Adult Comorbidity Evaluation-27 Score Research Articles

Adjuvant (chemo)radiotherapy for patients with head and neck cancer: can comorbidity risk scores predict outcome?

PurposeThis study compares the objective American Society of Anesthesiologists (ASA) and Adult Comorbidity Evaluation-27 (ACE-27) scores with the subjective Eastern Cooperative Oncology Group performance status (ECOG PS) for patient outcome prediction.MethodsWe retrospectively analyzed head and neck squamous cell carcinoma patients treated with adjuvant (chemo)radiotherapy at the LMU Munich from June 2008 to June 2015. The study focused on associations between patient outcomes; treatment failures; known risk factors (including human papillomavirus [HPV] status and tumor stage); and the comorbidity indices ECOG-PS, ASA score, and ACE-27. The Kaplan–Meier method and Cox proportional hazards model were used for survival analysis and identifying independent risk factors.ResultsA total of 302 patients were analyzed, 175 received concurrent chemotherapy. Median follow-up was 61.8 months, and median age at diagnosis was 61 years. The 3‑ and 5‑year overall survival (OS) and disease-free survival (DFS) rates were 70.5%/60.2% and 64.7%/57.6%, respectively. Both ACE-27 and ASA showed significant correlations with OS in univariate and multivariate analyses, while ECOG-PS was significant only in univariate analysis. ASA and ACE-27 scores were also significantly correlated with local and locoregional recurrence, but only HPV status and tumor stage were significant in multivariate models.ConclusionACE-27 and ASA score effectively categorize patients’ risks in adjuvant radiotherapy for head and neck cancer, proving more predictive of overall survival than ECOG-PS. These results underscore the importance of objective comorbidity assessment and suggest further prospective studies.

Predictive value of the Adult Comorbidity Evaluation 27 on adverse surgical outcomes and survival in elderly with advanced epithelial ovarian cancer undergoing cytoreductive surgery.

We aimed to evaluate the ability of Adult Comorbidity Evaluation 27 (ACE-27) to predict perioperative outcomes and survival in elderly women with advanced epithelial ovarian cancer (AEOC) undergoing cytoreductive surgery. We collected patients with AEOC in our hospital between January 1, 2012 and January 1, 2021. Patients younger than 65years old or those with non-epithelial ovarian cancer were excluded. ACE-27 was applied retrospectively to assess comorbidities in the selected patients, who were then classified into two groups based on their ACE-27 scores: low ACE-27 score group (none to mild) and high ACE-27 score group (moderate to severe). A total of 222 elderly women with AEOC were included, of whom 164 patients accepted debulking surgery. Among those who have undergone surgery, Clavien-Dindo grade III + perioperative complications or unintended intensive care unit (ICU) admission occurred more often in patients of high ACE-27 score group, with statistically significant difference (odds ratio [OR]: 4.21, 95% confidence interval [CI], 1.28-14.35, p = 0.018). Further stratified analyses by age, BMI, FIGO stage and pathology also prove that OS of patients graded severe was shorter than patients graded none to moderate in cohort of age < 70, BMI < 25kg/m2, FIGO III stage and pathology of serous, respectively. Kaplan-Meier survival curves analyzed by log-rank test showed that the overall survival (OS) of patients with severe comorbidities were shorter than with none to moderate (HR 3.25, 95%CI 1.55-6.79, p = 0.002). Our findings demonstrate the ability of ACE-27 to predict grade III + perioperative complications or unintended ICU admission and survival in elderly patients with AEOC. This highlights the possibility for ACE-27 to play an instrumental role in identifying AEOC patients who are more susceptible to adverse surgical outcomes and have a poor survival rate and assisting in decisions regarding treatment.

Neoadjuvant chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in elderly patients with stage III-IVa nasopharyngeal carcinoma: A real-world study based on medical comorbidities.

To evaluate the outcomes and toxicities of adding neoadjuvant chemotherapy (NAC) to concurrent chemoradiotherapy (CCRT) in elderly (≥65 years) patients with locoregionally advanced nasopharyngeal carcinoma (LANPC, stage III-IVa). Using an NPC-specific database, 245 elderly patients with stage III-IVa NPC, receiving CCRT +/- NAC, and an Adult Co-morbidity Evaluation 27 (ACE-27) score <2 were included. Recursive partitioning analysis (RPA) based on TNM stage and Epstein-Barr virus (EBV) DNA were applied for risk stratification. The primary end point was disease-free survival (DFS). Two risk groups were generated by the RPA model. In the high-risk group (EBV DNA < 4000 copy/ml with stage IVa & EBV DNA ≥4000 copy/ml with stage III-IVa), patients treated with NAC plus CCRT achieved improved 5-year DFS rates compared to those who received CCRT alone (56.9% vs. 29.4%; p = 0.003). But we failed to observe the survival benefit of additional NAC in the low-risk group (EBV DNA <4000 copy/ml with stage III). The most common severe acute toxic effects were leucopenia (46.8% vs. 24.4%) and neutropenia (43.7% vs. 20.2%) in the NAC plus CCRT group versus CCRT group with statistically significant differences. The addition of NAC to CCRT was associated with better DFS for the high-risk group of elderly LANPC patients with ACE-27 score <2. However, the survival benefit of additional NAC was not observed in low-risk patients.

Experience With the Routine Use of Electronic Patient-Reported Outcome Measures for Patients With Lung Cancer.

