Survival In Advanced Cancer Research Articles

Non-invasive technology to assess hydration status in advanced cancer to explore relationships between fluid status and symptoms: an observational study using bioelectrical impedance analysis

BackgroundOral fluid intake decreases in advanced cancer in the dying phase of illness. There is inadequate evidence to support the assessment, and management, of hydration in the dying. Bioelectrical impedance analysis (BIA) is a body composition assessment tool. BIA has the potential to inform clinal management in advanced cancer, by examining the relationships between hydration status and clinical variables.AimBIA was used to determine the association between hydration status, symptoms, clinical signs, quality-of-life and survival in advanced cancer, including those who are dying (i.e. in the last week of life).Materials and methodsWe conducted a prospective observational study of people with advanced cancer in three centres. Advance consent methodology was used to conduct hydration assessments in the dying. Total body water was estimated using the BIA Impedance index (Height – H (m)2 /Resistance – R (Ohms)). Backward regression was used to identify factors (physical signs, symptoms, quality of life) that predicted H2/R. Participants in the last 7 days of life were further assessed with BIA to assess hydration changes, and its relationship with clinical outcomes.ResultsOne hundred and twenty-five people participated (males n = 74 (59.2%), females, n = 51 (40.8%)). We used backward regression analysis to describe a statistical model to predict hydration status in advanced cancer. The model demonstrated that ‘less hydration’ (lower H2/R) was associated with female sex (Beta = -0.39, p < 0.001), increased appetite (Beta = -0.12, p = 0.09), increased dehydration assessment scale score (dry mouth, dry axilla, sunken eyes - Beta = -0.19, p = 0.006), and increased breathlessness (Beta = -0.15, p = 0.03). ‘More hydration’ (higher H2/R) was associated with oedema (Beta = 0.49, p < 0.001). In dying participants (n = 18, 14.4%), hydration status (H2/R) was not significantly different compared to their baseline measurements (n = 18, M = 49.6, SD = 16.0 vs. M = 51.0, SD = 12.1; t(17) = 0.64, p = 0.53) and was not significantly associated with agitation (rs = -0.85, p = 0.74), pain (rs = 0.31, p = 0.23) or respiratory tract secretions (rs = -0.34, p = 0.19).ConclusionsThis is the first study to use bioimpedance to report a model (using clinical factors) to predict hydration status in advanced cancer. Our data demonstrates the feasibility of using an advance consent method to conduct research in dying people. This method can potentially improve the evidence base (and hence, quality of care) for the dying. Future BIA research can involve hydration assessment of cancers (according to type and stage) and associated variables (e.g., stage of illness, ethnicity and gender). Further work can use BIA to identify clinically relevant outcomes for hydration studies and establish a core outcome set to evaluate how hydration affects symptoms and quality-of-life in cancer.

The Glasgow Prognostic Score as a Predictor of Survival after Chemoradiotherapy for Limited-Disease Small Cell Lung Cancer.

Established biomarkers for predicting chemoradiotherapy efficacy for limited-disease small cell lung cancer (LD-SCLC) are lacking. The inflammation-based Glasgow Prognostic Score (GPS), comprising serum C-reactive protein (CRP) and albumin levels, can predict survival in advanced cancer. This study investigated whether metabolic and inflammatory markers, including the GPS, can predict the efficacy of chemoradiotherapy in patients with LD-SCLC. We retrospectively analyzed 124 patients who underwent chemoradiotherapy for LD-SCLC at two institutions between April 2007 and June 2021, and assessed the prognostic significance of various metabolic and inflammatory markers. The GPS was calculated using the CRP and albumin concentrations, and categorized as follows: 0, CRP &lt;1.0 mg/dL and albumin ≥3.5 mg/dL; 1, elevated CRP or decreased albumin; and 2, CRP ≥1.0 mg/dL and albumin&lt;3.5 mg/dL. Differences in progression-free survival (PFS) and overall survival (OS) were examined using Kaplan-Meier curves and Cox proportional-hazard models. The overall response rate was 95.1% (95% confidence interval [CI]: 89.6-97.9%). The median PFS and OS from chemoradiotherapy initiation were 12.6 (95% CI: 9.9-15.4) and 29.0 (95% CI: 24.8-45.5) months, respectively. The GPS demonstrated independent predictive ability for the effectiveness of chemoradiotherapy, wherein favorable scores (GPS 0-1) were significantly correlated with superior PFS and OS compared to unfavorable scores (GPS 2: PFS: 14.8 vs. 6.7 months, p = 0.0001; OS: 35.4 vs. 11.0 months, p &lt; 0.0001). This preliminary examination revealed that the GPS was significantly associated with PFS and OS in patients undergoing chemoradiotherapy for LD-SCLC, indicating its potential utility in assessing the therapeutic outcomes in LD-SCLC.

