.1 mos). Median age at death was 70 (range 22-101), 62.8% were male, and 90.2% were white. Most patients (52.5%) received Ipi/Nivo first line, and 79.8% of patients received both anti-PD1 and anti-CTLA4 treatment at some point. The median number of metastatic sites at death was 4 (range 0-13). The majority (90.1%) of patients with measurable disease had multi-system involvement of melanoma. Eleven patients had no evidence of disease at death and died due to non-melanoma causes. The most common sites of metastatic disease at death were distant lymph nodes (62.8%), lung (57.9%), liver (50.8%), brain (38.8%), and bone (37.7%). In total, 80.3% (147/183) experienced hospitalization within 3 months prior to death or hospice enrollment. Most died in the hospital (31.7%) or while enrolled in hospice (31.2% inpatient vs. 29.4% home). Overall, 10.9% of patients had survival > 5 years after metastatic diagnosis; 76.2% of long-term survivors died due to melanoma. Of 174 patients with evaluable causes of death, 87.9% of deaths were due to melanoma (Table 1). Patients with pleural metastases were more likely to die of respiratory failure (p = 0.036, OR 2.41 95% CI 1.06-5.50). Conclusions: The majority of deaths were a consequence of metastatic melanoma, with the most common causes including FTT, respiratory failure, and infection. [Table: see text]

Case report of two long term ovarian cancer survivors with brain metastases following multimodal treatment including chemotherapy, radiotherapy and maintenance olaparib: An institutional case series and literature review

Brain metastasis from ovarian cancer is a very rare condition with a poor prognosis. However, due to its rarity, there is no established treatment strategy. We present a case series of brain metastasis with ovarian cancer, focusing on two long-term survivors treated with multimodal therapy. Among the nine cases, the median survival time after brain metastases was six months (range: 0–58 months). Eight patients had high-grade serous carcinoma (HGSC). Three of the four patients who underwent genetic testing tested positive for germline BRCA2 (gBRCA2) mutation. Two patients survived longer than 4 years after the diagnosis of brain metastases. Both of these patients received chemotherapy, radiation therapy, and olaparib, a molecularly targeted drug, as maintenance therapy. This case series suggests that patients with gBRCA2 mutation-positive HGSC may be at a high risk of developing brain metastases. A multidisciplinary approach, including PARP inhibitors, may improve the prognosis of patients with brain metastases from ovarian cancer.

Sexual health and testosterone concentration in male lymphoma survivors: A systematic review

Advancements in lymphoma treatment have increased the number of long-term survivors who may experience late effects such as impaired sexual function and testosterone deficiency. The aim of this review was to determine the prevalence of testosterone deficiency and sexual dysfunction among male lymphoma survivors; and associations between the two. A systematic search identified 20 articles for inclusion. The prevalence of low total testosterone was 0%–50 %, with mean values within reference levels, and for luteinizing hormone above reference levels in 0%–80 %. Four studies included SHBG and free testosterone, with mixed results. Compromised sexual health was found in 23%–61 %. Overall, total testosterone and sexual health were associated. The risk of bias (ROBINS-E and RoB 2) was high/very high, leading to low/very low overall confidence in the bulk of evidence (GRADE). Longitudinal studies evaluating biologically active testosterone and sexual health are needed, to develop evidence based standard procedures for follow-up of sexual health.

Female sexual function in long-term cervical cancer survivors compared with healthy women and women affected by benign gynecological disorders

