Outcomes after Surgery for Early Stage Breast Cancer in Women Staged With Preoperative Breast Magnetic Resonance Imaging According to Breast Tissue Density.

PURPOSE: To determine surgical outcomes and breast cancer disease-free survival outcomes of women with early stage breast cancer with and without use of preoperative breast MRI according to breast tissue density. METHODS: Women with early stage breast cancer diagnosed from 2004 to 2009 were classified into 2 groups: 1) those with dense and heterogeneously dense breasts (DB); 2) those with nondense breasts (NDB) (scattered fibroglandular and fatty replaced tissue). The 2 groups were reviewed to determine who underwent preoperative MRI. Breast tissue density was determined with mammography according to ACR BI-RADS. Patients were compared according to tumor size, grade, stage, and treatment. Survival analysis was performed using Kaplan-Meier estimates. RESULTS: In total, 261 patients with mean follow-up of 85 months (25-133) were included: 156 DB and 105 NDB. Disease-free survival outcomes were better in the DB group in patients with MRI than in those without MRI: patients with MRI had significantly fewer local recurrences (P < 0.016) and metachronous contralateral breast cancers (P < 0.001), but this was not the case in the NDB group. Mastectomies were higher in the DB group with preoperative MRI than in those without MRI (P < 0.01), as it was in the NDB group (P > 0.05). CONCLUSIONS: Preoperative breast MRI was associated with reduced local recurrence and metachronous contralateral cancers in the DB group, but not in the NDB group; however, the DB patients with MRI had higher mastectomy rates.

Prophylactic Cranial Irradiation in Extensive Stage Small Cell Lung Cancer: Outcomes at a Comprehensive Cancer Centre.

PURPOSE: The role of prophylactic cranial irradiation (PCI) remains controversial in extensive stage small cell lung cancer (ES-SCLC) with the publication of 2 randomized control trials demonstrating differing outcomes in overall survival. The aim of this study is to determine the impact of PCI on survival and the development of brain metastasis while addressing the disparate use of postchemotherapy brain imaging in the aforementioned trials. METHODS AND MATERIALS: The medical records of 397 consecutive patients with ES-SCLC between Jan. 1, 2005 and Dec. 31, 2011 were retrospectively reviewed. In those eligible patients (n = 155) without baseline brain metastases and who had at least a partial response to chemotherapy, overall survival and time to brain metastasis were estimated using the Kaplan-Meier method comparing patients receiving PCI or not, using both univariate and multivariate analyses. Patients were stratified by their receipt of initial postchemotherapy brain imaging. Follow-up did not include serial brain imaging, which was performed when clinically indicated. Differences between the groups with covariates were analyzed using χ2 statistics and Student's t-tests. RESULTS: By multivariate analysis, statistically significant predictors of overall survival were the presence of extrathoracic metastases, performance status and use of PCI. There was a statistically significant difference in overall survival (HR 0.55; 95% CI: 0.39-0.77; P = .0005) and time to brain metastasis (HR 0.40; 95% CI: 0.23-0.66; P = .0004) with the use of PCI. Median survival for the PCI and non-PCI groups was 13.5 and 8.5 months respectively. A survival difference with PCI was observed in both patients that received postchemotherapy brain imaging (HR 0.55; 95% CI: 0.35-0.88; P = .012) and those who did not (HR 0.48; 95% CI: 0.29-0.77; P = .0025). CONCLUSIONS: PCI in the setting of at least a partial response to chemotherapy was found to have a survival benefit and prolongation of the time to development of brain metastases, when factoring in the use of initial postchemotherapy but not routine surveillance brain imaging.

Age Bias in Time From Diagnosis Comparisons of Prostate Cancer Treatment.

