Long-term Cancer Survivors Research Articles

Comprehensive Medicine Approach Towards Cancer Sufferers and Survivors: A Review

Despite significant improvements in cancer diagnosis, prevention, and care, cancer is still expected to be the biggest cause of mortality worldwide. Cancer prevalence and fatality rates are both increasing. There are numerous cancer treatment options. The type of cancer and its stage determine the sort of treatment required. Surgery, chemotherapy, and radiation are examples of traditional therapeutic procedures. At the same time, significant advances have been made recently, including stem cell therapy, targeted therapy, natural antioxidants, radionics, chemodynamic therapy, and ferroptosis-based therapy. Most patients have a combined approach- surgery, chemotherapy, and radiation therapy. Current methods in oncology focus on developing safe cancer nanomedicines. To obtain novel diagnostic and therapeutic alternatives, stem cell treatment has demonstrated potential success. Cancer cell spread can be slowed by targeted treatment, which protects healthy cells from harm. The long-term cancer survivors suffered in terms of body image concerns, emotional and social, and spiritual/ philosophical issues leading to poor quality of life in these patients. The positive attribute of complementary medicine and alternative therapies is that they enable patients to help themselves while undergoing cancer treatment and afterward. This review explores recent comprehensive approaches for cancer and associated effects leading to psychological issues.

Effect of chemotherapy on hippocampal volume and shape in older long-term breast cancer survivors.

The objective of this study was to assess changes in hippocampal volume and shape in older long-term breast cancer survivors who were exposed to chemotherapy 5-15 years prior. This study recruited female long-term breast cancer survivors aged 65 years or older with a history of chemotherapy (C+), age-matched breast cancer survivors who did not receive chemotherapy (C-), and healthy controls (HC). The participants were recruited 5-15 years after chemotherapy at time point 1 (TP1) and were followed up for 2 years at time point 2 (TP2). Assessments included hippocampal volume and shape from brain MRI scans and neuropsychological (NP) tests. At TP1, each of the three groups was comprised of 20 participants. The C+ group exhibited a hippocampal volume loss estimated in proportion with total intracranial volume (ICV) in both the left and right hemispheres from TP1 to TP2. Regarding the hippocampal shape at TP1, the C+ group displayed inward changes compared to the control groups. Within the C+ group, changes in right hippocampal volume adjusted with ICV were positively correlated with crystalized composite scores (R = 0.450, p = 0.044). Additionally, in C+ groups, chronological age was negatively correlated with right hippocampal volume adjusted with ICV (R = -0.585, p = 0.007). The observed hippocampal volume reduction and inward shape deformation within the C+ group may serve as neural basis for cognitive changes in older long-term breast cancer survivors with history of chemotherapy treatment.

Abstract A095: Long-term ovarian cancer survivors: spatial transcriptomics depict ligand-receptor crosstalk heterogeneity at the tumor-stroma interface