Evaluation of the inflammation-based modified Glasgow Prognostic Score (mGPS) as a prognostic and predictive biomarker in patients with metastatic colorectal cancer receiving first-line chemotherapy: a post hoc analysis of the randomized phase III XELAVIRI trial (AIO KRK0110)

The inflammation-based modified Glasgow Prognostic Score (mGPS) combines serum levels of C-reactive protein and albumin and was shown to predict survival in advanced cancer. We aimed to elucidate the prognostic impact of mGPS on survival as well as its predictive value when combined with gender in unselected metastatic colorectal cancer (mCRC) patients receiving first-line chemotherapy in the randomized phase III XELAVIRI trial. In XELAVIRI, mCRC patients were treated with either fluoropyrimidine/bevacizumab followed by additional irinotecan at first progression (sequential treatment arm; Arm A) or upfront combination of fluoropyrimidine/bevacizumab/irinotecan (intensive treatment arm; Arm B). In the present post hoc analysis, survival was evaluated with respect to the assorted mGPS categories 0, 1 or 2. Interaction between mGPS and gender was analyzed. Out of 421 mCRC patients treated in XELAVIRI, 362 [119 women (32.9%) and 243 men (67.1%)] were assessable. For the entire study population a significant association between mGPS and overall survival (OS) was observed [mGPS= 0: median 28.9 months, 95% confidence interval (CI) 25.9-33.6 months; mGPS= 1: median 21.4 months, 95% CI 17.6-26.1 months; mGPS= 2: median 16.8 months, 95% CI 14.3-21.2 months; P < 0.00001]. Similar results were found when comparing progression-free survival between groups. The effect of mGPS on survival did not depend on the applied treatment regimen (P= 0.21). In female patients, a trend towards longer OS was observed in Arm A versus Arm B, with this effect being clearly more pronounced in the mGPS cohort 0 (41.6 versus 25.5 months; P= 0.056). By contrast, median OS was longer in male patients with an mGPS of 1-2 treated in Arm B versus Arm A (20.8 versus 17.4 months; P= 0.022). We demonstrate the role of mGPS as an independent predictor of OS regardless of the treatment regimen in mCRC patients receiving first-line treatment. mGPS may help identify gender-specific subgroups that benefit more or less from upfront intensive therapy.

Associations of concomitant medications with immune-related adverse events and survival in advanced cancers treated with immune checkpoint inhibitors: a comprehensive pan-cancer analysis

BackgroundWhile concomitant medications can affect the efficacy of immune checkpoint inhibitors (ICIs), few studies have assessed associations of concomitant medications with the occurrence and profile of immune-related adverse events (irAEs).MethodsThis...

Contemporary vocational rehabilitation strategies for people with advanced cancer: A literature review and conceptual framework

BACKGROUND: People with advanced cancer constitute an emerging vocational rehabilitation (VR) consumer population. OBJECTIVE: Following an overview of the nature and needs of Americans who have advanced forms of cancer, the authors present strategies to meet the service and support needs of these individuals across the phases of the VR process. METHODS: The authors present the sequential stages of the VR process, including implications for working with advanced cancer survivors during each stage. RESULTS: The importance of individualized case planning, employer consultation, workplace accommodations, interface with medical and mental health professionals, and adherence to self-care and symptom management regimens is emphasized throughout the article. CONCLUSION: Growing numbers of people worldwide are surviving advanced cancers for longer periods of time than ever before, which makes them an emerging disability population and rehabilitation clientele.

Automating the identification of patients admitted to tertiary care hospital with immunotherapy related adverse events (irAEs).