The Christie NHS Foundation Trust launched their electronic patient-reported outcome measures (ePROMs) service in January 2019 in the routine clinical setting. The lung cancer questionnaires consist of 14 symptom items, adapted from the Common Terminology Criteria for Adverse Events (version 5.0) and the EuroQol EQ-5D-5L quality-of-life (QoL) tool. Patients with lung cancer are invited to complete questionnaires assessing their symptoms and QoL using an online platform. The ePROM responses and clinical, pathologic, and treatment data for patients who completed the questionnaires between January 2019 and December 2020 were extracted from electronic medical records. The symptom and QoL scores of patients who completed baseline pretreatment ePROMs and also those who completed ePROMs pre- and postpalliative lung systemic anticancer therapy (SACT) or radical thoracic radiotherapy were evaluated. Pretreatment questionnaires were analyzed according to age, Eastern Cooperative Oncology Group performance status (ECOG PS), and Adult Comorbidity Evaluation-27 (ACE-27) comorbidity score. One thousand four hundred eighty patients with lung cancer were included. There were no statistically significant differences in symptoms and QoL scores between age groups. Cough (P = .006) and EQ-5D-5L mobility scores (P = .006) were significantly worse for patients with an ECOG PS of 0-1. Dyspnea (P = .035), hemoptysis (P = .023), nausea (P = .041), mobility (P = .004), and self-care (P = .0420) were significantly worse for those with higher ACE-27 scores (2-3 v 0-1). Palliative SACT was associated with a significant improvement in cough (P < .001) and hemoptysis (P = .025), but significantly negatively affected mobility (P = .013). Patients receiving radical thoracic radiotherapy reported a significant improvement in hemoptysis (P = .042) but worse pain (P = .002) and fatigue (P = .01). Other changes in symptom and QoL scores were not significant. The symptoms and QoL reported at baseline and before and after both palliative SACT and radical thoracic radiotherapy are clinically relevant and meaningful. We have demonstrated that routine implementation of ePROMs into clinical practice is feasible and can inform clinical practice and future research.

Impact of Comorbidity Scores on the Overall Survival of Patients With Advanced Non-small Cell Lung Cancer: A Real-World Experience From Eastern India.

Introduction Lung cancer is the most common cancer, and it is the leading cause of cancer-related death. Smoking is the most common risk factor for the development of lung cancer. There is a lack of data on the comorbidities and outcomes of advanced non-small cell lung cancer (NSCLC) in the eastern part of India. This prospective study evaluated the impact of comorbidity scores on overall survival (OS) in these patients. Method This prospective cohort study was conducted on newly diagnosed advanced NSCLC patients between June 2020 and April 2021. These patients were given platinum-based doublet chemotherapy guided by histology and targeted therapy based on molecular studies. Comorbidities were assessed using the Charlson Comorbidity Index (CCI), Simplified Comorbidity Score (SCS), and Adult Comorbidity Evaluation-27 (ACE-27). The outcome assessed was OS. Overall survival was calculated in days from the date of start of anticancer therapy to the date of last follow-up or date of death. All enrolled patients were followed at regular intervals whenever they visited the hospital and telephonically until April 2022. The patients who were alive on April 30, 2022, were censored. The survival probability and median OSwere calculated by Kaplan-Meier analysis, and group differences in comorbidity scores were analyzed with the log-rank test. A Cox proportional hazard analysis was performed to look for factors affecting overall survival. Results A total of 114 patients were enrolled in the study period, and the mean age of patients was 56.54 ± 11.03 years. Most of the patients were males (68.4%), and 52.6% were smokers. Adenocarcinoma was the most common histology (73.7%), followed by squamous cell carcinoma (25.4%). The median OS was 127 days (95% CI, 60-193 days). 33.4% of the patients had a CCI score of 0, a CCI score of 1 was seen in 57%, and ≥2 scores in 9.6%. SCS scores ≤9 and >9 were seen in 92.1% and 7.9% of patients, respectively. The ACE-27 score was none in 41 subjects, mild in 59, moderate in 12, and 2 NSCLC subjects had severe ACE-27 scores. The median OS for patients with a CCI score of 0 was 275 days (95% CI, 7-543 days), 114 days (95% CI, 85-142 days) for subjects with a CCI score of 1, and 402 days (95% CI, 0-844 days) for patients with a CCI score ≥2 (log-rank p = 0.215). Individuals with an SCS score ≤9 had a median OS of 175 days (95% CI, 91-258 days), and the median OS was 92 days (95% CI, 80-103 days) for patients with an SCS score >9 (log-rank p = 0.302). Median OS of the patients with ACE-27 score 0,1,2,3 were 297 days (95% CI, 76- 517 days), 117 days (95% CI, 81-152 days), 87 days (95% CI, 49-124 days) and 66 days, respectively (log-rank p=0.457). There was no statistical significance between comorbidity scores and OS. Worse OS was independently associated with poor performance status Eastern Cooperative Oncology Group (ECOG) ≥2 (hazard ratio [HR]3.266; 95% CI 1.785-5.978; p = 0.00), neutrophil-to-lymphocyte ratio (NLR) <3 (HR, 2.35 95% CI 1.18-4.702; p = 0.015) and patients who were given compassionate tyrosine kinase inhibitors (TKIs) (HR, 7.396 95% CI 3.531-15.490; p = 0.000). Conclusions In our study, the advanced NSCLC patients who were given chemotherapy or oral TKIs showed no significant influence of comorbidities on overall survival. Factors independently associated with the worst survival were poor performance status (ECOG ≥ 2), NLR < 3, and patients who were given TKIs on a compassionate basis.

Risk factors for evaluating early mortality after microvascular reconstruction of head and neck cancers.

Free tissue transfer reconstruction carries significant complication rates in surgical head and neck oncology. A registry-based approach offers a possibility to investigate the factors affecting increased morbidity and early mortality, that is, death within 6 months of treatment. A retrospective registry review was conducted on a series of 317 consecutive microvascular free tissue transfers in head and neck cancer patients performed during 2013-2017 at the Helsinki University Hospital (Helsinki, Finland). All surviving patients had a minimum follow-up of 2 years (range 24-84 months). Overall, 36 (11.4%) early deaths occurred in this series. In multivariable logistic regression analysis, patients aged 75 years and older (p = 0.019), Adult Comorbidity Evaluation-27 (ACE-27) score of 3 (p = 0.048), tumor class T3 (p = 0.005), lymph node class N2 (p = 0.014), or thrombocyte count of 360 (× 109 L) or more (p = 0.001) were more likely to die within 6 months of surgery. Of these 36 patients, 27 (75%) had a complication warranting hospital care and most (n = 22, 61%) had several complications. Early postoperative mortality most frequently affects patients aged 75 years and above, with a high ACE-27 score, advanced tumor stage, or high thrombocyte count. Therefore, preoperative assessment and patient selection should have a crucial role in this patient population.

