scholarly journals Improving the Lung Cancer Clinical Trial Development by Incorporating Competing Risk Factors

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Zhu Wenbo ◽  
Zhao Qing ◽  
Wang Li ◽  
Zhu Hangju ◽  
Zhang Junying ◽  
...  

Introduction. Distinct from other diseases, as cancer progresses, both the symptoms and treatments evolve, resulting in a complex, time-dependent relationship. Many competing risk factors influence the outcome of cancer. An improved method was used to evaluate the data from 6 non-small-cell lung cancer (NSCLC) clinical trials combined in our center since 2016 to deal with the bias caused by competing risk factors. Material and Methods. Data of 118 lung cancer patients were collected from 2016 to 2020. Fine and Gray’s model for competing risk was used to evaluate survival of different treatment group compares with the classic survival analysis model. Results. Immunotherapy had better progression-free survival than chemotherapy. (HR: 0.62, 95% CI: 0.41-0.95, p = 0.0260 ). However, there were no significant differences in patients who withdrew due to treatment-related adverse events from different groups. ( Z = 0.0508 , p = 0.8217 ). The PD-1/PD-L1 inhibitors in our study did not significantly improve overall survival compared with chemotherapy (HR:0.77, 95% CI:0.48-1.24, p = 0.2812 ), estimated 1-year overall survival rates were 55% and 46%, and 3-year overall survival rates were 17% and 10%, respectively. Conclusion. When the outcome caused by competing risk exists, the corresponding competing risk model method should be adopted to eliminate the bias caused by the classic survival analysis.

2021 ◽  
Author(s):  
Junxia Huang ◽  
Juanjuan Hu ◽  
Yan Gao ◽  
Fanjun Meng ◽  
Tianlan Li ◽  
...  

Abstract Background: Advanced lung cancer inflammation index (ALI) is known to predict the overall survival of patients having some solid tumors or B-cell lymphoma. The study investigates the predictive value of ALI in multiple myeloma (MM) patients and the correlation between ALI and prognosis.Methods: A database of 269 MM consecutive patients who underwent chemotherapy between December 2011 and June 2019 in the Affiliated Hospital of Qingdao University was reviewed. ALI cut-off value calculated before the initial chemotherapy and post 4 courses treatment were identified according to the receiver operating characteristic (ROC) curve, and its association with clinical characteristics, treatment response, overall survival (OS), and progression-free survival (PFS) were assessed.Results: Patients in the low ALI group (n=147) had higher risk of β2 microglobulin elevation, more advanced ISS (International Classification System stage), and TP53 gene mutation, with significantly lower median overall survival (OS; 36.29 vs. 57.92 months, P = 0.010) and progression-free survival (PFS; 30.94 vs. 35.67 months, P = 0.013). Independent risk factors influencing the OS of MM patients were ALI (P = 0.007), extramedullary infiltration (P = 0.001), TP53 (P = 0.020), Plt (P = 0.005), and bone destruction (P = 0.024). ALI (P = 0.005), extramedullary infiltration (P = 0.004), TP53 (P = <0.001), Plt (P = 0.017), and complex chromosome karyotype (P = 0.010) were independent risk factors influencing the PFS of MM patients.Conclusions: ALI is a potential independent risk factor predicting the prognosis of newly diagnosed MM patients.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2030-2030
Author(s):  
Philip Bierman ◽  
Fausto Loberiza ◽  
Bhavana Dave ◽  
Warren Sanger ◽  
R. Gregory Bociek ◽  
...  