566 Background: Immune checkpoint inhibitors (ICIs) have revolutionized oncology by offering prolonged survival in advanced cancers that were previously treatment-refractory. However, the effectiveness of these agents is accompanied by the potential for autoimmune toxic effects known as immune-related adverse events (irAEs). These adverse effects are difficult to predict, can be long-lasting, and occasionally fatal. Early identification and treatment of irAEs can reduce morbidity and enable prompt resumption of anti-cancer therapy, ultimately improving patient outcomes. Methods: We manually reviewed 658 patient charts of individuals who received ICIs and were admitted to a tertiary care hospital over a three-month period. This process identified 750 phrases indicative of irAEs. Subsequently, an in-house Epic reporting team developed a program to search for these specific phrases within the charts of patients admitted to the hospital who had received ICIs in the 24 months prior to their admission. During the program's development, its performance was compared to the previous manual chart review process. Results: A comparative analysis was conducted between the new program and the current manual chart review over a three-month period. Implementing the new program resulted in a 68% reduction in the average number of charts requiring manual review (69 vs. 219 per month). Furthermore, the program identified an additional 17% of cases (21 vs. 18 per month). The positive predictive value increased by 400% (32% vs. 8% per month), and the time required to complete the task decreased by 70% (4.6 vs. 15 hours per month). Conclusions: Utilizing an EMR-based program that automatically searches for patients admitted with irAEs can significantly shorten the time required for identification and subsequent management of these complex patients.

Abstract ED5-2: Support for patients with MBC

Abstract ED5-2: Support for patients with MBC

Development and Validation of a Machine Learning Approach Leveraging Real-World Clinical Narratives as a Predictor of Survival in Advanced Cancer.

Predicting short-term mortality in patients with advanced cancer remains challenging. Whether digitalized clinical text can be used to build models to enhance survival prediction in this population is unclear. We conducted a single-centered retrospective cohort study in patients with advanced solid tumors. Clinical correspondence authored by oncologists at the first patient encounter was extracted from the electronic medical records. Machine learning (ML) models were trained using narratives from the derivation cohort, before being tested on a temporal validation cohort at the same site. Performance was benchmarked against Eastern Cooperative Oncology Group performance status (PS), comparing ML models alone (comparison 1) or in combination with PS (comparison 2), assessed by areas under receiver operating characteristic curves (AUCs) for predicting vital status at 11 time points from 2 to 52 weeks. ML models were built on the derivation cohort (4,791 patients from 2001 to April 2017) and tested on the validation cohort of 726 patients (May 2017-June 2019). In 441 patients (61%) where clinical narratives were available and PS was documented, ML models outperformed the predictivity of PS (mean AUC improvement, 0.039, P < .001, comparison 1). Inclusion of both clinical text and PS in ML models resulted in further improvement in prediction accuracy over PS with a mean AUC improvement of 0.050 (P < .001, comparison 2); the AUC was > 0.80 at all assessed time points for models incorporating clinical text. Exploratory analysis of oncologist's narratives revealed recurring descriptors correlating with survival, including referral patterns, mobility, physical functions, and concomitant medications. Applying ML to oncologists' narratives with or without including patient's PS significantly improved survival prediction to 12 months, suggesting the utility of clinical text in building prognostic support tools.

The efficacy of immune checkpoint inhibitors in elderly patients: a meta-analysis and meta-regression

BackgroundImmune checkpoint inhibitor (ICI) therapy has improved patient survival in advanced cancers; however, the efficacy of ICIs in elderly patients is still elusive. This study assessed the efficacy of ICIs in elderly patients with advanced cancer in terms of overall survival (OS) and progression-free survival (PFS).Materials and methodsWe carried out a systematic review and identified 30 head-to-head phase II/III randomized controlled trials that compared immunotherapy with the standard of care in advanced solid tumor patients. The data on patients younger or over 65 years of age were indexed from PubMed-Medline, Embase, and Scopus and obtained for meta-analysis. The subgroup analyses were stratified by primary tumor type, line of treatment, or type of immunotherapy, and a meta-regression analysis was carried out after adjusting for all other variables.ResultsThe study included 17 476 patients, comprising 58% (10 119) younger (<65 years old) and 42% (7357) elderly (≥65 years old) patients. The hazard ratio (HR) for OS was 0.77 [95% confidence interval (CI) 0.70-0.85] and 0.77 (95% CI 0.70-0.85) in the younger and elderly groups, respectively, suggesting similar efficacies of ICIs in these two age groups. The subgroup analyses revealed no significant relationship between age and treatment outcomes, except for the PFS benefit in younger patients with melanoma than in elderly patients (HR 0.44 in younger patients versus 0.65 in elderly patients, P = 0.04). These results were further supported by meta-regression analysis, which showed no statistically significant difference in OS (P = 0.954) and PFS (P = 0.555) between the two age groups.ConclusionsThe findings suggest that age-associated impairments of the immune system did not affect the efficacy of ICIs in elderly patients compared to younger patients. Therefore, the choice of ICIs for elderly patients can be considered, regardless of chronological age.

