Adult Comorbidity Evaluation-27 Research Articles

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.

Individual Patient Comorbidities and Effect on Cochlear Implant Performance.

To examine the association between preoperative comorbidities and cochlear implant speech outcomes. Retrospective cohort. Tertiary referral center. A total of 976 patients who underwent cochlear implantation (CI) between January 2015 and May 2022. Adult patients with follow-up, preoperative audiologic data, and a standardized anesthesia preoperative note were included. Adult Comorbidity Evaluation 27 (ACE-27) based on standardized anesthesia preoperative notes. Postoperative change in consonant-nucleus-consonant (CNC) score, AzBio Sentence score in quiet, and AzBio + 10 dB signal-to-noise ratio (SNR). Sentence score of the implanted ear at 3, 6, and 12 months. A total of 560 patients met inclusion criteria; 112 patients (20%) had no comorbidity, 204 patients (36.4%) had mild comorbidities, 161 patients (28.8%) had moderate comorbidities, and 83 patients (14.8%) had severe comorbidities. Mixed model analysis revealed all comorbidity groups achieved a clinically meaningful improvement in all speech outcome measures over time. This improvement was significantly different between comorbidity groups over time for AzBio Quiet ( p = 0.045) and AzBio + 10 dB SNR ( p = 0.0096). Patients with severe comorbidities had worse outcomes. From preop to 12 months, the estimated marginal mean difference values (95% confidence interval) between the no comorbidity group and the severe comorbidity group were 52.3 (45.7-58.9) and 32.5 (24.6-40.5), respectively, for AzBio Quiet; 39.5 (33.8-45.2) and 21.2 (13.6-28.7), respectively, for AzBio + 10 dB SNR; and 43.9 (38.7-49.0) and 31.1 (24.8-37.4), respectively, for CNC. Comorbidities as assessed by ACE-27 are associated with CI performance. Patients with more severe comorbidities have clinically meaningful improvement but have worse outcome compared to patients with no comorbidities.

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.

The impact of comorbidity on the diagnosis delay, treatment options and prognosis for advanced oral cancer: A retrospective result of the POROMS database

This study aimed to reveal the underlying mechanisms linking advanced oral squamous cell carcinoma (OSCC) with its comorbidities. Data extracted from the POROMS database included 448 advanced OSCC patients in stage III or IV (AJCC 8th) with primary tumors between August 2015 and August 2021. Time to diagnosis delay increased from 4.5, 5.3–6.5 months when the Adult Comorbidity Evaluation-27 (ACE-27) worsened from none, mild (RR: 1.155, 1.043–1.279; P = 0.006) to moderate-severe (RR: 1.431, 1.251–1.636; P < 0.001). With the number of comorbidities increased from 0, 1–2 (RR: 1.188, 1.078–1.310; P = 0.001) to 3 (RR: 1.563, 1.296–1.885; P < 0.001), the time to diagnosis delay increased from 4.5, 5.4–7.1 months. As the level and number of comorbidities increased, the likelihood of treatment completion gradually declined, especially in those older than 65 years (P = 0.003). The presence of comorbidity was an independent prognostic factor for disease-free survival (HR: 1.431, 1.022–2.005; P = 0.037). Comorbidities may lead to poorer prognosis by directly causing delays in diagnosis, limiting treatment options, and increasing the risk of death in advanced OSCC patients.

Significance of chemotherapy for older patients with nasopharyngeal carcinoma in the intensity-modulated radiotherapy era: A propensity score matching analysis