Abstract Rearrangements of the c-myc oncogene can be seen in 5–10% of patients with diffuse large B-cell lymphoma. However, studies examining the significance of this finding have yielded conflicting results. Therefore, we performed a retrospective analysis to determine the clinical significance of c-myc rearrangements in diffuse large B-cell lymphoma. The results of classical cytogenetic studies and FISH analyses were used to identify diffuse large B-cell lymphoma cases in the database of the Nebraska Lymphoma Study Group with or without c-myc rearrangements. Patients who were HIV positive and those with post-transplant lymphoproliferative disease were excluded. We identified 16 patients with diffuse large B-cell lymphoma and c-myc rearrangements. All patients were initially treated with doxorubicin- or mitoxantrone-containing chemotherapy regimens. The median age of these 16 patients was 61 years (range 40 to 80), and 5 (31%) were males. The International Prognostic Index (IPI) was 0–2 at diagnosis in 9 patients (56%), and 3–5 in 7 patients (44%). Eleven patients (69%) had bulky disease (≥ 5 cm) at diagnosis. No significant differences in outcome were identified when the 16 c-myc positive patients were compared with 97 c-myc negative diffuse large B-cell lymphoma patients in the same age range. The actuarial 5-year progression-free survival for the c-myc positive patients was 23% (95% CI 6% to 46%), as compared with 38% (95% CI 29% to 48%) for c-myc negative patients (p=0.17). The actuarial 5-year overall survival rates were 36% (95% CI 14% to 59%) and 47% (95% CI 36% to 56%), respectively (p=0.19). Classical cytogenetics and FISH analyses were also used to examine the 16 c-myc positive cases for bcl-2 rearrangements. Eight (50%) cases had rearrangements of bcl-2 in addition to c-myc rearrangements. These patients were similar to the c-myc positive/bcl-2 negative patients except for a higher likelihood of an elevated LDH level at diagnosis (88% vs. 25%; p=0.03). The actuarial 5-year progression-free survival for c-myc positive/bcl-2 positive patients was 0%, as compared to 33% (95% CI 6% to 66%) for patients with rearrangements of c-myc alone, and 37% (95% CI 28% to 47%) for c-myc negative patients. The actuarial 5-year overall survival rates were 12% (95% CI 1% to 42%), 47% (95% CI 12% to 76%), and 41% (95% CI 31% to 51%), respectively. A multivariate analysis, adjusting for IPI score, demonstrated that the relative risk (RR) of treatment failure was significantly worse for the c-myc positive/bcl-2 positive patients, as compared to the c-myc negative patients (RR 2.86, 95% CI 1.32–6.23; p=0.008). Similarly, mortality was also significantly worse for the c-myc positive/bcl-2 positive patients, as compared to the c-myc negative patients (RR 2.69, 95% CI 1.18–6.11; p=0.02). In contrast, no significant differences in treatment failure or overall survival were demonstrated when c-myc positive/bcl-2 negative patients were compared with c-myc negative patients. Our results demonstrate that the c-myc rearrangement is not associated with poorer survival in patients with diffuse large B-cell lymphoma. However, patients with rearrangements of bcl-2 in addition to c-myc had significantly worse progression-free survival and overall survival.


1996 ◽  
Vol 114 (6) ◽  
pp. 1298-1302 ◽  
Author(s):  
Flávio Xavier ◽  
Lucélia de Azevedo Henn ◽  
Oliveira Marja ◽  
Luciane Orlandine

The frequency of smoking among patients with primary lung cancer diagnoses admitted to the Hospital de Clinicas de Porto Alegre (HCPA) during the 1980's was investigated. The objective of this study was to analyze cigarette consumption patterns through the number of cigarettes smoked per day and the age at which smoking began, correlating this data to the overall survival rate and histological type of the lung cancer. Methods: This retrospective study analyzed patients with primary lung cancer diagnosed at the HCPA between January 1980 and December 1989. All patients considered underwent follow-up for at least three years. Patient information was obtained either from the hospital's records or by contacting patients via letter or phone. Results: More than 90 percent of the patients were smokers or had smoked previously; most had started smoking before the age of 20.The overall 24-month survival rate after diagnosis varied depending on whether the patient had smoked less than 40 cigarettes per day or not. The percentage of smokers and non-smokers was established for each histological type, with the bronchoalveolar adenocarcinoma type showing the highest percentage of non-smokers (40 percent). Conclusion:The overall survival rates of patients with lung cancer was related to the number of cigarettes smoked, and not to the fact of the patient having smoked or not.The number of smokers among patients with lung cancer was not so high only for the bronchoalveolar adenocarcinoma histological type.


2021 ◽  
Author(s):  
Peipei Wang ◽  
Kaibo Guo ◽  
Anlai Zhang ◽  
Wendi Li ◽  
Shuning Ding ◽  
...  

Abstract This research aimed to investigate the prognostic factors of oral squamous cell carcinoma (OSCC), especially the role of age. A total of 33619 cases of OSCC were received from the Surveillance, Epidemiology, and End Results database during 2005–2015. Kaplan-Meier curves of 5-year overall survival rates and 5-year cancer specific survival rates were performed, and univariate and multivariate Cox regression analysis as well as competing risk model were used to help understand the relationship between various factors and mortality of OSCC. Compared to 18–39 years old group, the older age was an important predictor of worse prognosis. The multivariate analysis of overall survival (OS) were 50–59 years old (HR, 1.32; 95% CI, 1.17–1.48; p ≤ .001), 60–69 years old (HR, 1.66; 95% CI, 1.42–1.87; p ≤ .001) and 70 + years old (HR, 3.21; 95% CI, 2.86–3.62; p ≤ .001) respectively, while the specific value of competing risk model were 60–69 years old (HR, 1.21; 95% CI, 1.07–1.38; p = .002) and 70 + years old (HR, 1.85; 95% CI, 1.63–2.10; p ≤ .001). In addition, female gender, unmarried, Blacks, tumor in floor of mouth, size and higher TNM classification were also other predictors that signify significant clinically deterioration of OS / CSS. Our research revealed that age was an important factor in explaining the difference of survival in the whole process of OSCC. It’s suggested that we should pay attention to the influence of age on diagnosis, treatment and prognosis in the clinical process.


