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Results for “distant metastasis”

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PubMed1996

Prognostic value of paranasopharyngeal extension of nasopharyngeal carcinoma. A significant factor in local control and distant metastasis.

BACKGROUND: This study was conducted to evaluate the prognostic value of paranasopharyngeal extension in local control and distant metastasis in patients with nasopharyngeal carcinoma. METHODS: Three hundred and sixty-four patients with newly diagnosed nasopharyngeal carcinoma without distant metastasis were reviewed. Patients were staged according to Ho's staging system. Using a semiquantitative method, tumor extension into the paranasopharyngeal space was graded as: 0: no extension; 1: extension to the retrostyloid space; 2: extension to the prestyloid space; and 3: extension to the anterior part of the masticator space. All patients received radiotherapy as primary treatment. Median follow-up time was 45 months (range, 4.7 to 76.5 months). Relapse free, local relapse free, and distant metastasis free survival were estimated using the Kaplan-Meier method. Cox regression was also performed to adjust for prognostic factors. RESULTS: The incidence of paranasopharyngeal extension was high (72.5%). Of these patients, 65.5% had Grade 2 or 3 extension. The 5-year relapse free survival rates for Grade 0, 1, 2, and 3 extension were 76%, 70%, 46%, and 43%, respectively. The main difference was between Grade 0/1 and Grade 2/3 extension, the latter having a lower 5-year local control rate (86% in Grade 0/1 vs. 72% in Grade 2/3; P < 0.0001) and distant metastasis free survival rate (87% in Grade 0/1 vs. 68% in Grade 2/3; P = 0.0002). Multivariate analysis showed that Grade 2/3 paranasopharyngeal extension was an independent factor in predicting overall relapse, local relapse, and distant metastasis. Advanced T classification (T3) was another independent factor in predicting overall and local relapse, whereas advanced N classification (N3) was another independent factor in predicting overall relapse and distant metastasis. CONCLUSIONS: Extensive paranasopharyngeal extension (Grade 2/3) was an independent prognostic factor associated with poorer treatment outcome, both in local control and distant metastasis. Ho's T2 disease should be further subclassified into T2a and T2b, which include Grade 0/1 and Grade 2/3 paranasopharyngeal disease, respectively.

Adult↗

PubMed2004

[Clinical value of vascular endothelial growth factor detection in forecasting distant metastasis risk of nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: Vascular endothelial growth factor (VEGF)closely relates with the malignancy and metastasis of various kinds of cancers. This study was designed to evaluate the value of VEGF detection in forecasting distant metastasis risk of nasopharyngeal carcinoma(NPC)patients. METHODS: Tumor biopsies,and serum specimens were collected before treatment from 59 pathologically diagnosed NPC patients, hospitalized in our hospital from Mar. 1999 to Feb. 2000. Immunohistochemistry LSAB method was used to detect VEGF in NPC tissues. VEGF in NPC serum was detected by quantitative enzyme-linked immunosorbent assay (ELISA) method. Through follow-up study, the relationship between VEGF and distant metastasis of NPC patients was observed. RESULTS: The expression of VEGF in NPC tissue,and serum positively related with the distant metastasis (P< 0.05). Non-distant metastasis survival rates of different tissue VEGF groups were 100%(-), 95.24%(+), 65.19%(++), and 58.93%(+++), significant difference existed between every 2 groups (P=0.019 3). Non-distant metastasis survival rates of different serum VEGF groups were 82.57% (< 466.78 ng/L), and 59.11% (>/=466.78 ng/L)(P=0.021 1). Multi-prognostic factors analysis showed that VEGF expression in NPC tissue and serum had significant effects on distant metastasis of NPC. CONCLUSIONS: The detection of VEGF either in NPC tissue or in serum could be regarded as a valuable indicator for predicting distant metastasis risk of NPC patients. Combined detection of them could increase the chances of forcasting distant metastasis in NPC patients.

Adult↗

PubMed2001

[Expression of nm23 in breast cancer: correlation with distant metastasis and prognosis].

