Multivariate Analysis Of Patients Research Articles

Protective ileostomy increased the incidence of rectal stenosis after anterior resection for rectal cancer

BackgroundIn most of the views, rectal stenosis after anterior resection for rectal cancer results from pelvic radiotherapy. However, patients without receiving radiotherapy also suffer stenosis. In this study, we evaluated the factors associated with rectal stenosis after anterior rectal resection (ARR).MethodsWe conducted a retrospective study with ARR patients who underwent neoadjuvant chemoradiotherapy and the patients without radiotherapy. Patients who received watch and wait strategy with a clinical complete response after chemoradiotherapy were also included. Patients with colonoscopy follow-up were included for further analyses; 439 patients who underwent neoadjuvant chemoradiotherapy; 545 patients who received ARR without radiotherapy and 33 patients who received watch and wait strategy. Stenosis was diagnosed when a 12-mm diameter colonoscopy could not be passed through the rectum. Univariate and multivariate logistic regression analyses were performed to identify variables associated with rectal stenosis.ResultsAccording to the multivariate analysis in patients receiving ARR, both protective stoma and preoperative radiotherapy affected the occurrence of stenosis, with the odds ratios (ORs) of 3.375 and 2.251, respectively. According to the multivariate analysis, a preventive ileostomy was the only factor associated with stenosis both in patients receiving preoperative radiotherapy and without radiotherapy. Non-reversal ileostomy and long time between ileostomy and restoration increased the possibility of stenosis. In 33 patients who received watch and wait strategy, only one patient (3%) experienced stenosis.ConclusionBoth surgery and radiotherapy are risk factors for rectal stenosis in rectal cancer patients. Compared to preoperative radiotherapy, a protective ileostomy is a more critical factor associated with rectal stenosis.

Clinico-bacterial and prognostic factors in patients with suspected blood stream infection and elevated serum procalcitonin levels.

ABSTRACTThis study determined prognostic factors by comparing clinico-bacterial factors based on significant elevated serum procalcitonin levels in patients with suspected bloodstream infection (BSI). We retrospectively analyzed the medical records of 1,052 patients (age ≥16 years) with fever (temperature ≥38°C) and serum procalcitonin levels of ≥2.0 ng/mL, and blood culture results. The optimal cutoff value of the significant elevation of procalcitonin was determined using the minimum P-value approach. Clinico-bacterial factors were analyzed per the procalcitonin levels, and significant independent factors for short-term survival were investigated in 445 patients with BSI. Patients with suspected BSI were aged, on average, 72.3 ± 15.1 years, and the incidence of positive blood culture was 42.3%; and the 14-day survival was 83.4%. Procalcitonin ≥100 ng/mL was the most significant predictor for survival. Multivariate analysis in patients with suspected BSI showed that estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 and procalcitonin ≥100 ng/mL were significant independent unfavorable prognostic factors. Microorganisms were similar between patients with procalcitonin level 2–99 ng/mL (n=359) and those with ≥100 ng/mL (n=86). Multivariate analysis in patients with BSI showed that eGFR <30 mL/min/1.73 m2, procalcitonin ≥100 ng/mL, and primary infectious foci were significant independent prognostic factors. Patients with foci in the gastrointestinal tract and respiratory system had unfavorable 14-day survival. In conclusions, eGFR <30 mL/min/1.73 m2 and procalcitonin ≥100 ng/mL were significant independent unfavorable prognostic factors for suspected BSI. Primary infectious foci (gastrointestinal tract and respiratory system) were associated with unfavorable short-term survival in patients with positive blood culture.

PN0(i+) and pN1mi Breast Cancer: Treatment and Outcomes in Comparison With pN0 and pN1a in the Modern Era

