Probability Of Distant Metastases Research Articles

A PET/CT radiomics model for predicting distant metastasis in early-stage non–small cell lung cancer patients treated with stereotactic body radiotherapy: a multicentric study

ObjectivesStereotactic body radiotherapy (SBRT) is a treatment option for patients with early-stage non-small cell lung cancer (NSCLC) who are unfit for surgery. Some patients may experience distant metastasis. This study aimed to develop and validate a radiomics model for predicting distant metastasis in patients with early-stage NSCLC treated with SBRT.MethodsPatients at five institutions were enrolled in this study. Radiomics features were extracted based on the PET/CT images. After feature selection in the training set (from Tianjin), CT-based and PET-based radiomics signatures were built. Models based on CT and PET signatures were built and validated using external datasets (from Zhejiang, Zhengzhou, Shandong, and Shanghai). An integrated model that included CT and PET radiomic signatures was developed. The performance of the proposed model was evaluated in terms of its discrimination, calibration, and clinical utility. Multivariate logistic regression was used to calculate the probability of distant metastases. The cutoff value was obtained using the receiver operator characteristic curve (ROC), and the patients were divided into high- and low-risk groups. Kaplan-Meier analysis was used to evaluate the distant metastasis-free survival (DMFS) of different risk groups.ResultsIn total, 228 patients were enrolled. The median follow-up time was 31.4 (2.0-111.4) months. The model based on CT radiomics signatures had an area under the curve (AUC) of 0.819 in the training set (n = 139) and 0.786 in the external dataset (n = 89). The PET radiomics model had an AUC of 0.763 for the training set and 0.804 for the external dataset. The model combining CT and PET radiomics had an AUC of 0.835 for the training set and 0.819 for the external dataset. The combined model showed a moderate calibration and a positive net benefit. When the probability of distant metastasis was greater than 0.19, the patient was considered to be at high risk. The DMFS of patients with high- and low-risk was significantly stratified (P < 0.001).ConclusionsThe proposed PET/CT radiomics model can be used to predict distant metastasis in patients with early-stage NSCLC treated with SBRT and provide a reference for clinical decision-making.Plain language summaryIn this study, the model was established by combining CT and PET radiomics signatures in a moderate-quantity training cohort of early-stage NSCLC patients treated with SBRT and was successfully validated in independent cohorts. Physicians could use this easy-to-use model to assess the risk of distant metastasis after SBRT. Identifying subgroups of patients with different risk factors for distant metastasis is useful for guiding personalized treatment approaches.

Nomogram of baseline CT-radiomics from small-cell lung cancer patients: evaluation of added prognostic value for overall survival and probability of distant metastasis

Objectives: To evaluate the added prognostic value of baseline CT-radiomics using nomogram for overall survival and probability of distant metastasis in small-cell lung cancer patients. Materials and methods: This retrospective study consisted of 122 patients with stage IIA-IIIB small-cell lung cancer,which 97 patients for training dataset and 25 for validation dataset. The function defined as rad_score was constructed by the linear combination of selected radiomics features from baseline CT images weighted by their respective logistic coefficients and intercept in the LASSO-Cox model. The nomogram was developed based on the above function for overall survival (OS) and calibrated by the Harrell’s concordance index (C-index). The performance of the classifiers for DM was evaluated by receiver operating characteristics (ROC) curves with the indictor of area under curves (AUC). Furthermore, survival curve depicted by Kaplan-Meier method was compared with Log-rank test between low- and high-risk group. Results: The nomogram performance of radiomics features and risk clinical factors (c-index of 0.64) don’t take advantage over the one of risk clinical factors-based alone (c-index of 0.596). The probability prediction of combination of the radiomics and clinical risk factor, radiomics alone, and clinical factors alone was shown, namely AUC of 0.673, 0.640 and 0.650, respectively. No significant different was found between ROCs (p-value &gt; 0.4, Delong test). Moreover, we compared the Kaplan-Meier curves between low- and high-risk group, and showed p&lt;0.001 with Log-rank test. Conclusion: In the study, we can not confirm the hypothesis that baseline CT-radiomics contribute to predict the OS and probability of DM significantly. Moreover, the nomogram model based on combination of radiomics and clinical parameters has disadvantage over clinical parameters alone, probably affected by heterogeneity of datasets or SCLC need more valuable information for prediction outcomes.

Bioinformatics analysis identifies biomarkers associated with poor prognosis in diffuse‑type gastric cancer.