OBJECTIVE: To investigate the relationship between expression of nm23 gene and distant metastasis and prognosis in breast cancer. METHODS: To detect nm23 protein expression in 101 patients with breast cancer by means of immunohistochemistry and nm23 mRNA expression in 68 patients with breast cancer by RT-PCR. RESULTS: Expression of nm23 gene was inversely correlated with distant metastasis and lymph node metastasis. Among 9 patients with negative node but with distant metastasis, 7 had low expression of nm23. In 29 patients with positive nodes but without distant metastasis, 24 had high expression of nm23, while 6 of 6 patients with positive nodes and distant metastasis expressed high levels of nm23 mRNA. CONCLUSION: Expression of nm23 gene, tumor size and status of axillary lymph node are independent prognostic indicators to breast cancer prognosis.

Adult↗

PubMed1995

[Distant metastasis after irradiation alone in carcinoma of the uterine cervix--the patterns and results].

From 1988 to May, 1992, there were 286 patients with pathology-proved carcinoma of the uterine cervix referred to Chang Gung Memorial Hospital, Kaohsiung to receive definite radiotherapy. Sixty-one (21%) patients were found to develop distant metastasis after radiotherapy for at least 2 years follow-up. By FIGO stage, the incidence of distant metastasis was as follows: I :2/39, II a:1/19, II b:20/118, III :34/101, IV a: 4/9. Eighty-five percent patients (52/61) began to develop distant metastasis within the first 2 years after radiotherapy. Twenty-three patients developed single organ metastasis, and 38 patients developed multiple organ metastasis. Lymph nodes (38 patients), lung (28 patients), bone (27 patients), and abdomen (20 patients) were the common sites of distant metastasis. Lymph nodes metastasis occurred most often at supraclavicular lymph nodes (15 patients), para-aortic lymph nodes (18 patients), and inguinal lymph nodes (5 patients). Spine (23 patients), especially the lumbar spine (20 patients) was the most common site of bony metastasis. Abdominal metastasis occurred in abdominal cavity (15 patients) or liver (5 patients). The incidence of metastasis within the first two years after radiotherapy was lung: 75% (21/28), bone: 62% (18/29), left supraclavicular lymph nodes: 60% (9/15), para-aortic lymph nodes: 72% (13/18), intra-abdominal cavity: 86% (13/15), liver: 66% (2/3), brain: 0% (0/4). The 2-year actuarial survival rate for the 61 patients after developing distant metastasis was 14%, with a median survival time of 6.4 months. There was no significant difference in survival when comparing patients with single organ metastasis and with multiple organ metastasis (p > 0.05), or patients with distant metastasis alone and with distant metastasis combined with local recurrence (p > 0.05). Otherwise, after distant metastasis twenty-three patients receiving chemotherapy or radiotherapy had a significantly higher 2-year survival rate than 38 patients receiving supportive care only after distant metastasis (34% vs. 2.4%, p < 0.05).

Female↗

PubMed2006

[Relationship between the expression of estrogen and progestogen receptors in distant metastasis of nasopharyngeal carcinoma].

OBJECTIVE: To explore the relationship between the expression of estrogen and progestogen receptors (ER/PR) in distant metastasis of nasopharyngeal carcinoma (NPC). METHOD: The expression of ER/PR were detected with immunohistochemical SP method in 81 nasopharyngeal carcinoma who had been treated and followed-up. RESULT: (1) The positive rates of ER and PR in the tissue of NPC were 35.8% and 53.1%. (2) The expression intensity of PR in T stage has obvious statistically significance (P < 0.01), the expression intensity and positive rates of ER in IVb stage were obviously higher than the other stage (P < 0.01). (3) The positive rates of ER and PR in patients of the distant metastasis group (including the distant metastasis found before and after radiotherapy) were obviously higher than the group who have been alive with no evidence of disease for five or more than five years after radiotherapy (P < 0.01) and P < 0.05). CONCLUSION: The positive expression of ER and PR in NPC were well correlated with the distant metastasis, and it increased gradually. Positive expression, especially the strong positive expression points out the bad prognosis. Endocrine treat may reduce and postpone the distant metastasis.

Adult↗

PubMed1992

[Recurrence following surgery for primary renal pelvic and ureter cancer--clinicopathologic analysis of distant metastasis].