Locoregional recurrence risk and the role of locoregional radiation therapy (LRRT) in pN0(i+) and pN1mi breast cancer are unclear. This study compares locoregional relapse-free survival (LRRFS) in patients with pN0(i+) and pN1mi relative to pN0 and pN1a disease and evaluates LRRFS according to locoregional treatment. We studied 10,271 patients referred between 2006 and 2011 with newly diagnosed pT1-T2, pN0, pN0(i+), pN1mi, or pN1a, M0 breast cancer. Outcomes were 10-year Kaplan-Meier LRRFS, relapse-free survival (RFS), distant relapse-free survival, and breast cancer-specific survival. Multivariable analysis of LRRFS and RFS was performed in pN0(i+) and pN1mi cohorts. Median follow-up was 9.3 years. In patients with pN0 (n = 7492), pN0(i+) (n = 305), pN1mi (n = 619), and pN1a (n = 1855) disease, LRRT was used in 1.1%, 24.3%, 45.7%, and 71.1%, respectively. Ten-year outcomes were LRRFS 96%, 92%, 97%, and 96% (P < .001), distant RFS 94%, 91%, 90%, and 84% (P < .001), and breast cancer-specific survival 95%, 90%, 93%, and 87% (P < .001), respectively. Ten-year LRRFS for patients treated with breast-conserving surgery alone, with breast RT, and with LRRT were 81%, 93%, and 91% for patients with pN0(i+) (P = .16) and 94%, 96%, and 100% for patients with pN1mi (P = .02), respectively. Among patients treated with mastectomy, 10-year LRRFS with surgery alone and with LRRT were 93% and 100% for patients with pN0(i+) (P = .12) and 95% and 99% for patients with pN1mi (P = .09). On multivariable analysis of patients with pN0(i+) and pN1mi, systemic therapy was associated with improved LRRFS in patients with pN0(i+) (hazard ratio [HR], 0.2; [0.06-0.6]; P = .005) and patients with pN1mi (HR, 0.1; [0.03-0.5]; P = .006). In patients with pN1mi, LRRT was associated with a trend toward increased LRRFS (HR, 0.2; [0.03-1.1]; P = .07). LRRT was not significantly associated with improved RFS in pN0(i+) or pN1mi disease. In the era of sentinel node staging and modern systemic therapy, patients with pN0(i+) and PN1mi treated with LRRT experienced 10-year LRR risks ≤10% after breast-conserving surgery or mastectomy and RT. LRRT was associated with a trend toward increased LRRFS in pN1mi but not pN0(i+) disease.

Association between clinical outcomes and local treatment in stage IV non-small cell lung cancer patients with single extrathoracic metastasis.

BackgroundLocal treatment (LT) such as radiotherapy and metastasectomy on metastatic sites may improve outcomes in oligometastatic NSCLC patients, but more data are necessary to support LT in oligometastatic diseases. Patients with single extrathoracic metastatic lesion are more likely to benefit from local therapy. In this study, we evaluated the impact of LT in NSCLC patients with a single extrathoracic metastatic lesion.MethodsData were obtained from the Korean Association for Lung Cancer Registry (KALC‐R), a database created using a retrospective sampling survey by the Korean Central Cancer Registry (KCCR) and the Lung Cancer Registration Committee.ResultsA total of 787 NSCLC patients with a single extrathoracic metastatic lesion were evaluated. In the multivariate analysis for OS, age, female sex, poor performance score, squamous histological subtype, LT, and initial treatment modality showed significant associations. Regarding LT, groups that underwent curative LT were significantly associated with better OS compared to groups that did not undergo LT (p = 0.011, HR 0.448, 95% CI: 0.242–0.829). In the multivariate analysis of patients who underwent LT, poor performance score, initial treatment modality, and T stage were independently associated with poor OS. Compared to the T1 stage, T3 stage showed an HR of 2.470 (95% CI: 1.309–4.663; p = 0.005) and T4 stage showed an HR of 2.063 (95% CI: 1.093–3.904; p = 0.026).ConclusionIn NSCLC with a single extrathoracic metastatic lesion, LT, especially for curative purposes, has an independent association with OS. Moreover, among the patients who received LT, factors such as T stage, poor performance score, and initial treatment modality were significantly associated with OS.

Survival and Prognostic Factors in Patients with Aggressive Cutaneous T-cell Lymphomas.

Aggressive primary cutaneous T-cell lymphomas include advanced-stage mycosis fungoides (stage ≥ IIB mycosis fungoides), Sézary syndrome, gamma/delta cutaneous lymphoma, nasal type lymphoma, aggressive epidermotropic CD8+ T-cell lymphoma and some cutaneous lymphomas not otherwise specified. To evaluate their long-term prognosis, we conducted a retrospective cohort study of 85 patients diagnosed between 2005 and 2020 with advanced-stage mycosis fungoides (n = 48), Sézary syndrome (n = 28) or aggressive non-mycosis fungoides/Sézary syndrome subtypes (n = 9). The median survival times in these 3 groups were 118.7, 45.7 and 11.2 months, respectively, and the 5-year survival rates were 55.3%, 27.8% and 33.3%, respectively. Multivariate analyses in patients with mycosis fungoides/Sézary syndrome identified age ≥ 70 years, Eastern Cooperative Oncology Group Performance Status ≥ 2, and the high-risk group according to the Cutaneous Lymphoma International Consortium prognostic model, as adverse prognostic factors. Seven patients in this mycosis fungoides/Sézary syndrome group were in complete long-term remission after treatment with bexarotene, including 4 patients living without any treatment for 16–101 months.

Proposal for a New Pathologic Prognostic Index After Neoadjuvant Chemotherapy in Pancreatic Ductal Adenocarcinoma (PINC).