OBJECTIVES: Observational studies of prostate cancer treatment have demonstrated a major survival benefit with prostatectomy; randomized trials have been less certain in this regard. This discrepancy is hypothesized to be due to the use survival calculations based on time from diagnosis (TFD), which can bias toward better survival for younger cohorts. Attained age is an alternative timescale that can mitigate this effect. A Surveillance, Epidemiology and End Results comparison of prostatectomy, radiotherapy (XRT), and conservative management for localized prostatic cancer was conducted to compare these 2 timescales. METHODS: Kaplan-Meier analysis was used to contrast overall survival based on TFD and attained age from 279,064 prostate cancer cases. Proportional hazards models were constructed and baseline hazard functions estimated. RESULTS: The prostatectomy cohort averaged 9 to 12 years younger than the radiotherapy or conservative management cohorts, and the baseline hazard depended more strongly upon age than TFD. Survival calculations based on TFD demonstrated a major benefit with prostatectomy compared with XRT and conservative management, consistent with prior observational studies. Calculations based on attained age, however, demonstrated lesser differences between treatment cohorts and were more consistent with published randomized trials. CONCLUSIONS: The survival benefit apparent to prostatectomy in conventional observational cohort studies could reflect an age-related bias attributable to their use of TFD analysis. Care is warranted in the choice of timescale in observational analysis if large age differences exist between treatment cohorts. Randomized controlled trials remain the most reliable means to compare prostate cancer treatments.

Pancreatectomy Versus Conservative Management for Pancreatic Cancer: A Question of Lead-time Bias.

OBJECTIVES: Pancreatectomy is regarded as the only curative treatment for cancer of the pancreas. A population-based study was conducted to examine its efficacy within the general community. METHODS: Overall and cancer-specific survivals were compared between individuals treated with pancreatectomy and those managed nonsurgically. Kaplan-Meier analysis was used, based on both time from diagnosis and attained age (age at diagnosis plus time from diagnosis). RESULTS: A total of 7830 Surveillance Epidemiology and End Results cases of localized cancer of the pancreatic head were retrieved, diagnosed from 2000 to 2008. Median follow-up was 12 months; the pancreatectomy cohort was 5 years younger and had 7-fold less stage III disease. Overall and cancer-specific survivals were 17% and 21% at 5 years from time of diagnosis in the pancreatectomy cohort versus 2% and 4% in the nonsurgical cohort, respectively (P<0.001). However, the overall and cancer-specific survival curves were nearly superimposed on each other when based on attained age. Moreover, the proportion of deaths attributable to pancreatic cancer exceeded 85% in both cohorts. CONCLUSIONS: A lead-time bias is hypothesized to explain the survival discrepancies seen between time from diagnosis and attained age analyses; the pancreatectomy cohort was diagnosed earlier, with less disease. If most of these individuals had occult metastases at diagnosis, which manifested later and caused death at similar ages as the nonsurgical cohort, their survival from time of diagnosis would appear speciously improved. A randomized controlled trial would be necessary to confirm whether or not the survival advantage ascribed to pancreatectomy should be attributed to lead-time bias.

Role of fine-needle aspiration in the surgical management of pancreatic neuroendocrine tumors: utility and limitations in light of the new World Health Organization classification.

CONTEXT: Pancreatic neuroendocrine tumors (Panc-NETs) are rare and tend to get overshadowed by their more prevalent and aggressive ductal adenocarcinoma counterparts. The biological behavior of PancNETs is unpredictable, and thus management is controversial. However, the new World Health Organization classification has significantly contributed to the prognostic stratification of these patients. Concurrently, there have been advances in surgical techniques for benign or low-grade pancreatic tumors. These procedures include minimally invasive and parenchyma-sparing operations such as laparoscopy and enucleation. OBJECTIVE: To report on the utility and limitations of fine-needle aspiration in the preoperative evaluation and management of PancNETs. DESIGN: This was a retrospective review of our institutional tumor database from 2002 to 2012. There were 25 cases of PancNETs that were localized and staged by medical imaging and diagnosed by fine-needle aspiration. RESULTS: Fourteen patients underwent laparotomy, with some requiring only limited surgery; 4 had laparoscopic resections; 4 were serially observed without surgical intervention; and another 3 were inoperable. After a mean follow-up of 37 months, more than half of the patients had no evidence of disease, including most of those who underwent minimally invasive surgery. CONCLUSIONS: Fine-needle aspiration is a useful diagnostic adjunct to medical imaging in the preoperative evaluation and management of PancNETs. However, there are limitations with regard to grading PancNETs using this technique.

Oligometastasis as a predictor for occult disease.