Risk of non-colorectal cancer-related death in elderly patients with the disease: A comparison of five preoperative risk assessment indices.

A considerable number of elderly patients with colorectal cancer (CRC) die of non-CRC-related causes. The Controlling Nutritional Status (CONUT) score, American Society of Anesthesiologists Physical Status classification, Charlson Comorbidity Index, National Institute on Aging, and National Cancer Institute Comorbidity Index, and Adult Comorbidity Evaluation-27 score are all known predictors of survival in patients with CRC. However, the utility of these indices for predicting non-CRC-related death in elderly CRC patients is not known. The study population comprised 364 patients aged 80 years or more who received curative resection for stage I-III CRC between 2000 and 2016. The association of each index with non-CRC-related death was compared by competing-risks analysis such as the cumulative incidence function and proportional subdistribution hazards regression analysis as well as time-dependent receiver-operating characteristic (ROC) analysis. There were 85 deaths (40 CRC-related and 45 non-CRC-related) during a median observation period of 53.2months. Cumulative incidence function analysis identified CONUT score as the most suitable for risk stratification for non-CRC-related death. In proportional subdistribution hazards regression, risk of non-CRC-related death increased significantly as CONUT score worsened (2/3/4 vs. 0/1, hazard ratio 1.73, 95% confidence interval [CI] 0.91-3.15; ≥5 vs. 2/3/4, hazard ratio 2.71, 95% CI 1.08-6.81). Time-dependent ROC curve analysis showed that CONUT score were consistently superior to other indices during the 5-year observation period. The majority of deaths in elderly patients with CRC were not CRC-related. CONUT score was the most useful predictor of non-CRC-related death in these patients.

Body fat composition as biomarker for clinical outcomes and treatment tolerance in high-risk prostate cancer.

159 Background: Androgen deprivation therapy (ADT) is a standard of care for high-risk prostate cancer, but treatment tolerance is variable. Prior work has demonstrated the correlation between body composition (BC) and clinical outcomes in prostate cancer. Specifically, high visceral fat density has been associated with fat depletion phenomenon and poor prognosis in prostate cancer. However, the interaction of long-term ADT tolerance and body fat composition is less studied. We investigated if BC could predict for outcomes and treatment tolerance in patients with high-risk prostate cancer with planned ADT. Methods: An IRB-approved retrospective review was conducted at a tertiary care center of patients with high-risk (T3a or prostate-specific antigen [PSA] &gt; 20 ng/mL or Gleason score 8-10 or N/M+) prostate cancer who received definitive external beam radiation therapy (RT) from 2006 to 2013. A previously validated, fully automated deep learning BC analysis pipeline was performed on RT simulation scans to compute BC at the top of L3 slice, including total skeletal muscle (SM), subcutaneous fat (SF), and visceral fat (VF) surface area (cm2) and average CT density (Hounsfield Units (HU)); results were manually validated by experts. BC was stratified by median value. Adult Comorbidity Evaluation-27 (ACE) was used to measure co-morbidity. Long-term ADT was defined as &gt; 2 years, tolerance was defined as unplanned discontinuation &gt; 3-month difference in intended/actual duration of ADT. The association between BC markers, oncologic outcomes, and treatment tolerance was analyzed using univariable Cox regression and chi-square test. Results: A total of 207 men were analyzed with a median follow up time of 10.8 years (range 0.7-17.3y). Median age was 65 (range 42-83), with 61 (29.4%) patients classified as high-risk, 134 (64.7%) very-high-risk, and 12 (5.8%) N+/M+ at diagnosis. High VF density was associated with worse overall survival (OS) (HR 1.71, 95%CI 1.09-2.68, p = 0.0204) but not cancer-specific survival (CSS) (p = 0.08) or biochemical-relapse free survival (bRFS) (p = 0.97). SM and SF density, as well as area of SM, VF, SF, and total fat were not associated with outcomes. N/M stage was associated with bRFS (p = 0.0139), and N/M stage (p = 0.0101) and higher ACE score (p = 0.0218) were associated with OS. Among 88 (42.5%) patients planned for long-term ADT use, 24 (27%) patients discontinued ADT prior to duration, of which 15 (17%) patients discontinued due to toxicity. BC markers did not correlate with tolerance to long-term ADT (p = 0.17). Tolerance to long-term ADT was not associated with bRFS or OS. Conclusions: High VF density is associated with worse OS but not bRFS or CSS in high-risk prostate cancer patients, and not associated with adipose area or ADT tolerance. VF density may be a biomarker of underlying metabolic health in prostate cancer patients independent of disease, and a potential area of intervention.