IntroductionThis study aimed to evaluate the survival and prognosis of older patients with nasopharyngeal carcinoma (NPC) who received intensity-modulated radiotherapy (IMRT) alone versus IMRT plus chemotherapy using propensity score matching (PSM). Materials and MethodsWe enrolled 841 older patients with NPC aged 60 years and above without metastasis receiving IMRT alone or chemoradiotherapy from 2012 to 2019. The comorbidity was assessed by adult comorbidity evaluation (ACE-27). PSM (1:3 ratio) was conducted between the two treatment groups based on four clinical factors including age, T-stage, N-stage, and ACE-27. Differences in overall survival (OS) and cancer-specific survival (CSS) were analyzed by the Kaplan-Meier method and Cox proportional hazard model. ResultsA total of 841 patients with NPC were included in the study, there were 94 patients in the IMRT alone group and 747 patients in the chemoradiotherapy (CRT) group. After a 1:3 ratio PSM, 89 patients underwent IMRT alone and 223 patients underwent CRT. The baseline analysis showed an insignificant difference after PSM (P > 0.05). In multivariate analysis, we found that ACE-27 (≥2) was associated with worse five-year OS and CSS (HR = 1.994, 95%CI: 1.276–3.116, P = 0.002; HR = 1.849, 95%CI: 1164–2.935, P = 0.009, respectively). Chemotherapy was an independent prognosticator of better five-year OS and CSS (HR = 0.333, 95%CI: 0.213–0.552, P < 0.001; HR = 0.327, 95%CI: 0.204–0.524, P < 0.001, respectively). In terms of subgroup analysis, chemotherapy was a statistically beneficial predictor for stage III-IV patients (P < 0.05), but no significant difference in stage II patients (P > 0.05). About the adverse events, the incidence of hepatotoxicity (P = 0.002), neutropenia (P < 0.001), anemia (P < 0.001), and thrombocytopenia (P < 0.001) were significantly higher in the CRT group. DiscussionCombined modality therapy was associated with improved five-year OS and CSS in older adults with stage III-IV NPC, but was not associated with improved survival over IMRT alone in patients with stage II disease. Risk factors including T3–4 disease, positive lymph nodes, ACE-27 score ≥ 2, and IMRT alone were were associated with worse OS and CSS. There was a significantly higher incidence of hepatotoxicity and blood toxicity in the CRT group.

Hypopharyngeal cancer trends in a high-incidence region: A retrospective tertiary single center study.

Hypopharyngeal cancer has the bleakest prognosis among head and neck cancers due to its extensive submucosal involvement, advanced tumor stage, and limited surgical reconstruction options. Its primary causes include alcohol consumption, tobacco use, genetic predisposition, 1` diet, and socioeconomic conditions. While squamous cell carcinoma (SCC) accounts for 95% of hypopharyngeal tumors, it remains a rare form, comprising only 3%-5% of all SCC cases in the head and neck region. Globally, Central and Eastern Europe have the highest incidence rates for males (3.9 per 100000) and the third highest for females (2.26 per 100000), underscoring the significance of this seemingly uncommon condition. In Romania, hypopharyngeal cancer ranked 24th in incidence rate, with 634 new cases in 2020. To study the incidence, treatment and survival rates of hypopharyngeal tumor cases in a major ear, nose, throat (ENT) surgical center. A retrospective epidemiological clinical study was conducted on patients diagnosed and treated for hypopharyngeal cancer at the ENT department of "Carol Davila Central University Emergency Military Hospital" in Bucharest between January 2018 and August 2022. The study included 53 patients and was authorized by the Ethics Committee of Titu Maiorescu Doctoral School (Bucharest, Romania) and the Ethics Committee of Carol Davila Central University Emergency Military Hospital (Bucharest, Romania). Inclusion criteria required a positive histopathological diagnosis of hypopharyngeal cancer, tumor localization in the hypopharyngeal region, and informed consent for data usage. Exclusion criteria involved major psychiatric pathologies and disagreement for data usage. Diagnosis was based on ENT assessment, imaging reports, and laboratory data. Treatment methods were determined based on various factors. Additional tools, such as Adult Comorbidity Evaluation-27 and Karnofski Performance Status Scale, were used for risk assessment and functional capacity evaluation. Quality of life aspects were measured using the European Organisation for Reasearch and Treatment of Cancer Quality of Life Questionnaire Head and Neck-35 questionnaire. Our retrospective study examined 53 patients with hypopharyngeal cancer between January 2018 and August 2022. The majority of patients were male (94.3%), with an average age at diagnosis of 62.5 years. Among the patients, 20.75% were employed, 66.03% were retired, and 9.43% were unemployed. Smoking was prevalent among 69.81% of patients, while alcohol consumption was frequent in 32.07% of cases. The tumors were mostly diagnosed at an advanced stage (stage IV) and were predominantly SCC. Comorbidities were present in 83.01% of patients, with cardiovascular diseases being the most common. Dysphagia and neck mass were the most common symptoms reported. Treatment methods included surgery, radiation therapy, and chemotherapy. A favorable treatment response was observed in 22.64% of cases, while relapse occurred in 6 cases. Follow-up data was unavailable for some patients. In summary, our findings align with existing literature; however, we observed a higher severity.

