Five‐year lung cancer survival

BACKGROUND:

The core strategy of American College of Chest Physicians lung cancer guidelines is identification of the earliest symptoms of lung cancer and the immediate initiation of diagnosis and treatment. In the absence of screening, most symptomatic lung cancer is discovered at advanced stages, with the goal of long‐term survival entirely dependent on effective treatment of stage III and IV lung cancer.

METHODS:

In a retrospective review, all patients diagnosed with stage IIIA, IIIB, and IV nonsmall cell lung cancer (NSCLC) between the years 1986 and 2001 at City of Hope National Medical Center who survived 5 years or longer were analyzed to identify parameters that might predict long‐term survival.

RESULTS:

Of 846 patients presenting with stage III or IV disease, 56 (6.6%) survived 5 years or longer. Sixteen patients died of primary tumor progression beyond 5 years. Two 5‐year survivors died of second tobacco‐caused neoplasms, and 16 died from medical conditions potentially related to prior treatment. A substantial majority of survivors were from specific pathologic subsets including: 1) resectable N2 disease (n = 17, 30.4%), 2) multiple lung tumors (n = 7, 12.5%), 3) T3N0 (n = 5, 8.1%), and 4) single site distant metastasis (n = 8, 14.2%).

CONCLUSIONS:

Despite aggressive multimodality therapy, 5‐year survival in patients with advanced stage NSCLC was very poor and limited to small pathological subsets. Patients with advanced stage NSCLC who did not belong to 1 of these subsets had a small chance of long‐term survival. Cancer 2010. © 2010 American Cancer Society.     

Up‐to‐date cancer survival: Period analysis and beyond

Since its introduction in 1996, period analysis has been shown to be useful for deriving more up‐to‐date cancer survival estimates, and the method is now increasingly used for that purpose in national and international cancer survival studies. However, period analysis, like other commonly employed methods, is just a special case from a broad class of design options in the analysis of cancer survival data. Here, we explore a broader range of design options, including 2 model‐based approaches, for deriving up‐to‐date estimates of 5‐ and 10‐year relative survival for patients diagnosed in the most recent 5‐year interval for which data are available. The performance of the various designs is evaluated empirically for 20 common forms of cancer using more than 50‐year long time series of data from the Finnish Cancer Registry. Period analysis as well as the 2 model‐based approaches, one using a “cohort‐type model” and another using a “period‐type model”, all performed better than traditional cohort or complete analysis. Compared with “standard period analysis”, the cohort‐type model further increased up‐to‐dateness of survival estimates, whereas the period‐type model increased their precision. While our analysis confirms advantages of period analysis over traditional methods in terms of up‐to‐dateness of cancer survival data, further improvements are possible by flexible use of model‐based approaches. © 2008 Wiley‐Liss, Inc.     

Long‐term survival and conditional survival of cancer patients in Japan using population‐based cancer registry data

Although we usually report 5‐year cancer survival using population‐based cancer registry data, nowadays many cancer patients survive longer and need to be followed‐up for more than 5 years. Long‐term cancer survival figures are scarce in Japan. Here we report 10‐year cancer survival and conditional survival using an established statistical approach. We received data on 1 387 489 cancer cases from six prefectural population‐based cancer registries in Japan, diagnosed between 1993 and 2009 and followed‐up for at least 5 years. We estimated the 10‐year relative survival of patients who were followed‐up between 2002 and 2006 using period analysis. Using this 10‐year survival, we also calculated the conditional 5‐year survival for cancer survivors who lived for some years after diagnosis. We reported 10‐year survival and conditional survival of 23 types of cancer for 15–99‐year‐old patients and four types of cancer for children (0–14 years old) and adolescent and young adults (15–29 years old) patients by sex. Variation in 10‐year cancer survival by site was wide, from 5% for pancreatic cancer to 95% for female thyroid cancer. Approximately 70–80% of children and adolescent and young adult cancer patients survived for more than 10 years. Conditional 5‐year survival for most cancer sites increased according to years, whereas those for liver cancer and multiple myeloma did not increase. We reported 10‐year cancer survival and conditional survival using population‐based cancer registries in Japan. It is important for patients and clinicians to report these relevant figures using population‐based data.     