Oligometastasis can be defined as a state of limited metastases that is potentially amenable to ablative local therapy; the success of such therapy depends on whether or not additional occult metastases exist. A model is presented here to predict occult metastases given detectable oligometastases. Predictions were based on Bayes' theorem, in conjunction with descriptions of the statistical distributions for the sizes and numbers of hematogenous metastases. The background probability for occult metastases in individuals with oligometastases increased markedly with relatively minor increases in metastatic potential. With each additional metastasis detected the chance of further occult metastases increased. These latter increases were incremental and proportionately smaller with the more metastatic tumors. Long disease free intervals had a major effect to decrease in the probability of further occult disease. Demonstration of oligometastases depends heavily upon the sensitivity of radiological imaging techniques, where the proportion of detectable metastases relates to the position of the distribution of metastasis growth times with respect to the detection threshold. Given the limitations of radiological methods, and the possibility that the oligometastases detected may be the only disease, an aggressive approach appears indicated.

Comparative risk factors for accidental and suicidal death in cancer patients.

BACKGROUND: Cancer patients appear at higher risk of accidental death and suicide. The reasons for this and how suicide and accidental death relate remain unclear. AIMS: To clarify and contrast risk factors for such deaths among cancer patients. METHODS: A SEER (1973-2007) analysis was conducted on 4,449,957 cancer patients comparing all causes of death (COD) to accidental and suicidal deaths through competing hazards, relative risk and proportional hazards models. SEER did not provide psychological assessments; the analysis was confined to their standard epidemiological and clinicopathological parameters. RESULTS: 2,557,385 overall deaths yielded 16,879 (0.66%) accidents and 6,589 (0.26%) suicides. Mortality reached its highest incidence immediately after diagnosis and obeyed Pareto type II distributions. The major identifiable risk factor for suicide was male gender; for accidental death, First Nations ethnicity; and all COD, metastases. Minor factors for suicide included metastases, advanced age, and respiratory as well as head and neck tumors, whereas for accidental death they were male gender, metastases, advanced age, and brain tumors. CONCLUSIONS: Differences were observed in the risk patterns of suicide and accidental death, suggesting distinct etiologies. A high incidence of suicides and accidental deaths following diagnosis (attributed by some to stress from the diagnosis of cancer) correlated here with overall mortality and indicators of physical morbidity. Cancer patients with the above identifiable risk factors warrant supportive attention.

Taylor's power law and fluctuation scaling explained by a central-limit-like convergence.

A power function relationship observed between the variance and the mean of many types of biological and physical systems has generated much debate as to its origins. This Taylor's law (or fluctuation scaling) has been recently hypothesized to result from the second law of thermodynamics and the behavior of the density of states. This hypothesis is predicated on physical quantities like free energy and an external field; the correspondence of these quantities with biological systems, though, remains unproven. Questions can be posed as to the applicability of this hypothesis to the diversity of observed phenomena as well as the range of spatial and temporal scales observed with Taylor's law. We note that the cumulant generating functions derived from this thermodynamic model correspond to those derived over a quarter century earlier for a class of probabilistic models known as the Tweedie exponential dispersion models. These latter models are characterized by variance-to-mean power functions; their phenomenological basis rests with a central-limit-theorem-like property that causes many statistical systems to converge mathematically toward a Tweedie form. We review evaluations of the Tweedie Poisson-gamma model for Taylor's law and provide three further cases to test: the clustering of single nucleotide polymorphisms (SNPs) within the horse chromosome 1, the clustering of genes within human chromosome 8, and the Mertens function. This latter case is a number theoretic function for which a thermodynamic model cannot explain Taylor's law, but where Tweedie convergence remains applicable. The Tweedie models are applicable to diverse biological, physical, and mathematical phenomena that express power variance functions over a wide range of measurement scales; they provide a probabilistic description for Taylor's law that allows mechanistic insight into complex systems without the assumption of a thermodynamic mechanism.

Tweedie convergence: a mathematical basis for Taylor's power law, 1/f noise, and multifractality.