Abstract Advanced high-grade serous ovarian cancer (HGSC) is an aggressive disease that accounts for 70% of all ovarian cancer deaths. Nevertheless, 15% of patients diagnosed with advanced HGSC survive more than 10 years. The elucidation of predictive markers of these long-term survivors (LTS) could help identify therapeutic targets for the disease, and thus improve patient survival rates. Reports to date have not fully established the heterogeneity of the tumor microenvironment (TME) in ovarian cancer and its association with clinical outcomes. The TME, which is composed primarily of fibroblasts, endothelial cells, lymphocytic infiltrates, and extracellular matrix proteins, can directly affect cancer cell growth, migration, and differentiation, and thus presents a unique opportunity for cancer diagnosis and treatment. To investigate the stromal heterogeneity of the TME in ovarian cancer, we used spatial transcriptomics to generate spatially resolved transcript profiles in treatment naïve advanced HGSC from LTS and short-term survivors (STS) and determined the association between cancer-associated fibroblasts (CAF) heterogeneity and survival in patients with advanced HGSC. Spatial transcriptomics and single-cell RNA sequencing data were integrated to distinguish tumor and stroma regions, and a computational method was developed to investigate spatially resolved ligand-receptor interactions between various tumor and CAF subtypes in the TME. Our spatial transcriptomics analysis demonstrated the presence of different tumor clusters represented by different transcriptome signatures within a tumor tissue, suggesting high levels of heterogeneity not only among different HGSC samples but also within single HGSC samples. Moreover, our spatial transcriptomics analysis of treatment-naïve STS and LTS samples demonstrated high levels of both intra- and inter-stromal heterogeneity among HGSCs. Annotated stroma clusters, which were identified predominantly in STS samples, had high levels of both periostin and CD36 expression as well as high levels of COL1A1 expression. Furthermore, a specific subtype of CAFs expressing αSMA, VIM and PDGFRβ and its spatial location relative to a particular ovarian cancer cell subtype in the TME correlated with long-term survival in advanced HGSC patients. We also characterized region-specific ligand-receptor interactions by analyzing crosstalk signaling in neighboring spots at the stroma-tumor interface. Using this method and subsequent validation studies by multiplex immunohistochemistry we found that increased APOE-LRP5 crosstalk occurred at the stroma-tumor interface in tumor tissues from STS compared to LTS. These findings suggest that a strong crosstalk signaling network between tumor-derived LRP5 and CAF-derived APOE may confer a more aggressive phenotype of the HGSC, which contribute to poorer patient survival rates. Further studies to confirm whether such crosstalk plays a role in modulating the malignant phenotype of HGSC and could serve as a predictive biomarker of patient survival are warranted. Citation Format: Sammy Ferri-Borgogno, Ying Zhu, Jianting Sheng, Jared K. Burks, Javier A. Gomez, Kwong Kwok Wong, Stephen TC Wong, Samuel C. Mok. Long-term ovarian cancer survivors: spatial transcriptomics depict ligand-receptor crosstalk heterogeneity at the tumor-stroma interface [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A095.

Novel insights into cardiovascular toxicity of cancer targeted and immune therapies: Beyond ischemia with non-obstructive coronary arteries (INOCA)

Novel immune and targeted therapies approved over the past 2 decades have resulted in dramatic improvements in cancer-specific outcomes for many cancer patients. However, many of these agents can induce cardiovascular toxicity in a subset of patients. The field of cardio-oncology was established based on observations that anti-neoplastic chemotherapies and mantle radiation can lead to premature cardiomyopathy in cancer survivors. While conventional chemotherapy, targeted therapy, and immune therapies can all result in cardiovascular adverse events, the mechanisms, timing, and incidence of these events are inherently different. Many of these effects converge upon the coronary microvasculature to involve, through endocardial endothelial cells, a more direct effect through close proximity to cardiomyocyte with cellular communication and signaling pathways. In this review, we will provide an overview of emerging paradigms in the field of Cardio-Oncology, particularly the role of the coronary microvasculature in mediating cardiovascular toxicity of important cancer targeted and immune therapies. As the number of cancer patients treated with novel immune and targeted therapies grows exponentially and subsequently the number of long-term cancer survivors dramatically increases, it is critical that cardiologists and cardiology researchers recognize the unique potential cardiovascular toxicities of these agents.

Impact of Pre-Diagnostic Risk Factors on Short- and Long-Term Ovarian Cancer Survival Trajectories: A Longitudinal Observational Study.

Tumor- and treatment-related factors are established predictors of ovarian cancer survival. New studies suggest a differential impact of exposures on ovarian cancer survival trajectories (i.e., rapidly fatal to long-term disease). This study examined the impact of pre-diagnostic risk factors on short- and long-term ovarian cancer survival trajectories in the Canadian context. This population-based longitudinal observational study included women diagnosed with invasive epithelial ovarian cancer from 1995 to 2004 in Ontario. Data were obtained from medical records, interviews, and the provincial cancer registry. Extended Cox proportional hazard models estimated the association between risk factors and all-cause and ovarian cancer-specific mortality by survival time intervals (<3 years (i.e., short-term survival), 3 to <6 years, 6 to <10 years, and ≥10 years (i.e., long-term survival)). Among 1421 women, histology, stage, and residual disease were the most important predictors of all-cause mortality in all survival trajectories, particularly for short-term survival. Reproductive and lifestyle factors did not strongly impact short-term overall survival but were associated with long-term overall survival. As such, among long-term survivors, history of breastfeeding significantly decreased the risk of all-cause mortality (HR 0.65; 95% CI 0.46, 0.93; p < 0.05), whereas smoking history (HR 1.75; 95% CI 1.27, 2.40; p < 0.05) and obesity (HR 1.81; 95% CI 1.24, 2.65; p < 0.05) significantly increased the risk of all-cause mortality. The findings were consistent with ovarian cancer-specific mortality. These findings suggest that pre-diagnostic exposures differentially influence survival time following a diagnosis of ovarian cancer.

