Diagnosis and Management of Spinal Metastasis of Glioblastoma.

BACKGROUND: When patients with cranial glioblastoma develop weakness, a rare differential diagnosis is spinal metastases. METHODS: Chart and literature reviews were performed. RESULTS: The reported patient had delayed onset spinal drop metastasis that was only detected by magnetic resonance imaging (MRI). A 48-year-old patient had supratentorial glioblastoma, treated with radiotherapy (RT) and concurrent temozolomide followed by six cycles of adjuvant temozolomide. Four years after completion of all treatments (62 months from initial presentation), he developed low backache and weakness in both legs. Positron emission tomography/computed tomography scans demonstrated intracranial recurrence only. Spinal drop metastases were detected only by MRI scan. Local spinal RT 40 Gy in 20 fractions with concurrent and maintenance temozolomide were given. Because of disease progression after nine cycles of temozolomide, systemic therapy was changed to bevacizumab, which greatly improved his symptoms for 4 months before deterioration of mental status. He is still alive with disease at 22 months after diagnosis of spinal metastases (84 months from initial glioblastoma diagnosis). CONCLUSIONS: MRI is the diagnostic imaging of choice for spinal metastases. This illustrative case of delayed-onset spinal metastases shows unusual slow progression. Local RT, temozolomide, and targeted therapy may improve survival. This illustrative case is the first report of bevacizumab as a second-line therapy in drop metastasis of glioblastoma.

Long-term outcome of breast cancer patients with one to two nodes involved - application of nodal ratio.

Nodal ratio (NR) is defined as the number of involved nodes to the number of nodes examined. There is limited information on the application of NR on population data. Previous reports in breast cancer generally analyzed one to three positive axillary nodes as a single group. This study investigates whether one to three positive axillary nodes is a homogeneous group in prognosis by comparing one to two positive nodes to three positive nodes. The population-based registry of a Canadian province from 1981 through 1995 was searched. As the reliability of nodal assessment depends on the number of nodes sampled, we also studied the subgroup of patients with greater than or equal to eight nodes dissected. Of a total of 5,996 breast cancer patients, 1187 had one to three positive axillary nodes. The 263 patients with three positive nodes compared to the 924 patients with one to two nodes fared worse with a significantly reduced cause-specific survival (CSS) and overall survival (OS). Patients with one to two positive nodes had similar CSS (p=0.31) and OS (p=0.63). Among those with greater than or equal to eight nodes dissected, there were 677 patients with one to two positive nodes. CSS and OS were not significantly different between one versus two positive nodes (p=0.16 and 0.34, respectively), but with NR, the corresponding p values were 0.0068 and 0.08, respectively. The cutoff value of NR 0.15 was found to be most useful and confirmed by the validation dataset. NR is able to segregate patients better than the absolute number of positive nodes used in the current staging system. NR should be incorporated into the staging system.

Outcome analysis of breast cancer patients who declined evidence-based treatment.

BACKGROUND: To analyze the characteristics and outcomes of women with breast cancer in the Northern Alberta Health Region (NAHR) who declined recommended primary standard treatments. METHODS: A chart review was performed of breast cancer patients who refused recommended treatments during the period 1980 to 2006. A matched pair analysis was performed to compare the survival data between those who refused or received standard treatments. RESULTS: A total of 185 (1.2%) patients refused standard treatment. Eighty-seven (47%) were below the age of 75 at diagnosis. The majority of those who refused standard treatments were married (50.6%), 50 years or older (60.9%), and from the urban area (65.5%). The 5-year overall survival rates were 43.2% (95% CI: 32.0 to 54.4%) for those who refused standard treatments and 81.9% (95% CI: 76.9 to 86.9%) for those who received them. The corresponding values for the disease-specific survival were 46.2% (95% CI: 34.9 to 57.6%) vs. 84.7% (95% CI: 80.0 to 89.4%). CONCLUSIONS: Women who declined primary standard treatment had significantly worse survival than those who received standard treatments. There is no evidence to support using Complementary and Alternative Medicine (CAM) as primary cancer treatment.