Plants and animals of a given species tend to cluster within their habitats in accordance with a power function between their mean density and the variance. This relationship, Taylor's power law, has been variously explained by ecologists in terms of animal behavior, interspecies interactions, demographic effects, etc., all without consensus. Taylor's law also manifests within a wide range of other biological and physical processes, sometimes being referred to as fluctuation scaling and attributed to effects of the second law of thermodynamics. 1/f noise refers to power spectra that have an approximately inverse dependence on frequency. Like Taylor's law these spectra manifest from a wide range of biological and physical processes, without general agreement as to cause. One contemporary paradigm for 1/f noise has been based on the physics of self-organized criticality. We show here that Taylor's law (when derived from sequential data using the method of expanding bins) implies 1/f noise, and that both phenomena can be explained by a central limit-like effect that establishes the class of Tweedie exponential dispersion models as foci for this convergence. These Tweedie models are probabilistic models characterized by closure under additive and reproductive convolution as well as under scale transformation, and consequently manifest a variance to mean power function. We provide examples of Taylor's law, 1/f noise, and multifractality within the eigenvalue deviations of the Gaussian unitary and orthogonal ensembles, and show that these deviations conform to the Tweedie compound Poisson distribution. The Tweedie convergence theorem provides a unified mathematical explanation for the origin of Taylor's law and 1/f noise applicable to a wide range of biological, physical, and mathematical processes, as well as to multifractality.

Extinction kinetics for metastatic cancer stem cells.

PURPOSE: Cancer Stem Cells (CSC) are hypothesised to influence tumour growth through their self-replication, cell loss, and differentiation into growth-limited cell types. A model for the random gain and loss of metastatic CSC is developed to investigate how the balance between these processes might affect metastatic efficiency, tumour involution and treatment response. MATERIALS AND METHODS: A stochastic birth-death model for metastasis was constructed for the replication and loss of CSC. The model was extended to account for single and sequential cancer treatments, with CSC repopulation. RESULTS: If CSC losses exceed gains, the metastasis would become extinct. The resultant extinction probability was greatest during a period of stochastic susceptibility; treatment could extend, or reestablish, this period. CONCLUSION: Random CSC losses, with 'seed and soil' selection, provided a mechanistic explanation for the involution of metastases, as well as for metastatic inefficiency. With such background losses, and the growth limitations of differentiated cells, a metastasis could take years to reach macroscopic size. The susceptibility period could be protracted, providing for a window for therapeutic opportunity. Metastases with a high background CSC loss would be more responsive to treatment than stabler metastases. Modulation of this loss could enhance the efficacy of conventional cancer treatment.

Histological subtypes of prostatic cancer: a comparative survival study.

INTRODUCTION: Variant histological subtypes of prostatic cancer occur uncommonly and are associated with poor survival, as has been ascertained through limited series and case reports. Here a population-based analysis of prostatic cancer is provided, to better analyze the survival behavior of these subtypes. MATERIALS AND METHODS: The American SEER registry was used to review prostatic cancer diagnosed from 1988 to 2003, classified according to the International Classification of Diseases for Oncology. Kaplan-Meier and proportional hazards analyses were performed on adenocarcinomas and five infrequent variant subtypes to determine their overall survival behavior, allowing corrections for follow up inequity, age, stage, histological grade, and year of diagnosis. RESULTS: A total of 455,296 cases of prostatic cancer were reviewed, of which over 99% were conventional adenocarcinomas. The remaining variants studied included ductal carcinomas (0.141%), mucinous adenocarcinomas (0.103%), small cell carcinomas (0.056%), carcinosaromas (0.07%) and embryonal carcinosarcomas (0.06%). With age, stage and grade effects were corrected for in the multivariate analysis, conventional adenocarcinomas, mucinous adenocarcinomas and ductal carcinomas exhibited similar survival behavior. Small cell carcinomas and carcinosarcomas exhibited poor survival, even with correction. The embryonal variant of carcinosarcoma affected pediatric patients and had an overall survival similar to conventional prostatic cancer. Ductal carcinomas, small cell carcinomas and both types of carcinosarcoma tended to present with metastases more frequently than conventional disease. CONCLUSIONS: Prostatic cancer subtype can have a major bearing on overall survival and likely reflects intrinsic differences in biological behavior.

Dying with cancer: the influence of age, comorbidity, and cancer site.