Association between surgical quality and long-term survival in lung cancer

ObjectivesThere are significant variations in both perioperative and long-term outcomes after lung cancer resection. While perioperative outcomes are often used as comparative measures of quality, they are unreliable, and their association with long-term outcomes remain unclear. In this context, we evaluated whether historical perioperative mortality after lung cancer resection is associated with 5-year survival. Patients and MethodsThe National Cancer Database (NCDB) was queried to identify patients diagnosed with non-small cell lung cancer (NSCLC) in 2010–2016 who underwent surgical resection (n = 234200). Hospital-level reliability-adjusted 90-day mortality rate quartiles for 2010–2013 was used as the independent variable to analyze 5-year survival for patients diagnosed in 2014–2016 (n = 85396). ResultsThere were 85,396 patients in the 2014–2016 cohort across 1,086 hospitals. Overall observed 90-day mortality rate was 3.2% (SD 17.6%) with 2.6% (SD 16.0%) for the historically best performing quartile vs. 3.9% (SD 19.4%) for the worst performing quartile (p < 0.0001). Patients who underwent resection at hospitals with the best historical mortality rate had significantly better 5-year survival across all stages compared to those treated at hospitals in the worst performing quartile in multivariate Cox regression analysis (all stages – HR 1.21 [95% CI 1.15–1.26]; stage I – HR 1.19 [95% CI 1.12–1.25]; stage II – HR 1.20 [95% CI 1.09–1.32]; stage III – HR 1.36 [95% CI 1.20–1.54]) and Kaplan-Meier survival estimates (all stages – p < 0.0001, stage I – p < 0.0001; stage II – p = 0.0004; stage III – p < 0.0001). ConclusionWith expanded lung cancer screening criteria and likely increase in early-stage detection, profiling performance is paramount to ensuring mortality benefits. We found that episodes surrounding surgical resection may be used to profile long-term outcomes that likely reflect quality across a broader context of care. Evaluating lung cancer care quality using perioperative outcomes may be useful in profiling provider performance and guiding value-based payment policies.

A Somatic BRCA2-Mutated Pancreatic Adenocarcinoma With Sustained Exceptional Response to Modified FOLFIRINOX.

Homologous recombination repair (HRR) pathway deficiency opens multiple therapeutic avenues within pancreatic cancer. Patients with HRR deficiency-associated gene mutations such as BRCA1, BRCA2, and PALB2 are more susceptible to platinum-based chemotherapies and in those with somatic BRCA mutations, PARP inhibitor therapy prolongs progression-free survival. The case discussed herein illustrates the therapeutic opportunities offered through the identification of HRR deficiency in pancreatic cancer, as well as the challenges associated with treatment and prevention of central nervous system metastases in long-term survivors of pancreatic cancer.

The Impact of Enhanced Recovery on Long-Term Survival in Rectal Cancer.