Treatment Responses, Toxicity and Survival in Patients with Classical Hodgkin Lymphoma Aged 50 Years and Older: A Single-Center Experience over 2 Decades

Abstract Introduction: The prognosis of classical Hodgkin lymphoma (cHL) is generally inferior in elderly patients (pts) than in younger pts. Tolerance of conventional therapy decreases in elderly pts, and in addition, treatment-related toxicities and death are more common. While the 5-year overall survival (OS) of pts with cHL is 86.6%, this rate is 57.5% in elderly pts. Objective and Methods: The aim of this study was to retrospectively evaluate the demographic, histopathological, clinical, and laboratory features, prognosis determination according to German Hodgkin Study Group (GHSG) in early-stage, International Prognostic Score (IPS)-3 and IPS-7 in advanced-stage, ECOG (Eastern Cooperative Oncology Group) performance scale (PS), Cumulative Disease Rating Score (CIRS) , Charlson Comorbidity Index (CCI), Adult Comorbidity Evaluation-27 (ACE-27) values, treatment responses, toxicities, and survival among cHL pts aged 50 years and older who were diagnosed between 1999 and 2020. Results: There were 101 pts in total, of which 52 were between 50-59 years of age, and 49 pts were ≥60 years. Sixty-two pts were male, and the most common histopathological subtype was mixed cellularity CHL with 58.4%. Fifty-four pts had advanced-stage disease, while there were 31 and 16 pts with early-stage unfavorable and favorable diseases, respectively. Sixty-one pts (60.4%) had B symptoms (Table 1). ECOG PS, CIRS, CCI, and ACE-27 scores were significantly higher in pts aged ≥60 years than those of 50-59 age group (Table 2). While all pts aged 50-59 years received ABVD as first-line therapy, 79% (n=39) of pts aged ≥60 years had ABVD. Among pts receiving ABVD as a first-line treatment, 82% (n=41) of pts aged 50-59 years and 73.2% (n=30) of pts aged ≥60 years had complete response following first-line treatment (p=0.312). Overall, at interim evaluation, response rates to first-line therapy were significantly higher in pts with IPS-7 value 0-3 (71.8%) than those with IPS-7 value 4-7 (42.9%) (p=0.028). While full-dose treatment was administered to 71 pts (70.3%), 30 pts (29.7%) needed a dose reduction. The percentage of pts needed a dose reduction was 38.8% among pts ≥60 years, whereas this was 21.2% for pts aged 50-59 years (p=0.053). During the follow-up, grades 3-4 hematological and non-hematological toxicities were observed in 50 (49.5%) and 15 pts (14.9%), respectively. Age groups were comparable in terms of hematological and non-hematological toxicities (p=0.369, p=0.127, respectively). None of the pts in the ≥60 age group had received high-dose chemotherapy with autologous hematopoietic stem cell transplantation (HDC with AHSCT)/allogeneic hematopoietic stem cell transplantation (allo-HSCT). On the other hand, 8 pts (15.4%) diagnosed between 50-59 years of age underwent HDC with AHSCT, in one patient (1.9%) allo-HSCT was performed, and one patient (1.9%) received both HDC with AHSCT and allo-HSCT (p=0.004). There was no significant difference in terms of OS between those with and without transplantation (p=0.069). In the multivariate analysis, the risk of progression was higher in pts with lymphocyte ≤600/mm 3 and the risk of mortality was higher in pts with B symptoms (p=0.002, p=0.012, respectively). In addition, progression-free survival (PFS) was inferior in pts who were unresponsive to first-line treatment, and worse OS was associated with higher age and CIRS (p&amp;lt;0.001, p=0.001, p=0.038, respectively) (Fig. 1A-C). During their follow-up, 26 pts (25.7%) died, and the causes of death could be determined in 19 of them. The most common cause of death was treatment complications (n=7). Secondary malignancies were detected in 5 pts, of which 3 died. In 2 pts, the cause of death was HL-related, and 7 pts died due to other causes. Conclusion: Although not statistically significant, the percentage of pts needing a dose reduction was higher in pts aged ≥60 years, on the other hand, treatment responses and toxicities were similar in both groups, most probably due to personalized treatment selection and dose reduction according to age, comorbidities, and the performance status. Pts undergoing a transplant had a more favorable outcome than pts without a transplant, but the difference did not reach statistical significance. Response to first-line therapy was associated with superior PFS, and pts with higher age and CIRS had inferior OS. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Efficacy and toxicity hypofractionated radiotherapy for centrally located non-small cell lung cancer

Abstract Aim: Centrally located early-stage non-small cell lung cancer in patients who are unfit for surgery are treated with fractionated radiotherapy. We present the outcomes of a moderately hypofractionated accelerated dose regimen of 50 Gy in 15 fractions from a single centre in the UK. Materials and methods: Electronic case notes and radiotherapy records of lung cancer patients treated between January 2014 and December 2016 were retrospectively reviewed. Adult Comorbidity Evaluation-27 score was used to evaluate comorbidities. Mean lung doses and percentage of lung receiving more than 20 Gy were calculated for all patients. Survival outcomes were estimated using Kaplan–Meier curves. Results: Fifty-three patients were included in the study; the median follow-up was 20.2 months. 87% of patients had stage I disease. There was no 30-day post-treatment mortality. Ninety-day mortality rate after radiotherapy was 3.8%. Grade 2 pneumonitis was seen in five patients while no grade 3 or 4 pneumonitis was observed. The median progression-free survival (PFS) and overall survival (OS) were 18.5 months and 28.2 months, respectively. The estimated 1 and 2 years PFS were 62.3% and 41.3%, respectively, and OS were 77.4% and 56.6%, respectively. Worsening performance status was associated with worse survival on cox regression analysis. Disease relapsed in 36% of patients. 7.5% of patients with relapsed disease had infield recurrence. Findings: 50 Gy in 15 fractions radiotherapy for central early-stage lung cancer is a feasible choice that requires further randomised trials.

T cell fraction impacts oncologic outcomes in human papillomavirus associated oropharyngeal squamous cell carcinoma.