P11.66.A Immune checkpoint inhibitors related peripheral nerve disorders: clinical and electrophysiological particularities

Abstract Background The immune-checkpoint inhibitors (ICIs) announced a new era in cancer treatment allowing long-term survival in advanced cancers. However, immune related adverse events impose treatment limitations being one of the main challenges when dealing with ICI treated patients. Neurologic toxicities have unique presentations and can progress rapidly, requiring prompt recognition. Among them, ICI-related peripheral nerve disorders are highly heterogeneous, profoundly debilitating, and insufficiently explored. Material and Methods We reviewed the clinical and electrodiagnostic features of a retrospective cohort of patients hospitalized in our centre for ICI related neuropathies. We applied the EFNS 2021 electrodiagnostic criteria for neuropathies and we researched the outcome according to the treatment received. Results We included 16 patients: 4 men and 12 women, median age 61 years (31-72) treated by anti-PD1 monotherapy (10) or antiCTLA4-antiPD1 combination (6). Median delay from ICIs initiation to neuropathy symptoms was 58,5 days (4 cycles), it seemed lower in combination group (median 33,5 days vs 81,5 days in monotherapy patients p=0,02). Half of patients presented with concurrent non-neurological irAE. CSF was inflammatory in 56% of cases, pleocytosis was seen in 57% of these. Cranial nerve involvement was rare (3/16) the most frequent phenotype was demyelinating polyneuropathy fulfilling EFNS 2021 EMG criteria in 10 cases. The other 6 presented with non-length dependent sensory neuropathy, (3) dysautonomic neuropathy (1) or sensory motor neuropathy with incomplete EFNS 2021 EMG criteria (2). ICI treatment was stopped, and steroids were the first line of treatment for all patients. However, 12/16 patients received additional iv immunoglobulin. Supplementary immunomodulation (cyclophosphamide, tocilizumab) was required in 2 cases. 75% of patients improved within a median of 4.5 months, median decrease in mRS was 2 points. Noteworthy, the rechallenge by antiPD1 monotherapy was proposed in 4 patients with a single neuropathy relapse. Conclusion Our series expand the knowledge on the clinical and electrophysiological phenotype of ICI related neuropathies improving their recognition in clinical practice. Moreover, our findings argue for the benefit of adding iv immunoglobulin to steroids as a first line treatment for different phenotypes of ICI related neuropathies.

Effect of immunotherapy and time-of-day infusion chronomodulation on survival in advanced cancers.