Implementing perioperative interventions such as enhanced recovery pathways (ERPs) has improved short-term outcomes and minimized length of stay. Preliminary evidence suggests that adherence to the enhanced recovery after surgery protocol may also enhance 5-year cancer-specific survival (CSS) in colorectal cancer surgery. This retrospective study presents long-term survival outcomes and disease recurrence from a high-volume, single-center practice. All patients over 18years of age diagnosed with rectal adenocarcinoma and undergoing elective minimally invasive surgery (MIS) were retrospectively reviewed between February 2005 and April 2018. Relevant data were extracted from Mayo electronic records and securely stored in a database. Short-term morbidity and long-term oncological outcomes were compared between patients enrolled in ERP and those who received non-enhanced care. Overall, 600 rectal cancer patients underwent MIS, of whom 320 (53.3%) were treated according to the ERP and 280 (46.7%) received non-enhanced care. ERP was associated with a decrease in length of stay (3 vs. 5 days; p<0.001) and less overall complications (34.7 vs. 54.3%; p<0.001). The ERP group did not show an improvement in overall survival (OS) or disease-free survival (DFS) compared with non-enhanced care on multivariable (non-ERP vs. ERP OS: hazard ratio [HR] 1.268, 95% confidence interval [CI] 0.852-1.887; DFS: HR 1.050, 95% CI 0.674-1.635) analysis. ERP was found to be associated with a reduction in short-term morbidity, with no impact on long-term oncological outcomes, such as OS, CSS, and DFS.

Mechanisms of sleep disturbances in long-term cancer survivors: a childhood cancer survivor study report.

Sleep problems following childhood cancer treatment may persist into adulthood, exacerbating cancer-related late effects and putting survivors at risk for poor physical and psychosocial functioning. This study examines sleep in long-term survivors and their siblings to identify risk factors and disease correlates. Childhood cancer survivors (≥5 years from diagnosis; n = 12 340; 51.5% female; mean [SD] age = 39.4 [9.6] years) and siblings (n = 2395; 57.1% female; age = 44.6 [10.5] years) participating in the Childhood Cancer Survivor Study completed the Pittsburgh Sleep Quality Index (PSQI). Multivariable Poisson-error generalized estimating equation compared prevalence of binary sleep outcomes between survivors and siblings and evaluated cancer history and chronic health conditions (CHC) for associations with sleep outcomes, adjusting for age (at diagnosis and current), sex, race/ethnicity, and body mass index. Survivors were more likely to report clinically elevated composite PSQI scores (>5; 45.1% vs 40.0%, adjusted prevalence ratio [PR] = 1.20, 95% CI = 1.13 to 1.27), symptoms of insomnia (38.8% vs 32.0%, PR = 1.26, 95% CI = 1.18 to 1.35), snoring (18.0% vs 17.4%, PR = 1.11, 95% CI = 1.01 to 1.23), and sleep medication use (13.2% vs 11.5%, PR = 1.28, 95% CI = 1.12 to 1.45) compared with siblings. Within cancer survivors, PSQI scores were similar across diagnoses. Anthracycline exposure (PR = 1.13, 95% CI = 1.03 to 1.25), abdominal radiation (PR = 1.16, 95% CI = 1.04 to 1.29), and increasing CHC burden were associated with elevated PSQI scores (PRs = 1.21-1.48). Among survivors, sleep problems were more closely related to CHC than diagnosis or treatment history, although longitudinal research is needed to determine the direction of this association. Frequent sleep-promoting medication use suggests interest in managing sleep problems; behavioral sleep intervention is advised for long-term management.

Protective effect of height on long-term survival of resectable lung cancer: a new feature of the lung cancer paradox

IntroductionUnlike most malignancies, higher body mass index (BMI) is associated with a reduced risk of lung cancer and improved prognosis after surgery. However, it remains controversial whether height, one of...

Long-term survival with systemic therapy in the last decade: Can melanoma be cured?

Immune checkpoint inhibitors have been shown to prolong survival of patients with several types of cancer, and the finding was first established in melanoma. Previously, systemic therapy for advanced melanoma aimed only at tumor control and palliation of symptoms. However, in recent years, some patients who received systemic therapy have achieved a complete response and survived without continuous treatment for more than several years. This review discusses the long-term survival rates achieved with currently used systemic therapies and their future perspectives. Long-term survival is currently most likely to be achieved with the use of the standard-dose combination of nivolumab plus ipilimumab, however, this regimen is associated with a high frequency of serious or persistent immune-related adverse events. Several new anti-PD-1-based combination therapies with a better risk-benefit balance are currently under development. Although the acral and mucosal subtypes tend to be less responsive to immune checkpoint inhibitors, anti-PD-1-based combination therapy should continue to be investigated for these subtypes owing to its potential for better long-term survival. With the development of efficacious immunotherapy and targeted therapy, it is important to determine the optimal duration of systemic therapy to avoid unnecessary health and financial burdens as well as to improve efforts to support long-term cancer survivors. As the goal of systemic therapy shifts from tumor control to long-term survival, in future clinical trials, long-term clinical outcomes should be evaluated to assess the benefits of novel agents.