A retrospective analysis of 59 patients with renal pelvic and ureter cancer (56 transitional cell carcinomas, 2 squamous cell carcinomas, and 1 adenocarcinoma), which were treated surgically, was performed in relation to postoperative recurrence, particularly distant metastasis. Of the 59 cases, postoperative recurrences developed as distant metastasis in 9 cases (15.3%), as bladder cancer in 19 cases (32.2%) and as contralateral renal pelvic and ureter cancer (bilateral metachronous cancer) in 3 cases (5.1%). Three of the 9 cases with the development of distant metastasis were squamous cell carcinoma or adenocarcinoma, and the others transitional cell carcinoma. All the metastases occurred within 2 years. In cases with transitional cell carcinoma, nonpapillary tumor, grade 3, high stage (pT3 and pT4), positive vascular invasion and IFN beta or gamma had a significant influence on the rate of distant metastasis. On the other hand, location, diversity and previous or coexistent bladder cancer did not seem to be related to the frequency of the development of distant metastasis. Thus, tumor aggressiveness was the only predictive valuable of the development of distant metastasis after surgery for renal pelvic and ureter cancer.

Adenocarcinoma↗

PubMed1987

Distant metastasis in malignancies of the head and neck.

It is a well known fact that disease in head and neck cancer remains confined above the clavicle in a majority of cases for a considerable length of time. The causes of death in head and neck cancer patients are known to be due to lymph node metastasis, fungation, asphyxia, cachexia, invasion of major vessels and infection. Distant metastasis occurs late in the disease. However, many reports have appeared in the literature which indicate a high incidence of distant metastasis in head and neck malignancies. Merino et al. (1977), in a clinical study, have indicated an incidence of 10.9 per cent. Studies based on autopsy findings, however, quote a much higher figure (30 per cent, Papac, 1984; 57 per cent, Gowen and Dessuto Nagy, 1963). Dennington and Caster (1980) reported that at least seven per cent of patients with head and neck cancer have distant metastasis when first seen. The present study was designed to find out the incidence of distant metastasis in our head and neck cancer patients.

Adolescent↗

PubMed1997

Carcinoma of the nasopharynx treated by radiotherapy alone: determinants of distant metastasis and survival.

PURPOSE: This retrospective study was conducted to identify the prognostic factors for distant metastasis and survival in a population of 378 patients with nasopharyngeal carcinomas treated by radiation therapy alone. MATERIALS AND METHODS: All patients were treated at the University of Texas M.D. Anderson Cancer Center between 1954 and 1992, following a consistent dose and volume prescription policy. There were 286 males and 92 females. The median age was 52 years (range: 16-86 years). The majority of the patients were white Caucasians (282 patients,75%). Tumors were classified as squamous cell carcinomas (193; 51%), lymphoepitheliomas (154; 41%), or unclassified carcinomas (31, 8%). Three fourths of the patients presented with AJCC Stage IV disease (T4, N0-3, 118 patients; T1-3, N2-3 164 patients). The treatment techniques included opposed lateral fields with or without an anteroposterior or an anterior oblique pairs for dose supplementation to the primary site. Average total doses per T-stage ranged between 60.2 and 72.0 Gy. Median follow-up time was 10 years (range 0.3 to 28.6 years). RESULTS: A total of 103 patients (27%) developed distant metastases at a median time of 8 months (range: 1-90 months). Actuarial rates for distant metastasis were 30%, 32%, 32% at 5, 10, and 20 years, respectively. Actuarial rates for disease specific survival at the same time points were 53%, 45%, and 39% with 184 patients (49%) dying of their nasopharyngeal cancer. Advanced T-stage, N-stage, and non-lymphoepithelioma histology were independent adverse prognostic factors for disease specific survival. Advanced N-stage and low neck disease were independent adverse prognostic factors for distant metastasis with a very high rate of distant metastases for those patients who presented with both adverse factors (relative risk 7.86). On average, patients with distant metastasis lived 5 months after they were diagnosed with metastatic disease (range: 0-172 months), although four patients (4%) survived more than 5 years after diagnosis. CONCLUSIONS: This study demonstrates good long term survival rates after definitive radiotherapy for patients with nasopharyngeal carcinomas. Patients with advanced and lower neck disease have the highest risk of developing distant failures. Such patients can be considered the reference risk group to test the value of adjunctive chemotherapy.

Adolescent↗

PubMed2002

PCR detection of circulating tumor cells in nasopharyngeal carcinoma patients with distant metastasis: effect of enzyme and sampling.

