Therapeutic effect of cranial radiotherapy with or without anlotinib treatment for lung cancer patients with brain metastasis and non-EGFR/ALK-TKIs indication

2020 ◽  
Author(s):  
Zelai He ◽  
Jia Liu ◽  
Hongwei Li ◽  
Jing Qian ◽  
Zhen Cui ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Prognostic Factors ◽  
Brain Metastasis ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Small Cell ◽  
Cox Proportional Hazards Model ◽  
Cranial Radiotherapy ◽  
Hazards Model

Abstract Background: Cranial radiotherapy (CRT) is the main treatment for lung malignant tumor with brain metastasis (BM) and lacking EGFR/ALK-TKIs indication. For non-small cell lung cancer with BM, anlotinib can improve progression free survival (PFS). We retrospectively analyzed the clinical effects of anlotinib + CRT versus CRT alone.Methods: In patients with lung cancer (adenocarcinoma, squamous carcinoma, or small cell carcinoma) with BM and non-EGFR/ALK-TKIs indication, the overall survival (OS) and PFS of anlotinib + CRT treatment versus CRT treatment alone were separately calculated and compared. The Cox proportional hazards model was used to analyze the independent prognostic factors for intracranial PFS (iPFS) and OS. All confounding factors were adjusted, including age, gender, Karnofsky Performance Status (KPS) score, smoking history, physiological characteristics, T/N stage, histology, metastases, and pathological characteristics. Subgroup analysis for iPFS and OS was performed to assess the effects on BM of treatment pattern.Results: The study included 100 patients with BM at baseline and the follow-up data. Of the 100 patients, 67 patients received CRT treatment alone and 33 patients received CRT + anlotinib treatment. The overall response rates of the CRT + anlotinib group and the CRT alone group were 90.91% and 83.58%, respectively. There was significantly more iPFS in the CRT + anlotinib group compared to CRT alone (median iPFS [miPFS]: 9.0 vs 3.0 months; hazard ratio [HR] 1.59; 95% confidence interval [CI] 1.01-2.52; p = 0.038). The OS, extracranial PFS (ePFS), and systematic PFS (sPFS) of CRT + anlotinib group were longer than those of the CRT alone group, but there was no significant statistical difference (median OS [mOS]: 9.0 vs 7.0 months, HR 1.17, 95% CI 0.74-1.85; median ePFS [mePFS]: 9.0 vs 7.0 months, HR 1.23, 95% CI 0.72-2.11; median sPFS [msPFS]: 7.0 vs 4.0 months, HR 1.37, 95% CI 0.82-2.30). The Cox proportional hazards model analysis revealed that age was an independent prognostic factor of iPFS (HR 1.65, 95% CI 1.05-2.59, p = 0.03). Age (HR 1.74, 95% CI 1.09-2.77, p = 0.02) and KPS score (HR 1.88, 95% CI 1.17-3.01, p = 0.01) were identified as independent prognostic factors of OS. Further subgroup analysis of iPFS showed that when the number of BM in the CRT + anlotinib group was less than or equal to three lesions (≤ 3), the miPFS (12.0 months) was significantly longer than that for CRT alone (> 3) (3.0 months), for CRT alone (≤ 3) (3.0 months), and for CRT + anlotinib (> 3) (7.0 months) (p = 0.014). The OS of the CRT + anlotinib group (≤ 3) (mOS 37.0 months) was much longer than that in CRT alone (> 3) (mOS 6.0 months), CRT alone (≤ 3) (mOS 7.5 months), and CRT + anlotinib (> 3) (mOS 8.5 months) groups, but this difference was not statistically significant (p = 0.051).Conclusion: Anlotinib can improve the survival of patients with lung cancer BM, with better efficacy of a combined treatment of anlotinib + CRT compared to that of CRT alone, especially for the iPFS of patients with BM ≤ 3.