Management of Merkel cell carcinoma with emphasis on small primary tumors--a case series and review of the current literature.

A case series of Merkel cell carcinoma (MCC) is reported here and illustrates some of the current controversies in clinical management of this disease. From 1988-2007, 145 cases (74 men and 71 women) were analyzed. These were combined with other cases in the literature, hence the total number of patients was 433. Nodal metastases occurred clinically at presentation in 9/105 (9%) patients with primary tumor size <1 cm. The rate of nodal metastases is too high to obviate sentinel node biopsies even for these small tumors. For the 87 patients with intermediate tumor size (>1 - <2 cm), nodal metastases occurred clinically in 11 of 87 patients (13%) at presentation and 23 of 87 patients (26%) during follow-up. Distant metastases occurred in 20 of 87 patients (23%) only at follow-up. The risks of nodal and distant failures for tumors of intermediate sizes were sufficient to be classified as high-risk for clinical study purposes.

The effect of adjuvant radiotherapy on mortality differs according to primary tumor location in women with node-positive breast cancer.

PURPOSE: To evaluate the prognostic significance of primary tumor location and to examine whether the effect of adjuvant radiotherapy on survival varies according to tumor location in women with axillary node-positive (ALN+) breast cancer (BC). PATIENTS AND METHODS: Data were abstracted from the SEER database for 24,410 women aged 25-95 years, diagnosed between 1988-1997 with nonmetastatic T1-T2, ALN+ BC. Subgroup analyses were performed using interactions within proportional hazards models. Event was defined as death from any cause. Prognostic variables were selected using Akaike Information Criteria. Joint significances of subgroups were evaluated with Wald test. RESULTS: Median follow-up was 10 years. In joint models, statistically significant interactions were found between tumor location, nodal involvement, type of surgery, and radiotherapy. Factorial presentation of interactions showed consistent 13% proportional reduction of mortality in all subgroups, except in women with medial tumors with > or = 4 ALN+ treated with mastectomy. In this subgroup, use of radiotherapy was associated with a 16% proportional increase in mortality. CONCLUSION: Medial tumor location is a significant adverse prognostic factor that should be considered in treatment decision- making for women with ALN+ BC. Improved survival was observed with radiotherapy use in all subgroups, except in women with medial tumors with > or = 4 ALN+ treated with postmastectomy radiotherapy. These findings raise concern that the favorable effect of radiotherapy may be offset by excess toxicities in the latter subgroup.

Prognostic value of nodal ratios in node-positive breast cancer: a compiled update.

The number of positive axillary nodes is a strong prognostic factor in breast cancer, but is affected by variability in nodal staging technique yielding varying numbers of excised nodes. The nodal ratio of positive to excised nodes is an alternative that could address this variability. Our 2006 review found that the nodal ratio consistently outperformed the number of positive nodes, providing strong arguments for the use of nodal ratios in breast cancer staging and management. New evidence has continued to accrue confirming the prognostic significance of nodal ratios in various worldwide population settings. This review provides an updated summary of available data, and discusses the potential application of the nodal ratio to breast cancer staging and prognostication, its role in the context of modern surgical techniques such as sentinel node biopsy, and its potential correlations with new biologic markers such as circulating tumor cells and breast cancer stem cells.

Cysteine-rich protein reverses weight loss in lung cancer patients receiving chemotherapy or radiotherapy.