2005 ◽  
Vol 23 (15) ◽  
pp. 3480-3487 ◽  
Author(s):  
Jeffrey D. Bradley ◽  
Rebecca Paulus ◽  
Mary V. Graham ◽  
David S. Ettinger ◽  
David W. Johnstone ◽  
...  

Purpose To determine the overall survival, progression-free survival, and toxicity associated with concurrent paclitaxel/carboplatin and thoracic radiotherapy for completely resected patients with stage II and IIIA non–small-cell lung cancer (NSCLC). Patients and Methods Eighty-eight eligible patients had surgical resection for pathologic stage II or IIIA disease and received postoperative paclitaxel and carboplatin. Concurrent thoracic radiotherapy at 50.4 Gy in 28 fractions for 6 weeks (1.8 Gy/d, 5 days/wk) was given during cycles 1 and 2. A boost of 10.8 Gy in six fractions was given for extracapsular nodal extension or T3 lesions. Results Treatment compliance was acceptable, with 93% compliance for radiation therapy and 86% for chemotherapy completion. The median duration of follow-up was 56.7 months (range, 17 to 61 months). The median overall survival time was 56.3 months, with 1-, 2-, and 3-year survival rates of 86%, 70%, and 61%, respectively. The 1-, 2-, and 3- year progression-free survival rates were 70%, 57%, and 50%, respectively. Brain metastasis occurred as the sole site of first failure in 11%, and 9% failed in other metastatic sites as first failure. Of the 43 patients who died, the cause of death was the treated cancer in 31 (35%). Local failure was a component of first failure in 15% of patients. Toxicities were acceptable. An overall survival comparison to Eastern Cooperative Oncology Group 3590 is favorable. Conclusion The mature results of this trial suggest an improved overall and progression-free survival in this group of resected NSCLC patients, compared with previously reported trials. A phase III trial comparing this treatment regimen with standard therapy seems warranted.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2824-2824
Author(s):  
Elias J. Jabbour ◽  
Naval G. Daver ◽  
Tina (Xiao Qin) Dong ◽  
Tapan M. Kadia ◽  
Susan O'Brien ◽  
...  

Abstract Abstract 2824 Background: HMA are standard of care in pts with high-risk MDS and commonly used in pts with lower risk. Pts with high-risk disease post HMA failure have a poor prognosis with a median survival of 4 months (Jabbour et al. Cancer. 2010;116:3830–4). The prognosis of patients with low and intermediate-1 risk MDS after HMA failure is not known. Aims: To assess survival in patients with low and intermediate-1 risk disease at the time of HMA failure that might benefit from specific strategies or investigational agents. Methods: Data from 699 patients with MDS (n=397) and chronic myelomonocytic leukemia (n=302) treated with HMA at one institution between 2000 and 2011 were reviewed. 126 (18%) of them were of low and intermediate-1 risk disease by IPSS score. Results: A total of 30 (24%) patients with MDS (n=26) and CMML (n=4) who had failed HMA therapy and remained of low and intermediate-1 risk disease were analyzed. These included 6 patients with low- and 24 intermediate-1 risk disease. Eleven patients had secondary disease. At the start of HMA, 22 patients were low-risk and 8 were intermediate-1 risk disease. Seventeen patients had a diploid cytogenetic analysis. Seven and 23 patients received azacitidine and decitabine, respectively. These patients had discontinued HMA because of primary resistance in all patients. The characteristics of the study group are shown in Table 1. Upon HMA failure, 24 (80%) were low-risk disease and 6 (20%) intermediate-1-risk disease. A total of five (17%) patients transformed subsequently into acute myeloid leukemia. After a median of 18 months from HMA failure, 12 (40%) patients remained alive. The median overall survival was 22 months with estimated 1- and 2-year overall survival rates of 65% and 45%, respectively. Considering overall survival from the start of HMA therapy, the median survival was 29.5 months with estimated 1- and 2-year overall survival rates of 80% and 60%, respectively. The 30 patients with HMA failure were subsequently assessed by the lower-risk MDACC risk model (Garcia-Manero et al. Leukemia. 2008;22:538–43): 8 (27%) had low-risk, 8 (27%) intermediate-risk, and 14 (46%) high-risk disease. Their 1-year survival rates were 66%, 73%, and 86%, respectively. Considering survival from the time of the initiation of HMA therapy, the estimated 1-year survival rates were 60%, 70%, and 100%, respectively, for patients with high-risk, intermediate-risk, and low-risk disease according to the MDACC risk model. After HMA failure, 11 (37%) patients received salvage investigational therapy, of whom 3 responded with 2 achieving hematologic improvement for a median of 12 months (range, 5–19) and one patient achieving a complete remission for 14 months that was lost thereafter, 1 (3%) received immunotherapy, 1 (3%) received growth factors only, and 17 (57%) elected not to receive any further treatment. No response was observed in the 2 patients who received subsequent immunotherapy or growth factors. Conclusion: The outcome of patients with low and intermediate-1 risk MDS after HMA failure is poor and appears to be predictable. Disclosures: Ravandi: Genzyme/Sanofi: Honoraria. Faderl:Genzyme: Advisory Board Other, Research Funding.