Long-term results of postoperative and definitive (chemo)radiotherapy in sinonasal carcinoma. Adult Comorbidity Evaluation 27 score as a predictor of survival.

The objective was to evaluate the efficacy and toxicity of curative radiotherapy in patients with sinonasal carcinoma and to identify prognostic factors influencing treatment outcomes. The authors conducted a retrospective study of 61 consecutive patients treated with postoperative or definitive radiotherapy from 2002 to 2018 (median age 59 years, current/former smokers 71%, maxillary sinus 67%, nasal cavity 26%). The majority of patients were diagnosed with locally advanced disease (85% clinical stage ≥ III). Regional cervical metastases were initially diagnosed in 23% of patients. The most common histology was squamous cell carcinoma (61%). Radiation therapy was preceded by radical surgery in 64% of patients. 29 patients received chemotherapy (48%). The median follow-up was 53 months. The median total dose of radiotherapy achieved was 70 Gy. The 5- and 10-year locoregional control, distant control, overall survival, and disease-free survival were 74% and 64%, 90% and 90%, 51% and 35%, and 38% and 25%, respectively. Severe acute toxicity occurred in 36%, severe late toxicity in 23% of patients. Severe unilateral visual impairment occurred in 6 patients, temporal lobe necrosis in 1 patient, and osteoradionecrosis requiring surgery in 2 patients. The results of the study demonstrated the high effectiveness of curative treatment in patients with sinonasal carcinoma with long-term locoregional and distant control. The multivariate analysis indicated that N-staging, age, comorbidity score [as assessed by Adult Comorbidity Evaluation 27 (ACE-27)] and initial response to treatment were the strongest prognostic factors.

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 Tumor-Infiltrating Lymphocytes on Disease Progression in Human Papillomavirus-Related Oropharyngeal Carcinoma.

We aim to explore the prognostic value of tumor-infiltrating lymphocytes (TILs) in the primary tumor and metastatic lymph nodes of patients with HPV(+)OPSCC. We hypothesize that TILS density at both sites is associated with disease-free survival in HPV(+)OPSCC. Matched case-control study among HPV(+)OPSCC patients who underwent intent-to-cure surgery. Cases developed locoregional or distant recurrence. Controls were matched based on age, sex, pathologic T, N, and overall stage, year of surgery, type of adjuvant treatment received, and the Adult Comorbidity Evaluation-27 (ACE-27) score. Single tertiary care center, May 2007 to December 2016. Tumoral TILs (tTILs) density was defined as % TILs; stromal TILs (sTILs) density was defined as absent/sparse or moderate/dense crowding. Associations between TILs and time to disease progression were assessed using Cox regression models. Forty-four case-control pairs (N = 88) were included: 42 (48%) AJCC pStage I, 39 (44%) pStage II, and 7 (8%) pStage III. tTILs density ≥10% (hazard ratio [HR] 0.41, 95% confidence interval [CI] 0.17-0.99, p = .048) and a moderate/dense sTILs density (HR 0.21, 95% CI 0.06-0.75, p = .016) in the primary tumor were significantly associated with decreased risk of progression. TILs density in the lymph node was associated with decreased risk of progressionbut did not reach statistical significance. The tTILs and sTILs density correlated strongly between the primary tumor and lymph node. Concordance between the pathologists' was moderate (60%-70%). In HPV(+)OPSCC, a higher density of tumoral and stromal TILs in the primary tumor and possibly the lymph node may predict a lower risk of disease progression.

The total amount of fluid administered is associated with postoperative complications in head and neck cancer surgery.