Gastric cancer (GC) is one of the most common malignancies of the digestive system. In diffuse-type GC, differentiation is relatively poor, and the probability of distant metastasis and lymph node metastasis is high, resulting in poor clinical prognosis. The purpose of this study was to identify specific genes that can predict the prognosis of different types of GC. Differentially expressed genes (DEGs) were screened in the GSE62254 dataset obtained from the Gene Expression Omnibus using the ‘limma’ and ‘survival’ R packages. A total of 355 survival-related DEGs were selected according to specific screening criteria, of which 293 were associated with diffuse-type GC and 62 with intestinal-type GC. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used for functional annotation and pathway enrichment analysis of DEGs. Using protein-protein interaction networks and Cytoscape software, three hub genes were identified in diffuse-type GC-associated DEGs, including angiotensinogen (AGT), C-X-C motif chemokine ligand 12 (CXCL12) and adrenoceptor β2 (ADRB2). Immunohistochemical staining and reverse transcription-quantitative PCR revealed that the expression levels of the three genes in diffuse-type GC samples were upregulated compared with in intestinal-type GC samples. Kaplan Meier analysis indicated that a higher expression levels of these three hub genes were associated with a poorer prognosis of diffuse-type GC. In summary, the present findings suggested that AGT, CXCL12 and ADRB2 might contribute to the progression of diffuse-type GC, and could serve as potential biomarkers or therapeutic targets for this disease.

Prognostic Importance of Tumor Deposits in the Ipsilateral Axillary Region of Breast Cancer Patients.

Tumor deposits (TD) are irregular discrete tumor masses in adipose tissue, discontinuous from the primary tumor, that are described in various cancers. The incidence and/or prognostic value of TD in breast carcinomas have not been studied so far. We reevaluated 145 breast cancer patients, diagnosed and treated between 2001 and 2006 at our institution for the presence and incidence of TD. Histologic type, grade, size of the primary tumor, estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2 status of the tumor, and presence of peritumoral lymphovascular invasion were included in the data. TD were detected in 42 cases (29.0%). The mean age of the patients was 52.2years (27-82). Most patients (79.3%) had either invasive carcinoma of no special type (NST) or invasive lobular carcinoma, and most tumors (86.9%) were either grade 2 or 3. After excluding TD from the number of metastatic lymph nodes, the pN status of 9 patients changed. Univariate analysis of 110 patients with follow-up information revealed that the new pN status (p = 0.036), presence of local recurrence (p = 0.016) and TD (p = 0.003) were significantly correlated with distant metastases. The median follow-up of the patients was 84months (5-161), 10-year disease-free survival and overall survival were 67.2% and 73.7%, respectively. In multivariate analysis, presence of TD remained independently associated with distant metastasis (p = 0.002). The probability of distant metastasis was 3.3 times higher in patients with TD. These results emphasize that TD are present in breast cancer patients, and that their presence should warn the clinician in terms of possible distant metastasis. Therefore, presence of TD, the evaluation of which is neither time consuming nor require sophisticated methods, should be included in pathology reports.

Abstract A09: Urban neighborhood and residential factors associated with breast cancer in African American women: A systematic review

Abstract Certain residential characteristics in urban neighborhoods have shown to have negative impacts on health, especially in the African American population. The purpose of this systematic review is to understand the relationship between urban neighborhood and residential factors and breast cancer risk, incidence, stage at diagnosis/late stage diagnosis, survival, and mortality in African Americans. Using PubMed and Web of Science, the existing literature was reviewed. Observational, cross-sectional, cohort, and prospective studies until February 2017 were examined. Studies that included populations of African American women, setting in “urban” areas, and a measure of a neighborhood or residential factor were reviewed. Three parameters related to neighborhood/residential factors were extracted, including neighborhood socioeconomic status (SES), residential segregation, and residential pollution. Eighteen studies were identified for systematic review. 10 studies showed significantly higher odds of late-stage diagnosis, higher mortality, and lower survival in African American women living in lower socioeconomic neighborhoods. One study showed slightly higher odds of upward neighborhood change and probability of distant metastasis at diagnosis of African American woman compared to White women (OR=1.24). Similarly, 5 studies showed significantly high associations between residential segregation and late-stage diagnosis, as well as high associations of residential segregation and higher mortality in African American women. Two studies assessed residential pollution on breast cancer risk. The first study showed a weak rate of breast cancer risk in African American women between differentiating levels of trihalomethane in public water (RR=1.2). The second assessed the association of magnetic field exposure and breast cancer risk and found that the odds of getting breast cancer were not significant in African American women (OR=1.02). This review provides a qualitative synthesis of major neighborhood and residential factors on breast outcomes in African American women. By enacting health policies and utilizing tools such as health informatics, steps can be taken to drive the breast cancer disparity down in this population. Citation Format: Brandi Patrice Smith, Zeynep Madak-Erdogan. Urban neighborhood and residential factors associated with breast cancer in African American women: A systematic review [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A09.