1588 Background: Emerging clinical studies report correlation of time-of-day infusion (TOI) to immunotherapy outcomes and the intricate interplay of the human circadian rhythm and cancer and immunotherapy exposure. Preclinical and clinical studies have shown cancer chronotherapy to play important role in transcriptional rhythmicity of oncogenic process. We evaluated the association of TOI and immunotherapy outcomes in a large cohort to determine impact of TOI on overall survival (OS) and progression free survival (PFS). Methods: We reviewed charts of patients with solid tumors who received immunotherapy, specifically anti programmed cell death protein 1 (PD1) and anti-programmed death-ligand 1 (PD-L1) agents at MD Anderson Cancer Center. Infusion times were divided into two hours cohorts from 8am-8pm and one overnight cohort from 8pm-8am. Accelerated failure time models were used to model OS (log-normal distribution) and PFS (Weibull distribution) with relation to TOI after adjusting for factors such as age, gender, tumor type and prednisone &gt; 10mg daily use within 1 month of immunotherapy initiation to minimize confounding factors. Results: Of 6151 patients with advanced tumors, 4441 patients received immunotherapy therapy after adjusting for minimum 140 patients in each tumor cohort from 10/15/2016 until 10/15/2021. Tumor types included advanced lung cancer (31.4%), melanoma (28.7%), renal (14.4%), breast (7.6%), colon (6.2%), liver cancer (3.9%) and head and neck (H&amp;N) cancers (2.8%). Median age was 63 (15-99) with 58% males and 42% female. 1894 (43%) patients received investigational agents and 2547 (57%) received standard of care therapies. Mechanism of action of various agents: anti PD1, anti-PDL1, TGF-βRII and anti-PDL1, anti-PD-1 with OX40+ T Cell activation, PD-1 / PD-L1 bispecific antibody, PD-L1 dependent 4-1BB agonist and anti PD-1 and CTLA-4 activity. Among all patients, median OS was 26.4 months while median PFS was 4.8 months. Preponderance of immunotherapy TOI occurred between 12-2pm and 2-4pm in all patients. Patients receiving overnight TOI with lung, renal and breast cancer demonstrated significantly (p &lt; 0.05) poorer OS compared to TOI (10am-4pm) whereas in melanoma, significantly lower OS was seen with overnight, 8-10am and 6-8pm compared to 10am-4pm TOIs. Among H&amp;N cancer patients, early TOI (8-10am) was associated with significantly lower OS compared to afternoon TOI (12pm-4pm). PFS trends were less distinct than for OS but showed a slighted inverted tendency towards lower PFS following daytime TOI. Conclusions: In this large cohort of patients treated with immunotherapy, clinically significant association of TOI with overall survival is seen. These intriguing findings warrant prospective validation in a future randomized trial to harness the role of chronomodulation of cancer therapies for improving outcomes.

Prediagnostic Serum Vitamin D, Vitamin D Binding Protein Isoforms, and Cancer Survival.

Higher circulating vitamin D has been associated with improved overall cancer survival, but data for organ-specific cancers are mixed. We examined the association between prediagnostic serum 25-hydroxyvitamin D [25(OH)D], the recognized biomarker of vitamin D status, and cancer survival in 4038 men and women diagnosed with 1 of 11 malignancies during 22 years of follow-up (median = 15.6 years) within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Multivariable-adjusted proportional hazards regression estimated hazard ratios (HR) and 95% confidence intervals (CI) for associations between baseline 25(OH)D concentration and subsequent cancer survival; we also stratified on the common vitamin D binding protein isoforms (Gc1f, Gc1s, and Gc2) defined by two single-nucleotide polymorphisms (rs7041 and rs4588) in the vitamin D binding protein gene GC. All P values were 2-sided. Higher 25(OH)D concentrations were associated with greater overall cancer survival (HR for cancer mortality = 0.83, 95% CI = 0.70 to 0.98 for highest vs lowest quintile; Ptrend = .05) and lung cancer survival (HR = 0.63, 95% CI = 0.44 to 0.90; Ptrend = .03). These associations were limited to cases expressing the Gc2 isoform (HR = 0.38 for Gc2-2, 95% CI = 0.14 to 1.05 for highest vs lowest quintile; Ptrend = .02; and HR = 0.30 for Gc1-2/Gc2-2 combined, 95% CI = 0.16 to 0.56; Ptrend < .001 for overall and lung cancer, respectively). Higher circulating 25(OH)D was associated with improved overall and lung cancer survival. As this was especially evident among cases with the genetically determined Gc2 isoform of vitamin D binding protein, such individuals may gain a cancer survival advantage by maintaining higher 25(OH)D blood concentrations.

Knowledge and use of prognostic scales by oncologists and palliative care physicians in adult patients with advanced cancer: A national survey (ONCOPRONO study).

BackgroundPrognostic scales exist to estimate patient survival in advanced cancer. However, there are no studies evaluating their use and practice. The objective of this study was to evaluate in a nationwide study the proportion of oncologists and palliative care physicians who had knowledge of these scales.MethodsA descriptive, national, cross‐sectional study was conducted via an online questionnaire to oncologists and palliative care physicians across France.ResultsPalliative care physicians had better knowledge of the scales than oncologists (42.3% (n = 74) vs. 27.8% (n = 33), p = 0.015). The Palliative Performance Status (PPS) and Pronopall Scale were the best‐known (51.4% (n = 55) and 65.4% (n = 70), respectively) and the most widely used (35% (n = 28) and 60% (n = 48), respectively). Improved training in the use of these scales was requested by 85.4% (n = 251) of participants, while 72.8% (n = 214) reported that they did not use them at all. Limited training and lack of consensus on which scale to use were cited as the main obstacles to use.ConclusionThis is the first national study on the use of prognostic scales in advanced cancer. Our findings highlight a need to improve training in these scales and to reach a consensus on scale selection.