Patients with head and neck cancer often undergo extensive ablative and reconstructive surgery. Many risk factors are unalterable, but some operative variables are possible to adjust. The goal of this study was to estimate the association between operative variables and the incidence of perioperative complications in a contemporary tertiary care university-based head and neck patient population and a Veteran Administration hospital head and neck patient population from an earlier time period. We retrospectively reviewed all patients whounderwent major head and neck surgery. Two-hundred-two university patients and 122 veteran patients were reviewed. On multivariable analysis, the total amount of intravenous (IV) fluid received during the procedure was associated with postoperative complications as were patients' weight, American Societyof Anesthesiologists(ASA) score, and adult comorbidity evaluation-27 (ACE-27) score. These associations did not depend on whether the patient was treated at the university or veteran hospital. Our study suggests that the odds of a postoperative complication increase as the total amount of IV fluid increases.

Facial-submental island flap for reconstruction of hemitongue defects in young, middle-aged and elderly patients with early and middle stage oral tongue squamous cell carcinoma

BackgroundThis study evaluated the outcomes of facial-submental artery island flap (FSAIF) for reconstruction of the hemitongue following cancer ablation in patients with early and middle-stage oral tongue squamous cell carcinoma (OTSCC).MethodsIn total, 122 patients with early and middle-stage OTSCC were divided into young, middle-aged, and elderly groups. The Adult Comorbidity Evaluation-27 (ACE-27) index was used to determine the presence of comorbidities. The patients underwent surgical treatment with hemiglossectomy, neck dissection, and hemitongue reconstruction using FSAIF. In addition, stage I (n = 15) and II (n = 69) patients underwent ipsilateral selective neck dissection, whereas those with stage III (n = 38) underwent radical neck dissection. Six patients with T3N1 disease also underwent cobalt-60 adjuvant radiotherapy.ResultsYoung and elderly patients exhibited significant differences in comorbidities, as assessed by the ACE-27 (p < .05). The skin paddles in the young, middle-aged, and elderly patients were 3 × 9 to 4 × 12 cm, 3 × 11 to 4 × 12, and 3 × 10 to 5 × 13 cm in size, respectively. FSAIF failure occurred in four patients (success rate: 96.7%). No significant differences were observed in the skin paddle of the flap or rate of flap failure among the age groups (p > .05). Clavien-Dindo grades I, II, IIIa, IIIb, Iva, and IVb were assigned to 7.1, 36.1, 38.5, 9.8, 4.1, and 4.1% of the patients, respectively, with significant differences seen between the young and elderly patients (p < .05). In total, 52.5% of patients could eat normally, whereas 32.8% required a soft diet. Furthermore, 53.3 and 33.6% of patients achieved normal and intelligible speech, respectively. The aesthetic results were rated as excellent and good in 32.8 and 58.2% of patients, respectively. In total, 68.0% of the patients were alive and exhibited no evidence of disease, while 19.7% were alive with active disease. In addition, 12.3% of patients with stage III OTSCC died due to local recurrence or distant metastases. No differences in swallowing, speech, aesthetic, or survival outcomes were observed among the groups.ConclusionsFSAIF is a simple, safe, and reliable method for reconstructing hemitongue defects following cancer ablation in young, middle-aged, and elderly patients with early and middle-stage OTSCC.

Assessment of Comorbidities and Their Association with Outcomes in Adults with Acute Lymphoblastic Leukemia (ALL)Using Various Comorbidity-Based Scoring Systems