Immune Checkpoint Inhibitor for Non-small Cell Lung Cancer With Negative or Low Tumor PD-L1 Expression

2021 ◽  
Vol 1 (3) ◽  
pp. 173-177
Author(s):  
MINEHIKO INOMATA ◽  
NAOKI TAKATA ◽  
ISAMI MIZUSHIMA ◽  
KENJI AZECHI ◽  
KANA HAYASHI ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Small Cell ◽  
Cox Proportional Hazards Model ◽  
Small Cell Lung ◽  
Hazards Model

Background/Aim: We conducted a retrospective analysis of the survival durations of 25 patients diagnosed as having non-squamous cell non-small cell lung cancer with negative or low tumor programmed death-ligand 1 (PD-L1) expression treated with immune checkpoint inhibitor (ICI) monotherapy. Patients and Methods: The progression-free (PFS) and overall (OS) survival were calculated from the initiation of ICI monotherapy. The association between the patient characteristics and the PFS was analyzed using Cox proportional hazards model. Results: The median PFS was 2.6 months, and the 12-month PFS rate was 9.3%. The median OS was 5.5 months, and the 12-month OS rate was 39.8%. A Cox proportional hazards model identified the neutrophil/lymphocyte ratio and presence of liver metastasis as being significantly associated with PFS. Conclusion: Our findings suggest that a subset of patients with non-squamous cell non-small cell lung cancer who show negative or low tumor PD-L1 expression could benefit from ICI monotherapy.

scholarly journals Heregulin expression and its clinical implication for patients with EGFR-mutant non-small cell lung cancer treated with EGFR-tyrosine kinase inhibitors

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kimio Yonesaka ◽  
Eiji Iwama ◽  
Hidetoshi Hayashi ◽  
Shinichiro Suzuki ◽  
Ryoji Kato ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Kinase Inhibitors ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Small Cell ◽  
Cox Proportional Hazards Model ◽  
Small Cell Lung ◽  
Hazards Model ◽  
Egfr Tkis

AbstractEpidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are standard therapy for EGFR-mutant non-small cell lung cancer (NSCLC). Preclinically, HER3 ligand heregulin induces resistance to EGFR-TKIs, whereas the pan-human EGFR family inhibitor afatinib remains effective. Here, we examined whether soluble heregulin levels have clinical implications for EGFR-mutant NSCLC treated with EGFR-TKIs. Soluble heregulin was immunologically measured in plasma from EGFR-mutant NSCLC patients. Cutoff values were determined by 1-year PFS ROC curve. The relationship between soluble heregulin and PFS following EGFR-TKI therapy was analyzed by Cox proportional hazards model. Seventy-three patients were enrolled: 44 were treated with 1st-generation and 29 with 2nd-generation EGFR-TKIs. Soluble heregulin levels varied (range: 274–7,138 pg/mL, median: 739 pg/mL). Among patients treated with 1st-generation EGFR-TKIs, those with high heregulin (n = 20, >800 pg/mL) had a tendency for shorter PFS than those with low heregulin (n = 24, <800 pg/mL), with median PFS of 322 and 671 days, respectively. Cox proportional hazards model also indicated a trend toward resistance against 1st-generation EGFR-TKIs (HR: 1.825, 95% CI: 0.865–4.318) but not against 2nd-generation EGFR-TKIs. Soluble heregulin potentially correlates with resistance to EGFR-TKIs but not 2nd-generation EGFR-TKIs in patients with EGFR-mutant NSCLC.

Overall survival (OS) prognostic factors in metastatic castrate-resistant prostate cancer (mCRPC) patients retreated with docetaxel (D).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15213-e15213
Author(s):  
Shilpa Rashmikant Shah ◽  
Costantine Albany ◽  
Noah M. Hahn
Keyword(s):  
Prognostic Factors ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Cancer Center ◽  
Gleason Grade ◽  
First Line ◽  
Hazards Model ◽  
Baseline Psa

