Prognostic factors for progression-free and overall survival with sunitinib targeted therapy and with cytokine as first-line therapy in patients with metastatic renal cell carcinoma

BackgroundAnalysis of prognostic factors for progression-free survival (PFS) and overall survival (OS) was performed using final data from a randomized phase III trial of sunitinib versus interferon-α (IFN-α) as first-line metastatic renal cell carcinoma (RCC) therapy.DesignA multivariate Cox regression model analyzed baseline variables for prognostic significance. Each variable was investigated univariately and then multivariately using a stepwise algorithm.ResultsEach treatment arm comprised 375 patients. For sunitinib, multivariate analysis of PFS identified five independent predictors, including serum lactate dehydrogenase (LDH) level, presence of ≥2 metastatic sites, no prior nephrectomy, Eastern Cooperative Oncology Group (ECOG) performance status, and baseline platelet count, while multivariate analysis of OS identified serum LDH level, corrected serum calcium level, time from diagnosis to treatment, hemoglobin level, ECOG performance status, and presence of bone metastasis as predictors. For IFN-α, LDH level and presence of ≥2 metastatic sites were common predictors of PFS to those for sunitinib, as were all predictors of OS except ECOG status.ConclusionsThis analysis identified prognostic factors for PFS and OS with sunitinib as first-line metastatic RCC therapy and confirmed that the Memorial Sloan-Kettering Cancer Center model is applicable in the era of targeted therapy.     

Prognostic factors and long-term survivorship in patients with recurrent or metastatic carcinoma of the head and neck

BACKGROUND: The current study was conducted to identify prognostic factors and report the characteristics of long-term survivors in patients with recurrent or metastatic carcinoma of the head and neck who were treated with cisplatin-based combination chemotherapy in two randomized, Phase III trials conducted by the Eastern Oncology Cooperative Group (ECOG) (E1393 and E1395). METHODS: The authors analyzed prognostic factors for response and survival by combining data from the E1393 trial, which compared cisplatin plus paclitaxel at two dose levels, with data from the E1395 trial, which compared cisplatin plus paclitaxel with cisplatin plus 5-fluorouracil (5-FU), using logistic regression and Cox regression models. RESULTS: A total of 399 eligible patients were included. The median follow-up was 4.7 years. The 1-year overall survival (OS) rate for all patients was 32%, the median OS was 7.8 months, and the objective response rate was 32%. On multivariate analysis, the following were found to be independent unfavorable predictors of objective response: weight loss of > 5%, an ECOG performance status of 1 (vs. 0), residual disease at the primary tumor site, a primary tumor site other than the oropharynx, prior radiation therapy (RT) (P = 0.056), and well/moderate tumor cell differentiation (P = 0.067). Independent unfavorable prognostic factors for OS were weight loss, an ECOG performance status of 1 (vs. 0), well/moderate tumor cell differentiation, a primary tumor in the oral cavity or hypopharynx, and prior RT. The following were found to be independent unfavorable prognostic factors for time to disease progression: well/moderate tumor cell differentiation, a oral cavity or hypopharyngeal primary tumor, and prior RT. Patients with < or = 2 adverse prognostic factors were reported to have a median OS of 1 year, whereas patients with 3-5 adverse prognostic factors were found to have a median OS of 0.5 years (P < 0.0001). Forty-nine patients (12%) survived for > or = 2 years and 6 patients were alive at 5 years. Two-year survivors were more likely to have achieved an objective response to chemotherapy, have poor tumor cell differentiation, be white, have an ECOG performance status of 0, and have received no prior RT. CONCLUSIONS: Clinical parameters and tumor cell differentiation appear to be strong pretreatment predictors of outcome in patients with carcinoma of the head and neck and should be considered in the design of future randomized trials. A small percentage of patients with recurrent head and neck carcinoma can achieve long-term survival.     