BACKGROUND: Nasopharyngeal carcinoma (NPC) has a high potential to develop distant metastasis after radiotherapy. Cytokeratin 19 (CK-19) mRNA has been frequently used as a marker in the detection of circulating tumor cells of epithelial origin, but has rarely been investigated in NPC. This study was performed to evaluate the effect of blood sampling and different Taq DNA polymerase on the results of nested reverse transcriptase-polymerase chain reaction (RT-PCR) assay. METHODS: Peripheral blood samples from a total of 37 NPC patients with well-documented distant metastasis (M1) were collected before treatment. Eighteen patients had more than one blood sampling. Five different Taq DNA polymerases were used to test the blood from 17 patients. Peripheral blood of 37 nonmetastatic (M0) NPC patients was tested by the same nested RT-PCR system using multiple Taq DNA polymerases to evaluate the impact of multienzyme assay in the prediction of subsequent distant metastasis. RESULTS: Among M1 NPC patients, the accumulative positive rates of CK-19 mRNA were 22.2%, 44.4%, 70.6%, 75.0%, and 80.0% when one, two, three, four, or five blood sampling were taken, respectively. The accumulative positive rates increased as the numbers of different enzymes increased-from 35.5% by one enzyme to 82.4% by five enzymes. Six of 37 M0 patients had distant metastasis develop after a median follow-up time of 20 months. The detection sensitivity for four-enzyme test (5 of 6 = 83.3%) is better than that of one-enzyme test (2 of 6 = 33.3%). CONCLUSIONS: Our data demonstrate that multiple blood sampling or using multiple enzymes for nested RT-PCR assay significantly enhances the sensitivity in the molecular diagnosis of NPC metastasis.

Adolescent↗

PubMed2005

[Correlation between infiltration of local lesion and distant metastasis of nasopharyngeal carcinoma].

OBJECTIVE: The aim of this study was to study the correlation between local and regional infiltration and distant metastasis of nasopharyngeal carcinoma(NPC). METHOD: Materials of 204 NPC cases primarily treated (including 101 cases with tumor free and a period of survived time for 5 or more years after radiotherapy and 103 cases with distant metastasis after radiotherapy ). The extent and the way of local aggressiveness were made sure by studying their CT. Then the single-factor and COX analysis were adopted to analyze. RESULT: Single-factor analysis showed the extent of aggressiveness of nasal sinuses, base of skull, cranial nerves, parapharyngeal space, laterals and number, size, fixation of neck lymph nodes of metastasis, clinical stage, T and N stage had statistical significance (P <0.05); Multi-factor analysis merely showed aggressiveness of nasal sinuses, cranial nerves, laterals and number, size of neck lymph nodes, clinical stage had statistical significance; Analysis of correlation between the situations of local aggressiveness and regional infiltration showed that the occurrence of metastasis of lymph nodes and its degree in metastasis group of post-radiotherapy was obviously higher than that in non-metastasis group (P < 0.05, P < 0.01), while the degree of local aggressiveness, the involvement of base of skull and the parapharyngeal space were not. CONCLUSION: Regional infiltration and its degree are the most important and stable factors that affect the distant metastasis in NPC patients after radiotherapy, and primary lesion intrigues distant metastasis mainly through occurrence of metastasis of regional lymph nodes.

Adult↗

PubMedDate not supplied

Prediction of distant metastasis in follicular adenocarcinoma of the thyroid.

Follicular adenocarcinoma of the thyroid sometimes displays distant metastasis in spite of its low histological grade of malignancy. We have studied whether distant metastasis can be detected by the presence of blood vessel invasion. We have also examined the problem from the viewpoint of cell-to-cell conjugation. This study examined 160 cases of follicular adenocarcinoma of the thyroid. Histological specimens were made by sectioning tumors at their largest diameter. Blood vessel endothelia were specifically stained immunohistochemically with factor VIII-related antigen and Ulex europeaus agglutinin I (UEA-1). Then, the presence of blood vessel invasion was examined in detail. Furthermore, the conjugation of lectin-derived wheat germ agglutinin (WGA) to tumor cells was examined. Conjugation of tumor cells was also examined using sialic acid as a marker. Blood vessel invasion was recognized in 95 (59.4%) of 160 cases. Distant metastases were identified in 25 cases (15.6%) in which blood vessel invasion was also found. Relative to the group without distant metastases, the group with distant metastases showed not only a significantly higher sialic acid content but also higher levels of WGA-binding protein in the tissues. The risk of distant metastasis in patients with follicular adenocarcinoma of the thyroid appears to be related both to the extent and to the frequency of blood vessel invasion. Furthermore, assessment of the conjugation of cells appears to have predictive value for occurrence of distant metastases.