BackgroundLimited information is available on the relevant prognostic variables after surgery for patients with pancreatic ductal adenocarcinoma (PDAC) subjected to neoadjuvant chemotherapy (NACT). NACT is known to induce a spectrum of histological changes in PDAC. Different grading regression systems are currently available; unfortunately, they lack precision and accuracy. We aimed to identify a new quantitative prognostic index based on tumor morphology.Patients and MethodsThe study population was composed of 69 patients with resectable or borderline resectable PDAC treated with preoperative NACT (neoadjuvant group) and 36 patients submitted to upfront surgery (upfront-surgery group). A comprehensive histological assessment on hematoxylin and eosin (H&E) stained sections evaluated 20 morphological parameters. The association between patient survival and morphological variables was evaluated to generate a prognostic index.ResultsThe distribution of morphological parameters evaluated was significantly different between upfront-surgery and neoadjuvant groups, demonstrating the effect of NACT on tumor morphology. On multivariate analysis for patients that received NACT, the predictors of shorter overall survival (OS) and disease-free survival (DFS) were perineural invasion and lymph node ratio. Conversely, high stroma to neoplasia ratio predicted longer OS and DFS. These variables were combined to generate a semiquantitative prognostic index based on both OS and DFS, which significantly distinguished patients with poor outcomes from those with a good outcome. Bootstrap analysis confirmed the reproducibility of the model.ConclusionsThe pathologic prognostic index proposed is mostly quantitative in nature, easy to use, and may represent a reliable tumor regression grading system to predict patient outcomes after NACT followed by surgery for PDAC.Supplementary InformationThe online version contains supplementary material available at 10.1245/s10434-022-11413-7.

Surgical and anatomic factors predict development of leptomeningeal disease in patients with melanoma brain metastases.

Leptomeningeal disease (LMD) is a devastating complication of systemic malignancy, of which there is an unclear etiology. The aim of this study is to determine if surgical or anatomic factors can predict LMD in patients with metastatic melanoma. A retrospective chart review was performed of 1162 patients treated at single institution for melanoma brain metastases (MBM). Patients with fewer than 3 months follow-up or lacking appropriate imaging were excluded. Demographic information, surgical, and anatomic data were collected. Eight hundred and twenty-seven patients were included in the final review. On multivariate analysis for the entire cohort, female gender, dural-based and intraventricular metastasis, and tumor bordering CSF spaces were associated with increased risk of LMD. Surgical resection was not significant for risk of LMD. On multivariate analysis of patients who have undergone surgical resection of a metastatic tumor, dural-based and intraventricular metastasis, ventricular entry during surgery, and metastasis in the infratentorial space were associated with increased risk of LMD. On multivariate analysis of patients who did not undergo surgery, chemotherapy after initial diagnosis and metastasis bordering CSF spaces were associated with increased risk of LMD. In a single-institution cohort of MBM, we found that surgical resection alone did not result in an increased risk of LMD. Anatomical factors such as dural-based and intraventricular metastasis were significant for developing LMD, as well as entry into a CSF space during surgical resection. These data suggest a strong correlation between anatomic location and tumor cell seeding in relation to the development of LMD.

Survival and Prognostic Factors in Patients with Aggressive Cutaneous T-cell Lymphomas.

Aggressive primary cutaneous T-cell lymphomas include advanced-stage mycosis fungoides (stage ≥ IIB mycosis fungoides), Sézary syndrome, gamma/delta cutaneous lymphoma, nasal type lymphoma, aggressive epidermotropic CD8+ T-cell lymphoma and some cutaneous lymphomas not otherwise specified. To evaluate their long-term prognosis, we conducted a retrospective cohort study of 85 patients diagnosed between 2005 and 2020 with advanced-stage mycosis fungoides (n = 48), Sézary syndrome (n = 28) or aggressive non-mycosis fungoides/Sézary syndrome subtypes (n = 9). The median survival times in these 3 groups were 118.7, 45.7 and 11.2 months, respectively, and the 5-year survival rates were 55.3%, 27.8% and 33.3%, respectively. Multivariate analyses in patients with mycosis fungoides/Sézary syndrome identified age ≥ 70 years, Eastern Cooperative Oncology Group Performance Status ≥ 2, and the high-risk group according to the Cutaneous Lymphoma International Consortium prognostic model, as adverse prognostic factors. Seven patients in this mycosis fungoides/Sézary syndrome group were in complete long-term remission after treatment with bexarotene, including 4 patients living without any treatment for 16-101 months.

Oral findings as predictors of obstructive sleep apnea- A case-control study.

To evaluate the role of dental parameters that may contribute to increasing apneic activity in patients with or without obstructive sleep apnea (OSA). The study comprises a total of 120 patients (60 diagnosed with sleep apnea visiting a sleep center at Delhi and 60 controls). Patients were assessed based on body mass index, age, neck circumference, and gender (BANG), which were recorded for both the patients and controls. Oral and general examination was carried out using predetermined criteria for Angle's class of malocclusion, maxillary arch constriction, facial profile, Mallampati score for uvula, tongue size, depth of palatal vault, mouth breathing, and periodontitis. Among 120 study subjects, 92 were males and 28 females, with a mean age of 49.08 + 13.13 years in the study group and 45.28 + 14.78 years in the control group. All the variables except Angle's class of malocclusion, periodontitis, mouth breathing, and hypertension showed significant differences in the study group. Multivariate analysis for patients with OSA revealed that obese patients were almost 1.5 times more possibly to report OSA symptoms than their non-obese counterparts. It was also found that patients with OSA were 4.12 times more likely to have neck circumference >40 cm, 2.25 times more likely to have maxillary arch constriction, 1.43 times deeper palatal vault, 8.7 times macroglossia, and 1.7 times class III & IV Mallampati score for uvula. The oral structural findings appear to be more closely related with OSA.