Pretreatment neutrophil to lymphocyte ratio in determining the prognosis of head and neck cancer: a meta-analysis

BackgroundRecent studies have reported a relationship between prognosis and neutrophil-to-lymphocyte ratio (NLR) in patients with head and neck cancer (HNC). As the results are still controversial, we conducted a meta-analysis of pretreatment NLR in peripheral blood and prognosis in HNC patients.MethodsWe retrieved articles from PubMed, Medline, Cochrane Library, Embase and Web of Science. A comparative analysis was conducted for the effect of pretreatment NLR in peripheral blood on overall survival (OS), progression-free survival, disease-free survival (DFS), disease-specific survival, metastasis-free survival, and recurrence-free survival of HNC patients. The analysis applied the criteria for systematic reviews described in the Cochrane Handbook and was conducted using hazard ratios (HRs) to estimate effect size, and calculated by Stata/SE version 13.0.ResultsThe meta-analysis included eligible cohort studies (5475 cases). The OS data indicated increased mortality risk in HNC patients with a high NLR (HR = 1.84, 95% confidence interval (CI): 1.53–2.23; P < 0.001; heterogeneity, I2 = 37.2%, P = 0.074). Analysis of subgroups stratified by NLR cutoff values revealed increased mortality risk and significantly shorter DFS in patients with high NLR compared to those with low NLR (HR = 2.18, 95% CI: 1.46–3.24; P < 0.001). Patients with high NLR had a higher probability of tumor recurrence after treatment than those with low NLR (HR = 1.63, 95% CI: 1.09–2.45; P = 0.017; heterogeneity, I2 = 68.7%; P = 0.022). The probability of distant metastasis following treatment was greater in patients with high compared with low NLR (HR = 1.92, 95% CI: 1.36–2.72; P < 0.001; heterogeneity, I2 = 0.0%; P = 0.614). Funnel plots of the meta-analysis results were stable, as shown by sensitivity analysis. No publication bias was detected by the Egger test (P = 0.135).ConclusionsHNC patients with elevated pretreatment NLR in peripheral blood have poor prognosis and are prone to local invasion and distant metastasis. NLR values are easily obtained from routinely collected blood samples and could assist clinicians to determine prognosis of HNC patients.

Effect of Tumor Size on Risk of Metastatic Disease and Survival for Thyroid Cancer: Implications for Biopsy Guidelines.

In many risk-stratification systems, the decision to biopsy thyroid nodules is determined by their sonographic features and size. Nevertheless, even low-suspicion nodules are often biopsied at small size thresholds because it is assumed that larger malignant nodules are associated with poorer outcomes. The aim of this study was to quantify the effect of thyroid cancer tumor size on survival and risk of T4 stage, nodal disease, and distant metastases. The Surveillance, Epidemiology, and End Results 18 database was queried to obtain tumor size, staging information, and survival data for cases of differentiated thyroid cancer (DTC) and non-DTC reported between 2004 and 2014. Observed probabilities of tumor extent at diagnosis, including regional nodal disease and distant metastases, as a function of size and tumor histology were estimated for thyroid cancers measuring between 1 and 150 mm. A multivariate Cox regression model was used to describe all-cause mortality as a function of patient and tumor characteristics, and the functional dependence of mortality on size was computed. A total of 112,128 patients were analyzed, with 67% having thyroid cancers ≥1 cm, and 29% ≥ 2.5 cm. For DTC tumors <4 cm, the risk of local invasion, nodal metastases, or distant metastases was low, and there was no size threshold associated with a sharp rise in adverse outcomes. For DTC tumors <4 cm, the probability of distant metastases was <3%. Older age, male sex, non-DTC histology, T4 stage, and regional and distant metastatic disease increased the all-cause mortality rate. Tumor size did not increase the mortality rate above baseline until tumors were >2.5 cm. Increasing tumor size does not affect survival until a threshold of 2.5 cm. Since the dimension of nodules on ultrasound has been shown to be larger than their size at gross pathology, these findings suggest that recommended size thresholds to biopsy low-suspicion thyroid nodules can be increased.