ObjectiveTo compare the female sexual function between cervical cancer survivors and healthy women or with benign gynecological diseases. Study designFrom January 1, 2010 to January 31, 2019, a case-control study was conducted to compare the female sexual function of 106 cervical cancer survivors from a tertiary hospital and 185 women admitted to a gynecological outpatient clinic from the same health area for a routine gynecological examination (n=46) or for a benign gynecological disorder (symptomatic, n=113; asymptomatic, n=26).We prospectively assessed the female sexual function using the Female Sexual Function Index (FSFI). For the contrastive analysis hypothesis, we employed R statistical software. ResultsCervical cancer survivors reported lower sexual activity rates than controls, in general, did (47.12% vs. 88.65%, p=0.0001), and, particularly, compared with healthy and symptomatic controls (47.12% vs. 82.61%, p=0.003; 47.12% vs. 87.61%, p=0.0001, respectively).Sixty and fifty-eight hundredths percent of the cervical cancer survivors experienced female sexual dysfunction, mainly due to hypoactive sexual desire (93.27%). Female sexual dysfunction was diagnosed in 64.32% of the controls, with sexual arousal disorders being the most common diagnosis (44.86%).Compared with controls, cervical cancer survivors exhibited considerably lower FSFI total scores and in sexual desire and lubrication domains (p <0.000; p <0.0001; p=0.023). ConclusionsCervical cancer survivors had worse female sexual function and less sexual activity than controls did, although scores in both groups were in range of FSD. Rates of female sexual dysfunction were similar across cervical cancer survivors and controls, with hypoactive sexual desire and sexual arousal disorders as the most common diagnoses, respectively.

Proteomics of tumor and serum samples from isocitrate dehydrogenase-wildtype glioblastoma patients: is the detoxification of reactive oxygen species associated with shorter survival?

Proteomics has been little used for the identification of novel prognostic and/or therapeutic markers in isocitrate dehydrogenase (IDH)-wildtype glioblastoma (GB). In this study, we analyzed 50 tumor and 30 serum samples from short- and long-term survivors of IDH-wildtype GB (STS and LTS, respectively) by data-independent acquisition mass spectrometry (DIA-MS)-based proteomics, with the aim of identifying such markers. DIA-MS identified 5422 and 826 normalized proteins in tumor and serum samples, respectively, with only three tumor proteins and 26 serum proteins displaying significant differential expression between the STS and LTS groups. These dysregulated proteins were principally associated with the detoxification of reactive oxygen species (ROS). In particular, GB patients in the STS group had high serum levels of malate dehydrogenase 1 (MDH1) and ribonuclease inhibitor 1 (RNH1) and low tumor levels of fatty acid-binding protein 7 (FABP7), which may have enabled them to maintain low ROS levels, counteracting the effects of the first-line treatment with radiotherapy plus concomitant and adjuvant temozolomide. A blood score built on the levels of MDH1 and RNH1 expression was found to be an independent prognostic factor for survival based on the serum proteome data for a cohort of 96 IDH-wildtype GB patients. This study highlights the utility of circulating MDH1 and RNH1 biomarkers for determining the prognosis of patients with IDH-wildtype GB. Furthermore, the pathways driven by these biomarkers, and the tumor FABP7 pathway, may constitute promising therapeutic targets for blocking ROS detoxification to overcome resistance to chemoradiotherapy in potential GB STS.

For the Long Haul: Management of Long-Term Survivors after Melanoma Systemic Therapy.

This review summarizes the latest advancements in survivorship care for patients with advanced melanoma who received systemic therapy and emphasizes the areas where more research is needed. Over the last decade there have been remarkable advances in the treatment of advanced and metastatic melanoma. Due to these novel treatments, including several immune checkpoint inhibitors and tyrosine kinase inhibitors, there are and will continue to be increasing numbers of long-term melanoma survivors who have been treated with systemic therapy. These patients will navigate new challenges are they are essentially among the first long term survivors after these novel therapies. Survivorship care focuses on improving the health-related quality of life of patients including the physical, emotional, social and functional effects of cancer that begin at diagnosis and continue through the end of life. Survivorship also includes screening for cancer recurrence and second cancers. As the number of melanoma survivors who received systemic therapy continues to grow, the survivorship care plan will become increasingly important for optimal care of patients even after their cancer treatments. Understanding the many domains of survivorship care for this group of patients is imperative for their care now and to identify unmet needs for future research.

Major Pancreatic Resection Increases Bone Mineral Density Loss, Osteoporosis, and Fractures.