Background: Outcomes of adults with ALL has remained poor as compared to pediatric ALL. While biological characteristics of the disease can increase the risk of poor treatment responses and resistance, age and concurrent comorbidities limit patient's tolerability to aggressive therapies and predispose to treatment related adverse effects, ultimately affecting survival. Despite similar chronological age, patients vary widely with respect to comorbidities and other aspects of health such that routine performance assessment scales such as Eastern Cooperative Oncology Group (ECOG) or Karnofsky Performance Scale (KPS) may not be accurate in assessing their fitness for therapy. Several measures such as Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI), Charlson Comorbidity Index (CCI), Cumulative Illness Rating Scale-Geriatric (CIRS-G) and Adult Comorbidity Evaluation-27 (ACE-27) have been reported in the literature to assess comorbidities in patients receiving intensive treatments, but their utility when it comes specifically to ALL patients is unknown, given the lack of studies assessing role comorbidities in ALL. Methods: We conducted a retrospective single center analysis of adults (age >=18) with ALL to assess the effect of comorbid conditions using available scales and determined their association with outcomes. Patients with a diagnosis of ALL (B/T-cell) who received first line therapy between 2009-2021 were included. Key exclusion criteria were patients with relapsed/refractory ALL and with incomplete follow-up. Comorbid conditions prior to first line therapy were calculated using four scales - HCT-CI, CCI, CIRS-G and ACE-27. Baseline demographic and disease characteristics, first line treatment, response, outcomes were collected using chart review. Descriptive statistics, logistic regression, Cox Proportional Hazards regression method was used for analysis. Concordance (C-statistic) and 95% confidence interval was reported for each model for comparison. A receiver operating characteristic (ROC) curve was also created for each outcome to compare the performance of base and comorbidity score models. Results: A total of 201 patients were included for analysis. Median age was 54(range 39-65), 53% were males, 82% were Caucasians, 8.5% Hispanics. 86% had B-ALL (32% were Philadelphia chromosome positive), 83% received intensive therapy. Median OS was 3.8 years (3.7-not reached) and Event free survival was 2.0(1.5,3.3) for the entire patient population. Patients were categorized in 0(22%), 1 (19%),2(13%) and 3+(46%) per HCT-CI, 0(32%), 1(23%),2(12%) and 3+(33%) per CCI. In CIRS-G scale patients were categorized in to 2 groups of <6 and >=6(51.5% vs 48.5%). In ACE-27 scale there were 4 categories (none(0),mild(1) moderate(2) and severe(3)) with 19%, 41%, 21% and 18% in each group consecutively. All four comorbidity scales were able to predict overall and event-free survival with statistical significance. Patients with HCT-CI category of <=1 had statistically significant OS and EFS advantage when compared to patients with a score of >=2 (Not reached vs 3.1-3.7 yrs for OS, 2.4-5.2 vs 1.4-1.6 yrs for EFS). Patients with CCI category 0 (not reached, 3.4) had better median OS and PFS than categories 1,2 (3.7 years OS, 1.8-3.1 yrs PFS) and 3+ (3.4, 1.4 yrs). CIRS-G category of <6 score had better median OS and PFS (not reached) than 6+ category (3.0 yrs). In ACE-27 scale, 0 and 1 categories had better OS and PFS (not reached and 3.4 yrs, not reached and 2.3 yrs vs 3.0-3.2 and 1.4 yrs) than moderate and severe (2,3) categories. Though all scales could predict OS and EFS, the overall survival model with CIRS-G scale had a significantly higher C-statistic compared to the base model than other scales. The HCT-CI and CIRS scores were each significant in their models for complete remission, but there were no significant differences between c-statistics among any of the CR models. None of the comorbidity scores were significant in predicting 90-day readmission or ED visit. Conclusions: Comorbidities as assessed by HCT-CI, CCI, ACE-27 or CIRS-G were significantly associated with survival in adults with ALL. Incorporation of these formal methods of comorbidity assessment in clinical practice is needed to assess ALL patients at baseline and tailor therapy accordingly. Prospective studies to validate and identify the optimal comorbidity determination scale in ALL is needed. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

More Than Ten Years Follow-up of Frontline Tyrosine Kinase Inhibitor Therapy in Patients with Chronic Myeloid Leukemia