Role of Nutraceuticals in Counteracting Inflammation in In Vitro Macrophages Obtained from Childhood Cancer Survivors.

The advancement of anti-cancer therapies has markedly improved the survival rate of children with cancer, making them long-term childhood cancer survivors (CCS). Nevertheless, these treatments cause a low-grade inflammatory state, determining inflamm-aging and, thus, favoring the early onset of chronic diseases normally associated with old age. Identification of novel and safer therapeutic strategies is needed to counteract and prevent inflamm-aging. Macrophages are cells involved in immune and inflammatory responses, with a pivotal role in iron metabolism, which is related to inflammation. We obtained macrophages from CCS patients and evaluated their phenotype markers, inflammatory states, and iron metabolism by Western blotting, ELISA, and iron assays. We observed a strong increase in classically activated phenotype markers (M1) and iron metabolism alteration in CCS, with an increase in intracellular iron concentration and inflammatory markers. These results suggest that the prevalence of M1 macrophages and alteration of iron metabolism could be involved in the worsening of inflammation in CCS. Therefore, we propose macrophages and iron metabolism as novel therapeutic targets to counteract inflamm-aging. To avoid toxic regimens, we tested some nutraceuticals (resveratrol, curcumin, and oil-enriched lycopene), which are already known to exert anti-inflammatory properties. After their administration, we observed a macrophage switch towards the anti-inflammatory phenotype M2, as well as reductions in pro-inflammatory cytokines and the intracellular iron concentration. Therefore, we suggest-for the first time-that nutraceuticals reduce inflammation in CCS macrophages through a novel anti-inflammatory mechanism of action, modulating iron metabolism.

Incidence of late recurrence and second primary cancers 5-10 years after non-metastatic colorectal cancer.

The fraction of patients who are cancer-free survivors 5 years after curative-intended surgery for colorectal cancer (CRC) is increasing, suggesting that extending surveillance beyond 5 years may be indicated. Here we estimate the incidence of late recurrence, metachronous CRC, and second primary cancers 5-10 years postoperative. All patients resected for UICC stage I-III CRC in Denmark through 2004-2013 were identified. Through individual-level linkage of nationwide health registry data, recurrence status was determined using a validated algorithm. Cancer-free survivors 5 years after surgery, were included. Cumulative incidence functions (CIF) of late recurrence, metachronous CRC, and second primary cancer 5-10 years postoperative were constructed. Subdistribution hazards ratios (sHR) were computed using Fine-Gray regression. Among 8883 patients, 370 developed late recurrence (5-10-year CIF = 4.1%, 95%CI: 3.7%-4.6%), 270 metachronous CRC (5-10-year CIF = 3.0%, 95%CI: 2.7%-3.4%), and 635 a second primary cancer (5-10-year CIF = 7.2%, 95%CI: 6.7%-7.7%). The risk of late recurrence was reduced for patients operated in 2009-2013 compared to 2004-2008 (2.9% vs. 5.6%, sHR = 0.52, 95% CI: 0.42-0.65). The risk of metachronous CRC was likewise reduced from 4.1% to 2.1% (sHR = 0.50, 95%CI: 0.39-0.65). While the risk of second primary cancer did not change between 2009-2013 and 2004-2008 (7.1% vs. 7.1%, sHR = 0.98, 95% CI: 0.84-1.15). Using nation-wide 10-year follow-up data, we document that the incidences of late recurrence and metachronous CRC are low and decreasing from 2004 to 2013. Thus, despite increasing numbers of long-term cancer survivors, the data do not advocate for extending CRC-specific surveillance beyond 5 years.