Clinical Factors Associated with Long-Term Survival in Metastatic Melanoma Treated with Anti-PD1 Alone or in Combination with Ipilimumab

Immune checkpoint inhibitors (ICIs) for treatment of metastatic melanoma (MM) offer lasting overall survival (OS) benefit in a subset of patients. However, outcomes remain poor for non-responders. Clinical predictors of long-term survival remain elusive. We utilized the Alberta Immunotherapy Database to investigate the association of host and disease characteristics, and treatment factors with overall survival (OS) greater than 3 years. We identified patients treated between August 2013 and May 2020 with single-agent anti-PD1 or combination (anti-PD1 and anti-CTLA4) ICI regimens. A logistic regression model was used to assess for independent association between clinical factors captured and survival greater than 3 years. Statistically significant factors on univariable analysis were assessed using multivariable analysis. In total, 284 of 460 patients were identified to have short-term (<1 year) or long-term (>3 years) survival with 186 surviving <1 year and 98 surviving >3 years. The median age was 64 and 18.4% of patients were ECOG ≥ 2. On logistic regression, Breslow’s Depth ≤ 4 mm, normal serum LDH, normal serum albumin and M-stage 1a/b were associated with OS > 3 years on univariable and multivariable analysis. ECOG < 2, dNLR ≤ 3, normal hemoglobin were only associated with survival on the univariable analysis but not in the multivariable analysis. The objective response rate in long-term survivors was 83.7% compared to 7.5% in the short-term survivors. Our study identifies four easily accessible predictors of long-term survival in a large real-world MM cohort treated with ICI.     

Clinicopathological and prognostic factors for long-term survival in Chinese patients with metastatic renal cell carcinoma treated with sorafenib: a single-center retrospective study

Data on long-term survival and prognostic significance of demographic factors and adverse events (AEs) associated with sorafenib, an orally administered multikinase inhibitor in Chinese population with advanced renal cell carcinoma (RCC) are limited. Outcome data from adult patients (n = 256) with advanced RCC who received sorafenib (400 mg twice daily) either as first-line or second-line therapy between April 2006 and May 2013 were analyzed retrospectively. The primary endpoint was median overall survival (OS), determined to be 22.2 (95% CI: 17.1–27.4) months, and the secondary endpoint was overall median progression-free survival (PFS), determined to be 13.6 (95% CI: 10.7–16.4) months at a median follow-up time of 61.8 (95% CI: 16.2–97.4) months. Analysis of the incidence of AEs revealed the most common side effect as hand-foot skin reactions (60.5%) followed by diarrhea (38.7%), fatigue (35.5%), alopecia (34.0%), rash (24.6%), hypertension (21.5%) and gingival hemorrhage (21.1%). Multivariate regression analysis revealed older age (≥ 58 years), lower Memorial Sloan-Kettering Cancer Center score, time from nephrectomy to sorafenib treatment, number of metastatic tumors and best response as significant and independent demographic predictors for improved PFS and/or OS (p ≤ 0.05). Alopecia was identified as a significant and independent predictor of increased OS, whereas vomiting and weight loss were identified as significant predictors of decreased OS (p ≤ 0.05). Sorafenib significantly improved OS and PFS in Chinese patients with advanced RCC. Considering the identified significant prognostic demographic factors along with the advocated prognostic manageable AEs while identifying treatment strategy may help clinicians select the best treatment modality and better predict survival in these patients.     

Selection of a patient subgroup with advanced esophageal squamous carcinoma who could benefit from second-line chemotherapy

Despite first-line therapy, most patients with advanced esophageal squamous cell carcinoma (ESCC) experience disease progression and may become eligible for second-line chemotherapy. Although commonly used, the role of salvage chemotherapy in patients with recurrent or metastatic ESCC has not yet been established. We analyzed 53 patients who had received second-line chemotherapy after the failure of cisplatin-based combination chemotherapy with or without radiotherapy as first-line therapy in ESCC between March 2000 and June 2008. Median progression-free survival (PFS) and overall survival (OS) for second-line chemotherapy were 2.4 and 5.2 months, respectively, with an overall response rate of 18.9%. In multivariate analysis, Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 2 or more and PFS under first-line therapy <4 months were independent prognostic factors for decreased OS. OS was estimated based on the number of adverse prognostic factors: 0 = good; 1 = intermediate, and 2 = poor. The median OS for the good, intermediate, and poor prognostic groups were 11.2, 4.5 and 4.3 months, respectively (p < 0.001). The good prognostic group showed better OS than the intermediate or poor groups (p < 0.001). Second-line chemotherapy may be beneficial for OS in ESCC patients with ECOG PS 0-1 and PFS under first-line therapy ≥4 months.     