1840P Impact of age, comorbidities and polypharmacy on survival in advanced cancers

With an aging population, global cancer burden continues to rise. Increased age is an independent risk factor for not receiving aggressive therapy and is associated with shorter overall survival (OS). However, the interplay between age, cancer therapy and other factors has not been explored in depth. Here we explore the impact of and interaction between age, comorbidity and polypharmacy on OS in advanced malignancies.

Impact of surgeon type and rurality on treatment and survival of ovarian cancer patients

<h3>Objectives:</h3> We aimed to determine if rurality impacts type of surgeon and estimate if the interaction between rurality and type of surgeon impacts cytoreductive surgery, chemotherapy initiation, and survival. <h3>Methods:</h3> Our population-based cohort of Iowan (N=675) ovarian cancer patients included women diagnosed with histologically confirmed stages IB-IV cancer in 2010-2016 at the ages of 18-89 years old and who received cancer-directed surgery in Iowa. Multivariable logistic regression analysis was used to determine the independent impact of rurality on type of surgeon, and the interaction between rurality and type of surgeon on cytoreductive surgery and chemotherapy initiation. Cox proportional hazards models were used to assess if the interaction between rurality and type of surgeon impacted 3-year all-cause and cause-specific mortality. <h3>Results:</h3> 83% (N=563) of Iowans who received in-state surgical care had a gynecologic oncologist surgeon. Rural patients had lower odds of having a gynecologic oncologist (adjusted odds ratio (aOR) 0.48; 95% confidence interval (CI) 0.30-0.78). Compared to rural patients with a non-gynecologic oncologist, rural and urban patients with a gynecologic oncologist surgeon were more likely to receive guideline-recommended cytoreduction (aOR 2.84, 2.58; 95% CI 1.31-6.14, 1.29-5.16, respectively) and chemotherapy (aORs 4.22, 7.94; 95% CI 1.82-9.78, 3.64-17.3, respectively). Compared to urban patients with a non-gynecologic oncologist, rural and urban patients with a gynecologic oncologist were more likely to receive cytoreduction (aORs 4.60, 4.19; 95% CI 2.13-9.94, 2.11-8.33, respectively) and urban patients with a gynecologic oncologist were more likely to receive chemotherapy (aOR 4.03; 95% CI 1.73-9.37). Rural patients with a non-gynecologic oncologist had the lowest 3-year cause-specific survival estimates controlling for patient/tumor factors. Urban patients with a non-gynecologic oncologist had higher 3-year cause-specific survival estimates than urban patients with a gynecologic oncologist. These differences became non-significant when controlling for treatment covariates. <h3>Conclusions:</h3> Rural patients were less likely to receive surgery from a gynecologic oncologist. Patients with non-gynecologic oncologist surgeons had lower odds of chemotherapy initiation and cytoreductive surgery. Gynecologic oncologist-provided surgery conferred a 3-year cause-specific survival advantage among rural patients and a survival disadvantage among urban patients in the model without treatment covariates. The significance dissipated when treatment variables were added to the model. The variation in the gynecologic oncologist survival advantage may be due to treatment differences, referral differences and/or differences in non-gynecologic oncologist volume or specialty by rurality. This is the first study to investigate the ovarian cancer survival advantage of having a gynecologic oncologist surgeon by rurality. Interventions are needed to determine the cause of variation by rurality and to ensure rurality does not impact treatment or survival.

P25-10 High sensitive troponin-I can be an effective predictive marker for drug-induced myocardial injury

Progression of chemotherapy may prolong overall survival in advanced cancer, and prediction of drug-induced myocardial injury is important for continuing treatment. In particular, anthracycline drugs can cause irreversible cardiac dysfunction. Thus, predictive biomarkers of cardiotoxicity are needed.