Pathological response and tumor stroma immunogenic features predict long-term survival in non-small cell lung cancer after neoadjuvant chemotherapy.

Major pathological response (MPR) has become a surrogate endpoint for overall survival (OS) in non-small cell lung cancer (NSCLC) after neoadjuvant therapy, however, the prognostic histologic features and optimal N descriptor after neoadjuvant therapy are poorly defined. We retrospectively analyzed data from 368 NSCLC patients who underwent surgery after neoadjuvant chemotherapy (NAC) from January 2010 to December 2020. The percentage of residual viable tumors in the primary tumor, lymph nodes (LN), and inflammation components within the tumor stroma were comprehensively reviewed. The primary endpoint was OS. Of the 368 enrolled patients, 12.0% (44/368) achieved MPR in the primary tumor, which was associated with significantly better OS (HR, 0.36 0.17-0.77, p = 0.008) and DFS (HR = 0.59, 0.36-0.92, p = 0.038). In patients who did not have an MPR, we identified an immune-activated phenotype in primary tumors, characterized by intense tumor-infiltrating lymphocyte or multinucleated giant cell infiltration, that was associated with similar OS and DFS as patients who had MPR. Neoadjuvant pathologic grade (NPG), consisting of MPR and immune-activated phenotype, identified 30.7% (113/368) patients that derived significant OS (HR 0.28, 0.17-0.46, p < 0.001) and DFS (HR 0.44, 0.31-0.61, p < 0.001) benefit from NAC. Moreover, the combination of NPG and the number of positive LN stations (nS) in the multivariate analysis had a higher C-index (0.711 vs. 0.663, p < 0.001) than the ypTNM Stage when examining OS. NPG integrated with nS can provide a simple, practical, and robust approach that may allow for better stratification of patients when evaluating neoadjuvant chemotherapy in clinical practice.

Characteristics and patient-reported outcomes of long-term lung cancer survivors.

Due to advances in screening and treatment of lung cancer, there has been increased interest in long-term lung cancer survivors (LTLCS). The aim of this study was to evaluate the prevalence of LTLCS, their characteristics and patient-reported outcomes (PROs) of LTLCS. Cross-sectional study that included patients diagnosed with primary lung cancer between Jan 2012 and Dec 2016 whose overall survival (OS) was greater than 5 years. A self-administered questionnaire was applied, including European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30), Patient Health Questionnaire-4 (PHQ-4) and two open questions regarding quality of life (QoL) and suggestions for improvements. Factors potentially related to QoL were analysed. Of 767 lung cancer patients, 158 (20.6%) were LTLCS and LTLCS' proportion increased yearly. Most patients were male (70.9%) with median age of 65 [interquartile range (IQR), 56-71] years. Fifty-seven percent had adenocarcinoma, 66.2% were diagnosed at early stages but 8.9% were at stage IV. During follow-up, 77.1% quitted smoking, 31.8% had disease progression/relapse and 15.2% developed other tumours. Of all living LTLCS, 100 (85%) patients answered the PROs questionnaire. The median Global Health score was 66.67 (IQR, 50-83), social functioning had the best score and emotional functioning the worst. Pain and fatigue were the symptoms with the worst impact on QoL. PHQ-4 identified mental distress in 36% and patients with a lower QoL were more likely to present anxiety (35.3% vs. 9.4%, P=0.007) or depression (27.9% vs. 3%, P=0.006). In the open questions, patients reported pain (17%), lack of familiar/financial support (16%), dyspnoea (14%), depression (8%), concern for the future (8%) and limitations performing daily activities (8%) as the aspects with most impact in QoL. The most suggested measures were improvement of care provided by health institutions (25%) and better social support (16%). Prevalence of LTLCS is increasing and survivors may experience a high prevalence of anxiety and depression as well as a high disease burden affecting QoL. Therefore, it's important to provide multidisciplinary continuous patient-centred care and a careful follow-up for all lung cancer patients, including LTLCS.

Challenges with Estimating Long-Term Overall Survival in Extensive Stage Small-Cell Lung Cancer: A Validation-Based Case Study.