Clinical factors associated with outcome in patients with metastatic clear-cell renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy

BACKGROUND: Therapy targeted against the vascular endothelial growth factor (VEGF) pathway is a standard of care for patients with metastatic renal cell carcinoma (RCC). The identification of patients who are more likely to benefit from these agents is warranted. METHODS: In total, 120 patients with metastatic clear-cell RCC received bevacizumab, sorafenib, sunitinib, or axitinib on 1 of 9 prospective clinical trials at the Cleveland Clinic. Clinical features associated with outcome were identified by univariate analysis; then, a stepwise modeling approach based on Cox proportional hazards regression was used to identify independent prognostic factors and to form a model for progression-free survival (PFS). A bootstrap algorithm was used to provide internal validation. RESULTS: The overall median PFS was 13.8 months, and the objective response according to the Response Criteria in Solid Tumors was 34%. Multivariate analysis identified time from diagnosis to current treatment <2 years; baseline platelet and neutrophil counts >300 K/microL and >4.5 K/microL, respectively; baseline corrected serum calcium <8.5 mg/dL or >10 mg/dL; and initial Eastern Cooperative Oncology Group performance status >0 as independent, adverse prognostic factors (PF) for PFS. Three prognostic subgroups were formed based on the number of adverse prognostic factors present. The median PFS in patients with 0 or 1 adverse prognostic factor was 20.1 months compared with 13 months in patients with 2 adverse prognostic factors and 3.9 months in patients with >2 adverse prognostic factors. CONCLUSIONS: Five independent prognostic factors for predicting PFS were identified and were used to categorize patients with metastatic RCC who received VEGF-targeted therapies into 3 risk groups. These prognostic factors can be incorporated into patient care and clinical trials that use such novel, VEGF-targeted agents.     

Clinicopathologic and molecular correlations of necrosis in the primary tumor of patients with renal cell carcinoma

BACKGROUND: The presence of histologic necrosis in the primary tumor of patients with renal cell carcinoma (RCC) has been suggested to be an important predictor of survival. The authors investigated the relation of tumor necrosis to other clinicopathologic factors known to be important prognostic indicators for patients with RCC. METHODS: The records of 311 patients undergoing treatment for RCC were evaluated for basic clinicopathologic information including TNM classification, nuclear grade, Eastern Cooperative Oncology Group (ECOG) performance status (PS), disease recurrence, and survival. The presence and extent of histologic necrosis of the primary tumors was recorded and correlated with clinicopathologic factors, carbonic anhydrase IX and Ki-67 expression, disease recurrence, and survival. RESULTS: The presence of necrosis in the primary tumor of patients with RCC compared with patients with RCC without necrosis was associated with higher T classification (P < 0.0001), the presence of lymph node disease (P = 0.009), the presence of metastases (P < 0.0001), higher grade (P < 0.0001), greater mean tumor size (P < 0.0001), an ECOG PS score > or = 1 (P = 0.007), higher University of California-Los Angeles Integrated Staging System (UISS) category (P < 0.0001), and higher Ki-67 expression (P < 0.0001). The extent of necrosis in the primary tumor was associated with the presence of lymph node disease (P = 0.009) and the presence of metastases (P < 0.0001), and correlated with higher T classification (sigma = 0.31, P < 0.0001), poorer ECOG PS (sigma = 0.18, P = 0.002), higher grade (sigma = 0.33, P < 0.0001), greater tumor size (sigma = 0.40, P < 0.0001), higher UISS category (sigma = 0.37, P < 0.0001), and higher Ki-67 staining (sigma = 0.32, P < 0.0001). Patients with the presence of necrosis in the primary tumor demonstrated a lower 5-year disease-specific survival compared with patients without necrosis in the primary tumor (36% vs. 75%; P < 0.0001). Multivariate analysis demonstrated that T classification (P < 0.0001), distant metastases (P < 0.0001), and ECOG PS (P < 0.0001) were independent predictors of DSS, whereas the presence of necrosis was not (P = 0.1100). Substratification into localized and metastatic disease demonstrated that the presence of necrosis was an independent predictor of survival in patients with localized (P = 0.025), but not metastatic (P = 0.44), disease. The extent of necrosis was not an independent predictor of survival (P > 0.05). Patients with the presence of necrosis in the primary tumor had a lower 5-year disease recurrence-free rate compared with patients without the presence of necrosis (62% vs. 92%, P < 0.0001). CONCLUSIONS: The presence of necrosis in the primary tumor was associated with adverse prognostic factors such as high T classification, presence of lymph node disease and metastases, high grade, large tumor size, and poor ECOG PS. The extent of necrosis was found to be associated with the presence of lymph node disease and metastases and correlated with higher T classification, higher grade, greater tumor size, poorer ECOG PS, and higher UISS category. The presence of this histologic variant was an independent predictor of poor survival in patients with localized, but not metastatic, disease. In addition, Ki-67 expression served as a valuable surrogate marker for the presence of histologic tumor necrosis.     