Stromal cell‐derived CSF‐1 blockade prolongs xenograft survival of CSF‐1‐negative neuroblastoma

The molecular mechanisms of tumor–host interactions that render neuroblastoma (NB) cells highly invasive are unclear. Cancer cells upregulate host stromal cell colony‐stimulating factor‐1 (CSF‐1) production to recruit tumor‐associated macrophages (TAMs) and accelerate tumor growth by affecting extracellular matrix remodeling and angiogenesis. By coculturing NB with stromal cells in vitro, we showed the importance of host CSF‐1 expression for macrophage recruitment to NB cells. To examine this interaction in NB in vivo, mice bearing human CSF‐1‐expressing SK‐N‐AS and CSF‐1‐negative SK‐N‐DZ NB xenografts were treated with intratumoral injections of small interfering RNAs directed against mouse CSF‐1. Significant suppression of both SK‐N‐AS and SK‐N‐DZ NB growth by these treatments was associated with decreased TAM infiltration, matrix metalloprotease (MMP)‐12 levels and angiogenesis compared to controls, while expression of tissue inhibitors of MMPs increased following mouse CSF‐1 blockade. Furthermore, Tie‐2‐positive and ‐negative TAMs recruited by host CSF‐1 were identified in NB tumor tissue by confocal microscopy and flow cytometry. However, host‐CSF‐1 blockade prolonged survival only in CSF‐1‐negative SK‐N‐DZ NB. These studies demonstrated that increased CSF‐1 production by host cells enhances TAM recruitment and NB growth and that the CSF‐1 phenotype of NB tumor cells adversely affects survival.     

Twenty‐four‐month postradiation prostate biopsies are strongly predictive of 7‐year disease‐free survival

BACKGROUND:

The objective of this study was to evaluate the predictive value of prostate biopsies that were obtained 24 months after the completion of radiotherapy (RT) with respect to disease‐free survival (DFS) in a randomized trial that compared 3 months versus 8 months of neoadjuvant hormone therapy before conventional dose external RT.

METHODS:

From February 1995 to June 2001, 378 men were randomized to receive either 3 months or 8 months of combined flutamide and goserelin before they received 66 Gray of RT at 4 participating centers. By risk group, 26% of patients were categorized as low risk, 43% were categorized as intermediate risk, and 31% were categorized as high risk. The 2 treatment arms were balanced in terms of age, Gleason score, clinical tumor classification, risk group, and presenting prostate‐specific antigen level. The median follow‐up for the patients who remained alive was 6.6 years (range, 1.6‐10.1 years). Of 361 evaluable patients, 290 patients remained alive. Post‐RT prostate biopsies were performed between 24 and 30 months after the completion of RT in 3 of the 4 centers. Biopsies that had residual tumor with severe treatment effect were considered indeterminate, and biopsies that had minimal or no treatment effect were considered positive.

RESULTS:

The 5‐year rate of actuarial freedom from any failure for the 3‐month arm versus the 8‐month arm was 72% versus 75% (P = .18). The DFS for patients who had negative and indeterminate biopsies was similar. Two‐year post‐treatment biopsy status was a strong predictor of 5‐year DFS rate (82% and 83% for negative and indeterminate biopsies, respectively, vs 27% for positive biopsies; P < .0001). Multivariate analysis indicated that biopsy status (P < .0001) and Gleason score (P < .0001) were the strongest determinates of biochemical DFS.

CONCLUSIONS:

Two‐year post‐RT prostate biopsies were strongly predictive of subsequent DFS. Biopsies with severe treatment effect were considered negative. Cancer 2009. © 2008 American Cancer Society.     

Why post‐progression survival and post‐relapse survival are not appropriate measures of efficacy in cancer randomized clinical trials

Comparisons of post‐relapse survival (PRS) and post‐progression survival have been used to measure efficacy in some cancer clinical trials. These comparisons are an attempt to account for second‐line therapies and to identify benefits that do not translate in longer overall survival. However, the use of PRS comparisons can be misleading (either a longer or shorter PRS may indicate a benefit, depending on the circumstances) and can result in biased estimates (because of selection). Here, we describe the problems surrounding PRS comparisons and propose alternative approaches to deal with non‐randomized therapies administered after progression to the experimental treatment.     

Model‐based projections for deriving up‐to‐date cancer survival estimates: An international evaluation

Model‐based projections were shown to be useful for deriving most up‐to‐date population‐based cancer survival estimates. However, the performance of these projections, which can be derived by various approaches, has only been evaluated in very few cancer patient populations. Using incidence and follow‐up data for 22 common cancers from 9 long‐standing population‐based cancer registries from diverse parts of Europe, we compared the performance of model‐based period and cohort analysis for predicting 5‐year relative survival of patients diagnosed in 1996–2000 against standard survival analysis approaches (cohort, complete and period analysis). Overall, model‐based predictions provided a best estimate of the later observed actual survival in 135 of 198 occasions, compared to 25, 18 and 33 occasions for cohort, complete and period analysis, respectively. Projections based on cohort and period type modeling performed essentially equally well on average, and their performance was better for more common cancers, in registries with larger population bases, and for cancers subjected to continuous clinical progress and/or ongoing screening efforts. Projections from model‐based analysis may contribute to improved timeliness of monitoring of concurrent trends in population‐based cancer survival in cancer registries operating in different populations and socioeconomic environments. © 2009 UICC     

Conditional probability of long‐term survival in glioblastoma

BACKGROUND:

Advances in glioblastoma care have resulted in a larger proportion of patients surviving beyond 2 years after diagnosis. It is not clear how long‐term survivors should be counseled with respect to future prognosis, or what factors influence that prognosis. The conditional probability of survival was evaluated from multiple time points in patients with glioblastoma, using Surveillance, Epidemiology, and End Results (SEER) data.