Estilo de vida asociado al control de hipertensión arterial y diabetes mellitus en un centro de atención en Lima, durante la pandemia de COVID-19

Introduction: Hypertension and diabetes mellitus 2 are prevalent diseases. The COVID-19 pandemic has changed lifestyle and disease control, potentially triggering serious complications. Objectives: To determine the association between lifestyle and the control of chronic non-communicable diseases: arterial hypertension and diabetes mellitus 2 during the COVID-19 pandemic in patients of an Urgent Care Center. Materials and methods: Observational, cross-sectional, and analytical study. A sample of 158 patients, between 30 and 79 years old, was included. Control files and medical records were analyzed, anthropometric values ​​were measured, and lifestyle was evaluated through surveys. Results: 51.3% were male, an average of 61 years, 57.6% with married marital status, and 51.9% with higher educational level. In the multivariate analysis of patients with arterial hypertension, a significant association between the lack of control of the hypertensive disease and an unhealthy lifestyle is evidenced (PR = 2.538; p = 0.000; 95% CI = 1.608-4.006). On the other hand, the diabetic population obtained a significant association between the lack of control of type 2 diabetes mellitus with an unhealthy lifestyle (PR = 5.498; p = 0.013; 95% CI = 1.440-20.995), in addition to the prevalence of glycemic lack of control in patients with abnormal abdominal girth it was 1.6 times more than in people with normal abdominal girth (PR = 2.623; p = 0.038; 95% CI = 1.057-6.508). Conclusions: Lifestyle is significantly associated with the control of arterial hypertension and diabetes mellitus. There is a significant association between abdominal circumference and control of type 2 diabetes mellitus.

Discordance Between Histopathologic Grading and Dual-Tracer PET/CT Findings in Metastatic NETs and Outcome of 177Lu-DOTATATE PRRT: Does InVivo Molecular PET Perform Better from the Viewpoint of Prediction of Tumor Biology?

Discordance between histopathologic grading and dual-tracer PET/CT (68Ga-DOTATATE and 18F-FDG) findings in neuroendocrine tumors (NETs), though not typical, can be encountered in real-world scenarios. The aim of this study was to assess patients with discordance between World Health Organization (WHO) 2017 grade-predicted molecular PET/CT imaging and the actual dual-tracer PET/CT findings (by exploring their histopathologic, immunohistochemical, and molecular imaging characteristics), with a view toward identifying the prognostic determinants affecting outcome in a peptide receptor radionuclide therapy setup. Methods: Thirty-six patients with histopathologically proven inoperable, locally advanced or metastatic NETs, referred for peptide receptor radionuclide therapy, were included in this study. The cohort was divided into 2 broad population groups: those with discordance (between WHO 2017 grade-predicted molecular imaging and the dual-tracer PET/CT findings) and control (showing both 18F-FDG and 68Ga-DOTATATE uptake). The cohort was divided on the basis of dual-tracer PET/CT into 3 groups: metabolically inactive (non-18F-FDG-avid) and somatostatin receptor (SSTR)-expressing tumors, metabolically active (18F-FDG-avid) and non-68Ga-DOTATATE-concentrating (non-SSTR-expressing) tumors, and matched imaging characteristics with the WHO 2017 grading system (showing both 18F-FDG- and 68Ga-DOTATATE-concentrating disease) for statistical analysis. Descriptive statistics were used to analyze categoric data; multivariate analysis was used to assess the correlation between different variables with progression-free survival (PFS) and overall survival (OS). Kaplan-Meier curves were used for survival analysis to calculate median survival and to analyze survival on the basis of WHO 2017 grading and dual-tracer PET. Cox proportional hazards regression analysis was used to determine predictors of survival (OS and PFS). Results: Of the 36-patient cohort, 24 (66.7%) showed discordance and 12 (33.3%) were in the control group. Among those showing discordance: 14 (38.9%) had metabolically inactive and SSTR-expressing disease and the remaining 10 (27.8%) had 18F-FDG-concentrating and non-SSTR-expressing disease. Among those in the control group, 12 (33.3%) had intermediate-grade NETs and showed matched (68Ga-DOTATATE- and 18F-FDG-concentrating lesions) disease. Multivariate analysis in patients with discordant findings showed a significant correlation of dual-tracer PET with OS, whereas no significant correlation could be established between WHO grade and OS in the discordant subgroups. No significant correlation could be appreciated between PFS and either dual-tracer PET or WHO grading. The Kaplan-Meier analysis and Cox analysis showed dual-tracer PET/CT imaging to be a significant prognostic determinant and predictor of outcome, respectively. Conclusion: In NET patients with discordance between the 2 parameters, dual-tracer PET/CT with 18F-FDG and 68Ga-DOTATATE performed better than WHO grading, differentiation status, and immunohistochemistry in prognosticating and predicting outcome.