Oxidative stress plays a role in the tumor-cytotoxic effect of cancer chemotherapy and radiotherapy and also in certain adverse events. In view of these conflicting aspects, a double-blind trial over a 6-month period was performed to determine whether a cysteine-rich protein (IMN1207) may have a positive or negative effect on the clinical outcome if compared with casein, a widely used protein supplement low in cysteine. Sixty-six patients with stage IIIB-IV non-small cell lung cancer were randomly assigned to IMN1207 or casein. Included were patients with a previous involuntary weight loss of > or =3%, Karnofsky status > or =70, and an estimated survival of >3 months. Thirty-five lung cancer patients remained on study at 6 weeks. Overall compliance was not different between treatment arms (42-44% or 13 g/day). The patients treated with the cysteine-rich protein had a mean increase of 2.5% body weight, whereas casein-treated patients lost 2.6% (p = 0.049). Differences in secondary endpoints included an increase in survival, hand-grip force, and quality of life. Adverse events were mild or moderate. Further studies will have to show whether the positive clinical effects can be confirmed and related to specific parameters of oxidative stress in the host.

Merkel cell cancer: update on biology and treatment.

PURPOSE OF REVIEW: This review highlights the most important developments in the biology and treatment of Merkel cell carcinoma published in the medical literature over the past year. RECENT FINDINGS: Adjuvant radiotherapy to the primary site with or without coverage of the nodal region is recommended in most older series, although a risk-adapted approach is more reasonable. Sentinel lymph node biopsy should be considered in all cases irrespective of primary size. If not feasible, prophylactic regional radiotherapy is recommended as the risk of regional relapse without nodal staging is about 45%. Adjuvant radiotherapy to nodal regions after lymphadenectomy is not studied in detail, but there is a suggestion from many series that the recurrence rate is high enough to justify its use. Recent research has revealed that adjuvant chemotherapy currently has no established role in the treatment of localized node-negative Merkel cell carcinoma. Its use in pathologically node-positive or recurrent cases requires further study. SUMMARY: Given the lack of randomized evidence and heterogeneity in published retrospective series, clinical judgment is required to assess risk factors of an individual patient to make treatment decisions.

Skin cancer management-updates on Merkel cell carcinoma.

There are many different types of skin tumors in the World Health Organization (WHO) classification. The natural course and treatment varies according to the histological type. This review summarizes clinical experience for treatment decision. Contemporary radiotherapy and systemic therapy are improving. Landmark studies for basal cell and Merkel cell carcinomas (MCC) trigger further research and impetus for improving treatment outcome. Avelumab, nivolumab, pembrolizumab, ipilimumab appear to be promising for treatment of advanced MCCs and adjuvant trials are underway.

Spontaneous Regression of Merkel Cell Carcinoma of the Male Breast with Ongoing Immune Response.

Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine tumor arising predominantly on sun-exposed skin among the elderly. The most common location is the head and neck, followed by the extremities. MCCs are highly aggressive tumors and rarely undergo spontaneous regression. We report a case of MCC which presented as a painless breast lump in an elderly male where the tumor regressed spontaneously after a biopsy.

Nodal ratios in node-positive breast cancer--long-term study to clarify discrepancy of role of supraclavicular and axillary regional radiotherapy.

PURPOSE: To study the absolute number of involved nodes/the number of nodes examined or the nodal ratio (NR) in breast cancer. The primary study endpoint was to evaluate the role of supraclavicular and axillary radiotherapy (SART) according to the NR. METHODS AND MATERIALS: From the Saskatchewan provincial registry of 1981-1995, the charts of 5,996 consecutive patients were retrieved to collect detailed prognostic factors. Among these patients, 1,985 were node positive. Because the NRs are more reliable the greater the number of nodes examined, we analyzed 1,255 patients with > or =10 nodes examined. Of these 1,255 patients, 667, 389, and 199 were categorized into three NR groups--low (< or =25%), medium (>25% to < or =75%), and high (>75%) nodal involvement, respectively. RESULTS: The NR correlated significantly with the primary tumor size (< or =2 cm, >2 to < or =5 cm, and >5 cm; p = 2.2 x 10(-16)), clinical stage group (p = 5.5 x 10(-16)), pathologic stage group (p < 2.2 x 10(-16)), and the risk of any first recurrence (p = 5.0 x 10(-15)) using chi-square tests. For a low NR, the 10-year overall survival rate with and without SART was 57% and 58% (p = 0.18), and the cause-specific survival rate was 68% and 71% (p = 0.32), respectively. For a medium NR, the 10-year overall survival rate with and without SART was 48% and 34% (p = 0.007), and the cause-specific survival rate was 57% and 43% (p = 0.002), respectively. For a high NR, the 10-year overall survival rate with and without SART was 19% and 10% (p = 0.005), and the cause-specific survival rate was 26% and 14% (p = 0.005), respectively. CONCLUSION: This is the first study demonstrating that for patients with > or =10 nodes examined, SART significantly improved the survival for the median and high NR groups but not for the low NR group.