Abstract P1-10-12: Differential benefit of intra-operative administration of ketorolac on breast cancer disease recurrence according to baseline body mass index

Abstract Background: According to the last estimates, 63% of the women in the US are either overweight or obese. Increased body mass index (BMI) has been recognized as a risk factor for developing breast cancer (BC) and associated with adverse survival. So far, few treatment modalities focusing on the biological features of BC patients with increased adiposity have been evaluated. In cancer patients, elevated leptin levels have been found, among others, to stimulate the Rho GTPase pathway, involved in cell adhesion and motility. Here, using a unique retrospective institutional cohort including a total of 847 BC patients, we aimed at assessing whether the intra-operative administration of ketorolac, a Non-Steroidal Anti-Inflammatory Drug (NSAID), with a recently documented Rho GTPase inhibitory activity, would be associated with an improvement in distant disease recurrence according to BMI. We further assessed in an independent series of 1,009 patients, the effect of intra-operative diclofenac, another NSAID without Rho GTPase inhibitory activity. Patients and methods: In the institutional retrospective and consecutive 'ketorolac' series of patients with primary BC surgery, 538 were treated with and 309 without a single-dose (typically 20 mg in patients under 60 kg and 30 mg in patients ≥60 kg) of intra-operative ketorolac. In the 'diclofenac' series, 789 patients were treated with intra-operative diclofenac (75 mg) and 220 without. Competing risk analysis of distant recurrences was done by crude cumulative incidence curves to be interpreted as the cumulative probability of distant metastases as first event and consistently by Fine &amp; Gray semi-parametric models on sub-distribution hazards. Subgroup analyses were conducted according to the Dixon&amp;Simon approach. These analyses were adjusted for standard clinico-pathological variables: NSAID use, tumor size, age, nodal status, grade, ER status, and BMI. The median follow-up time of the ketorolac and diclofenac cohort was 5.7 and 8.0 years, respectively. Results: In both cohorts, the administration of the NSAID was associated with younger age at diagnosis, consistent with previous reports. The administration of ketorolac was associated with decreased incidence of distant recurrences both in the unadjusted and adjusted analysis (HRadj= 0.55, 95%CI: 0.35-0.86, p=0.01). Subgroup analyses in patients with BMI&amp;lt;25 and ≥25 (overweight and obese) revealed that the effect was limited to the high BMI group of patients both in the unadjusted and adjusted analysis (HRadj= 0.58, 95%CI: 0.33-0.98). The administration of diclofenac was not associated with decreased incidence of distant recurrences, nor in the global population, neither in the BMI subgroups. Conclusion: The fact that only ketorolac but not diclofenac was associated with a significant reduction of distant recurrences in BC patients with elevated BMI could be explained by the specific Rho GTPase inhibitory effect of the R-enantiomer of ketorolac, absent in diclofenac. While this study is limited by its retrospective nature, it suggests a potentially important repositioning of ketorolac in the intra-operative treatment of BC patients with elevated BMI. A prospective study is on its way. Citation Format: Desmedt C, Demicheli R, Fornili M, Bachir I, Duca M, Viglietti G, Piccart M, Sotiriou C, Sosnowski M, Forget P, Biganzoli E. Differential benefit of intra-operative administration of ketorolac on breast cancer disease recurrence according to baseline body mass index [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-10-12.

Use of Concomitant Androgen Deprivation Therapy in Patients Treated with Early Salvage Radiotherapy for Biochemical Recurrence After Radical Prostatectomy: Long-term Results from a Large, Multi-institutional Series