To assess whether long-term survivors of pancreatic surgery show increased risk to develop impaired bone mineral density, osteoporosis, and vitamin D deficiency. Pancreatic resection poses a risk for malabsorption of fat-soluble vitamins and other micronutrients essential for bone mineralization. Here, we evaluated the long-term effects of pancreatic resection on bone mineral density (BMD) and its clinical sequelae. This was a two-pronged analysis of post-pancreatectomy patients with a follow-up period greater than 3 years comprising (1) a large, propensity score-matched, cohort study based on a multinational federated research network (FRN) and (2) a retrospective single institution review of clinical and radiographic patient data. In the FRN analysis, an initial cohort of 8,423 post-pancreatectomy patients were identified and propensity score-matched with normal controls. The primary endpoint was the 10-year risk of developing osteoporotic pathological fractures and secondary endpoints included diagnosis of osteoporosis, vitamin-D deficiency, and related therapies. The single institution retrospective analysis identified 224 patients who underwent pancreatic resection between 2005 and 2019. BMD was quantified in CT images acquired before and after surgery. BMD trends and related factors were assessed in a time-series mixed effect linear regression model. A total of 8,080 propensity score-matched pairs were included in the FRN analysis. The analysis revealed a 2.4-fold increase in pathological fractures (P<0.0001) and 1.4-1.5 fold increase in osteoporosis/osteomalacia (P<0.0001) and vitamin-D deficiency (P<0.0001) in post-pancreatectomy patients. Vitamin-D supplements were more common in the pancreatectomy group (OR 1.4, 95% CI 1.28-1.53, P<0.0001), as were specific osteoporosis/osteomalacia treatments such as calcitonin, denosumab, romosozumab, abaloparatide, and teriparatide (OR 2.24, 95%CI 1.69-2.95, P<0.0001). Retrospective analysis of CT imaging revealed that BMD declined more rapidly following pancreatic resection compared to normal historical controls (P=0.015). Older age, pancreatic cancer, and pancreaticoduodenectomy were associated with increased rates of BMD loss (P<0.05, each). After pancreatic resection, patients are at higher risk for BMD loss and subsequent fractures. As the cohort of pancreatic resection survivorship grows, attention will need to be paid to focused prevention efforts to reduce BMD loss, osteoporosis, and fractures in these vulnerable patients, with specific attention to the pancreatic cancer population.

Shorter long-term post-transplant life expectancy may be due to prior chemotherapy for the underlying disease: analysis of 3012 patients with acute myeloid leukemia enrolled on 9 consecutive ECOG-ACRIN trials.

Several studies reported that patients with acute myeloid leukemia (AML) who remain in long-term remission after allogeneic or autologous transplant have a shorter life expectancy, compared to the general population. However, little is known about the life expectancy of adult long-term survivors of AML who were treated with chemotherapy alone without a transplant and there have been no comparisons with survival among the general population. The current study indicates that the life expectancy of AML patients who achieved and maintained CR for at least 3 years is shorter than expected for age in the US population. This was observed also in patients who did not undergo a transplant including those who have not relapsed during the entire long follow-up period. Thus, late relapse does not explain why patients without transplants have a shortened life expectancy. Taken together, these data strongly suggest that prior chemotherapy for the underlying AML is at least a major contributing factor for the known shortened life expectancy post-transplant.

A novel conditional survival nomogram for monitoring real-time prognosis of non-metastatic colorectal cancer

AimsThe aim of this study is to enhance the accuracy of monitoring and treatment information for patients diagnosed with colorectal cancer (CRC).MethodsUtilizing the Surveillance, Epidemiology, and End Results (SEER) database, a cohort of 335,948 eligible CRC patients was included in this investigation. Conditional survival probability and actuarial overall survival were employed as methodologies to investigate the association between clinicopathological characteristics and cancer prognosis.ResultsAmong CRC patients, the 5-year survival rate was 59%, while the 10-year survival rate was 42%. Over time, conditional survival showed a consistent increase, with rates reaching 45% and 48% for individuals surviving 1 and 2 years, respectively. Notably, patients with unfavorable tumor stages exhibited substantial improvements in conditional survival, thereby narrowing the disparity with actuarial overall survival over time.ConclusionThis study underscores the significance of time-dependent conditional survival probability, particularly for patients with a poorer prognosis. The findings suggest that long-term CRC survivors may experience improved cancer prognosis over time.