Adenocarcinoma↗

PubMed2003

Natural killer cell activity and distant metastasis in rectal cancers treated surgically with and without neoadjuvant chemoradiotherapy.

BACKGROUND: We investigated whether impaired preoperative natural killer (NK) cell activity correlates with asynchronous distant metastasis after curative surgery for rectal cancers. In addition, we examined if preoperative chemoradiotherapy for rectal cancers impairs NK cell activity and contributes to the induction of distant metastasis. STUDY DESIGN: Preoperative NK cell activity was examined in 174 rectal cancer patients. All patients were enrolled in this study and followed until asynchronous distant metastasis occurred. RESULTS: The mean NK activity in patients with stage IV disease (n = 20) was significantly lower than seen in other stages. There were no differences among stage I to stage III patients. In stage III patients, the cumulative distant metastasis-free rate after curative surgery was significantly lower in cases with NK activity of 25% or less than those with more than 25%. Preoperative chemoradiotherapy for stage I to III patients significantly impaired NK cell activity (n = 39), and the metastasis-positive ratio significantly increased among patients with stage II or stage III diseases (n = 30). Multivariate analysis indicated that dichotomized NK cell activity was a significant risk factor that is associated with distant metastasis as well as nodal involvement. CONCLUSIONS: In primary rectal cancers, NK cell activity is not necessarily impaired in accordance with the disease progression. It is considered an important background factor for developing asynchronous distant metastases in stage III rectal cancers. Neoadjuvant chemoradiotherapy impaired NK cell activity in selected patients, suggesting the necessity of concurrent immunotherapy for better outcomes.

Chemotherapy, Adjuvant↗

PubMed1996

Patterns of nodal and distant metastasis based on histologic varieties in differentiated carcinoma of the thyroid.

BACKGROUND: Understanding of differentiated carcinoma of the thyroid has improved in recent years with the definition of prognostic factors and risk group analysis. We intend to review our experience of differentiated thyroid cancer in relation to the risk of nodal and distant metastasis based on various histologic subgroups. METHODS: This is a retrospective review of a consecutive series of 1,038 previously untreated patients with differentiated carcinoma of the thyroid treated over a period of 55 years. Univariate and multivariate analysis of various prognostic factors was performed. The incidence of nodal and distant metastasis was analyzed based on various histologic varieties of differentiated thyroid cancer. RESULTS: There were 337 male and 701 female patients. The various histologic subgroups included papillary (810), follicular (169), and Hurthle cell cancer (59). The cumulative risk of nodal metastasis based on histological group was 61%, 30%, and 21% for papillary, follicular, and Hurthle cell variety, respectively. The risk of distant metastasis for the same histologic varieties was 10%, 22%, and 33%, respectively. The 5- and 20-year survival for these histologic subgroups was papillary (94% and 87%, respectively), follicular (87% and 81%), and Hurthle cell tumors (81% and 65%; P < 0.001). CONCLUSIONS: The incidence of nodal metastasis is highest in the papillary subgroup; however, the incidence of distant metastasis was 33% in the Hurthle cell variety. The risk of nodal and distant metastasis varies considerably based on individual histologic variety.

Adenocarcinoma↗

PubMed2001

Isolated late local recurrences with high mitotic count and early local recurrences following breast-conserving therapy are associated with increased risk on distant metastasis.