Clinical significance of tumor mutation burden and DNA damage repair in advanced stage non-small cell lung cancer patients.

This study aimed to investigate the impact of tumor mutational burden (TMB) and DNA damage repair (DDR) gene alteration on overall survival (OS) in advanced non-small cell lung cancer (NSCLC) patients. A DNA library of cancer cells from 67 NSCLC patients in stages III-IV was constructed for next-generation sequencing (NGS). Geneseeq422 probes were used for hybridization enrichment. The target-enriched library was sequenced on HiSeqNGS platforms, and we analyzed the relevant signaling pathways. Then, we correlated the OS of the patients with TMB and DDR mutations. Many significant alterations were found, including in the EGFR, p53, KRAS, RB1, ERBB2, NF1, DNMT3A, ALK, MYC, PIK3CA, ROS1, BRAF, ARID1A, PTEN, CDKN2A, and FGF19 genes. We also identified many mutations in the genes relevant to the DDR pathway. Interestingly, we found that the TMB of patients with DDR gene mutations was dramatically higher than that in the DDR wild-type (WT). Univariable analysis showed that DNMT3A, RB1, DDR pathway-related gene mutations, and TMB were critical factors for the effects on OS. Multivariable analysis confirmed that DNMT3A and mutations in the DDR pathway-related genes were important for predicting OS. Multiple mutations in the genes of the DDR pathway caused higher TMB levels, which resulted in longer OS. By contrast, OS was significantly longer in patients with non-DNMT3A mutations than in those with DNMT3A variants. DNMT3A alteration in NSCLC patients led to poor outcomes.

Abstract PD10-07: Patient reported outcomes and early discontinuation of adjuvant endocrine therapy according to neighborhood poverty rate

Abstract Introduction: Early discontinuation (DC) of adjuvant endocrine therapy (AET) for hormone receptor positive breast cancer (BC) is associated with increased risk of recurrence and death. Symptoms and low socioeconomic status (SES) have both previously been associated with early AET DC. Prospective collection of patient-reported outcomes (PRO) is increasingly used in oncology practice, and can lead to improvements in quality of life and survival in advanced cancer. Compared to patients of high SES, those of low SES report higher symptom burden in multiple clinical settings. Whether PRO reporting during AET differs according to SES is unknown. Methods: We enrolled women initiating AET for stage 0-III BC in a prospective clinic-based cohort from March 2012 to Dec 2016. At baseline (BL), 3, 6, 12, and 24 months (mo), participants completed these PROs online: FACT-ES, MOS Sexual Problems, and NIH PROMIS measures for pain interference, fatigue, depression, anxiety, physical function and sleep disturbance. Neighborhood poverty (NP) rate, a surrogate for SES based on US Census estimates of the % of persons in a zip code below the federal poverty line, was categorized as 0-5% (low), &amp;gt;5-10% (moderate) and &amp;gt;10% (high). We assessed AET DC and cited reason for DC by chart review. Baseline characteristics were compared between NP groups using Fisher’s exact and t-tests. Changes in mean PRO scores from BL to follow-up (FU) time points for each NP group were estimated simultaneously from a linear mixed effects regression model with a random intercept for each patient. We evaluated differences in changes in mean scores for all 8 PRO measures over time according to NP group with an interaction test. Statistical significance of p &amp;lt; 0.05/8 = 0.006 was used, adjusting for multiple comparisons. Results: Among 320 women, mean age was 61 (range 26-90), 83% were White, 10% Black, 65% were post-menopausal and 84% had Stage I-II BC. NP categorization was: 97 (30.3%) low, 127 (39.7%) moderate and 96 (30%) high. Mean stage distribution, and proportions of participants who had mastectomy, chemotherapy and radiation did not differ by NP group. There were fewer post-menopausal women in the moderate/high NP groups (61%) compared to the low NP group (72%, p=0.04). The proportion of Black participants increased with NP group (low 5%, moderate 10%, high 16%, p=0.04). Overall, 180 (56%) were on an aromatase inhibitor (AI) and 140 (44%) were on tamoxifen. There was more AI use in the low NP group (64%) compared to the moderate/high NP groups (53%, p=0.08). At BL, there were no differences in mean score on any PRO by NP group. For all NP groups, endocrine symptoms worsened at all FU times (all p&amp;lt;0.05) and physical function improved at most FU times. Compared to BL, mean changes in pain interference over time differed by NP group (interaction p=0.005), with less pain interference at 6 and 12 mo in the moderate/high NP groups and no significant change in the low NP group. Mean changes in other PROs did not differ by NP group. At median FU of 41 mo (range 3-75), the proportion of participants who discontinued AET due to side effects/intolerance was similar across NP groups (low 12.6%, moderate 16%, high 17%, p=0.67). Discussion: We found that changes in PROs during AET were similar across SES based on NP rates with the exception of less reported pain interference over time in participants of lower SES. The lack of improvement in pain interference in participants of higher SES may be attributable to arthralgias due to more frequent AI use. Despite differences in pain interference, early DC of AET due to side effects/intolerance did not differ by SES in this cohort. Our findings suggest that PROs are generally similar among early BC patients of varied SES receiving AET and that factors other than symptoms may explain the previously reported association between early DC and low SES. Citation Format: Ramy Sedhom, Amanda Blackford, David Lim, Jennifer Ensminger, Claire Snyder, Vered Stearns, Karen Lisa Smith. Patient reported outcomes and early discontinuation of adjuvant endocrine therapy according to neighborhood poverty rate [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD10-07.