e15213 Background: Until recently, few post-D treatment options existed for mCRPC patients (pts). In pts taken off of first-line D for reasons other than progressive disease (PD), retreatment with D at the time of PD was a commonly used strategy. While several prognostic nomograms have been developed for mCRPC patients, none have exclusively examined prognostic factors in D retreated patients. In the present study, we aimed to characterize baseline clinical factors associated with OS outcomes in D retreated mCRPC pts. Methods: Between 1/2007 and 10/2010, all mCRPC pts seen in the Indiana University Simon Cancer Center oncology clinics were approached for recruitment to the IRB approved biorepository protocol. Participants completed a demographic and clinical questionnaire and provided a blood sample. Only mCRPC pts retreated with D with confirmed dates for D first-line completion, D retreatment, and OS were included in this analysis. At D retreatment, patient age, Gleason Grade (GG), presence of pain, time to progression after first-line D therapy, visceral metastases, ECOG performance status, PSA, and PSA doubling time (PSAdt) were examined by Cox proportional hazards model for significant associations (p < 0.05) with OS outcomes. Results: 30 mCRPC pts retreated with D were identified. Complete data were available on 22 pts which formed the analysis cohort. Demographics included: mean age – 69.1 yrs, Caucasian/African-American – 21/1, median GG 8, 55% pain present at baseline, median time from first-line D – 8.6 mo., 30% visceral mets, ECOG 0/1/2 – 3/17/2, mean baseline PSA – 536 ng/ml, mean baseline PSAdt – 2.7 mo. By Cox proportional hazards model, baseline PSA (p = 0.006) was significantly associated with D-retreatment OS with a trend toward significance in patients with pain at baseline (p = 0.059). No other significant associations were identified. Conclusions: Baseline PSA levels were significantly associated with OS outcomes in mCRPC pts retreated with D. Validation and examination of additional clinical variables is warranted in larger datasets.

Evaluation of brain metastasis in JAVELIN Renal 101: Efficacy of avelumab + axitinib (A+Ax) versus sunitinib (S).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 687-687 ◽  
Author(s):  
Eric Jonasch ◽  
Elshad Hasanov ◽  
Robert J. Motzer ◽  
Subramanian Hariharan ◽  
Toni K. Choueiri ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Brain Metastases ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Hazards Model ◽  
Kaplan Meier ◽  
Disease Site

687 Background: Patients (pts) with brain metastasis from renal cell carcinoma (RCC) have poor prognosis and are often excluded from randomized registrational trials. The phase 3 JAVELIN Renal 101 trial (NCT02684006) demonstrated significantly improved progression-free survival (PFS) for A+Ax vs S in pts with advanced RCC (Motzer NEJM 2019). The activity of A+Ax in pts with brain metastasis enrolled in JAVELIN Renal 101 is presented. Methods: PFS was compared between treatment arms for the subgroup of pts randomized in JAVELIN Renal 101 with brain metastases at enrollment (pts with brain disease site prior to randomization by blinded independent central review [BICR] or by investigator assessment). PFS time was summarized per BICR assessment by treatment arm using the Kaplan-Meier method. The Cox proportional hazards model was fitted to compute the hazard ratio (HR) and the corresponding CI. In addition, time to brain metastasis was assessed for pts without brain metastasis by BICR at enrollment after treating death as a competing risk. Results: Of all randomized pts (A+Ax arm, N=442; S, N=444), 23 in each arm (5.2%) had asymptomatic brain metastasis at enrollment; of these, pts assigned to A+Ax had a PFS of 4.9 mo (95% CI: 1.6, 5.7) vs 2.8 mo (95% CI: 2.3, 5.6) for pts assigned to S (HR: 0.90; 95% CI: 0.43, 1.88). Among pts without brain metastasis at enrollment, 8 pts on the A+Ax arm and 10 on the S arm developed brain metastasis during the trial, based on BICR assessment; 17/18 occurred ≤12 mo from randomization. The cumulative incidence rate of brain metastasis at 18 mo was 2% (95% CI: 0.6, 3.3) for the A+Ax arm and 3% (95% CI: 1.1, 4.8) for the S arm. Conclusions: In this post hoc exploratory analysis of JAVELIN Renal 101, the observed PFS among pts with brain metastasis at enrollment was similar between the two arms, with HR and median PFS numerically favoring A+Ax. Pts on the S arm had a numerically higher incidence of new brain metastases on trial. Outcomes are poor in pts with advanced RCC and brain metastasis; more effective treatments are needed. Clinical trial information: NCT02684006.

scholarly journals Analysis of Prognostic Factors of Patients with Small Cell Lung Cancer using Cox's Proportional Hazards Model.