We investigated T cell clonality (TCC) and T cell fraction (TCF) in human papilloma virus associated oropharyngeal squamous cell carcinoma (HPV(+)OPSCC) progressors [cases] vs. non-progressors [controls]. This nested case-control study included patients undergoing intent-to-cure surgery±adjuvant therapy from 6/1/2007-10/3/2016. Patients experiencing local/regional/distant disease (progressors), and a consecutive sample of non-progressors were matched (2 controls: 1 case) on tumor subsite, T-stage and number of metastatic lymph nodes. We performed imunosequencing of the CDR3 regions of human TCRβ chains. 34 progressors and 65 non-progressors were included. There was no statistically significant difference in baseline TCF (range: 0.039-1.084) and TCC (range: 0.007-0.240) (p>0.05). Female sex was associated with higher TCF (p=0.03), while extranodal extension (ENE) was associated with lower TCF (p=0.01). There was a positive correlation between tumor size and clonality (R=0.34, p<0.01). The strongest predictor of progression-free survival (PFS) was TCF (HR 0.80, 95%CI 0.66-0.96, p=0.02). The strongest predictors of cancer specific survival (CSS) were TCF (HR0.69, 95%CI 0.47-1.00, p<0.05) and Adult Comorbidity Evaluation-27 (ACE-27) score (p<0.05). Similarly, the strongest predictors of overall survival (OS) were TCF (HR 0.62, 95%CI 0.43-0.91, p=0.01) and ACE-27 score (p=0.03). On multivariable modeling, TCF≥0.4 was independently associated with PFS (HR 0.34, 95%CI 0.14-0.85, p=0.02) while an ACE-27 score of≥2 independently predicted CSS (HR 3.85, 95%CI 1.07-13.85, p=0.04) and OS (HR 3.51, 95%CI 1.10-11.20, p=0.03). In patients with HPV(+)OPSCC, TCF was higher in female patients and those without ENE, suggesting differential immune responses. Lower TCF was significantly and independently associated with disease progression. Better ACE-27 scores appear to predict improved oncologic control.

The prognostic role of medical comorbidities in surgically treated human papillomavirus-associated oropharyngeal squamous cell carcinoma.

Prognostic factors specific to surgically managed human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (HPV(+)OPSCC) are not fully understood. Medical co-morbidities may have an impact on survival after surgical treatment. We aimed to identify co-morbidities associated with distant metastases-free survival (DMFS) and cancer-specific survival (CSS) in HPV(+)OPSCCs. This is a retrospective case series of HPV(+)OPSCC patients at a tertiary referral center from 2007 to 2016. All patients in the study underwent primary intent-to-cure transoral resection with concomitant neck dissection±adjuvant radiation±chemotherapy. Exclusion criteria included a history of previous head and neck cancer or distant metastases at diagnosis. Associations with DMFS and CSS were evaluated using univariable and multivariable Cox regression and summarized with hazard ratios (HRs). 406 patients were included in the cohort (100% HPV(+), 90% Male). All had tumors of the tonsil (62%) or base of tongue (38%). Median follow-up for the cohort was 4.0years (IQR: 2.6-6.2). Higher tumor stage and a higher Adult Comorbidity Evaluation-27 score were significantly associated with worse DMFS and CSS (p<0.02 for all). A history of diabetes mellitus (N=36, 9%) was significantly associated with DMFS (HR 3.05 [95%CI 1.26-7.37], p=0.014) and CSS (HR 4.82 [95%CI 1.84-12.61], p=0.001). On multivariable analysis, after adjusting for tumor stage, diabetes remained significantly associated with worse DMFS (HR 2.58 [95%CI 1.06-6.26], p=0.037). Diabetes mellitus may be associated with worse DMFS and CSS in surgically managed HPV(+)OPSCC.

Comorbidity as a factor of prognosis in patients with locoregionally advanced, inoperable squamocellular head and neck cancers

Background/Aim. Patients (pts) with tumors often have other diseases or conditions in addition to their index cancer which are generally referred to as comorbidities. Due to the fact that well known risk factors for development of squamocellular head and neck cancers (HNSCC) such as tobacco and alcohol abuse can also damage other important organs, pts with this type of cancer are suitable for analyzing the influence of comorbid conditions on prognosis of the disease. The aim of our work was to assess the prevalence of comorbidities, most frequent conditions and their prognostic impact on overall survival in this particular population. Methods. Between July 2002 and January 2007 in the Institute for Oncology and Radiology of Serbia, 100 pts with locoregionally advanced, inoperable HNSCC were initially treated with neoadjuvant chemotherapy regimen, cytarabine- 5 fluorouracil-cisplatinum. Median age of pts was 55 years, most of them (91%) were males with median number of applied chemo cycles being 4. Data on comorbidities were collected in prospective manner from various sources prior to the treatment. For grading of the severity of comorbid conditions, the Adult Comorbidity Evaluation 27 (ACE-27) comorbidity index was used with four degree scale (0?3). The average follow-up of pts was 15 months with range from 3?59 months. Results. Comorbidities were present in 69 (69%) pts, and 31 (39%) pts had no comorbidities prior to the treatment. Among pts with comorbid conditions prevailed alcoholics, active and former (71%), pts with chronic lung diseases (25%) and cardiovascular diseases (18%). Overall comorbidity score was defined according to the highest ranked single ailment, except in the case where two or more grade 2 ailments occured in different organ systems in which case the overall comorbidity score was designated as grade 3. Median overall survival for the whole group was 12 months. Median ACE-27 score was grade 1 (range 0?3) which was observed in 43 (43%) pts. Pts without comorbidities survived significantly longer than those with any kind of comorbidity (p = 0.0089), and the same was observed comparing survival of pts without comorbidities and those with comorbidity index 2 and 3 taken together (p = 0.0047). Results of other intergroup comparisons were of no statistic significance. Conclusion. Comorbidity is important prognostic variable in patients with locoregionally advanced HNSCC and should be properly assessed prior to therapy.

Optimizing Survival Predictions of Hypopharynx Cancer: Development of a Clinical Prediction Model.