Disease-specific survival for limited-stage small-cell lung cancer affected by statistical method of assessment.

BACKGROUND: In general, prognosis and impact of prognostic/predictive factors are assessed with Kaplan-Meier plots and/or the Cox proportional hazard model. There might be substantive differences from the results using these models for the same patients, if different statistical methods were used, for example, Boag log-normal (cure-rate model), or log-normal survival analysis. METHODS: Cohort of 244 limited-stage small-cell lung cancer patients, were accrued between 1981 and 1998, and followed to the end of 2005. The endpoint was death with or from lung cancer, for disease-specific survival (DSS). DSS at 1-, 3- and 5-years, with 95% confidence limits, are reported for all patients using the Boag, Kaplan-Meier, Cox, and log-normal survival analysis methods. Factors with significant effects on DSS were identified with step-wise forward multivariate Cox and log-normal survival analyses. Then, DSS was ascertained for patients with specific characteristics defined by these factors. RESULTS: The median follow-up of those alive was 9.5 years. The lack of events after 1966 days precluded comparison after 5 years. DSS assessed by the four methods in the full cohort differed by 0-2% at 1 year, 0-12% at 3 years, and 0-1% at 5 years. Log-normal survival analysis indicated DSS of 38% at 3 years, 10-12% higher than with other methods; univariate 95% confidence limits were non-overlapping. Surgical resection, hemoglobin level, lymph node involvement, and superior vena cava (SVC) obstruction significantly impacted DSS. DSS assessed by the Cox and log-normal survival analysis methods for four clinical risk groups differed by 1-6% at 1 year, 15-26% at 3 years, and 0-12% at 5 years; multivariate 95% confidence limits were overlapping in all instances. CONCLUSION: Surgical resection, hemoglobin level, lymph node involvement, and superior vena cava (SVC) obstruction all significantly impacted DSS. Apparent DSS for patients was influenced by the statistical methods of assessment. This would be clinically relevant in the development or improvement of clinical management strategies.

Issues in Managing Hurthle Cell Carcinoma of Thyroid: A Case Report.

A 61-year-old woman noticed a right neck lump in October 2001. Fine needle aspiration showed follicular neoplasm, adenoma versus carcinoma. The ultrasound scan showed a solid mass of maximum dimension of 3.7 cm. She had a right thyroid lobectomy and isthmectomy in January 2002 (first surgery). The tissue specimen showed a 4.5 cm Hurthle cell carcinoma (HCC) with vascular invasion. There were no capsular invasion, extra-thyroidal extension, or margin involvement. A completion left lobectomy (second surgery) was performed two weeks later. Therefore the pathological stage is II (T3N0M0). She received adjuvant radioactive iodine ablation for residual thyroid tissue. By 2003, she developed local recurrence, which was resected (third surgery), followed by adjuvant external beam radiotherapy. Unfortunately, she developed further recurrence in the left main bronchus, as identified by Indium-111 Octreotide (Curium, Missouri, USA) and positron emission tomography-computed tomography PET-CT imaging in 2006. She underwent a left pneumonectomy (fourth surgery) in July 2006. In November 2007 she was found to have mediastinal recurrence which was treated with high-dose external beam radiotherapy. She initially responded but developed more local recurrence and a lung metastasis by 2011. She was treated with brivanib with ixabepilone, under a phase I clinical trial with mixed response. Her treatment was discontinued secondary to toxicity and she succumbed to her disease in 2012. This case report illustrates the natural history and clinical decision making for patients diagnosed with HCC of the thyroid. Specifically, we highlight the clinical issues surrounding the histopathological diagnosis, extent of surgical resection, radioiodine diagnostic imaging/ablative treatment, as well as external beam radiotherapy.