The study aimed to explore methods and highlight the challenges of extrapolating the overall survival (OS) of immunotherapy-based treatment in first-line extensive stage small-cell lung cancer (ES-SCLC). Standard parametric survival models, spline models, landmark models, mixture and non-mixture cure models, and Markov models were fitted to 2-year data of the CASPIAN Phase 3 randomised trial of PD-L1 inhibitor durvalumab added to platinum-based chemotherapy (NCT03043872). Extrapolations were compared with updated 3-year data from the same trial and the plausibility of long-term estimates assessed. All models used provided a reasonable fit to the observed Kaplan-Meier (K-M) survival data. The model which provided the best fit to the updated CASPIAN data was the mixture cure model. In contrast, the landmark analysis provided the least accurate fit to model survival. Estimated mean OS differed substantially across models and ranged from (in years) 1.41 (landmark model) to 4.81 (mixture cure model) for durvalumab plus etoposide and platinum and from 1.01 (landmark model) to 2.00 (mixture cure model) for etoposide and platinum. While most models may provide a good fit to K-M data, it is crucial to assess beyond the statistical goodness-of-fit and consider the clinical plausibility of the long-term predictions. The more complex cure models demonstrated the best predictive ability at 3 years, potentially providing a better representation of the underlying method of action of immunotherapy; however, consideration of the models' clinical plausibility and cure assumptions need further research and validation. Our findings underscore the significance of adopting a clinical perspective when selecting the most appropriate approach to model long-term survival, particularly when considering the use of more complex models.

Lifestyle factors on the long-term survival of gastric cancer patients after radical resection: A cohort study.

This retrospective cohort study aimed to evaluate the effect of lifestyle factors (e.g., smoking, drinking, physical exercise, and sleep duration) on the long-term survival of gastric cancer (GC) patients after radical resection. GC patients after radical resection were enrolled from January 2016 to December 2017. Their baseline clinical data, lifestyle factors, and prognosis were collected. The primary endpoint was all-cause death. The relationship between the variables and survival was examined using the Cox proportional hazards model. A total of 309 patients were enrolled and 296 patients were followed up for a median of 54.0 months, with 130 confirmed deaths. Older age (>60 years) (hazard ratio [HR]: 1.307, 95% confidence interval [CI]: 1.056-2.161, P = 0.006), advanced tumor, node, and metastasis stage (P < 0.05), poorly pathological differentiation (HR: 1.765, 95% CI: 1.080-2.884, P = 0.023), history of smoking (P < 0.001), never physical exercise (HR: 2.057, 95% CI: 1.170-3.617, P = 0.012), long sleep duration (≥8 h) (HR: 4.160, 95% CI: 1.501-11.533, P = 0.006), and short sleep duration (<6 h) (HR: 3.417, 95% CI: 1.312-8.900, P = 0.012) were independent indicators of a poor overall survival in GC patients after radical resection. Smoking cessation, proper sleep duration, and regular physical exercise habits can improve the long-term survival of GC patients after radical resection.

Effect of comorbidity and multimorbidity on adherence to follow-up recommendations among long-term breast cancer survivors

ObjectivesTo study the impact of comorbidities, multimorbidity, and multimorbidity clusters on adherence to recommended follow-up guidelines among long-term breast cancer survivors. Study designRetrospective cohort study based on 2078 women diagnosed with breast cancer from 2000 to 2006 and followed up from 2012 to 2016. Main outcome measuresAdherence to breast cancer follow-up recommendations (annual medical visit and imaging) was determined. Comorbidities were classified as acute/chronic. Multimorbidity was defined as the presence of two or more chronic comorbidities aside from breast cancer. Five multimorbidity clusters were considered. Multivariate logistic regression models were fitted to determine the relationship between adherence to recommendations and the presence of comorbidities and multimorbidity, considering both sociodemographic and clinical characteristics. ResultsOverall adherence to recommendations was 79.5 %. Adherence was lower among long-term breast cancer survivors with no comorbidities (75.8 %). Among multimorbidity clusters, adherence was highest in the anxiety and fractures cluster (84.3 %) and was lowest in the musculoskeletal and cardiovascular cluster (76.4 %). In adjusted multivariate models, multimorbidity was associated with higher levels of adherence (OR = 1.52 95 %CI 1.16–1.99), and adherence was highest in the metabolic and degenerative cluster (OR = 2.2 95 %CI 1.4–3.5). ConclusionAdherence to follow-up recommendations was higher among long-term breast cancer survivors with multimorbidity than among those without. Adherence also differed by multimorbidity cluster. These results suggest suboptimal adherence to the current follow-up recommendations in certain groups, suggesting the need to adapt clinical practice guidelines to reflect patients' comorbidities and different characteristics.