METHODS:

Patients diagnosed with glioblastoma from 1998 to 2008 who were treated with radiation‐containing regimens were identified within SEER data. Conditional survival probabilities from multiple survival points were calculated. Cox proportional hazards models were constructed to identify predictors of survival from diagnosis and from 1 and 2 years after diagnosis.

RESULTS:

A total of 10,022 patients with glioblastoma met study inclusion criteria; median survival was 12.61 months. Conditional probability of surviving an additional 2 years ranged from 19.8% at diagnosis to 65.9% at 5 years after diagnosis. The proportion of patients surviving 12 months from time of diagnosis as well as from 6, 12, and 18 months after diagnosis was significantly higher in patients diagnosed in 2005 through 2008 than those diagnosed in 1998 through 2004. Of demographic and treatment‐related factors evaluated, only age was associated with hazard of death at diagnosis and 1 and 3 years after diagnosis (P < .0001 at each time point).

CONCLUSIONS:

Patients surviving past 2 years from diagnosis have a relatively favorable conditional probability of survival into the future compared to newly diagnosed patients. This effect becomes more pronounced with increasing time since diagnosis. These data will assist in the counseling of glioblastoma survivors. Cancer 2012. © 2012 American Cancer Society.     

Response and survival benefit with chemoimmunotherapy in Epstein‐Barr virus‐positive diffuse large B‐cell lymphoma

Epstein‐Barr virus (EBV)‐positive diffuse large B‐cell lymphoma (DLBCL) is a haematologic malignancy with poor prognosis when treated with chemotherapy. We evaluated response and survival benefits of chemoimmunotherapy in EBV‐positive DLBCL patients. A total of 117 DLBCL patients were included in our retrospective analysis; 33 were EBV‐positive (17 treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R‐CHOP] and 16 with CHOP), and 84 were EBV‐negative (all treated with R‐CHOP). The outcomes of interest were complete response (CR) and overall survival (OS) in EBV‐positive DLBCL patients (R‐CHOP versus CHOP) and in DLBCL patients treated with R‐CHOP (EBV‐positive vs EBV‐negative). There were no differences in the clinical characteristics between EBV‐positive and EBV‐negative DLBCL patients. Among EBV‐positive DLBCL patients, R‐CHOP was associated with higher odds of CR (OR 3.14, 95% CI 0.75‐13.2; P = .10) and better OS (hazard ratio 0.30, 95% confidence interval [CI] 0.09‐0.94; P = .04). There were no differences in CR rate (OR 0.52, 95% CI 0.18‐1.56; P = .25) or OS (hazard ratio 0.93, 95% CI 0.32‐2.67; P = .89) between EBV‐positive and EBV‐negative DLBCL patients treated with R‐CHOP. Based on our study, the addition of rituximab to CHOP is associated with improved response and survival in EBV‐positive DLBCL patients. Epstein‐Barr virus status does not seem to affect response or survival in DLBCL patients treated with R‐CHOP.     

Season of cancer diagnosis exerts distinct effects upon short‐ and long‐term survival

Several epidemiological studies have shown an association between the season in which certain cancers are diagnosed and survival, with diagnosis in summer and autumn being associated with better survival. In this study, we have added resolution to the analysis of seasonality in cancer survival by considering mortality within several nonoverlapping time periods following diagnosis, thereby quantifying the separate contributions of mechanisms operating in the short term and in the longer term. We found evidence of seasonality acting on mortality within 2 distinct periods following diagnosis. Diagnosis in the summer was associated with substantially decreased mortality within the first month of diagnosis compared with winter in men with prostate cancer, those of both sexes with colorectal or lung cancer, and most strikingly, amongst women with breast cancer (hazard ratio 0.81 [95% confidence interval 0.75–0.86]). Adjusting for monthly variations in general mortality greatly attenuated the seasonal effects on short‐term mortality. At long‐term follow‐up (>5 years), there was a consistent shift in the seasonality pattern, with autumn diagnosis alone being associated with decreased mortality, both in female breast cancer cases and in lung cancer cases of both sexes. We conclude that the higher survival observed amongst patients diagnosed in summer and autumn is predominantly a short‐term phenomenon that is largely attributable to generally higher mortality in winter. However, the distinct mortality reduction observed in the long term amongst those diagnosed in the autumn, especially amongst breast cancer patients, may indicate the presence of a seasonally variable protective mechanism. © 2008 Wiley‐Liss, Inc.