Haigan ◽  
1993 ◽  
Vol 33 (7) ◽  
pp. 1011-1016
Author(s):  
Masahiko Takenaka ◽  
Noriaki Iwahashi ◽  
Takashi Nakano ◽  
Juichiro Maeda ◽  
Nobuyuki Aihara ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Prognostic Factors ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Small Cell ◽  
Small Cell Lung ◽  
Hazards Model ◽  
Cox's Proportional Hazards Model

scholarly journals Cox Proportional Hazards Model for Identification of the Prognostic Factors in the Survival of Acute Liver Failure Patients in India

2018 ◽  
Vol 2 ◽  
pp. 53-74
Author(s):  
Shankar Prasad Khanal ◽  
V. Sreenivas ◽  
S.K. Acharya
Keyword(s):  
Survival Analysis ◽  
Prognostic Factors ◽  
Liver Failure ◽  
Cerebral Edema ◽  
Goodness Of Fit ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Hazards Model

Background: Acute Liver Failure (ALF) is a kind of dangerous rare liver injury among all liver diseases. Different statistical methods such as Logistic regression, Kaplan-Meier estimate of survival function followed by Log-rank test and semi-parametric approaches of survival analysis has been applied in order to identify the significant risk factors of ALF patients. In most of the studies, regression models used in this setup has not been evaluated by model assumptions and their goodness of fit tests.Objective: To apply appropriate survival analysis technique to identify the prognostic factors in the survival of ALF patients, to develop prognostic index, and to predict survival probability for different scenario.Materials and Methods: The study is based on the retrospective cohort study design with altogether 1099 ALF patients taken from the liver clinic, All India Institute of Medical Sciences, New Delhi India. Cox regression has been considered as the suitable model for handling this time to event data, and the assumptions of the model, goodness of fit of the model was assessed and survival probabilities were predicted.Results: This study has identified six prognostic factors namely age, prothrombin time, cerebral edema, total serum bilirubin, serum creatinine and etiology for ALF patients. The hazards of mortality [HR: 2.38; 95% C.I.: (1.99, 2.85), p < 0.001] is the highest for cerebral edema among all these prognostic factors. Nearly 9%, 26%, 39%, 50%, 59% and 63% of ALF patients with a PI of 1, 3, 5, 7, 9 and 10 respectively die by 3 days of hospital stay.Conclusion: The developed Cox Proportional Hazards model with six prognostic factors has satisfied the model assumptions and goodness of fit tests. The risk score and the predicted survival probabilities will be immensely helpful to the hepatologists to make a quick decision regarding the likely prognosis of a patient at admission and helpful in triaging the ALF patients for liver transplant.Nepalese Journal of Statistics, Vol. 2, 53-74

Factors Predicting Survival for Cancer of the Ethmoid Sinus

2002 ◽  
Vol 16 (5) ◽  
pp. 281-286 ◽  
Author(s):  
Neil Bhattacharyya
Keyword(s):  
Radiation Therapy ◽  
Prognostic Factors ◽  
Survival Data ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Ethmoid Sinus ◽  
Cox Proportional Hazards Model ◽  
T Stage ◽  
Hazards Model

Objective The aim of this study was to determine survival and prognostic factors for ethmoid sinus cancer. Methods From the Surveillance, Epidemiology, and End Results database for the time period 1988–1998, all cases of ethmoid sinus malignancy were extracted. Demographic, staging, treatment, and survival data were computed. Survival analysis was conducted with the Kaplan-Meier method. Clinical factors influencing survival were determined with the Cox proportional hazards model. Results After excluding patients with metastatic disease on presentation (8.9%) and patients with missing data for T stage, a total of 180 cases were identified. Average age was 60.2 years. Squamous cell carcinoma was the most common tumor (27.8%), followed by adenocarcinoma (12.8%). Overall mean survival was 57 months (median, 38 months) with a 5-year survival of 40.3%. The percentage of patients presenting with T4 lesions was 45.6%, which had a notably lower mean survival of 38 months (median, 18 months). Only 2.3% of patients had positive nodal disease. Increasing age, T stage, and absence of radiation therapy predicted poorer survival in the multivariate model. Adenocarcinoma, adenoid cystic carcinoma, esthesioneuroblastoma, and melanoma showed more favorable survival than other tumor types. Conclusions T stage and tumor histology are the most important prognostic factors in ethmoid sinus carcinoma. Survival for T4 lesions is markedly worse than survival for T1-T3 lesions. Radiation therapy offers a survival benefit in ethmoid sinus malignancy.

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