BACKGROUND: Cancer survival is influenced by age, comorbidity, and type of cancer. A population-based study was conducted to compare the interplay between age and mortality for different cancers. METHODS: This study analyzed 784,378 cases, comprising 22 of the commonest SEER cancers diagnosed between 1984 and 1993. Competing hazards and proportional hazard analyses for cancer-specific and comorbid death were performed. RESULTS: Median follow-up was up to 159 months, and the median age of diagnosis was 67 years. Cancer-specific and comorbid deaths accumulated most within the first years of diagnosis. With the more biologically aggressive cancers, cancer deaths invariably exceeded comorbid deaths. For the remaining 70% of cancers, comorbidity remained the dominant mode of death. Deaths attributable to both cancer and comorbidity accumulated mostly after the seventh decade of life. Cancer site had a 3-fold greater effect on overall survival than age at diagnosis and a 30-fold effect with cancer-specific survival; age at diagnosis had a 5-fold greater effect on comorbid deaths than site. CONCLUSIONS: Both the age of the affected individual and the biology of the particular cancer have major influences on cancer survival and mode of death. Cancer is largely a disease of the elderly. Within affected individuals, fatalities attributable to cancer and comorbidity appeared inter-related, with cancer-specific deaths dominating for more lethal cancers and comorbid deaths dominating for the remaining majority. For these reasons, further improvements in overall survival may be best anticipated from better geriatric and general medical management as much as from better cancer management.

A population-based analysis of second primary cancers after irradiation for rectal cancer.

OBJECTIVE: To investigate the possible association between pelvic irradiation for rectal cancer and subsequent second primary cancers. PATIENTS AND METHODS: A population-based analysis of 20,910 individuals with rectal cancer from the Surveillance, Epidemiology, and End Results registry, for whom follow-up times were at least 5 years, was performed. Kaplan-Meier estimates for the development of second cancers within irradiated and nonirradiated cohorts provided a comparison that accounted for censored data. Cox proportional hazards analyses were further conducted to compensate for patient and tumor-related factors. RESULTS: A total of 656 (12%) and 2368 (16%) second primary cancers were enumerated from the irradiated and nonirradiated cohorts, respectively, with the proportion of second primary cancers within the irradiated cohort being significantly decreased (P < 0.001) on crude analysis. However, Kaplan-Meier and Cox analyses revealed no significant difference between the 2 cohorts when all second primary cancer sites were considered together (hazard ratio = 1.02; 95% confidence interval [CI], 0.92-1.12). Proportional hazards analysis for specific second primary sites revealed a decreased risk after pelvic irradiation for cancer of the prostate (hazard ratio = 0.63; 95% CI, 0.48-0.84), and an increased risk for cancers of the uterine corpus & cervix (hazard ratio = 2.5; 95% CI, 1.6-4.0). CONCLUSION: Second primary cancers after irradiation for rectal cancers appear relatively infrequent compared with the background incidence of spontaneous cancers, and should not factor into treatment decisions for this older population. We hypothesize that the incidence of second primary tumors within adjacent organs could represent a balance between the radiation-induction of tumors and the radiation-inhibition of spontaneously occurring tumors.

Empirically-based estimates for the burden of subclinical metastases.

PURPOSE: To describe the frequency distribution for the number of residual subclinical metastatic tumor cells after removal of the primary cancer. MATERIALS AND METHODS: Previously obtained autopsy, surgical pathological and laboratory data were used to characterize the size and number distributions for hematogenous and lymphatic metastases. Monte Carlo simulations were used to estimate the numbers of residual tumor cells based upon the assumption of a lognormal distribution for the sizes of metastases and Poisson, Poisson negative binomial, or negative binomial distributed numbers of metastases (corresponding to lymphatic metastases within individuals, hematogenous metastases within individuals, and lymphatic metastases within populations, respectively). RESULTS: In each of the scenarios the resultant distribution for the numbers of subclinical tumor cells was unimodal and positively skewed, with a tail extending to the higher numbers of metastases. When plotted with equal sized counting bins and according the logarithm of the number of tumor cells, the distributions showed deviations from the normal form no greater than several percentage points--a result considered acceptable given the variabilities inherent to metastasis data. CONCLUSIONS: The distribution for the number of residual subclinical metastases may be extrapolated from data and models derived from the size and number distributions for metastases. In the absence of a closed form description for this distribution, the lognormal distribution could provide a crude, but practical, approximation for cases limited to occult microscopic residual disease. These analyses will facilitate the definition of the dose-response for the adjuvant therapy of subclinical metastases.

The comparative survival of renal leiomyosarcoma.