ObjectivesTo develop and validate a clinical prediction model (CPM) for survival in hypopharynx cancer, thereby aiming to improve individualized estimations of survival.MethodsRetrospective cohort study of hypopharynx cancer patients. We randomly split the cohort into a derivation and validation dataset. The model was fitted on the derivation dataset and validated on the validation dataset. We used a Cox's proportional hazard model and least absolute shrinkage and selection operator (LASSO) selection. Performance (discrimination and calibration) of the CPM was tested.ResultsThe final model consisted of gender, subsite, TNM classification, Adult Comorbidity Evaluation‐27 score (ACE27), body mass index (BMI), hemoglobin, albumin, and leukocyte count. Of these, TNM classification, ACE27, BMI, hemoglobin, and albumin had independent significant associations with survival. The C Statistic was 0.62 after validation. The model could significantly identify clinical risk groups.ConclusionsACE27, BMI, hemoglobin, and albumin are independent predictors of overall survival. The identification of high‐risk patients can be used in the counseling process and tailoring of treatment strategy or follow‐up.Level of Evidence4 Laryngoscope, 130:2166–2172, 2020

The impact of Adult Comorbidity Evaluation-27 on the clinical outcome of elderly nasopharyngeal carcinoma patients treated with chemoradiotherapy or radiotherapy: a matched cohort analysis.

Objectives: To evaluate the prognostic significance of Adult Comorbidity Evaluation-27 (ACE-27) for elderly patients (age ≥70 years) with locoregionally advanced nasopharyngeal carcinoma (NPC) treated with Intensity-Modulated Radiotherapy (IMRT), with or without chemotherapy.Methods: 206 elderly patients with locoregionally advanced NPC treated from December 2006 to December 2016 were involved into analysis as the training cohort. Besides, a separate cohort of 72 patients from the same cancer center collected between January 2003 and October 2006 served as the validation cohort. By using propensity score matching (PSM), we created a balanced cohort by matching patients who received chemoradiotherapy with patients who received IMRT alone. Treatment toxicities were calculated between CRT and RT groups using the χ2 test. The primary endpoint was cancer-specific survival (CSS). Multivariate analysis was performed to assess the relative risk for each factor by using a Cox's proportional hazards regression model.Results: The median follow-up was 39.0 months (range = 3-137 months). In the PSM cohort, patients in the CRT group achieved comparable survival compared with patients in the RT group. The 3-year CSS rate was 64.3% and 65.2%, respectively (P =0.764). In multivariate analysis, the addition of chemotherapy to IMRT was not an independent prognostic factor for CSS, whereas a high ACE-27 score was an independent risk factor. In subgroup analysis with ACE-27 score ≥ 2, the 3-year CSS rate was worse in patients from the CRT group (63.5% vs. 46.3%, P = 0.041).Conclusions: CRT is comparable to IMRT alone for elderly patients with locoregionally advanced NPC. The ACE-27 tool may help to identify high-risk subgroup for poor disease outcome and tailor individualized treatment.

Imapct of Clonal Hematopoiesis of Indeterminate Potential (CHIP) Associated Mutations and Risk of Comorbidities in Patients with Myelodysplastic Syndrome

Abstract Introduction: Comorbidities have a significant impact on the prognosis and survival of patients with MDS (Naqvi et al, JCO. 2011). Separately, CHIP associated mutations (TET2, DNMT3A, JAK2 and ASXL1) have also been noted to be associated with comorbidities, particularly atherosclerotic heart disease (Ebert et al. NEJM. 2017). This association is however not well studied in patients in MDS. The objective of this study was to determine the association of these CHIP mutations including TP53 with comorbidities in patients with MDS. Patients and Methods: We conducted a retrospective analysis of 566 consecutive patients with MDS who presented to MD Anderson Cancer Center from August 2013 to December 2016. The Adult Comorbidity Evaluation-27 (ACE-27) scale was used to assess the severity of comorbid conditions. Data on the demographics and International Prognostic Scoring System Revised (IPSS-R) were collected. We used next-generation sequencing to detect the presence of CHIP mutations in bone marrow samples. Spearman's correlation coefficient was used to assess the association between CHIP associated gene mutations as binary variables by the presence of mutations, and continuous variables by variant allele frequency (VAF) and comorbidities. Kaplan-Meier methods and Cox regression were used to assess survival. A prognostic model incorporating the IPSS-R, comorbidities by ACE-27 and TP53 mutation status (I-RAT) was developed to predict survival. Results: Of the 566 patients included in this study, 66% were male, and 82% were white; median age at presentation was 69 years (range: 22-93). A total of 334 (58%) patients had an IPSS-R of Intermediate, low and very low; complex karyotype was noted in 128 (23%) patients. The ACE-27 comorbidity scores were as follows: none, 101 (17%); mild, 214 (38%); moderate, 146 (26%); and severe, 105 (19%). Mutations in DNMT3A, ASXL1, TET2, JAK2 and TP53 were noted in 9%, 18%, 20%, 2% and 21% patients respectively. Two hundred and fifty (44%) MDS patients had no CHIP-associated mutations. With respect to the cardiovascular system, patients harboring DNMT3A were noted to have a higher incidence of myocardial infarction than those without DNMT3A mutation (14% vs 6%; p= 0.03). As expected, patients with a JAK2 mutation had higher number of venous thromboembolic events (18% vs 4%; p= 0.013). TET2, ASXL1 and TP53 mutations however were not associated with increased cardiovascular events in our patients. TP53 mutations were highly associated with history of prior malignancy: solid tumors, 44% vs 21%; p= &lt;0.001; myeloma, 9% vs 3%; p= 0.003; lymphoma, 17% vs 3%; p= &lt;0.001. Patients with respiratory disease and diabetes mellitus were also noted to most likely harbor TP53 mutations: 16% vs 9%; p= 0.016 and 27% vs 16%; p= 0.009 respectively. Patients with ASXL1 were less likely to have prior malignancy (18% vs 27%; p= 0.057). Despite this association, the level of VAF of DNMT3A, JAK2, ASXL1 and TP53 were only weakly associated with the respective comorbidities. A trend towards higher ACE-27 comorbidity scores and increased number of mutations was noted (p= 0.075). CHIP-associated mutations were associated with higher ACE-27 comorbidity scores (p=0.036) and an overall inferior median survival (26.1 months versus 65.8 months; p=0.005). A final prognostic model including IPSS-R, ACE-27 score and TP53 mutation (I-RAT) predicted median survival of 66, 16, and 12 months for intermediate, high and very high-risk groups, respectively (p&lt;0.001). Median survival for very low and low-risk groups was not reached. Conclusion: Patients with MDS harboring CHIP associated mutations, mainly DNMT3A, have a higher incidence of myocardial infarction. This advocates for early intervention and optimization of the modifiable cardiovascular risk factors, such as hypertension, obesity and hyperlipidemia in patients with CHIP and MDS. Additionally incorporating IPSS-R with ACE-27 comorbidity score and TP53 mutation (I-RAT model) further improves the prediction for survival in patients with MDS. Disclosures Sasaki: Otsuka Pharmaceutical: Honoraria. Short:Takeda Oncology: Consultancy. Jabbour:Novartis: Research Funding; Takeda: Consultancy, Research Funding; Abbvie: Research Funding; Pfizer: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding. Ravandi:Amgen: Honoraria, Research Funding, Speakers Bureau; Abbvie: Research Funding; Orsenix: Honoraria; Astellas Pharmaceuticals: Consultancy, Honoraria; Macrogenix: Honoraria, Research Funding; Xencor: Research Funding; Astellas Pharmaceuticals: Consultancy, Honoraria; Seattle Genetics: Research Funding; Jazz: Honoraria; Bristol-Myers Squibb: Research Funding; Abbvie: Research Funding; Bristol-Myers Squibb: Research Funding; Amgen: Honoraria, Research Funding, Speakers Bureau; Sunesis: Honoraria; Sunesis: Honoraria; Orsenix: Honoraria; Seattle Genetics: Research Funding; Macrogenix: Honoraria, Research Funding; Xencor: Research Funding; Jazz: Honoraria. Kadia:Pfizer: Consultancy, Research Funding; BMS: Research Funding; Amgen: Consultancy, Research Funding; Novartis: Consultancy; Jazz: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Consultancy; Takeda: Consultancy; Takeda: Consultancy; Abbvie: Consultancy; Celgene: Research Funding; Celgene: Research Funding; BMS: Research Funding; Amgen: Consultancy, Research Funding; Jazz: Consultancy, Research Funding; Abbvie: Consultancy.