Cardiac-sparing radiation therapy using positioning breast shell for patients with left-sided breast cancer who are ineligible for breath-hold techniques.

PURPOSE: Patients with left-sided breast cancer (LSBC) are at increased risk of cardiac morbidity from adjuvant breast radiation therapy (ABRT). Breath-hold (BH) techniques substantially reduce the radiation received by heart during radiation therapy for LSBC. However, a subset of patients with LSBC are ineligible for BH techniques due to an inability to breath-hold or because of other comorbidities. To reduce radiation to the heart, we routinely use a custom-made breast shell for the treatment of patients with LSBC who are ineligible for BH techniques. This study evaluates the dosimetric impact of using a breast shell for patients with LSBC undergoing ABRT. METHODS AND MATERIALS: Sixteen consecutive patients with LSBC who failed BH and underwent ABRT using a breast shell during the period of 2014 to 2016 were identified. Treatment was planned using field-in-field tangents with a prescribed dose of 42.5 Gy in 16 fractions. Comparisons between plans with and without a shell were made for each patient using a paired t test to quantify the sparing of organs at risk (OARs) and target coverage. RESULTS: There was no statistically significant difference in the planning target volume of breast coverage. A statistically significant improvement was observed in sparing the heart, left ventricle (LV), and ipsilateral lung (P-value < .001). Plans with the shell spared OARs better than the no-shell plans with a mean dose of 2.15 Gy versus 5.15 Gy (58.2% reduction) to the heart, 3.27 Gy versus 9.00 Gy (63.7% reduction) to the LV, and 5.16 Gy versus 7.95 Gy (35% reduction) to the ipsilateral lung. The irradiated volumes of OARs for plans with and without shell are 13.3 cc versus 59.5 cc (77.6% reduction) for the heart, 6.2 cc versus 33.2 cc (81.2% reduction) for the LV, and 92.8 cc versus 162.5 cc (42.9% reduction) for the ipsilateral lung. CONCLUSIONS: A positioning breast shell offers significant benefit in terms of sparing the heart for patients with LSBC who are ineligible for BH techniques. It also can be used as a simple cardiac-sparing alternative in centers without BH capability.

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) in patients with limited stage small cell lung cancer.

A few series in the literature were published before 1987 on syndrome of inappropriate antidiuretic hormone secretion (SIADH) in small cell lung cancer (SCLC). This study examines the outcome in more recent era. From 1981-1998, there were 1417 new cases of SCLC diagnosed in the provincial registry, of which 244 were of limited stage (LS). A chart review and statistical analyses were performed using Mann-Whitney test, chi-square test and Kaplan-Meier method. Fourteen LS patients (group A) had SIADH at presentation. Group B consisted of 230 LS patients without SIADH. There were more patients with poorer performance status (ECOG 2-4) in group A than B (28.6% versus 7.8%, P=0.03). Otherwise, sex, age at diagnosis, nodal spread, pleural effusion, bronchial obstruction, superior vena cava obstruction, performance status, weight loss, and lactic dehydrogenase at presentation, were comparable between the two groups. Treatments given, e.g., extent of surgical resection (if performed, whether complete/incomplete), total number of chemotherapy cycles, radiotherapy doses, were comparable (P>0.05). The response to chemo-radiation was not significantly different (P=0.7). Five-year overall survival (8% versus 19%, P=0.08), and cause-specific survival (16% versus 20%, P=0.13) showed that group A patients had a worse outcome, though of borderline significance. Symptoms related to SIADH included: weakness, 4 patients; tiredness, 3; change in level of consciousness, 1; seizure, 1. The range of lowest sodium level was 110-129. Two patients also had paraneoplastic myopathy. SIADH resolved in 12 patients at 1.6-44.7 weeks (median: 4.3). Among the 14 patients who initially presented with SIADH and recurred later, 10 had recurrence of SIADH at the time of tumor recurrence. Serum sodium was useful for post-treatment surveillance in SCLC patients who presented with SIADH, with 71% (10/14) developing SIADH again at the time of recurrence. SIADH is a poor prognostic factor for LS SCLC.