2017 ◽  
Vol 25 (1) ◽  
pp. 44-51
Author(s):  
Valérie Couillard-Montminy ◽  
Pierre-Yves Gagnon ◽  
Sebastien Fortin ◽  
Jimmy Côté

Background Cisplatin and vinorelbine given intravenously is a well-established adjuvant chemotherapy regimen after surgery for early non-small cell lung cancer. However, few validated alternatives exist when cisplatin is not indicated or tolerated. Carboplatin is frequently used in this setting. We evaluated the 5-year overall survival, progression-free survival and toxicity in patients treated for stage IB to IIIB resected non-small cell lung cancer receiving adjuvant carboplatin-based chemotherapy compared to cisplatin in association with vinorelbine. Methods Single-center retrospective study of patients having received adjuvant chemotherapy between January 2004 and December 2013 at the oncology clinic at Institut Universitaire de Cardiologie et de Pneumologie de Québec (Canada). Three sub-groups, cisplatin/vinorelbine, carboplatin/vinorelbine and the substitution of cisplatin/vinorelbine for carboplatin/vinorelbine (cisplatin/vinorelbine/carboplatin/vinorelbine), were studied during treatment. Results One hundred twenty-seven patients were included in this study. The median PFS was not significantly different, with 50.4 months for cisplatin/vinorelbine, 57.3 months for cisplatin/vinorelbine/carboplatin/vinorelbine and not yet achieved for the carboplatin/vinorelbine group ( p = 0.80). Overall survival also did not differ significantly between the three groups. The 5-year overall survival rates were 66% in cisplatin/vinorelbine group, 55% in carboplatin/vinorelbine group and 70% in cisplatin/vinorelbine/carboplatin/vinorelbine group ( p = 0, 95). No differences were noted between groups concerning high-grade hematologic toxicity. Conclusions Although the effectiveness and hematologic toxicity are comparable between cisplat in and carboplatin in the adjuvant treatment of resected non-small cell lung cancer, the results obtained corroborate the practice used at our oncology clinic. Nevertheless, more prospective studies would be needed to confirm these results.


2005 ◽  
Vol 23 (21) ◽  
pp. 4602-4608 ◽  
Author(s):  
Hans von der Maase ◽  
Lisa Sengelov ◽  
James T. Roberts ◽  
Sergio Ricci ◽  
Luigi Dogliotti ◽  
...  

Purpose To compare long-term survival in patients with locally advanced or metastatic transitional cell carcinoma (TCC) of the urothelium treated with gemcitabine/cisplatin (GC) or methotrexate/vinblastine/doxorubicin/cisplatin (MVAC). Patients and Methods Efficacy data from a large randomized phase III study of GC versus MVAC were updated. Time-to-event analyses were performed on the observed distributions of overall and progression-free survival. Results A total of 405 patients were randomly assigned: 203 to the GC arm and 202 to the MVAC arm. At the time of analysis, 347 patients had died (GC arm, 176 patients; MVAC arm, 171 patients). Overall survival was similar in both arms (hazard ratio [HR], 1.09; 95% CI, 0.88 to 1.34; P = .66) with a median survival of 14.0 months for GC and 15.2 months for MVAC. The 5-year overall survival rates were 13.0% and 15.3%, respectively (P = .53). The median progression-free survival was 7.7 months for GC and 8.3 months for MVAC, with an HR of 1.09. The 5-year progression-free survival rates were 9.8% and 11.3%, respectively (P = .63). Significant prognostic factors favoring overall survival included performance score (> 70), TNM staging (M0 v M1), low/normal alkaline phosphatase level, number of disease sites (≤ three), and the absence of visceral metastases. By adjusting for these prognostic factors, the HR was 0.99 for overall survival and 1.01 for progression-free survival. The 5-year overall survival rates for patients with and without visceral metastases were 6.8% and 20.9%, respectively. Conclusion Long-term overall and progression-free survival after treatment with GC or MVAC are similar. These results strengthen the role of GC as a standard of care in patients with locally advanced or metastatic TCC.