Assessment of Interrater Reliability for Comorbidity Indices in Determining Eligibility for Treatment Intensification in Head and Neck Cancer

With an aging population, reliable measures of comorbidity are increasingly crucial for clinical decision-making in head and neck cancer patients. Concomitant medical conditions are recognized as significant predictors of survival and treatment tolerance. Multiple validated tools exist to evaluate various fitness measurements and assist in determining eligibility for treatment with concurrent chemotherapy and clinical trial enrollment in head and neck cancer patients. We measured the interrater reliability (IRR) in scoring comorbidity indices and determining fitness for treatment intensification between users in various clinical roles. We analyzed a cohort of twenty patients with locoregionally advanced head and neck cancer. Baseline characteristics, self-rating of health, and comorbidities were collected at time of initial consultation. Four independent observers evaluated each patient based on six previously validated metrics. The indices included a Generalized Competing Event (GCE) model based on RTOG data, G8, Charlson Comorbidity Index (CCI), Cancer and Aging Research Group (CARG) model, Adult Comorbidity Evaluation-27 (ACE-27), and Cumulative Illness Rating Scale for Geriatrics (CIRS-G). Intraclass correlation coefficient (ICC) was generated for continuous GCE values and Fleiss’ kappa statistics were used for binary, nominal, and ordinal variables to evaluate interrater reliability. Fleiss’ kappa greater than 0.6 is generally accepted to indicate substantial agreement. The ICC for the GCE model was 0.909; when the GCE score was transformed into a binary variable using eligibility criteria of GCE <0.6, the kappa statistic was 0.918. Fleiss’ kappa scores for G8, CCI, CARG, ACE-27 and CIRS-G were 0.463, 0.537, 0.727, 0.527, and 0.223, respectively. After converting individual scores to binary values based on eligibility criteria from an ongoing randomized trial, the kappa scores for G8, CCI, CARG, ACE-27 and CIRS-G were 0.817, 0.682, 0.614, 0.624, and 0.733, respectively. The kappa statistic for treatment intensification eligibility was 0.722, and all raters agreed on eligibility status for eighteen of twenty patients. Of the two patients for which raters disagreed, the ACE-27 score was the source of discrepancy. Variability in IRR between comorbidity indices suggests potential issues when applying any one of these measures to head and neck cancer patients in the context of clinical trial enrollment and practice. Despite differences in IRR between evaluation models and various user backgrounds, there was 90% agreement on patient eligibility for treatment intensification after comprehensive calculation of comorbidity metrics. Additional systematic study is required to determine consistent methods of quantifying comorbid conditions and their magnitude of effect on a patient’s fitness for and tolerance of treatment intensification.