Background: Tyrosine kinase inhibitor (TKI) therapy improved survival in patients (pts) with chronic myeloid leukemia (CML). Treatment-free remission (TFR) can be considered for a minority of pts, particularly in those who achieved sustained deep molecular response (DMR). Given most pts needs TKI therapy over decades, the aim of this study is to evaluate the very long-term outcome of pts (pts) treated with frontline TKI. Methods: We analyzed 557 pts with newly diagnosed CML in chronic phase (CP) and accelerated phase (AP; based solely on the presence of clonal evolution) who were treated with frontline TKI therapy (standard-dose imatinib, 73 pts; higher-dose imatinib, 210 pts; dasatinib, 144 pts; and nilotinib, 130 pts) from July 2000 to September 2014. The presence of comorbidity was assessed by the Adult Comorbidity Evaluation-27. Responses criteria were previously defined (complete cytogenetic response, CCyR; major molecular response, MMR; molecular response with a 4-log reduction, MR4; molecular response with a 4.5-log reduction, MR4.5). Failure-free survival (FFS) was calculated from the start of therapy to the treatment discontinuation for any reason except of TFR; event-free survival (EFS), to the date of any of the events while on study as defined in the IRIS study; transformation-free survival (TFS), to the date of transformation to accelerated or blast phases during study; overall survival (OS), to the date of death from any cause at any time or date of last follow-up. We evaluated prognostic factors with univariate and multivariate Cox proportional hazard models with a p-value cutoff of 0.100 or less by univariate analysis for variable selections; cumulative incidence of response was assessed with a competing risk model. Multiple imputation was performed for missing variables to reduce bias. Time to complete cytogenetic response was analyzed as a time-dependent variable in the Cox regression Results: The median age at the start of TKI therapy was 49 years (range, 15.1-86.4). The overall median follow-up was 178 months (range, 5.3-253.9) (standard-dose imatinib, 231 months; higher-dose imatinib, 212 months; dasatinib 137 months; nilotinib 138 months) (Table 1). Overall, the 10-year cumulative incidence rates of CCyR, MMR, MR4, and MR4.5 were 91%, 87%, 76%, and 72%, respectively; among pts who responded, the median time to CCyR, MMR, MR4, and MR4.5 were 3.1 months, 5.9 months, 9.5 months, and 12.5 months, respectively. The cumulative incidence rates of CCyR, MMR, MR4, and MR4.5 were higher in the higher-dose imatinib, dasatinib, and nilotinib cohorts compared to standard-dose imatinib. The 10-year FFS rates were 48%, 52%, 67%, and 44% in the standard-dose imatinib, higher-dose imatinib, dasatinib, and nilotinib cohorts, respectively (P<0.001); the 10-year TFS rates were 84%, 98%, 98%, and 96%, respectively (P<0.001); the 10-year EFS rates were 67%, 80%, 89%, 86%, respectively (P=0.001); the 10-year OS rates were 67%, 80%, 89%, and 86%, respectively (P=0.206) (Figure 1). Backward multivariate Cox regression analysis identified older age at TKI therapy, the presence of smoking history, higher severity of comorbidity by the Adult Comorbidity Evaluation-27, higher percentage of blasts in peripheral blood, and longer time to achieve CCyR as adverse prognostic factors for survival. With the minimum median follow-up of more than 10 years in all the TKI groups, the 10-year relative survival rate was 91.4%; among pts who achieved CCyR within 1 year of frontline TKI therapy, the 10-year relative survival rate was 94.4%; MMR, 97.0%; MR4, 96.7%; MR4.5, 96.2%. Conclusion: TKI therapy has significantly improved outcomes of pts with CML-CP. Frontline second-generation TKIs achieve higher rates of DMR response than standard-dose imatinib. The assessment of comorbidity is essential assessment for the optimal selection of frontline TKI therapy. The survival of pts with CML-CP is similar to that of general population at 10 years. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Prognostic Model of Transformation to Blast Phase in Patients with Chronic Myeloid Leukemia