BackgroundHormonal manipulation concomitant to salvage radiotherapy (SRT) given for biochemical recurrence (BCR) after radical prostatectomy (RP) improved outcomes in two randomized trials. However, neither of these studies focused on men treated at low prostate-specific antigen (PSA) levels. ObjectiveTo test if the impact of androgen deprivation therapy (ADT) on metastasis in patients undergoing early SRT varies according to prostate cancer (PCa) features. Design, setting, and participantsA total of 525 patients received SRT at PSA levels ≤2ng/ml. Outcome measurements and statistical analysesMultivariable Cox regression analyses assessed factors associated with metastasis. We tested the hypothesis that the impact of ADT varied according to the risk of metastasis. An interaction with groups (concomitant ADT vs no ADT) and the probability of distant metastasis according to a newly developed model was tested. A nonparametric curve explored the relationship between the risk of metastasis and 10-yr metastasis rates according to ADT. Results and limitationsMedian PSA and radiotherapy dose were 0.42ng/ml and 66Gy, respectively. Overall, 178 (34%) patients received ADT. At a median follow-up of 104 mo, 71 patients experienced metastasis. Grade group ≥4 (hazard ratio [HR]: 1.66; 95% confidence interval [CI]: 1.01–3.30), pT3b/4 (HR: 2.61; 95% CI: 1.51–4.52), and dose (HR: 0.82; 95% CI: 0.76–0.89) were associated with metastasis. The impact of ADT differed according to the risk of metastasis calculated using a multivariable model (p=0.01). This was confirmed when considering patients treated with early SRT (p=0.046), where ADT was associated with a reduction in the rate of metastasis only in eSRT; patients with more aggressive characteristics (ie, pT3b/4 and grade group ≥4, or pT3b/4 and PSA at eSRT ≥0.4ng/ml). ConclusionsThe beneficial effect of ADT concomitant to eSRT varied significantly according to disease characteristics, such that only men with more aggressive PCa features benefit from ADT in the eSRT setting for BCR after RP. Patient summaryThe oncological benefits of concomitant androgen deprivation therapy (ADT) in patients undergoing salvage radiotherapy (SRT) vary according to pathological characteristics. Only patients with more aggressive disease characteristics seemed to benefit from the use of hormonal manipulation at the time of early SRT. Conversely, the potential side effects of ADT could be spared in patients with low prostate-specific antigen levels and favorable pathological features.

An unmet need: tailoring extended adjuvant endocrine therapy

An unmet need: tailoring extended adjuvant endocrine therapy

Rectum Sarcoma: Challenging Diagnostic and Therapeutic Modalities

Sarcomas are malignant tumors that arise from mesenchymal tissue at any of the body sites. They incorporate the wide category of GISTs and are classified in various histological types. Histological grading is another indicator of the degree of malignancy, the probability of distant metastases, and survival but remains a poor definition of local recurrence. The size and depth of invasion are the most important prognostic factors. Since they grow within the intestinal wall, the symptoms are usually few or late, leading to delays in diagnosis. Most common signs are rectal bleeding, abdominal or anal pain, diarrhea, tenesmus and weight loss. The diagnostic and staging protocol of stromal tumors of the rectum includes mainly endoscopic surveillance, computed tomography, and magnetic resonance imaging. Therefore, rectum sarcoma (RS) consists one of the most biologically virulent cancers and is difficult to cure by conventional procedures. The treatment is primarily surgical, where possible, and should guarantee complete clearance of the tumor, which often requires an aggressive approach. Unfortunately, the minority of patients is eligible to undergo surgical intervention. In addition, surgical removal of RS does not necessarily indicate a patient's long-term recovery. Alternative therapies, such as radio- and chemotherapy, proved insufficient. Elucidation of its molecular basis may prove useful in developing and identifying prognostic biomarkers.

Abstract 1463: Detection of cancer before distant metastasis.

Abstract Introduction: The majority of deaths from cancer are due to disseminated disease rather than the primary tumor. As metastases are often discovered years after surgical removal of the primary tumor, probably at least one metastasis was already present at the time of surgery. To establish a distant metastasis cells must disseminate from the primary tumor and overcome a series of obstacles, the metastatic cascade. In this study we develop a mathematical model for this cascade to estimate the technology requirements for detection of a primary tumor before the first metastasis has been formed. Methods: The metastatic cascade is described in discrete steps: 1. local tumor growth; 2. dissemination into circulation; 3. survival in circulation; 4. extravasation into tissue; and 5. growth into a metastasis. The model was built using data and relationships described in the literature to predict the relationship between tumor size and probability of distant metastasis for 38715 patients with surgically removed TxNxM0 primary breast cancer from the Netherlands Cancer Registry. The model was calibrated using primary tumor size, probability of distant metastasis and time to distant metastasis for 1489 patients with stage T1bNxM0 (25% of total patients with T1bNxM0). Validation of the model was done with data for all patients. Results: From the time to distant metastasis of these 38715 breast cancer patients, we determined a tumor doubling time of 1.7 ± 0.9 months. Fitting the data for 25% of T1b patients estimates a metastatic efficiency of 1 metastasis formed per 60 million disseminated tumor cells. Validation of the model to data of patients in all T-stages shows good agreement between model and epidemiological data. To reduce the 5-year risk of distant metastasis for TxNxM0 from 9.2% to 1.0%, the primary tumor needs to be detected and removed before it reaches a diameter of 2.7 ± 1.6 mm. At this size, the model predicts that there will be 9 ± 6 CTC/L blood. Conclusions: To reduce the rate of distant metastasis in surgically treated TxNxM0 breast cancer to 1%, imaging technology will need to be able to detect lesions of 2.7 mm in diameter or smaller. Before CTC detection can be applied in the early disease setting, sensitivity will need to be improved by at least 15-fold and combined with technology that minimizes false positives. Citation Format: Frank AW Coumans, Sabine Siesling, Leon WMM Terstappen. Detection of cancer before distant metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1463. doi:10.1158/1538-7445.AM2013-1463