P2.16-17 Hypo-Fractionated Accelerated Radiotherapy in Central Early Non-Small Cell Lung Cancer: Leeds Cancer Centre Experience

Centrally located early stage lung cancers in patients who are unfit for surgery and stereotactic ablative body radiotherapy (SABR) are routinely treated with radical radiotherapy. There are no standard dose regimens but evidence seems to favour acceleration. We present the outcomes of a moderately hypo-fractionated accelerated dose regimen of 50Gy in 15 fractions (BED (a/b=10) corrected for time = 58.85Gy) from a single centre in the UK. Electronic case notes and radiotherapy records of lung cancer patients treated between January 2014 to December 2016 were retrospectively reviewed. Adult Comorbidity Evaluation-27 (ACE-27) score was used to evaluate comorbidities. Survival outcomes were estimated using Kaplan-Meier curves and compared using log-rank test. Fifty-three patients were treated with 50Gy in 15 fractions with a median age of 74.0 years (IQR: 69.5–79). 4 patients had a poor WHO PS of 3. Thirty-seven (69.8%) were females. A similar number had Grade 2 or 3 ACE-27 score while one had Grade 0. Forty-six patients were stage I, whilst four and three patients were stage II and III respectively. Thirty-seven (70%) patients had a radiological diagnosis. The treatment was well tolerated, 90-day mortality rate after radiotherapy was 3.8% (n=2). Grade 2 pneumonitis was seen in 5 patients while no grade 3 or 4 pneumonitis was observed. At the time of cut-off for analysis, the median follow-up was 20.2 months. The median progression-free survival (PFS) and overall survival (OS) were 18.5 months (95% CI 12.2–24.8) and 28.2 months (95%CI 14.4–42.1) respectively. The estimated 1 and 2 year PFS were 62.3% and 41.3% respectively and OS were 77.4% and 56.6% respectively. Only PS significantly impacted survival on univariate analysis, while PS and ACE-27 both were shown to have significant effect on multivariate analysis. Of the nineteen patients who relapsed, 4 (7.5%) had infield recurrence, 10 had out-of-field lung recurrence and the rest had distant metastases. One patient underwent salvage surgery. 6 patients received further radical therapy with 3 each being treated with conventional and SABR. This moderately hypo-fractionated accelerated radiotherapy regimen for central early stage lung cancer seems similar in efficacy but is associated with significantly less toxicity when compared to SABR.

Prognostic impact of preoperative comorbidities in geriatric patients with early-stage lung cancer: Significance of sublobar resection as a compromise procedure

In high-risk operable geriatric patients undergoing palliative sublobar resection (SR), noncancerous comorbidities may contribute to unfavorable outcomes. The purpose of this retrospective study was to evaluate the perioperative safety and long-term survival of palliative SR in this patient population. We reviewed 232 patients (141 male, 91 female) aged ≥75 years who underwent surgical resection of clinical stage I lung cancer from 2006 to 2014. The patients were divided into two groups, lobectomy and SR, and preoperative comprehensive comorbidities were assessed using the Adult Comorbidity Evaluation 27 (ACE-27) and compared between the two groups. The operative safety was compared using the Clavien-Dindo classification. Survival rates were calculated with a Kaplan-Meier model under propensity score matching, and prognostic factors were analyzed using a Cox proportional hazard model. Lobectomy was performed in 156 patients and SR in 76 (segmentectomy, n = 50; wedge resection, n = 26). Age (p = 0.0137), tumor size on computed tomography (p < 0.0001), central tumor location (p = 0.0008), and high ACE-27 scores (p = 0.0202) were significantly associated with selection of SR. No mortality occurred, and the incidence of Grade 3b or greater postoperative complications in lobectomy and SR was 5.1% and 5.3%, respectively. According to the analysis of propensity score-matched patients (n = 57, tumor size = 23 mm, and consolidation/tumor ratio = 83%), the 5-year survival rate in lobectomy and SR was 81.1% and 73.5%, respectively (p = 0.4374). The ACE-27 score was a more significant prognostic factor than the type of surgical procedure, as well as consolidation/tumor ratio and nodal metastatic status. The severity of preoperative comorbidities is a significant prognostic factor, and SR as a compromise surgical procedure may provide promising short- and long-term outcomes in selected geriatric patients with clinical stage I lung cancer.

The Characteristics and Survival Outcomes in Patients Aged 70 Years and Older with Nasopharyngeal Carcinoma in the Intensity-Modulated Radiotherapy Era.

PurposeWe aim to examine nasopharyngeal carcinoma (NPC) characteristics and survival outcomes in patients aged 70 years and older in the intensity-modulated radiotherapy (IMRT) era.Materials and MethodsFrom 2006 to 2013, 126 non-metastatic NPC patients aged ≥ 70 years who were treated with IMRT +/‒ chemotherapy were included. Adult Comorbidity Evaluation 27 (ACE-27) was used to measure patient comorbidities. The overall survival (OS) and cancer-specific survival (CSS)were calculatedwith the Kaplan-Meier method, and differenceswere compared using the log-rank test. The Cox proportional hazards model was used to carry out multivariate analyses.ResultsFor the entire group, only two patients (1.6%) presented stage I disease, and up to 84.1% patients had stage III-IVB disease. All patients had a comorbidity score of 0 in 24 (19.0%), 1 in 45 (35.7%), 2 in 42 (33.3%), and 3 in 15 (11.9%) patients. The main acute grade during radiotherapy was 3-4 adverse events consisting of mucositis (25.4%), bone marrow suppression (16.7%), and dermatitis (8.7%). After treatment, four patients (3.2%) developed temporal lobe injury. Five-year CSS and OS rates were 67.3% (95% confidence interval [CI], 58.6% to 77.4%) and 54.0% (95% CI, 45.6% to 63.9%), respectively. Five-year OS was significantly higher for ACE-27 score 0-1 than ACE-27 score 2-3 (72.9% and 39.9%, respectively; p < 0.001). Multivariate analyses showed ACE-27 score 0-1 was significantly associated with superior OS (hazard ratio [HR], 3.02; 95% CI, 1.64 to 5.55; p < 0.001). In addition, the rate of OS was higher for stage I-III than that of stage IV, with borderline significance (HR, 1.67; 95% CI, 0.99 to 2.82; p=0.053). But no significant advantage was observed in OS when chemotherapy was used (p > 0.05).ConclusionOur findings suggest IMRT +/– chemotherapy has a manageable toxicity and provides an acceptable survival in patients aged ≥ 70 years with NPC. ACE-27 score was significantly associated with survival outcomes in this group population.