Risk of second cancers in long term survivors of neuroendocrine tumors of the large intestine.

600 Background: There is an increasing incidence of neuroendocrine tumors (NET) of the colon and rectum likely related to increased screening colonoscopy and availability of better diagnostics. Most of these tumors identified during screening are low grade early-stage tumors with high cure rates. Data on long term risk of recurrence of NET and other second cancers is lacking. We studied the incidence rates of all second malignancies in survivors of NET of the colon and rectum. Methods: We analyzed data from the Surveillance, Epidemiology and End Results (SEER), Research Data 17 Registries, Nov 2022 Sub (2000-2022) to determine the risk of second malignancies in patients with an initial cancer diagnosis of NET of the colon and rectum. With these criteria we had overall 17,907 patients and 157,720 patient years of follow up. The relative risk of subsequent malignancies is reported as a standardized incidence ratio (observed incidence [O]/expected incidence [E]). Incidence ratios are analyzed over time from initial diagnosis to assess long term risk. Results: Survivors of NET of the large intestine are at highest risk of malignancy of the rectum (O/E: 6.4, CI: 7.26 - 5.21, N= 239) and this increased risk of rectal cancer persists even 10 years after the initial diagnosis (0/E: 3.8, CI: 5.37- 2.6, N= 32). There is no increased risk of cancer of the colon excluding rectum (O/E: 0.98, CI: 1.18-0.81, N= 114). Even after 10 years from diagnosis there is increased risk of recurrence of the NET of the Colon (O/E: 1.28, CI: 1.55-1.06, N=110) and NET of the Rectum (O/E: 1.12, CI: 1.23- 1.02, N= 433). There is also increased incidence of small intestine cancer (O/E: 2.92, CI: 4.17- 1.97, N=30), Prostate cancer (O/E: 1.28, CI: 1.41- 1.15, N=400), Kidney and renal pelvis cancer (O/E: 1.53, CI: 1.86 -1.25, N= 104), Thyroid cancer (O/E: 1.63, CI: 2.12-1.23, N= 55) and Nodal Non-Hodgkins Lymphoma (O/E: 1.34, CI: 1.71-1.03, N=64). Conclusions: Survivors of NET of the large intestine are at risk of developing subsequent malignancies. The information presented may help physicians in effectively monitoring survivors for second cancers at various timeframes from their initial diagnosis.

Late Complications in Long-Term Childhood Cancer Survivors: What the Oral Health Professional Needs to Know.

With diagnostic and therapeutic advances, over 80% of children diagnosed with cancer become long-term survivors. As the number of childhood cancer survivors (CCS) continues to increase, dental practitioners become more likely to have CCS among their patients. CCS may develop late complications from damage caused by their cancer treatment to endocrine, cardiovascular, musculoskeletal, and other organ systems. These complications may surface decades after the completion of treatment. Adverse outcomes of childhood cancer treatment frequently involve oral and craniofacial structures including the dentition. Tooth development, salivary gland function, craniofacial growth, and temporomandibular joint function may be disturbed, increasing oral health risks in these individuals. Moreover, CCS are at risk of developing subsequent malignancies, which may manifest in or near the oral cavity. It is important that dental practitioners are aware of the childhood cancer history of their patients and have knowledge of potential late complications. Therefore, this narrative review aims to inform dental practitioners of late oral complications of cancer treatment modalities commonly used in pediatric oncology. Furthermore, selected common non-oral late sequelae of cancer therapy that could have an impact on oral health and on delivering dental care will be discussed.