Grading sarcomas: histologic and molecular approaches

Histological grading, that is, grading based only on histological parameters, evaluates the degree of malignancy and the probability of distant metastasis for cancer. Several grading systems have been reported for sarcomas but the two most widely-used systems are the National Cancer Institute and the French systems. Histological grade is recognized as the most important prognostic factor for soft tissue sarcomas. However, this approach presents several limitations such as moderate reproducibility, existence of an intermediate grade and the current nearly universal use of core needle biopsies. A molecular grading system which significantly outperforms histological grading has been recently described for sarcomas. It is based on the expression profile of 67 genes related to chromosome complexity and mitosis management (CINSARC for Complexity INdex in SARComas). In this article we discuss both approaches as well as the future of grading, regarding the respective values of histological and molecular grading systems, validation, extension, refinement and practical use of the molecular grading.

Melanoma Metastases to the Neck Nodes: Role of Adjuvant Irradiation

To review experiences in the treatment of regionally advanced melanoma to the neck and/or parotid with emphasis on the role of adjuvant radiotherapy. Clinical and histopathologic data, treatment details, and outcomes in patients treated during the period 2000-2006 at the Institute of Oncology, Ljubljana, Slovenia, were reviewed. A total of 40 patients with 42 dissections underwent surgery, and 43 patients with 45 dissections received irradiation postoperatively to a median equivalent dose (eqTD(2): 2 Gy/fraction, 1 fraction/day, 5 fractions/week) of 60 Gy (range, 47.8-78.8). Regional control 2 years after surgery was 56% (95% confidence interval [CI] 40-72%) and after postoperative radiotherapy 78% (CI 63-92%) (p = 0.015). On multivariate analysis, postoperative radiotherapy (yes vs. no: hazard ratio [HR] 6.3, CI 2.0-20.6) and sum of the risk factors present (i.e., risk factor score; HR 1.7 per score point, CI 1.2-2.6) were predictive for regional control. On logistic regression testing, the number of involved nodes was associated with the probability of distant metastases (p = 0.021). The incidence of late toxicity did not correlate with the mode of therapy, eqTD(2), or fractionation pattern. Adjuvant radiotherapy has the potential to compensate effectively for the negative impact of adverse histopatologic features to disease control in a dissected nodal basin. More conventionally fractionated radiotherapy regimens using fraction doses of 2-2.5 Gy, with cumulative eqTD(2)> or =60 Gy, are recommended. The number of involved lymph nodes is proposed as an additional criterion for limiting the implementation of adjuvant irradiation.

Neighborhood Change and Distant Metastasis at Diagnosis of Breast Cancer

To test whether upward socioeconomic neighborhood change has an effect on probability of distant metastasis at diagnosis of breast cancer among women who live there. Census tract data (N = 1,137) from Cook County. IL, from 1990 and 2000 and cancer registry data for female breast cancer cases for these census tracts from 1994-2000 (N = 21,516) were used. A multilevel model of 1990 baseline socioeconomic status (SES) of neighborhoods and degree of neighborhood change 1990-2000 (compositional characteristics) and patient's age and race/Hispanic status (individual characteristics) was constructed to predict distant metastasis (vs. local and regional stage) at diagnosis. While residence in a census tract with lower baseline SES in 1990 (higher concentrated disadvantage and immigration and lower concentrated affluence) and being African American were associated with increased odds of distant metastasis at diagnosis, residence in an improving census tract was also associated with increased odds of distant metastasis at diagnosis. Paradoxically, both measures of initial neighborhood disadvantage and upward neighborhood socioeconomic change were independently associated with greater odds of distant metastasis at diagnosis of breast cancer. Neighborhood social and economic change can affect health.