Risk Factors Leading to Radical Cystectomy in Patients Who Had Undergone Nephroureterectomy

Purpose: To identify the risk factors leading to radical cystectomy in patients who had undergone nephroureterectomy (NUx).Materials and Methods: We retrospectively reviewed the medical records of patients with upper tract urothelial carcinoma who underwent NUx during 2011–2019 and excluded patients with metastatic cancer. In total 646 patients were included in this study; of these, 532 had no previous bladder cancer history. Follow-up was performed every 3 months for 2 years after NUx was administered, and recurrence was confirmed using cystoscopy, urine cytology, computed tomography, and chest radiography. Bladder recurrence was confirmed through biopsy, urine cytology, or radiologic examination. Univariate and multivariate Cox regression analyzes were performed for statistical analysis of risk factors leading to radical cystectomy in patients undergoing NUx.Results: Lymphovascular invasion (LVI) (hazard ratio [HR], 4.728; 95% confidence interval [CI], 1.463–15.570; p=0.011), previous transurethral resection of bladder tumor history (HR, 3.825; 95% CI, 1.164–12.571; p=0.027), and intravesical recurrence (IVR) within 6 months (HR, 3.733; 95% CI, 1.091–12.778; p=0.036) in patients undergoing NUx are predictors of radical cystectomy implementation. In a multivariate analysis of patients without bladder cancer history, bladder recurrence was identified as a predictor of radical cystectomy implementation, if it occurred within 6 months of NUx (HR, 8.608; 95% CI, 1.545–47.976; p=0.014).Conclusions: LVI and IVR within 6 months and previous bladder cancer history are factors that can predict the need for radical cystectomy after NUx. Even in patients without bladder cancer history, early bladder recurrence within 6 months is a major predictor of radical cystectomy.

Obstructive Sleep Apnoea in Stanford Type B Aortic Dissection Is Associated With Multiple Imaging Signs Related to Late Aortic Events.

Background: Obstructive sleep apnoea (OSA) is highly prevalent in patients with Stanford type B aortic dissection (TBAD). Few studies have evaluated the effects of OSA on vascular changes in TBAD patients. This study aimed to explore the effect of OSA on aortic morphological changes in TBAD patients and its relation to late aortic events (LAEs).Methods: This case-control study included 143 TBAD patients. The diameters of different parts of the aorta were measured based on computed tomography angiography (CTA). According to the apnoea-hypopnoea index (AHI), OSA was classified as mild (5 ≤ AHI ≤ 15), moderate (15 < AHI ≤ 30), or severe (AHI > 30). The false lumen (FL) status was evaluated and classified as partially thrombosed, patent, or completely thrombosed.Results: The OSA prevalence in TBAD patients was 64.3%, and image differences related to LAEs between TBAD patients with and without OSA included the maximum aortic diameter at onset (37.3 ± 3.9 vs. 40.3 ± 4.5 mm, p < 0.001), the FL diameter of the proximal descending thoracic aorta (16.0 ± 6.8 vs. 20.3 ± 4.7 mm, p < 0.001), and the proportion of the FL that was partially thrombosed (39.2 vs. 64.1%, p = 0.004). Additionally, in the multivariable analysis of patients with OSA, the risks of an aortic diameter ≥40 mm, a proximal descending aorta FL ≥ 22 mm and a partially thrombosed FL were 4.611 (95% CI: 1.796–11.838, p = 0.001), 2.544 (95% CI: 1.050–6.165, p = 0.039), and 2.565 (95% CI: 1.167–5.637, p = 0.019), respectively, after adjustment for confounding factors. Trend tests showed that the risks of an aortic diameter ≥40 mm and a partially thrombosed FL increased with increasing OSA severity.Conclusions: TBAD patients with moderate to severe OSA have aortic dilatation in different parts of the aorta. OSA is an independent risk factor for multiple imaging signs related to LAEs, suggesting that OSA is an important factor affecting the prognosis of TBAD patients.

Effectiveness of Postoperative or Preoperative Radiotherapy on Prognosis in Patients with Stage II Resectable Non-Small Cell Lung Cancer: A Retrospective Study Based on the SEER Database.