Background: Since the advent of Tyrosine kinase inhibitor (TKI) therapy, the survival of patients with chronic myeloid leukemia (CML) is approaching to that of general population. The European LeukemiaNet recommends monitoring reverse transcriptase quantitative PCR for the guidance of molecular response. However, the rare incidence of progression to blast phase may occur during frontline TKI therapy. The aim of this study is to identify prognostic factors for the progression to blast phase during frontline TKI therapy and to develop a nomogram to calculate the risk of transformation at 1 year. Methods: We analyzed 347 patients with newly diagnosed CML in chronic phase (CP) and accelerated phase (AP) who were treated with frontline TKI therapy (standard-dose imatinib, 73 patients; dasatinib, 144 patients; and nilotinib, 130 patients) from July 2000 to September 2014. The presence of comorbidity was assessed by the Adult Comorbidity Evaluation-27. Given the rare incidence of transformation to blast phase and equivalent efficacy of second-generation TKIs between dasatinib and nilotinib, we compared the cumulative incidence of transformation to blast phase between imatinib 400 mg/day and second-generation TKI therapy. We performed univariate and multivariate competing risk regression to identify prognostic factors for cumulative incidence of transformation to blast phase with treatment failure (intolerance, resistance, and/or others) during frontline TKI therapy as a competing events. Multiple imputation was performed for missing variables to reduce bias. Nomogram was developed to estimate 1-year cumulative incidence of transformation to blast phase. Results: The median age at the start of TKI therapy was 49 years (range, 15.1-86.4) with a median follow-up of 146 months (range, 5.3-253.9) (standard-dose imatinib, 231 months; dasatinib 137 months; nilotinib 138 months) (Table 1). Overall, the incidence of transformation to blast phase was observed in 8 patients during frontline TKI therapy; 4 patients received imatinib; and 4 patients received second-generation TKIs (1 patient, dasatinib; 3 patients, nilotinib). Competing risk regression identified percentage of blasts in peripheral blood and bone marrow, and standard-dose imatinib therapy as prognostic factors for transformation to blast phase during frontline TKI therapy. The 1-year cumulative incidence of transformation rates were 4% and 1% in the imatinib and second-generation TKI groups, respectively; the 5-year cumulative incidence rates were 5% and 1%, respectively (P=0.043 by Gray's test). The nomogram was developed for the risk calculations for 1-year transformation to blast phase (Figure 1). Conclusion: The incidence of transformation to blast phase is rare in the era of TKI therapy. The nomogram helps physicians select optimal TKI therapy to prevent the transformation to blast phase. Given the dismal outcome of patients who progressed to blast phase, we propose frontline second-generation TKI therapy in patients with estimated 1-year cumulative incidence of transformation above 5% or higher. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

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.

Influence of Frailty and Life Expectancy on Guideline Adherence and Outcomes in Cutaneous Squamous Cell Carcinoma of the Head and Neck: A Prospective Pilot Study

Background: Cutaneous squamous cell carcinoma is the second most common malignancy of the skin, often occurring in older patients and in the head and neck area (cSCCHN). Age, life expectancy, and frailty are not taken into consideration by current guidelines. Objectives: The objective of this study was to evaluate the influence of frailty and life expectancy on guideline deviation, treatment outcomes, and quality of life (QoL) after treatment in patients with cSCCHN. Methods: Patients with cSCCHN were prospectively included. A geriatric assessment was performed, including the Geriatric 8 (G8), Groningen Frailty Indicator, and Timed Up and Go test (TUG). The Lee index was used to predict a limited life expectancy, and the Adult Comorbidity Evaluation-27 was used as a comorbidity index. QoL was assessed by the Basal and Squamous cell carcinoma Quality of Life (BaSQoL) questionnaire at three time points. Results: Seventy-seven patients with cSCCHN were included. Frail patients had significantly more high-risk tumours. Guideline deviation occurred in 7.8% and was more common in patients who were frail (G8), with high-risk tumours (≥T2), with a limited life expectancy or an increased TUG. Guideline deviation did not lead more often to progression of disease in our study. No predictors for post-operative complications were found. BaSQoL subscores were very low at each time point and did not change significantly with time in the total group. Frail patients reported more fear of recurrence or new tumours 3 months after treatment, and less concern about other people’s skin 6 months after treatment, compared to non-frail patients. Complication rate, gender, or guideline deviation did not affect any subscale scores. Conclusions: Assessment of frailty and life expectancy can guide physicians and patients in treatment decisions. Deviation from guidelines towards less aggressive treatment schedules can be considered in frail patients with a limited life expectancy, since it did not negatively affect short-term outcomes or QoL in patients with cSCCHN in our study. However, these results should be confirmed by other, larger prospective studies with a longer follow-up period.