Prognostic factors for survival in 1059 patients treated with sunitinib for metastatic renal cell carcinoma

Background:

Prognostic factors for progression-free survival (PFS), overall survival (OS), and long-term OS (⩾30 months) were investigated in sunitinib-treated patients with metastatic renal cell carcinoma (RCC).

Methods:

Data were pooled from 1059 patients in six trials. Baseline variables, including ethnicity, were analysed for prognostic significance by Cox proportional-hazards model.

Results:

Median PFS and OS were 9.7 and 23.4 months, respectively. Multivariate analysis of PFS and OS identified independent predictors, including ethnic origin, Eastern Cooperative Oncology Group performance status, time from diagnosis to treatment, prior cytokine use, haemoglobin, lactate dehydrogenase, corrected calcium, neutrophils, platelets, and bone metastases (OS only). Characteristics of long-term survivors (n=215, 20%) differed from those of non-long-term survivors; independent predictors of long-term OS included ethnic origin, bone metastases, and corrected calcium. There were no differences in PFS (10.5 vs 7.2 months; P=0.1006) or OS (23.8 vs 21.4 months; P=0.2135) in white vs Asian patients; however, there were significant differences in PFS (10.5 vs 5.7 months; P<0.001) and OS (23.8 vs 17.4 months; P=0.0319) in white vs non-white, non-Asian patients.

Conclusion:

These analyses identified risk factors to survival with sunitinib, including potential ethnic-based differences, and validated risk factors previously reported in advanced RCC.     

Neutrophil Number After Interferon-Alfa Treatment is an Independent Predictive Marker of Overall Survival in Metastatic Renal Cell Carcinoma

BackgroundThe purpose of this study was to assess the outcome in patients treated by immunotherapy using interferon-alpha (IFN-α) and to evaluate the significance of the neutrophil count after IFN-α immunotherapy as a predictive marker for metastatic renal cell carcinoma (RCC).Patients and MethodsWe identified 84 patients with metastatic RCC who underwent immunotherapy with IFN-α between 1998 and 2006. The predictive values of the neutrophil count before and after IFN-α treatment as well as other clinical and laboratory parameters were assessed retrospectively.ResultsOn univariate analysis, the significant correlation with overall survival (OS) was recognized in the Eastern Cooperative Oncology Group (ECOG) performance score (PS), lactate dehydrogenase (LDH) levels, corrected calcium levels, interval from diagnosis to treatment, and the ratio of neutrophil number before and after treatment with INF-α. Multivariate analysis showed that ECOG PS, corrected calcium levels, interval from diagnosis to treatment and neutrophil number after IFN-α treatment were independent factors for OS. Using the number of neutrophils after IFN-α treatment, subgroups were identified using the Memorial Sloan-Kettering Cancer Center (MSKCC) model. The 1-year survival rate was 93% vs. 63% in the intermediate-risk group and 34% vs. 8% in the poor-risk group. In the favorable-risk group, all patients had a good decrease in neutrophil number after treatment with IFN-α.ConclusionNeutrophil number after IFN-α treatment can be a good predictive marker for OS in metastatic RCC. By combining MSKCC score with neutrophil number after treatment with IFN-α, we can subdivide each group.     

阿帕替尼治疗晚期胃癌的疗效预测和预后分析

背景与目的：阿帕替尼是全球首个针对晚期胃癌的口服抗血管生成药物,随着其在临床上的广泛应用,寻找合适的疗效预测标志物及筛选敏感人群成为亟待解决的重要问题。该研究旨在观察阿帕替尼治疗晚期胃癌的疗效及安全性,寻找有效的临床预测预后因素。方法：回顾性分析2015年1月—2016年8月收治的105例晚期胃癌患者的临床资料,均给予单药口服阿帕替尼。观察指标为治疗相关不良反应、疾病控制率(disease control rate,DCR)及无进展生存期(progression-free survival,PFS)。分析临床病理特征及治疗相关不良反应与疗效及预后的关系。结果：全组患者总体中位PFS(median DFS,mPFS)为71 d(95%CI：50.1~91.9 d),客观缓解率(objective response rate,ORR)为5.71%,DCR为65.71%。单因素分析显示,年龄大于56岁、ECOG评分0~1分、药物剂量500 mg、高血压、手足皮肤反应(hand-foot skin reaction,HFSR)、蛋白尿者PFS显著延长;而ECOG评分0~1分、药物剂量500 mg、高血压、HFSR、蛋白尿、腹泻者DCR较高。Cox和Logistic多因素分析显示,ECOG评分(P=0.007)、药物剂量(P=0.014)、高血压(P=0.012)及治疗相关HFSR(P=0.046)是阿帕替尼治疗晚期胃癌PFS的独立预后因素。ECOG评分0~1分(P=0.014)、高血压(P=0.043)及HFSR(P=0.012)与DCR高显著相关。结论：阿帕替尼治疗晚期胃癌患者具有良好的有效性和可控的安全性。ECOG评分、治疗期间出现高血压及HFSR是阿帕替尼治疗晚期胃癌DCR和PFS的独立预测因素,而药物剂量可作为PFS的独立预测因素。     