Background and Objectives: The research on the therapeutic effect of preoperative radiotherapy (PRRT) for patients with early non-small cell lung cancer (NSCLC) is still insufficient, and the impact of postoperative radiotherapy (PORT) on the prognosis of patients with early NSCLC remains controversial. We conducted this study to investigate the effect of PORT and PRRT on prognosis for these patients. Materials and Methods: In total, 3640 patients with stage II NSCLC who underwent a lobectomy or pneumonectomy were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate regression was adopted to identify the independent influence of PORT or PRRT on patients’ prognosis. Subgroup analysis of survival was performed in patients with different combinations of key clinical features. We also used Kaplan-Meier analysis and competitive risk analysis to explore to which extent PORT or PRRT impacted the overall survival and cumulative mortality. Results: PORT was an independent risk factor of NSCLC-specific death among patients with N0 stage (HR, 1.648; 95% CI, 1.309–2.075, p < 0.001) and in N1 stage with <3 positive lymph nodes (HR, 2.698; 95% CI, 1.910–3.812, p < 0.001) in multivariate analysis. Findings from subgroup analysis for the risk of NSCLC-specific death, competitive risk analysis of NSCLC-specific cumulative mortality, and overall survival analysis also demonstrated PORT was detrimental to patients in these two subgroups above (p < 0.05). However, in patients with N1 stage with ≥3 positive lymph nodes, PORT may help prolong median survival. PRRT was an independent risk factor for NSCLC-specific death in multivariate analysis of patients with N0 stage (HR, 1.790; 95% CI, 1.201–2.668, p = 0.004), and significantly decreased overall survival in these patients (p < 0.001). Conclusion: PORT is associated with worse survival outcome and better cumulative mortality of stage II patients of NSCLC with N0 disease or N1 disease (<3 nodes), while PRRT is associated with reduced prognosis in patients with N0 stage. On the other hand, PORT may help to improve the prognosis of patients with N1 stage who have three or more lymph node metastases. Hence, PORT and PRRT should not be recommended for patients with N0 stage. However, in patients with “high volume” N1 stage, PORT might improve oncological outcomes.

Role of Adjuvant Radiation in pN2 Non-Small Cell Lung Cancer (NSCLC) Patients

Past studies have shown mixed results of postoperative radiation (PORT) for pN2 NSCLC patients and the recent LungART trial has shown no disease free survival or overall survival (OS) benefits with PORT for pN2 NSCLC patients. High lymph node ratio (LNR = number of positive lymph nodes in the resected specimen/number of total lymph nodes resected) has been shown to correlate with worse outcomes. We hypothesize that PORT can improve survival outcomes in pN2 NSCLC patients with high LNR.The National Cancer Database was queried for cases of NSCLC from 2004-2016. Patients without neoadjuvant treatment, with at least a lobectomy with resection of at least 10 lymph nodes, with pN2 disease, with histology of squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma and large cell carcinoma were included. Exclusion criteria were neoadjuvant therapy, lack of pathological confirmation or lack of information about chemotherapy and metastatic disease. For patients with PORT, RT was directed to thorax with dose≥30Gy. Log-rank test and Cox proportional hazards models were used to compare survival adjusted for age, sex, CCI, pT, grade, chemotherapy, LNR, and PORT. Predictors for overall survival (OS) were identified.Among 10272 patients, 6266 (61%) did not have PORT, and 4006 (39%) had PORT. Median follow up was over 5 years. PORT was given to 51.3% and 37.7% patients with non-R0 and R0 resection, respectively (P < 0.001). PORT was given to 48.4% and 9.91% of patients with and without adjuvant chemotherapy, respectively (P < 0.001). The average LNR for patients with and without PORT were 0.33 and 0.29 (P < 0.001), respectively. In multivariate analysis (MVA) of patients with R0 resection, predictors of OS were listed in Table 1. PORT was not associated with better OS (HR, 1.04, P = 0.63) for patients with LNR of 1-15%. However, PORT was associated with better survival in patients with higher LNRs (HR, 0.90, P = 0.23 for LNR of 15-29% and HR, 0.82, P = 0.01 for LNR ≥ 30%). In MVA of patients with non-R0 resection, PORT was associated with better survival (HR, 0.56, P = 0.01).High LNR after R0 surgery in pN2 NSCLC patients portends worse survival. PORT is associated with better survival for pN2 NSCLC patients after R0 resection with high LNR after accounting for multiple confounders including adjuvant chemotherapy. PORT is also associated with better survival in pN2 NSCLC patients after R1 or R2 surgery.