The landscape of etiological patterns of hepatocellular carcinoma and intrahepatic cholangiocarcinoma in Thailand.

Thailand is among countries with the highest global incidence and mortality rates of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). While viral hepatitis and liver fluke infections have been associated with HCC and iCCA, respectively, other environmental risk factors, overall risk factor commonality and combinatorial roles, and effects on survival have not been systematically examined. We conducted a TIGER-LC consortium-based population study covering all high-incidence areas of both malignancies across Thailand: 837 HCC, 1474 iCCA, and 1112 controls (2011-2019) were comprehensively queried on lifelong environmental exposures, lifestyle, and medical history. Multivariate logistic regression and Cox proportional hazards analyses were used to evaluate risk factors and associated survival patterns. Our models identified shared risk factors between HCC and iCCA, such as viral hepatitis infection, liver fluke infection, and diabetes, including novel and shared associations of agricultural pesticide exposure (OR range of 1.50; 95% CI: 1.06-2.11 to 2.91; 95% CI: 1.82-4.63) along with vulnerable sources of drinking water. Most patients had multiple risk factors, magnifying their risk considerably. Patients with lower risk levels had better survival in both HCC (HR 0.78; 95% CI: 0.64-0.96) and iCCA (HR 0.84; 95% CI: 0.70-0.99). Risk factor co-exposures and their common associations with HCC and iCCA in Thailand emphasize the importance for future prevention and control measures, especially in its large agricultural sector. The observed mortality patterns suggest ways to stratify patients for anticipated survivorship and develop plans to support medical care of longer-term survivors, including behavioral changes to reduce exposures.

Mental Health Support Is an Unmet Need for Long-Term Burn Survivors: A Web-Based Survey.

A National Trauma Research Action Plan identified the involvement of burn survivors as critical informants to determine the direction of research. This study employed a web-based survey to identify care gaps in a sample of burn survivors. We surveyed burn survivors from around the United States through social media and email contact with the Phoenix Society for Burn Survivors. We elicited demographic info, burn history, and unmet needs. Statistical analysis was performed to test our hypothesis that lack of access to mental health support/professionals would be identified as an unmet need in long-term burn survivors. Of 178 survey respondents, most were at least ten years removed from the date of their burn injury (n=94, 53%). Compared to those less than 3 years from their burn injury, individuals greater than 10 years were at least 5 times more likely to note lack of access to mental health support [11-20 years OR 8.7, p< 0.001; >20 years OR5.7, p=0.001]. 60% of Spanish speakers reported lack of support group access was among their greatest unmet needs, compared to 37% of English speakers (p=0.184). This study highlights the need for ongoing access to mental health resources in burn survivors. Our findings emphasize that burn injury is not just an acute ailment, but a complex condition that evolves into a chronic disease. Additional studies should focus on the experiences of Spanish-speaking burn survivors, given small sample size leading to a likely clinically significant but not statistically different lack of access to support groups.

Social relationships and their impact on health-related quality of life in a long-term breast cancer survivor cohort.

Health-related quality of life (HRQOL) has become increasingly important for breast cancer survivors, but clinically relevant declines often persist for many years after treatment. This study aimed to investigate whether social relationships can mitigate or prevent this decline in HRQOL. Data were used from the German population-based Mamma Carcinoma Risk Factor Investigation (MARIE) cohort of 2022 breast cancer cases with follow-up information for more than 15 years after diagnosis. Correlations between social integration, social support, and global health status (GHS) as an overall measure of HRQOL were analyzed, and linear regression analysis was performed with structural equation modeling. The majority of participants reported high levels of social integration and social support and moderate levels of GHS. Social integration 5 years after diagnosis was associated with GHS 5 years after diagnosis (β=1.12; 95% CI,0.25-1.99), but no longitudinal effects were found. Social support 5 years after diagnosis was associated with better GHS 5 years (β=0.42; 95% CI,0.36-0.48) and 10 years after diagnosis (β=0.12; 95% CI,0.02-0.22), whereas social support 10 years after diagnosis was associated with GHS 10 years (β=0.29; 95% CI,0.20-0.39) and 15 years after diagnosis (β=0.10; 95% CI,0.01-0.21). These results confirm that social relationships positively influence HRQOL in long-term breast cancer survivors and that their association should receive more attention clinically and beyond routine care.