Prognosis of metastatic renal cell carcinoma with first‐line interferon‐α therapy in the era of molecular‐targeted therapy

The RCC‐SELECT study showed the correlation between single nucleotide polymorphisms (SNP) in STAT3 gene and survival in metastatic renal cell carcinoma (mRCC) patients with first‐line interferon‐α (IFN‐α). In that study, even patients with STAT3 SNP linked to shorter overall survival (OS) exhibited remarkably improved prognosis. All 180 patients evaluated in the above study were further analyzed for correlation between OS and demographics/clinicopathological parameters. OS was estimated using the Kaplan–Meier method. Associations between OS and potential prognostic factors were assessed using the log‐rank test and the Cox proportional hazards model. The median OS was 42.8 months. Univariate analysis showed that worse Eastern Cooperative Oncology Group‐performance status (ECOG‐PS), high T stage, regional lymph node metastasis, distant metastasis, higher grade, infiltrative growth pattern, the presence of microscopic vascular invasion (MVI), hypercalcemia, anemia, thrombocytopenia and elevated C‐reactive protein were significantly associated with OS. Multivariate analysis revealed that ECOG‐PS (hazard ratio [HR] = 3.665, P = 0.0004), hypercalcemia (HR = 6.428, P = 0.0005) and the presence of MVI (HR = 2.668, P = 0.0109) were jointly significant poor prognostic factors. This is the first study analysing prognostic factors of mRCC patients with first‐line IFN‐α using large cohort of the prospective study. The present study suggests that first‐line IFN‐α is still a useful therapy for mRCC even in the era of molecular targeted therapy.     

Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma.

PURPOSE: To identify prognostic factors and a model predictive for survival in patients with metastatic renal-cell carcinoma (RCC). PATIENTS AND METHODS: The relationship between pretreatment clinical features and survival was studied in 670 patients with advanced RCC treated in 24 Memorial Sloan-Kettering Cancer Center clinical trials between 1975 and 1996. Clinical features were first examined univariately. A stepwise modeling approach based on Cox proportional hazards regression was then used to form a multivariate model. The predictive performance of the model was internally validated through a two-step nonparametric bootstrapping process. RESULTS: The median survival time was 10 months (95% confidence interval [CI], 9 to 11 months). Fifty-seven of 670 patients remain alive, and the median follow-up time for survivors was 33 months. Pretreatment features associated with a shorter survival in the multivariate analysis were low Karnofsky performance status (<80%), high serum lactate dehydrogenase (> 1.5 times upper limit of normal), low hemoglobin (< lower limit of normal), high "corrected" serum calcium (> 10 mg/dL), and absence of prior nephrectomy. These were used as risk factors to categorize patients into three different groups. The median time to death in the 25% of patients with zero risk factors (favorable-risk) was 20 months. Fifty-three percent of the patients had one or two risk factors (intermediate-risk), and the median survival time in this group was 10 months. Patients with three or more risk factors (poor-risk), who comprised 22% of the patients, had a median survival time of 4 months. CONCLUSIONS: Five prognostic factors for predicting survival were identified and used to categorize patients with metastatic RCC into three risk groups, for which the median survival times were separated by 6 months or more. These risk categories can be used in clinical trial design and interpretation and in patient management. The low long-term survival rate emphasizes the priority of clinical investigation to identify more effective therapy.     