PURPOSE: Local recurrence (LR) after breast-conserving therapy (BCT) is associated with an increased risk for the development of distant metastasis. We studied risk factors for distant metastasis risk (DMR) and poor prognosis within a group of patients with LR as first event. PATIENTS AND METHODS: From a cohort of 1481 breast carcinomas treated with BCT in the period 1980-1994, a total of 68 pT1-3 N0-1 patients developed LR as first event. We have studied risk factors for the development of distant metastasis within this group of patients with LR. In addition to clinical factors (age at BCT and LR, mode of detection, location of LR, and treatment of LR), the histology slides of the primary and the recurrent tumor were reviewed. Immunohistochemical staining was performed for the following proteins: bcl-2, cyclin D1, E-cadherin, EGF receptor, ER, PR, Ki-67, c-erbB-2/neu, and p53. Statistical analyses were performed using conditional logistic regression. RESULTS: At a median follow-up after LR of 5.6 years, the 5-year DMR was 53%. In univariate analysis, none of the factors of the primary tumor was found to be associated with DMR after LR. Of the recurrent tumor the following factors were found to be risk factors for high DMR after LR: interval between treatment of the primary tumor and LR at 2 years or less (relative risk, 2.38; 95% confidence interval, 1.22-4.76; p = 0.008) and high mitotic count (relative risk, 2.51; 95% confidence interval, 1.03-6.15; p = 0.04). All patients with noninvasive recurrent tumor were alive at the time of analysis. Patients with an interval of greater than 2 years and a recurrent tumor with high mitotic count were found to have an equally poor prognosis compared to patients with LRs detected after a short interval. CONCLUSION: LR after BCT is associated with higher DMR and poor prognosis. Patients with LR within 2 years after BCT are especially at high risk. Late recurrences with high mitotic count have the same poor prognosis as early recurrences. For these patients, systemic treatment at time of the detection of LR should be considered.

Analysis of Variance↗

PubMed2002

Potential markers predicting distant metastasis in axillary node-negative breast carcinoma.

Prognostic parameters for axillary node-negative (ANN) breast cancer are still rare. Our aim was to establish potential markers that predict distant metastasis in ANN breast carcinoma and permit detection of the patients with high metastasis risk. A case control study was designed that comprised 64 ANN patients who developed distant metastasis during a 5-10 year follow-up period, 64 ANN patients with recurrence-free survival and 64 node-positive (ANP) comparitors. Immunohistochemistry and/or in situ hybridization were used to detect nm23, Cathepsin-D (Cath-D), Epidermal Growth Factor Receptor (EGFR) and Laminin Receptor (LR) in 192 cases. A significantly lower expression of both nm23 mRNA and protein was found in the ANN-group with poor prognosis compared with the ANN-group with good prognosis (p < 0.01). The protein levels of Cath-D, EGFR and LR were significantly higher in the ANN-group with poor prognosis and in the ANP-group compared with the ANN-group with good prognosis (p < 0.01 or p < 0.05), but no differences were found between the poor ANN-group and the ANP-group. Multiple regression analysis showed a close correlation of nm23, Cath-D and EGFR expression with occurrence of distant metastasis of ANN breast carcinoma. All markers except nm23 correlated with conventional histopathologic criteria such as tumor grade, margin and vessel invasion. The results suggest the combined detection of nm23, Cath-D and EGFR as predictive markers of distant metastasis in ANN breast cancer patients. Quantitative analysis together with clinicopathologic factors could contribute to estimate the potential risk of metastasis and select individual therapy regimen.

Adult↗

PubMed1999

Higher frequency of Smad4 gene mutation in human colorectal cancer with distant metastasis.

We have previously detected an increased frequency of loss of heterozygosity (LOH) on chromosome 18q during progression of colorectal carcinomas. To clarify the target of 18qLOH, mutation of Smad4 and Smad2 genes was analysed in 176 colorectal tumors with different stages, including liver metastasis, from 111 sporadic, 52 familial adenomatous polyposis (FAP) and nine hereditary nonpolyposis colorectal cancer (HNPCC) patients. Mutation of other Smad gene families in the TGF-beta signaling pathway was also examined. Twenty-one Smad4 mutations and one Smad2 mutation were detected, whereas mutation of Smad3, 6 and 7 genes was not detected. Smad4 mutations included seven frameshift, one inframe deletion, four nonsense and nine missense mutations, 95% of which resulted in alteration of Smad4 protein regions included in homo-oligomer and hetero-oligomer formation. Frequencies of tumors with Smad4 mutation were 0/40 (0%) in adenoma, 4/39 (10%) in intramucosal carcinoma, 3/44 (7%) in primary invasive carcinoma without distant metastasis, 6/17 (35%) in primary invasive carcinoma with distant metastasis, and 11/36 (31%) in distant metastasis (metastatic/non-metastatic: P=0.006 approximately 0.01). Loss of the other allele was observed in 19 of 20 (95%) invasive and metastasized carcinomas with Smad4 mutations. In four cases both primary and metastasized carcinomas in the same patients showed the same mutations. The present results suggest that Smad4 gene is one of true targets of 18qLOH, and that its inactivation is involved in advanced stages, such as distant metastasis, in human colorectal carcinogenesis.