Radiotherapy in Gorlin Syndrome: Can It Be Safe and Effective in Adult Patients?

Gorlin syndrome, also known as nevoid basal cell carcinoma syndrome, is a rare autosomal dominant disorder with multiple manifestations including early onset of cutaneous basal cell carcinomas (BCCs). Radiotherapy has traditionally been contraindicated due to reports of BCC induction. We describe here a patient treated successfully with radiotherapy with no tumour induction at 57 months of follow-up. A comprehensive literature review of radiotherapy outcomes in patients with Gorlin syndrome suggests radiotherapy may be a feasible treatment option for adult patients with treatment refractory lesions or surgical contraindication.

Long-term survival rates of laryngeal cancer patients treated by radiation and surgery, radiation alone, and surgery alone: studied by lognormal and Kaplan-Meier survival methods.

BACKGROUND: Validation of the use of the lognormal model for predicting long-term survival rates using short-term follow-up data. METHODS: 907 cases of laryngeal cancer were treated from 1973-1977 by radiation and surgery (248), radiation alone (345), and surgery alone (314), in registries of Connecticut and Metropolitan Detroit of the SEER database, with known survival status up to 1999. Phase 1 of this study used the minimum chi-square test to assess the goodness of fit of the survival times of those who died with disease to a lognormal distribution. Phase 2 used the maximum likelihood method to estimate long-term survival rates using short-term follow-up data. In order to validate the lognormal model, the estimated long-term cancer-specific survival rates (CSSR) were compared with the values calculated by the Kaplan-Meier (KM) method using long-term data. RESULTS: The 25-year CSSR were predicted to be 72%, 68% and 65% for treatments by radiation and surgery, by radiation alone, and by surgery alone respectively, using short-term follow-up data by the lognormal model. Corresponding results calculated by the KM method were: 72+/-3%, 68+/-3% and 66+/-4% respectively. CONCLUSIONS: The lognormal model was validated for the prediction of the long-term survival rates of laryngeal cancer patients treated by these different methods. The lognormal model may become a useful tool in research on outcomes.

Minimum follow-up time required for the estimation of statistical cure of cancer patients: verification using data from 42 cancer sites in the SEER database.

BACKGROUND: The present commonly used five-year survival rates are not adequate to represent the statistical cure. In the present study, we established the minimum number of years required for follow-up to estimate statistical cure rate, by using a lognormal distribution of the survival time of those who died of their cancer. We introduced the term, threshold year, the follow-up time for patients dying from the specific cancer covers most of the survival data, leaving less than 2.25% uncovered. This is close enough to cure from that specific cancer. METHODS: Data from the Surveillance, Epidemiology and End Results (SEER) database were tested if the survival times of cancer patients who died of their disease followed the lognormal distribution using a minimum chi-square method. Patients diagnosed from 1973-1992 in the registries of Connecticut and Detroit were chosen so that a maximum of 27 years was allowed for follow-up to 1999. A total of 49 specific organ sites were tested. The parameters of those lognormal distributions were found for each cancer site. The cancer-specific survival rates at the threshold years were compared with the longest available Kaplan-Meier survival estimates. RESULTS: The characteristics of the cancer-specific survival times of cancer patients who died of their disease from 42 cancer sites out of 49 sites were verified to follow different lognormal distributions. The threshold years validated for statistical cure varied for different cancer sites, from 2.6 years for pancreas cancer to 25.2 years for cancer of salivary gland. At the threshold year, the statistical cure rates estimated for 40 cancer sites were found to match the actuarial long-term survival rates estimated by the Kaplan-Meier method within six percentage points. For two cancer sites: breast and thyroid, the threshold years were so long that the cancer-specific survival rates could yet not be obtained because the SEER data do not provide sufficiently long follow-up. CONCLUSION: The present study suggests a certain threshold year is required to wait before the statistical cure rate can be estimated for each cancer site. For some cancers, such as breast and thyroid, the 5- or 10-year survival rates inadequately reflect statistical cure rates, and highlight the need for long-term follow-up of these patients.