Estimating survival in advanced cancer: a comparison of estimates made by oncologists and patients.

To compare estimates of expected survival time (EST) made by patients with advanced cancer and their oncologists. At enrolment patients recorded their "understanding of how long you may have to live" in best-case, most-likely, and worst-case scenarios. Oncologists estimated survival time for each of their patients as the "median survival of a group of identical patients". We hypothesized that oncologists' estimates of EST would be unbiased (~ 50% longer or shorter than the observed survival time [OST]), imprecise (< 33% within 0.67 to 1.33 times OST), associated with OST, and more accurate than patients' estimates of their own survival. Twenty-six oncologists estimated EST for 179 patients. The median estimate of EST was 6.0 months, and the median OST was 6.2 months. Oncologists' estimates were unbiased (56% longer than OST), imprecise (27% within 0.67 to 1.33 times OST), and significantly associated with OST (HR 0.88, 95% CI 0.82 to 0.93, p < 0.01). Only 41 patients (23%) provided a numerical estimate of their survival with 107 patients (60%) responding "I don't know". The median estimate by patients for their most-likely scenario was 12 months. Patient estimates of their most-likely scenario were less precise (17% within 0.67 to 1.33 times OST) and more likely to overestimate survival (85% longer than OST) than oncologist estimates. Oncologists' estimates were unbiased and significantly associated with survival. Most patients with advanced cancer did not know their EST or overestimated their survival time compared to their oncologist, highlighting the need for improved prognosis communication training. Trial registration ACTRN1261300128871.

Clinicopathologic factors associated with short-term survival in advanced epithelial ovarian cancer

Background: Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy, and there is a deficiency of information in the literature on the early recognition of short-term survivor (STS). This study aimed to identify the clinicopathological factors associated with STS in late-stage EOC and to establish a predictive model to identify STS. Methods: Selected patients with International Federation of Gynecology and Obstetrics (FIGO) stage III or IV EOC were included in the study, and a retrospective analysis was performed. The characteristics of the patients who survived not more than 2 years (STS) were compared to those who survived at least 2 years (defined as long-term survivors, LTS). Binary logistic regression and receiver operating characteristic curve (ROC) were used to identify the independent prognostic factors associated with EOC and assess the predictive accuracy for STS. Results: We identified 254 patients with advanced EOC including 57 STS and 197 LTS. A univariate analysis revealed that STS had a tendency to have omental metastasis and larger tumor size, to be platinum resistant, to have non-serous histology, to undergo suboptimal cytoreduction, to have comorbidity, and to undergo primary chemotherapy less than 6 courses. Binary regression analysis revealed that tumor size (P=0.033), platinum resistance (P Conclusions: Tumor size, omental metastasis, platinum resistance, non-serous histology, and number of primary chemotherapy are predictors associated with STS when controlling other confounding factors. Tumor size and omental metastasis may be considered novel, important prognostic factors for advanced EOC patients. Platinum resistance was the most important prognosticator for STS; hence, more work is needed for the early identification and treatment of these EOC patients.