索拉非尼治疗进展期肝细胞癌的疗效及预后因素分析

  目的  评价索拉非尼治疗进展期肝细胞癌（HCC）的疗效及分析其预后影响因素。  方法  前瞻性分析2007年8月至2009年7月间110例接受索拉非治疗的进展期HCC患者,评价其疗效、不良反应,以总生存期和无肿瘤进展生存期为预后指标进行单因素和Cox比例风险模型多因素分析。  结果  110例患者随访中位时间9（2~18）个月,服用索拉非尼中位时间6.5（2~18）个月。14例（12.7%）获得完全缓解（CR）,16例（14.5%）部分缓解（PR）,40例（36.4%）病情稳定（SD）,总有效率为70例（63.6%）。中位生存期和无肿瘤进展生存期分别为10.5个月（95%CI:8.7~12.3）和5.0个月（95%CI:3.7~6.3）。多因素分析显示:联合局部治疗（肝动脉化疗栓塞或氩氦刀）、美国东部肿瘤协作组活动状态评分（Eastern Cooperative Oncology Group performance status score,ECOG PS）和Child-Pugh分级是影响无肿瘤进展生存时间的独立预后因素,而联合局部治疗、ECOG PS评分和AFP（alfa-fetopro? tein）水平是影响总生存期的独立预后因素。亚组分析显示:在肝癌进展组患者中继续服用索拉非尼其总生存期明显长于终止索拉非尼治疗者（11个月vs. 7.5个月,P < 0.001）。  结论  索拉非尼治疗进展期HCC,ECOG PS评分是影响生存期的一个重要因素,联合局部治疗有益于改善生存期。      

Prognostic factors for survival in patients with advanced renal cell carcinoma treated with recombinant interleukin-2.

A database of 327 patients with advanced Renal Cell Carcinoma (RCC) has been analyzed in order to identify potential baseline prognostic factors predicting for survival, following recombinant Interleukin-2 treatment (rIL-2). All patients received a continuous infusion (CIV). Eligibility criteria were uniform across studies, and included patients with an ambulatory performance status (PS), measurable disease, no CNS metastases, and no major organ compromise. Multivariate analyses identified baseline PS (ECOG 0 vs. 1), time from diagnosis to treatment (DTI greater than 24 months vs. less than or equal to 24 months), and the number of metastatic sites (1 vs. greater than or equal to 2, where lung, bone and other sites are considered as separate sites) as important predictors for survival. Patients can be classified into 4 subgroups, which are a function of the number of risk factors present. Median survival for each subgroup is 28, 17, 10 and 5 months, respectively. The model was validated in an independent cohort of 125 patients with RCC treated with subcutaneous (s/c) rIL-2, and predicted for survival accurately. By determining in which risk group category patients may fall, treating physicians may be better equipped to decide on patient management. The model may also be of value in order to stratify patients in randomized clinical trials.     

Long-term outcomes and prognostic factors of patients with advanced gastric cancer treated with S-1 plus cisplatin combination chemotherapy as a first-line treatment

Background

The long-term outcomes of advanced gastric cancer (AGC) patients treated with S-1 plus cisplatin (SP) combination chemotherapy remain unclear. Therefore, we sought to evaluate these outcomes to identify the prognostic factors affecting patient survival.

Methods

We retrospectively analyzed 153 AGC patients treated with SP at a single institution between January 2005 and July 2011.

Results

Median overall survival (OS) was 15.0 months [95 % confidence interval (CI), 12.5–17.9 months]. Three independent prognostic factors affecting poor survival were identified: performance status (PS) ≥ 1 [hazard ratio (HR) = 2.39, 95 % CI, 1.58–3.62); >1 metastatic site (HR = 1.57, 95 % CI, 1.10–2.26], and elevated alkaline phosphatase levels (HR = 1.70, 95 % CI, 1.16–2.49). A simple prognostic index was generated using three risk groups: good (no risk factor), moderate (one or two risk factors), and poor (three risk factors). The median OS for good-, moderate-, and poor-risk groups was 28.6, 14.8, and 7.3 months, respectively (log-rank test; P < 0.0001). Among the twelve 3-year survivors, 9 (75 %) had a PS of 0 and 8 (67 %) had only one metastatic site.

Conclusions

Three prognostic factors were identified in AGC patients treated with SP. Using a simple prognostic index, the patients were divided into three risk groups, in which the survival differences were markedly significant, suggesting that patients with good PS and only one metastatic site may have a higher chance of long-term survival than those with poor PS and multiple metastatic sites.     