Spatial Heterogeneity of Immune Drivers Coordinates the Organisation of Antitumor Immunity in Pancreatic Cancer, Affecting Patient Outcome

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is considered low immunogenic with “cold” tumor microenvironment (TME) and is mostly unresponsive to immune checkpoint blockade therapies. Aims We aim to decipher the impact of intratumoral heterogeneity of immune determinants on antitumor response. Methods 130PDAC specimens were classified according to overall survival in long-term survivors (LTSs, n=29, OS≥60 months) and short-term survivors (STSs, n=101, OS&amp;lt;60 months). Spatial compartment masks were defined by immunofluorescence imaging (tumor cells: Pancytokeratin+CD45-, leukocytes: CD45+Pancytokeratin-, stroma cells: PanCK-CD45-). 4regions of interest from tumor center (TC) and the invasive front (IF) were examined by transcriptomic and proteomic analysis using the Nanostring platform for immune pathway targets. Results of NGS and morphological features were integrated. 20samples underwent immunophenotypic analysis by multiplex immunofluorescence. Results LTSs displayed mostly homogeneous morphology with extended glandular differentiation and immunogenic TME both at TC and IF, with increasing gradient towards the IF. There was higher presence of immune checkpoint-associated and immunogenic genes and proteins at the IF as compared to the TC, including CD40, CD3, CD8, CD4, GZMB and PD-L1. In contrast, STSs were characterized by morphologic heterogeneity, including areas with reduced glandular differentiation and high tumor budding, and a mostly immunosuppressive TME with negative gradient towards the IF. Moreover, there was reduced gene expression and protein abundance at the IF as compared to the TC, including CD3, CD8, CXCL10, GZMB, IFNG, HLA-DR and CD40. Conclusion LTSs display a highly immunogenic TME, underscoring their effective antitumor immunity, especially at the area of IF compared with STSs. A significant intratumoral heterogeneity between TC and IF exists with regards to immune determinants in both, LTSs and STSs, which might explain the different antitumor immune responses, affecting patient outcome. The differential expression of immune drivers may help selecting patients for combination therapies to improve antitumor immunity and harness the responsiveness to immune checkpoint inhibitors in PDAC.

Construction of a prognostic model for extensive-stage small cell lung cancer patients undergoing immune therapy in northernmost China and prediction of treatment efficacy based on response status at different time points