Short- and long-term cause-specific survival of patients with inflammatory breast cancer.

BACKGROUND: Inflammatory breast cancer (IBC) had been perceived to have a poor prognosis. Oncologists were not enthusiastic in the past to give aggressive treatment. Single institution studies tend to have small patient numbers and limited years of follow-up. Most studies do not report 10-, 15- or 20-year results. METHODS: Data was obtained from the population-based database of the Surveillance, Epidemiology, and End Results program of the National Cancer Institute from 1975-1995 using SEER*Stat5.0 software. This period of 21 years was divided into 7 periods of 3 years each. The years were chosen so that there was adequate follow-up information to 2000. ICD-O-2 histology 8530/3 was used to define IBC. The lognormal model was used for statistical analysis. RESULTS: A total of 1684 patients were analyzed, of which 84% were white, 11% were African Americans, and 5% belonged to other races. Age distribution was < 30 years in 1%, 30-40 in 11%, 40-50 in 22%, 50-60 in 24%, 60-70 in 21%, and > 70 in 21%. The lognormal model was validated for 1975-77 and for 1978-80, since the 10-, 15- and 20-year cause-specific survival (CSS) rates, could be calculated using the Kaplan-Meier method with data available in 2000. The data were then used to estimate the 10-, 15- and 20-year CSS rates for the more recent years, and to study the trend of improvement in survival. There were increasing incidences of IBC: 134 patients in the 1975-77 period to 416 patients in the 1993-95 period. The corresponding 20-year CSS increased from 9% to 20% respectively with standard errors of less than 4%. CONCLUSION: The improvement of survival during the study period may be due to introduction of more aggressive treatments. However, there seem to be no further increase of long-term CSS, which should encourage oncologists to find even more effective treatments. Because of small numbers of patients, randomized studies will be difficult to conduct. The SEER population-based database will yield the best possible estimate of the trend in improvement of survival for patients with IBC.

Modeling the effect of age in T1-2 breast cancer using the SEER database.

BACKGROUND: Modeling the relationship between age and mortality for breast cancer patients may have important prognostic and therapeutic implications. METHODS: Data from 9 registries of the Surveillance, Epidemiology, and End Results Program (SEER) of the United States were used. This study employed proportional hazards to model mortality in women with T1-2 breast cancers. The residuals of the model were used to examine the effect of age on mortality. This procedure was applied to node-negative (N0) and node-positive (N+) patients. All causes mortality and breast cancer specific mortality were evaluated. RESULTS: The relationship between age and mortality is biphasic. For both N0 and N+ patients among the T1-2 group, the analysis suggested two age components. One component is linear and corresponds to a natural increase of mortality with each year of age. The other component is quasi-quadratic and is centered around age 50. This component contributes to an increased risk of mortality as age increases beyond 50. It suggests a hormonally related process: the farther from menopause in either direction, the more prognosis is adversely influenced by the quasi-quadratic component. There is a complex relationship between hormone receptor status and other prognostic factors, like age. CONCLUSION: The present analysis confirms the findings of many epidemiological and clinical trials that the relationship between age and mortality is biphasic. Compared with older patients, young women experience an abnormally high risk of death. Among elderly patients, the risk of death from breast cancer does not decrease with increasing age. These facts are important in the discussion of options for adjuvant treatment with breast cancer patients.