Role of Adjuvant Radiation in pN1 Non-Small Cell Lung Cancer (NSCLC) Patients

Previous studies have shown a detrimental effect of postoperative radiation (PORT) in pN1 NSCLC patients after R0 surgery. High lymph node ratio (LNR = number of positive lymph nodes in the resected specimen/number of total lymph nodes resected) has been shown to correlate with worse outcomes. We hypothesize that PORT can improve survival outcomes in pN1 NSCLC patients with high LNR after R0 surgery.The National Cancer Database was queried for cases of lung cancer from 2004-2016. Patients without neoadjuvant treatment, with at least a lobectomy with resection of at least 10 lymph nodes, with pN1 disease, with histology of squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma and large cell carcinoma were included. Exclusion criteria were neoadjuvant therapy, lack of pathological confirmation or lack of information about chemotherapy and metastatic disease. For patients with PORT, RT was directed to thorax with dose≥30Gy. Log-rank test and Cox proportional hazards models were used to compare survival adjusted for age, sex, CCI, pT, grade, chemotherapy, LNR, and PORT. Predictors for overall survival (OS) were identified.Among 13742 patients, 12542 (91.3%) did not have PORT, and 1200 (8.7%) had PORT. Median follow up was over 5 years. For years of 2004-2010 and 2011-2016, PORT was given to 8% (413 out of 5132) and 5.5% (423 out of 7622) of patients after R0 resection, respectively. PORT was given to 36.8% and 6.55% patients with non-R0 and R0 resection, respectively (P < 0.001). PORT was given to 11.6% and 3.37% of patients with and without adjuvant chemotherapy, respectively (P < 0.001). The average LNR for patients with and without PORT were 0.2 and 0.14 (P < 0.001), respectively. In multivariate analysis (MVA) of patients with R0 resection, predictors of OS were listed in Table 1. In patients with intermediate LNR (15-29%), PORT was marginally correlated with better OS (HR, 0.80, P = 0.07). In patients with high LNR (≥30%), PORT was correlated with better OS (HR, 0.80, P = 0.047). In MVA of patients with non-R0 resection, high LNR was associated with worse OS (HR, 1.35 and 1.66 for LNR of 15-29% and ≥30%, respectively). In patients with intermediate (15-29%) and high (≥30%) LNR, PORT was numerically correlated with better OS (HR, 0.89 and 0.77 respectively, P non-significant).For pN1 NSCLC patients after R0 resection, use of PORT is decreasing. High LNR after R0 surgery in pN1 NSCLC patients portends worse survival. PORT does not benefit pN1 NSCLC patients with low LNR after R0 surgery, but it is associated with better survival for patients with high LNR after accounting for multiple confounders including adjuvant chemotherapy.

Retrospective analysis of Schlafen11 (SLFN11) to predict the outcomes to therapies affecting the DNA damage response

BackgroundThe absence of the putative DNA/RNA helicase Schlafen11 (SLFN11) is thought to cause resistance to DNA-damaging agents (DDAs) and PARP inhibitors.MethodsWe developed and validated a clinically applicable SLFN11 immunohistochemistry assay and retrospectively correlated SLFN11 tumour levels to patient outcome to the standard of care therapies and olaparib maintenance.ResultsHigh SLFN11 associated with improved prognosis to the first-line treatment with DDAs platinum-plus-etoposide in SCLC patients, but was not strongly linked to paclitaxel–platinum response in ovarian cancer patients. Multivariate analysis of patients with relapsed platinum-sensitive ovarian cancer from the randomised, placebo-controlled Phase II olaparib maintenance Study19 showed SLFN11 tumour levels associated with sensitivity to olaparib. Study19 patients with high SLFN11 had a lower progression-free survival (PFS) hazard ratio compared to patients with low SLFN11, although both groups had the benefit of olaparib over placebo. Whilst caveated by small sample size, this trend was maintained for PFS, but not overall survival, when adjusting for BRCA status across the olaparib and placebo treatment groups, a key driver of PARP inhibitor sensitivity.ConclusionWe provide clinical evidence supporting the role of SLFN11 as a DDA therapy selection biomarker in SCLC and highlight the need for further clinical investigation into SLFN11 as a PARP inhibitor predictive biomarker.

The Influence of Adjuvant Chemotherapy Dose Intensity on Five-Year Outcomes in Resected Colon Cancer: A Single Centre Retrospective Analysis.

There is evidence that achieving a dose intensity > 80% in adjuvant colon cancer treatment improves survival. In total, 192 consecutive patients with resected stage III and high-risk stage II colon cancer that received adjuvant chemotherapy were retrospectively analyzed. Patients who received at least 6 weeks of adjuvant therapy were included. The primary objective was to assess the influence of dose index (DI) and relative dose intensity (RDI) on DFS and OS at 3 and 5 years in patients receiving fluorouracil-based doublet therapy with oxaliplatin (FOLFOX) (5-FU and oxaliplatin assessed separately), or capecitabine monotherapy. In the capecitabine group, DFS rates for 3 and 5 years were 66.7% and 57.6%, respectively, while OS rates were 80.3% and 66.7%, respectively. Those who received FOLFOX had DFS rates of 76.9% and 71.2% at 3 and 5 years, respectively. OS rates were 86.4% and 76.7% at 3 and 5 years, respectively. Median RDI was 73.8% for capecitabine and 76.3% and 85.6% for the oxaliplatin and 5-FU components respectively. Based on a multivariate analysis in patients receiving FOLFOX, those with an oxaliplatin DI > 80% had improvements in DFS and OS compared to those with an oxaliplatin DI of ≤80%. Otherwise, there was no significant difference in DFS or OS when comparing patients who achieved an RDI or a DI of above versus below 80% in the patients receiving adjuvant chemotherapy for resected colon cancer.