Background and purposeRecently, the emergence of immune checkpoint inhibitors has significantly improved the survival of patients with extensive-stage small cell lung cancer. However, not all patients can benefit from immunotherapy; therefore, there is an urgent need for precise predictive markers to screen the population for the benefit of immunotherapy. However, single markers have limited predictive accuracy, so a comprehensive predictive model is needed to better enable precision immunotherapy. The aim of this study was to establish a prognostic model for immunotherapy in ES-SCLC patients using basic clinical characteristics and peripheral hematological indices of the patients, which would provide a strategy for the clinical realization of precision immunotherapy and improve the prognosis of small cell lung cancer patients.MethodsThis research retrospectively collected data from ES-SCLC patients treated with PD-1/PD-L1 inhibitors between March 1, 2019, and October 31, 2022, at Harbin Medical University Cancer Hospital. The study data was randomly split into training and validation sets in a 7:3 ratio. Variables associated with patients’ overall survival were screened and modeled by univariate and multivariate Cox regression analyses. Models were presented visually via Nomogram plots. Model discrimination was evaluated by Harrell’s C index, tROC, and tAUC. The calibration of the model was assessed by calibration curves. In addition, the clinical utility of the model was assessed using a DCA curve. After calculating the total risk score of patients in the training set, patients were stratified by risk using percentile partitioning. The Kaplan–Meier method was used to plot OS and PFS survival curves for different risk groups and response statuses at different milestone time points. Differences in survival time groups were compared using the chi-square test. Statistical analysis software included R 4.1.2 and SPSS 26.ResultsThis study included a total of 113 ES-SCLC patients who received immunotherapy, including 79 in the training set and 34 in the validation set. Six variables associated with poorer OS in patients were screened by Cox regression analysis: liver metastasis (P = 0.001), bone metastasis (P = 0.013), NLR < 2.14 (P = 0.005), LIPI assessed as poor (P < 0.001), PNI < 51.03 (P = 0.002), and LDH ≥ 146.5 (P = 0.037). A prognostic model for immunotherapy in ES-SCLC patients was constructed based on the above variables. The Harrell’s C-index in the training and validation sets of the model was 0.85 (95% CI 0.76–0.93) and 0.88 (95% CI 0.76–0.99), respectively; the AUC values corresponding to 12, 18, and 24 months in the tROC curves of the training set were 0.745, 0.848, and 0.819 in the training set and 0.858, 0.904 and 0.828 in the validation set; the tAUC curves show that the overall tAUC is > 0.7 and does not fluctuate much over time in both the training and validation sets. The calibration plot demonstrated the good calibration of the model, and the DCA curve indicated that the model had practical clinical applications. Patients in the training set were categorized into low, intermediate, and high risk groups based on their predicted risk scores in the Nomogram graphs. In the training set, 52 patients (66%) died with a median OS of 15.0 months and a median PFS of 7.8 months. Compared with the high-risk group (median OS: 12.3 months), the median OS was significantly longer in the intermediate-risk group (median OS: 24.5 months, HR = 0.47, P = 0.038) and the low-risk group (median OS not reached, HR = 0.14, P = 0.007). And, the median PFS was also significantly prolonged in the intermediate-risk group (median PFS: 12.7 months, HR = 0.45, P = 0.026) and low-risk group (median PFS not reached, HR = 0.12, P = 0.004) compared with the high-risk group (median PFS: 6.2 months). Similar results were obtained in the validation set. In addition, we observed that in real-world ES-SCLC patients, at 6 weeks after immunotherapy, the median OS was significantly longer in responders than in non-responders (median OS: 19.5 months vs. 11.9 months, P = 0.033). Similar results were obtained at 12 weeks (median OS: 20.7 months vs 11.9 months, P = 0.044) and 20 weeks (median OS: 20.7 months vs 11.7 months, P = 0.015). Finally, we found that in the real world, ES-SCLC patients without liver metastasis (P = 0.002), bone metastasis (P = 0.001) and a total number of metastatic organs < 2 (P = 0.002) are more likely to become long-term survivors after receiving immunotherapy.ConclusionThis study constructed a new prognostic model based on basic patient clinical characteristics and peripheral blood indices, which can be a good predictor of the prognosis of immunotherapy in ES-SCLC patients; in the real world, the response status at milestone time points (6, 12, and 20 weeks) can be a good indicator of long-term survival in ES-SCLC patients receiving immunotherapy.

Treatment and Care of Patients with ST-Segment Elevation Myocardial Infarction—What Challenges Remain after Three Decades of Primary Percutaneous Coronary Intervention?

Primary percutaneous coronary intervention (pPCI) has revolutionized the prognosis of ST-segment elevation myocardial infarction (STEMI) and is the gold standard treatment. As a result of its success, the number of pPCI centres has expanded worldwide. Despite decades of advancements, clinical outcomes in STEMI patients have plateaued. Out-of-hospital cardiac arrest and cardiogenic shock remain a major cause of high in-hospital mortality, whilst the growing burden of heart failure in long-term STEMI survivors presents a growing problem. Many elements aiming to optimize STEMI treatment are still subject to debate or lack sufficient evidence. This review provides an overview of the most contentious current issues in pPCI in STEMI patients, with an emphasis on unresolved questions and persistent challenges.