INTRODUCTION: Leiomyosarcoma of the kidney and renal pelvis is a rare tumor that, on the basis of limited data, has been ascribed a particularly poor prognosis compared to other subtypes of renal malignancy. Here the population-based Surveillance, Epidemiology, and End Results (SEER) registry is used to study the survival of renal leiomyosarcomas. METHODS: There were 95,935 cases of invasive cancer of the kidney and renal pelvis retrieved from the SEER registry to provide 112 cases of leiomyosarcoma. Kaplan-Meier survival estimates and Cox proportional hazard models were constructed to compare the survival of leiomyosarcomas to other renal malignancies. RESULTS: Leiomyosarcomas constituted 0.12% of all invasive renal malignancies. They exhibited a median overall survival of 25 months, with a 25% 5-year overall survival, and a 60% 5-year cause-specific survival. Multivariate analysis of all renal malignancies together revealed that cancer stage was the strongest predictor for overall survival followed by age, histological grade, histological subtype, tumor size, and gender. The hazard ratio for leiomyosarcoma in this analysis was intermediate compared to the other malignancies. When leiomyosarcomas were analyzed separately, the major determinants to overall survival were stage and age at diagnosis. Kaplan-Meier analysis revealed that the overall survival curve for renal leiomyosarcoma essentially superimposed that of transitional cell carcinoma, and was better than that of clear cell carcinoma. These results provide a more optimistic outlook than has been conventionally afforded to this tumor.

Scale invariant correlations between genes and SNPs on Human chromosome 1 reveal potential evolutionary mechanisms.

The local density of gene structures and single nucleotide polymorphisms (SNPs) along human chromosomes appears inhomogeneous. In chromosome 1, the density patterns from both these elements are shown here to exhibit similar scale invariant clustering, as well as long-ranged and scale invariant auto- and cross-correlations. The local densities of these elements sites can be accurately represented by the scale invariant exponential dispersion models, a group of stochastic models that act as limiting distributions for a wide range of generalized linear models. The scale invariant Poisson-gamma (PG) distribution is the most applicable of these models, since it describes the above findings and it lends itself to a stochastic mechanism for the accumulation of segmental chromosomal changes. This PG model describes the summation of neutral chromosomal mutations, deletions, rearrangements and recombinations, within chromosomal segments that are distinguished by their evolutionary genealogies. Scale invariance is a necessary property if such a description is to remain valid at different measurement scales. The observed density patterns, and proposed model, presumably represent the convergent summation of multiple stochastic processes within the evolutionary history of the chromosome.

The number distribution for involved lymph nodes in cancer.

The number of involved lymph nodes exhibits considerable heterogeneity within populations. Here, the implications of population heterogeneity are explored with respect to the kinematics of nodal metastases. Data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program for 224656 breast, 12404 gastric, 18015 rectal, 4117 cervical and 2443 laryngeal cancers as well as 9118 melanomas were used to construct frequency distributions for the number of involved nodes which were then fitted to the negative binomial distribution. The negative binomial distribution described the heterogeneity in nodal involvement well. The patterns of nodal involvement can be explained by either of two models: one where involved nodes could seed further nodal metastases, the other where the number of nodal metastases in any individual was randomly distributed, with the deviations between patients accounted for by population heterogeneity. Since the number of sampled nodes similarly approximated a negative binomial distribution, random involvement with superimposed population heterogeneity would more credibly explain both sets of observations.

Lymph node-based prognostics: limitations with individualized cancer treatment.

OBJECTIVES: Clinicians will commonly individualize adjuvant cancer therapy, on the basis of the number of involved lymph nodes and other clinicopathological factors, under the assumption that despite the expected statistical variability of such data one can nonetheless garner useful information for the individual case. Here the scientific basis of this assumption will be examined. METHODS: Survival data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program for 19,107 breast, 4,234 gastric, and 4,058 rectal cancers were studied with Kaplan-Meier estimates and Cox proportionate hazard models. The minimal sample size required to discriminate between high and low-risk groups was determined from the hazard ratios between various comparative groups, and their respective frequencies. RESULTS: The number of involved nodes was the strongest prognostic factor for all 3 cancers, followed by tumor diameter and grade. Discrimination between high and low-risk nodal prognostic groups required samples of 30 to 200 cases, depending on the prognostics used and the specific tumor, to attain a two-sided alpha of 0.05% with 90% power. At the individual level such prognostications therefore were uninformative. CONCLUSIONS: Clinicopathological prognostics based upon the number of involved lymph nodes are subject to population heterogeneity that limits their application to large samples. At the individual level, these prognostics appear more spurious than useful. The use of such prognostics to tailor cancer treatment to individuals should be considered a specious practice; instead a more categorical approach, based on the results of randomized trials, should be used.