Patterns of failure in patients with locally advanced head and neck cancer treated postoperatively with irradiation or concomitant irradiation with Mitomycin C and Bleomycin

The long term results and patterns of failure in patients with squamous cell head and neck carcinoma (SCHNC) treated in a prospective randomized trial in which concomitant postoperative radiochemotherapy with Mitomycin C and Bleomycin (CRT) was compared with radiotherapy only (RT), were analyzed. Between March 1997 and December 2001, 114 eligible patients with Stage III or IV SCHNC were randomized. Primary surgical treatment was performed with curative intent in all patients. Patients in both groups were postoperatively irradiated to the total dose of 56-70 Gy. Chemotherapy included Mitomycin C 15 mg/m2 after 10 Gy and 5 mg of Bleomycin twice weekly during irradiation. Median follow-up was 76 months (48-103 months). At 5 years in the RT and CRT arms, the locoregional control was 65% and 88% (p = 0.026), disease-free survival 33% and 53% (p = 0.035), and overall survival 37% and 55% (p = 0.091) respectively. Patients who benefited from chemotherapy were those with high-risk factors. The probability of distant metastases was 22% in RT and 20% in CRT arm (p = 0.913), of grade III or higher late toxicity 19% in RT and 26% in CRT arm (p = 0.52) and of thyroid dysfunction 36% in RT and 56% in CRT arm (p = 0.24). The probability to develop a second primary malignancy (SPM) was 34% in the RT and 8% in the CRT arm (p = 0.023). One third of deaths were due to infection, but there was no difference between the 2 groups. With concomitant radiochemotherapy, locoregional control and disease free survival were significantly improved. Second primary malignancies in the CRT arm compared to RT arm were significantly less frequent. The high probability of post treatment hypothyroidism in both arms warrants regular laboratory evaluation.

Prostate specific antigen doubling time (PSADT) predicts for distant failure and prostate cancer specific survival (PCSS) in men with biochemical relapse after radical prostatectomy (RP)

4555 Background: Patients (pts) with biochemical (PSA) relapse after RP represent a rapidly rising population in whom appropriate standards of care remain undefined. Over the past several years we have focused on studying the natural history of these pts. Our previous report (Pound et al; JAMA 1999) suggests that the Gleason score, time of PSA relapse (>0.2 ng/ml) and PSADT are the strongest predictors of the probability of distant metastasis (DM) (Cox model). A recent update (Partin; AUA 2003, Eisenberger; ASCO 2003) suggests that PSADT overrides the other parameters in the prediction of DM. Our experience has been expanded (> 1000 additional pts and longer follow-up). We evaluate the relationship between PSADT and PCSS. Methods: 4,415 pts underwent a RP from 1982–2003 and 825 demonstrated evidence of PSA relapse. All pts were followed with yearly PSAs with no androgen deprivation given until development of DM. Cox-proportional hazards and Kaplan-Meier survival analyses were completed with time from PSA ...

Proton therapy for uveal melanomas and other eye lesions.

Charged particle beams are ideal for treating intra-ocular lesions, since they can be made to deposit their dose in the target, while significantly limiting dose received by non-involved ocular and orbital structures. Proton beam treatment of large numbers of uveal melanoma patients consistently achieves local control rates in excess of 95%, and eye retention rates of approximately 90%. Visual preservation is related to initial visual acuity, tumor size and location, and dose received by the macula, disc, and lens. The probability of distant metastasis is increased by larger tumor diameter, more anterior tumor location, and older patient age. Proton therapy is also effective treatment for patients with ocular angiomas, hemangiomas, metastatic tumors, and retinoblastomas, and may be beneficial for patients with exudative ("wet") age-related macular degeneration.

Prognostic factors in patients with carcinoma of the uterine cervix treated with external beam irradiation and IR-192 high-dose-rate brachytherapy