Colorectal Neoplasms↗

PubMed1984

Temperature elevation during brachytherapy for carcinoma of the uterine cervix: adverse effect on survival and enhancement of distant metastasis.

Possible effects of fever during intracavitary radiation therapy on patient survival, local-regional control or metastatic spread of disease were analyzed in a group of 398 patients with previously untreated, invasive carcinoma of the uterine cervix, managed with a combination of external beam irradiation and intracavitary radium (ICR) applications at Yale-New Haven Medical Center and affiliated hospitals from January 1953 through December 1977. Cox step-wise proportional hazard models were used to test for the influence of elevated temperatures during ICR placements, controlling for the influence of other pretreatment patient parameters, including FIGO stage, age, blood count, prior supracervical hysterectomy and number of prior pregnancies. Increasing maximum temperatures noted during ICR placements were associated with: decreased patient survival (p = 0.014) and increased frequency with time of distant metastasis as the initial sites of treatment failure (p = 0.038). When patients were dichotomized on the basis of maximum temperature during ICR, distant metastasis as the initial site(s) of treatment failure was noted twice as frequently in patients with maximum temperatures greater than or equal to 101.0 degrees F (12.5%; 10/80 patients) than in those with maximum temperatures less than 101.0 degrees F during ICR placement (6.3%; 20/318 patients). No statistically significant differences were noted between the two groups in their distributions by stage, age, histology, year of diagnosis, or pretreatment hemoglobin, and the sites of distant metastasis and time course for clinical detection were similar in both groups. These results are in agreement with prior clinical studies in cancer of the uterine cervix which noted a poor prognosis in patients with cancer of cervix who developed fever during treatment. In addition, the finding of an association between an increased frequency of distant metastasis and temperature elevation during the ICR provides, for the first time, clinical data supporting the reports of an alteration or enhancement of distant metastasis following the application of whole body hyperthermia in murine, rabbit and canine tumors.

Adenocarcinoma↗

PubMed1997

Development of distant metastasis after treatment of advanced-stage head and neck cancer.

BACKGROUND: The recognition of risk factors for the development of distant metastasis is necessary for identifying high-risk patients who may benefit from systemic therapy. Previous investigations studying possible risk factors have been heterogeneous, with patients having varied forms of therapy. This study is designed to evaluate the clinical and histologic risk factors for the development of distant metastasis (DM) in patients with only advanced-stage head and neck squamous cell carcinoma after surgery and radiotherapy. METHODS: Retrospective analysis of a cohort of potentials with-surgically treated stage III and IV squamous cell carcinoma of the hypopharynx, tongue, and supraglottic larynx between 1988-1992. The cohort consisted of 130 patients of which 30 patients developed DM as the initial site of failure. All patients underwent surgical resection of the primary. Neck dissection was performed in 26 of 30 (87%0 patients who developed distant metastasis. Almost all patients received radiation therapy. Patients who initially developed DM (DM group) were compared with patients who did not initially develop DM (no DM group) with respect to certain clinical and histo-pathological factors. RESULTS: The majority of patients in the DM group had advanced T stage and clinically palpable cervical lymph nodes (73% and 93% respectively). In the no DM group, most patients had advanced T stage (85%) but 42% of the patients had stage NO necks (p < .05). Eighty-eight percent of patients in the DM group and 60% of patients in the no DM group had histological evidence of extracapsular spread of tumor from cervical lymph nodes (p < .05). Three or more positive lymph nodes were found in 69% of patients who developed DM and in only 35% of patients in the no DM group (p < .05). Age, gender, primary site, history of radiation therapy, perineural invasion and tumor grade were not associated with a higher risk for DM (p > .05). CONCLUSION: Patients wit clinically palpable neck disease (N1-3), histological evidence of metastatic nodal disease, extracapsular spread, and three or more positive lymph nodes are at greater risk of developing failure at distant sites. This subset of patients should have an extensive evaluation for distant metastatic disease and should be considered for systemic therapy.

Adult↗