2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii461-iii461
Author(s):  
Daniel Indelicato ◽  
Ronny Rotondo ◽  
Raymond Vega ◽  
Adam Holtzman ◽  
Wen Shen Looi ◽  
...  

Abstract BACKGROUND Due to the location and high dose required for disease control, pediatric chordomas are theoretically well-suited for treatment with proton therapy, but their low incidence limits the clinical outcome data available in the literature. METHODS AND MATERIALS: Between 2008 and 2019, 29 patients with a median age of 14.8 years (range, 3.8–21.8) received proton therapy for non-metastatic chordoma at a single institution. Twenty-four tumors arose in the clivus/cervical spine region and 5 in the lumbosacral spine. Twenty-six tumors demonstrated well-differentiated histology and 3 were dedifferentiated or not otherwise specified (NOS). Approximately half of the tumors underwent specialized testing: 14 were brachyury-positive and 10 retained INI-1. Seventeen patients had gross disease at the time of radiation. The median radiation dose was 73.8 GyRBE. RESULTS With a median follow-up of 4.3 years (range, 1.0–10.7), the 5-year estimates of local control, progression-free survival, and overall survival rates were 85%, 82%, and 86%, respectively. Excluding 3 patients with dedifferentiated/NOS chordoma, the 5-year local control, progression-free survival, and overall survival rates were 92%, 92%, and 91%, respectively. Serious toxicities included 3 patients with hardware failure or related infection requiring revision surgery, 2 patients with hormone deficiency, and 2 patients with Eustachian tube dysfunction causing chronic otitis media. CONCLUSION In pediatric patients with chordoma, proton therapy is associated with a low risk of serious toxicity and high efficacy, particularly in well-differentiated tumors. Complete resection may be unnecessary for local control and destabilizing operations requiring instrumentation may result in additional complications following therapy.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21050-e21050
Author(s):  
Min Hu ◽  
Xiaojiang Sun ◽  
Yuanjun Liu ◽  
Yaoyao Zhu ◽  
Qinghua Xu ◽  
...  

e21050 Background: Stereotactic body radiotherapy (SBRT) is a highly focused radiation treatment, which is now recommended to treat non-small cell lung cancer (NSCLC) patients with early stage disease. The purpose of this study is to evaluate the efficacy and toxicity of SBRT for early stage NSCLC patients with subclinical interstitial lung disease (ILD). Methods: One hundred and nine patients with early stage NSCLC were treated with SBRT between December 2011 and August 2016 in our institution; patients with subclinical (untreated and oxygen-free) ILD were treated with SBRT, while those with clinical ILD (post- or under treatment) were not. The median SBRT dose was 50 Gy in 5 fractions and the median biologically effective dose (BED; α/β = 10) was 100 Gy (range:72-119 Gy). The presence of subclinical ILD in the pre-SBRT CT findings was reviewed by two chest radiologists. The relationships among the efficacy, radiation pneumonitis (RP) and clinical factors were investigated. Results: Subclinical ILD was recognized in 38 (35%) of 109 patients. Grade 2–4 RP was recognized in 48 (44%) of 109 patients, no Grade 5 RP was happened. Grade 2–4 RP was observed in 17 (45%) of 38 patients with subclinical ILD. Subclinical ILD was not found to be a significant factor influencing Grade 2–4 RP; however, extensive RP beyond the irradiated field, including the contralateral lung, was recognized in only two patients who were both suffering from subclinical ILD, and the rate of extensive RP was significantly high in the patients with subclinical ILD. Dosimetric factors of the lungs (V5, V10, V20, MLD, V12.5, V13.5) were significantly associated with Grade 2–4 RP. The three-year overall survival and progression-free survival rates of all patients were 82.8% and 62.5%, respectively. No significant differences were seen in either overall survival or progression-free survival rates among the patients with ILD and those without ILD, or with RP and those without RP. Conclusions: Subclinical ILD was not found to be a significant factor for Grade 2–5 RP or clinical outcomes in early stage NSCLC treated with SBRT; however, uncommon extensive RP can occur in patients with subclinical ILD.


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