Purpose: Prognostic factors in cancer of the cervix for patients treated with external beam irradiation (EBR) and low-dose-rate (LDR) brachytherapy have been characterized. However, despite the increasing use of high-dose-rate (HDR) intracavitary placements (ICP), few studies with adequate follow-up have analyzed prognostic factors. This study investigates pretreatment and treatment factors for their correlation with treatment outcome after EBR and HDR-ICP. Methods and Materials: Between September 1985 and December 1994, 181 patients with carcinoma of the cervix FIGO stages IB–IV received EBR and HDR brachytherapy. Hemoglobin (Hb) levels were maintained above a level of 11 g/dl during the treatment by transfusion. Patient age ranged from 34 to 84 years (median: 66). The median follow-up time for patients at risk is 69 months (range: 23–140). Pretreatment and treatment parameters analyzed to determine their prognostic value included age, FIGO stage, tumor size, tumor type and grade, pretreatment Hb level, number of HDR-ICP, total dose from HDR-ICP, overall dose to point A, and overall treatment time. Also evaluated was the prognostic value of enlarged lymph nodes noted on pretreatment CAT scan of the abdomen and pelvis. Endpoints studied in uni- and multivariate analyses were disease-specific survival (DSS), freedom from disease (FFD), pelvic control (PC), and probability of distant metastases (DM). Results: At 5 years the DSS, FFD, and PC rates for all patients were 60%, 58%, and 67%, respectively. The 5-year FFD by stage was: IB: 94%; II: 63%; IIIB: 43%; and IV: 0%. The PC rates were 94%, 66%, 59%, and 0%, respectively. In univariate analysis the prognostic factors identified for FFD were FIGO stage, tumor size, initial Hb level, and enlarged pelvic and/or paraaortic nodes (all: p < 0.0001). Age was inversely correlated with outcome ( p = 0.0081). The 5-year FFD rates for tumors (< 3, ≥ 3 < 6, ≥ 6 cm) were 97%, 65%, and 24%; patients with initial Hb levels ≤ 11g/dl had a FFD of 26% versus 69% for patients with levels > 11g/dl; and those with pelvic and/or paraaortal nodes ≥ 1 cm had a survival of 32% versus 68% in patients with negative readings. The same factors were also prognostically significant for DSS, PC, and DM. Patients with persistent disease or pelvic failures had a significantly higher incidence of DM than patients in whom pelvic disease was controlled ( p < 0.0001).Histological and treatment parameters including overall treatment time were not of prognostic significance for any of the endpoints studied. In multivariate analysis tumor size was the most powerful parameter for DSS, FFD, PC ( p < 0.0001) and DM ( p = 0.0001), followed by low initial Hb level (DSS: p = 0.0004, FFD: p = 0.0009, PC: p = 0.0012, DM: p = 0.0265), and enlarged pelvic and/or paraaortic nodes which were predictive for DSS ( p = 0.0210) and DM ( p = 0.0011). Conclusion: This study confirms that prognostic factors for patients treated with HDR brachytherapy are similar to those reported in previous series that employed LDR brachytherapy. The significance of tumor size, pretreatment Hb level, and enlarged pelvic and/or paraaortic lymph nodes on CAT scan over FIGO stage of disease were demonstrated. Future prospective trials should be undertaken to confirm the validity of these factors and to elucidate their therapeutic implications.

The effect of local control on metastatic dissemination in carcinoma of the prostate: Long-term results in patients treated with 1251 implantation

The study evaluates the effect of the locally recurring tumor on the incidence of metastatic disease in early stage carcinoma of the prostate. The probability of distant metastases was studied in 679 patients with Stage B-C/NO carcinoma of the prostate treated at MSKCC between 1970 and 1985 (median follow-up of 97 months). Patients were staged with pelvic lymph node dissection and treated with retropubic 125I implantation. The actuarial distant metastases free survival (DMFS) for patients at risk at 15 years after initial therapy was 37%. Cox proportional hazard regression analysis of covariates affecting the metastatic outcome showed that local failure, used in the model as a time dependent variable, was the most significant covariate, although stage, grade, and implant volume were also found to be independent variables. The relative risk of metastatic spread subsequent to local failure was 4-fold increased compared to the risk without evidence of local relapse. The 15-year actuarial DMFS in 351 patients with local control was 77% compared to 24% in 328 patients who developed local relapses ( p < 0.00001). The relation of distant spread to the local outcome was observed regardless of stage, grade, or implant dose. Even stage BI/NO-Grade I patient with local control showed a 15-year actuarial DMFS of 82%, compared to 22% in patients with local relapse; p < 0.00001). The median local relapse-free survival (LRFS) in the 268 patients with local recurrences who did not receive hormonal therapy before distant metastases were detected was 51 months, compared to a median of 71 months for DMFS in the same patients ( p < 0.001), consistent with the possibility that distant dissemination may develop secondary to local failure. Furthermore, distant metastases in patients with local control, apparently already existing as micrometastases before treatment, were detected earlier (median DMFS of 37 months) than in patients with local relapse (median DMFS of 54 months; p = 0.009). These data suggest that the existence and re-growth of local residual disease in localized prostatic carcinoma promotes an enhanced spread of metastatic disease, and that early and complete eradication of the primary tumor is required if a long term cure is to be achieved, although the clinical expression of secondary metastases may not become apparent for 6.5 years or more in one-half of the patients.