Impact of clinicopathological characteristics on survival in patients treated with immune checkpoint inhibitors for metastatic melanoma

Immune checkpoint inhibitors (ICIs) have unprecedented effects on the treatment of metastatic melanoma. However, little is known about the prognostic values of various clinicopathological characteristics. Here, PubMed, Embase and Cochrane database were searched from inception to April 2018 for random controlled trials (RCTs) that compared ICIs with controls. The hazard ratios (HRs) for overall survival (OS) according to gender, age, Eastern Cooperative Oncology Group (ECOG) performance status (PS), lactate dehydrogenase (LDH) level and metastasis stage were extracted. Four phase III RCTs involving 1,598 patients with metastatic melanoma were included in this study. Compared with conventional agents, ICIs were associated with prolonged OS (HR, 0.67; 95% CI, 0.50–0.88; p = 0.005). The pooled OS HR was 0.60 (95% CI, 0.42–0.84; p = 0.003) in men; 0.84 (95% CI, 0.69–1.01; p = 0.07) in women. The difference in efficacy between men and women was significant (p_interaction = 0.03). The OS HR was 0.59 (95% CI, 0.41–0.83; p = 0.003) in patients >65 years old; 0.74 (95% CI, 0.55–1.01; p = 0.054) in patients <65 years old. The OS HR was 0.75 (95% CI, 0.60–0.94; p = 0.01) in patients with ECOG PS = 1; 0.64 (95% CI, 0.38–1.06; p = 0.08) in patients with ECOG PS = 0. Additionally, the long-term benefits were independent of metastasis stage and LDH level. In summary, although immunotherapy significantly prolongs OS in metastatic melanoma, the long-term benefits in women, younger patients (<65 years old) and patients with ECOG PS = 0 were marginal. These results may assist in treatment decision-making, design and interpretation of clinical trials and economic analyses.     

A population based analysis of prognostic factors in advanced biliary tract cancer

Background

Data regarding prognostic factors in advanced biliary tract cancer (BTC) remains scarce. The aim of this study was to review our institutional experience with cisplatin and gemcitabine in advanced BTC as well as to evaluate potential prognostic factors for overall survival (OS).

Material and methods

Consecutive patients with advanced BTC who initiated palliative chemotherapy with cisplatin and gemcitabine from 2009 to 2012 at the BC Cancer Agency were identified using the pharmacy database. Clinicopathologic variables and treatment outcome were retrospectively collected. Potential prognostic factors were assessed by univariate and multivariate analyses.

Results

A total of 106 patients were included in the analysis. Median OS was 8.5 months (95% CI: 6.5-10.5). On univariate analysis, poor ECOG performance status (ECOG PS) at diagnosis, primary tumor location (extra-hepatic cholangiocarcinoma, and unknown biliary cancer), and sites of advanced disease (extra-hepatic metastasis) were significantly associated with worse OS (P<0.001, 0.036 and 0.034, respectively). Age, gender, CA19-9, CEA, hemoglobin, neutrophil count, and prior stent were not significantly associated with OS. On multivariate analysis, ECOG PS 2/3 was the only predictor of poor OS (P<0.001), while primary location (P=0.089) and sites of advanced disease (P=0.079) had a non-significant trend towards prognostic significance.

Conclusions

In this population based analysis, a poorer performance status was significantly prognostic of worse OS. Although not significant in our analysis, primary tumor location and sites of advanced disease may also have prognostic relevance.     

Long-term responders and survivors on pazopanib for advanced soft tissue sarcomas: subanalysis of two European Organisation for Research and Treatment of Cancer (EORTC) clinical trials 62043 and 62072

BackgroundPazopanib recently received approval for the treatment of certain soft tissue sarcoma (STS) subtypes. We conducted a retrospective analysis on pooled data from two EORTC trials on pazopanib in STS in order to characterize long-term responders and survivors.Patients and methodsSelected patients were treated with pazopanib in phase II (n = 118) and phase III study (PALETTE) (n = 226). Combined median progression-free survival (PFS) was 4.4 months; the median overall survival (OS) was 11.7 months. Thirty-six percent of patients had a PFS ≥ 6 months and were defined as long-term responders; 34% of patients survived ≥18 months, defined as long-term survivors. Patient characteristics were studied for their association with long-term outcomes.ResultsThe median follow-up was 2.3 years. Patient characteristics were compared among four subgroups based on short-/long-term PFS and OS, respectively. Seventy-six patients (22.1%) were both long-term responders and long-term survivors. The analysis confirmed the importance of known prognostic factors in metastatic STS patients treated with systemic treatment, such as performance status and tumor grading, and additionally hemoglobin at baseline as new prognostic factor. We identified 12 patients (3.5%) remaining on pazopanib for more than 2 years: nine aged younger than 50 years, nine females, four with smooth muscle tumors and nine with low or intermediate grade tumors at initial diagnosis. The median time on pazopanib in these patients was 2.4 years with the longest duration of 3.7 years.ConclusionsThirty-six percent and 34% of all STS patients who received pazopanib in these studies had a long PFS and/or OS, respectively. For more than 2 years, 3.5% of patients remained progression free under pazopanib. Good performance status, low/intermediate grade of the primary tumor and a normal hemoglobin level at baseline were advantageous for long-term outcome.NCT00297258 (phase II) and NCT00753688 (phase III, PALETTE).     