Effect of Dihydropyridine Calcium Channel Blocker on Mortality of Hypertension Patients With Moderate-Severe Pulmonary Acute Respiratory Distress Syndrome: A Multicenter Retrospective Observational Cohort Study.

A retrospective, observational, multicenter cohort study. A total of 307 patients without propensity score matching and 186 adult inpatients with propensity score matching diagnosed with hypertension and moderate-severe pulmonary acute respiratory distress syndrome in five teaching hospitals in Jiangsu province, China, from December 2015 to December 2020 were enrolled. A total of 307 patients without propensity score matching and 186 patients with propensity score matching diagnosed with hypertension and moderate-severe pulmonary acute respiratory distress syndrome were included in the final analysis. None. Demographic characteristics and clinical characteristics were recorded. The propensity score matching method was used to eliminate the difference between group with dihydropyridine calcium channel blocker and group without dihydropyridine calcium channel blocker. The primary outcome was in-hospital mortality. We used univariate and multivariate regression analyses for both patients with or without propensity score matching to assess the effect of these variables on mortality. In the subset of 186 patients with propensity score matching, in-hospital mortality was 53.2%. Inpatient mortality was significantly higher in patients treated with dihydropyridine calcium channel blocker than in those not treated with dihydropyridine calcium channel blocker of patients without propensity score matching (65.4% vs 40.4%; p < 0.01). Multivariate analysis for patients without propensity score matching showed that dihydropyridine calcium channel blocker (hazard ratio, 1.954; 95% CI, 1.415-2.699), lactate dehydrogenase greater than or equal to 600 U/L (hazard ratio, 3.809; 95% CI, 2.106-4.531), and lactate greater than or equal to 2 mmol/L (hazard ratio, 1.454; 95% CI, 1.041-2.029) were independently associated with in-hospital mortality. Based on univariate analysis for patients with propensity score matching, dihydropyridine calcium channel blocker (hazard ratio, 2.021; 95% CI, 1.333-3.064), lactate dehydrogenase greater than or equal to 600 U/L (hazard ratio, 4.379; 95% CI, 2.642-7.257), and lactate greater than or equal to 2 mmol/L (hazard ratio, 2.461; 95% CI, 1.534-3.951) were independently associated with in-hospital mortality. In contrast, patients not treated with dihydropyridine calcium channel blocker had a significant survival advantage over those treated with dihydropyridine calcium channel blocker in both patients without or with propensity score matching (p < 0.001; p = 0.001 by Kaplan-Meier analysis). Dihydropyridine calcium channel blocker, lactate dehydrogenase greater than or equal to 600 U/L, and lactate greater than or equal to 2 mmol/L at admission were independent risk factors for patients with hypertension and moderate-severe pulmonary acute respiratory distress syndrome.

Decrease in the cortex/striatum metabolic ratio on [18F]-FDG PET: a biomarker of autoimmune encephalitis.

The aim of this [18F]-FDG PET study was to determine the diagnostic value of the cortex/striatum metabolic ratio in a large cohort of patients suffering from autoimmune encephalitis (AE) and to search for correlations with the course of the disease. We retrospectively collected clinical and paraclinical data of patients with AE, including brain 18F-FDG PET/CT. Whole-brain statistical analysis was performed using SPM8 software after activity parametrization to the striatum in comparison to healthy subjects. The discriminative performance of this metabolic ratio was evaluated in patients with AE using receiver operating characteristic curves against 44 healthy subjects and a control group of 688 patients with MCI. Relationship between cortex/striatum metabolic ratios and clinical/paraclinical data was assessed using univariate and multivariate analysisin patients with AE. Fifty-six patients with AE were included. In comparison to healthy subjects, voxel-based statistical analysis identified one large cluster (p-cluster < 0.05, FWE corrected) of widespread decreased cortex/striatum ratio in patients with AE. The mean metabolic ratio was significantly lower for AE patients (1.16 ± 0.13) than that for healthy subjects (1.39 ± 0.08; p < 0.001) and than that for MCI patients (1.32 ± 0.11; p < 0.001). A ratio threshold of 1.23 allowed to detect AE patients with a sensitivity of 71% and a specificity of 82% against MCI patients, and 98% against healthy subjects. A lower cortex/striatum metabolic ratio had a trend towards shorter delay before 18F-FDG PET/CT (p = 0.07) in multivariate analysis. The decrease in the cortex/striatal metabolic ratio has a good early diagnostic performance for the differentiation of AE patients from controls.