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.

Long-term results of radio(chemo)therapy in metastatic carcinoma to cervical lymph nodes from an unknown primary. Adult Comorbidity Evaluation 27score as apredictor of survival.

To evaluate the effectiveness and toxicity of curative (chemo)radiotherapy in patients with metastatic carcinoma to cervical lymph nodes from an unknown primary. Retrospective study of 90consecutive patients, treated with curative radiotherapy from 2003 to 2018 (median age 59 years; current/former smokers 76%) was conducted. The distribution of nodal staging was as follows: N1: 12%, N2a: 21%, N2b: 43%, N2c: 10%, N3: 13%. In 62% of patients, neck dissection was performed before radiotherapy. Concomitant chemotherapy was given to 64% of patients. The median follow-up of surviving patients was 86months. The median total radiotherapy dose achieved was 70 Gy. The 5‑ and 10-year locoregional control were 84% in both cases, while 5‑ and 10-year distant control were 90% and 89%, respectively. Aprimary tumor in the head and neck area was detected in only 2patients. No patient had an initial failure in the pharyngeal axis or contralateral cervical nodes. The 5‑ and 10-year overall survival were 55% and 42%, respectively. Severe early toxicity occurred in 71%; severe late toxicity in 33% of patients. Multivariate analysis demonstrated N‑status (hazard ratio [HR] 2.424; 95% confidence interval [CI] 1.121-5.241; p = 0.024) and comorbidity scores assessed by ACE-27 (Adult Comorbidity Evaluation; HR 3.058; 95% CI 1.489-6.281; p = 0.002) as two independent prognostic factors for overall survival. The results of our work study demonstrate the high effectiveness of curative (chemo)radiotherapy on the pharyngeal axis and bilateral cervical nodes with long-term locoregional and distant control in 3/4 of the treated patients. N‑status and comorbidity scores were shown as strong prognostic factors influencing overall survival.

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.

Prognostic Value of Comorbidity for Patients with Upper Tract Urothelial Carcinoma after Radical Nephroureterectomy.

Simple SummaryUpper tract urothelial carcinoma (UTUC) is a rare malignancy that occurs mostly in elderly individuals with a high prevalence of comorbidities. However, the prognostic impact of comorbidities in these patients is not well evaluated. The aim of this retrospective study was to assess the significance of Adult Comorbidity Evaluation-27 (ACE-27) grade on the clinical outcomes of 409 patients with non-metastatic UTUC who underwent radical nephroureterectomy. We found that a high ACE-27 grade was an independent risk factor for UTUC progression, UTUC-specific death, and all-cause mortality in multivariate analyses. A prognostic model combining ACE-27 grade, tumor stage, and tumor grade showed good predictive performance and accuracy. Integrating the ACE-27 grade with standard pathological features can help physicians in clinical decision-making and risk stratification.Patients with upper tract urothelial carcinoma (UTUC) have a high prevalence of comorbidities. However, the prognostic impact of comorbidities in these patients is not well studied. We aimed to outline the comorbidity burden in UTUC patients and investigate its relationship with overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). We retrospectively reviewed the clinicopathological data of 409 non-metastatic UTUC patients who received radical nephroureterectomy between 2000 and 2015. The comorbidity burden was evaluated using the Adult Comorbidity Evaluation-27 (ACE-27). Kaplan-Meier survival analysis showed that high ACE-27 grade was significantly associated with worse PFS, CSS, and OS. In multivariate Cox regression and competing risk analyses, we found that ACE-27 grade, tumor stage, and tumor grade were independent prognosticators of OS, CSS, and PFS. We combined these three significant factors to construct a prognostic model for predicting clinical outcomes. A receiver operating characteristic curve revealed that our prognostic model had high predictive performance. The Harrel’s concordance indices of this model for predicting OS, CSS, and PFS were 0.81, 0.85, and 0.85, respectively. The results suggest that the UTUC patient comorbidity burden (ACE-27) provides information on the risk for meaningful clinical outcomes of OS, CSS, and PFS.