Long-Term Survival of Patients With Non-Small Cell Lung Cancer Treated With Immune Checkpoint Inhibitor Monotherapy in Real-World Settings

BackgroundImmune checkpoint inhibitor (ICI) monotherapy is more effective than cytotoxic chemotherapy in improving overall survival (OS) among patients with advanced-stage non-small cell lung cancer (NSCLC). Recently, chemotherapy combined with ICI has been found to yield good outcomes. However, ICI monotherapy is still considered an important treatment option. Data on long-term progression-free survival (PFS) and OS in real-world settings are limited.Patients and MethodsThis was a multicenter retrospective observational study. A total of 435 consecutive patients histologically diagnosed with advanced, metastatic, or recurrent NSCLC treated with ICI monotherapy were enrolled in this study from December 2015 to December 2018. Clinical data were collected from electronic medical records and pharmacy databases.ResultsThe PFS and OS of the patients were 3.4 and 13.0 months, respectively. The objective response and disease control rates were 22.8% and 54.9%, respectively, and the 4-year survival rate was 17.9%. Multivariate analyses revealed that elder patients (>70 years), good Eastern Cooperative Oncology Group Performance Status (ECOG PS) score, programmed death-ligand 1 tumor proportion score (PD-L1 TPS) of ≥ 50%, absence of bone metastasis, and presence of immune-related skin toxicity, which is an immune-related adverse event, were correlated with good PFS. Moreover, good ECOG PS score, PD-L1 TPS of ≥ 50%, absence of bone metastasis, and presence of skin toxicity were correlated with good OS.ConclusionsThe 4-year survival rate was 17.9%. Good ECOG PS score, PD-L1 TPS of ≥ 50%, absence of bone metastasis, and presence of skin toxicity were correlated with good PFS and OS.     

Prognostic value of baseline functional status measures and geriatric screening in vulnerable older patients with metastatic colorectal cancer receiving palliative chemotherapy – The randomized NORDIC9-study

IntroductionAppropriate patient selection based on functional status is crucial when considering older adults for palliative chemotherapy. This pre-planned analysis of the randomized NORDIC9-study explored the prognostic value of four functional status measures regarding progression-free survival (PFS) and overall survival (OS) in vulnerable older patients with metastatic colorectal cancer (mCRC) receiving first-line palliative chemotherapy.Materials and methodsPatients ≥70 years of age with mCRC not candidates for standard full-dose combination chemotherapy were randomized to receive full-dose S1 or reduced-dose S1 + oxaliplatin. At baseline, functional status was assessed using ECOG performance status (ECOG PS), frailty phenotype, Geriatric 8 (G8), and Vulnerable Elderly Survey-13 (VES-13). Multivariable regression models were applied and C-statistics were estimated.ResultsIn total, 160 patients with a median age of 78 years (IQR: 76–81) were included. While in univariate analyses, ECOG PS, frailty phenotype, and VES-13 were statistically significantly associated with differences in OS between subgroups, G8 was not (HR = 1.55, 95%CI: 0.99–2.41, p = 0.050). In multivariable analyses adjusted for age, sex, body mass index, and treatment allocation, we found significant differences between subgroups for all applied tools and with C-statistics in the moderate range for ECOG PS and VES-13.Concerning PFS, statistically significant differences were observed between subgroups of ECOG PS, G8, and VES-13 both in uni- and multivariable analyses, but not for frailty phenotype.DiscussionIn this Nordic cohort of vulnerable older patients with mCRC, baseline ECOG PS, frailty phenotype, G8, and VES-13 showed prognostic value regarding overall survival, and moderate predictive value of models based on ECOG PS and VES-13 was demonstrated.