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PubMed2002

Treatment failure and margin status in head and neck cancer. A critical view on the potential value of molecular pathology.

Molecular pathology may demonstrate tumour cells not detected by histology. The idea has emerged that these cells influence the prognosis negatively and that their detection will lead to more appropriate treatment and improved patient survival. We theorized that tumour cells at surgical margins overlooked by the pathologist should demonstrate their clinical significance by causing recurrences at the primary site in the patients reported to have tumour-free margins by histology. To assess this assumption, we investigated the prognostic influence of the histologically determined status of the surgical margins. The material that formed the basis of this study consisted of 394 patients that underwent resection for their primary tumour during the years 1990-1995. In 207 patients, initial treatment was complete as assessed by conventional histopathological examination of the surgical specimen. In 187 patients, initial treatment was incomplete, defined as tumour in or close to the margin, or mild, moderate or severe dysplasia or in situ cancer at the margin. Causes for treatment failure were recorded for both groups separately. In the group with tumour-free margins, 16.9% had a second primary head and neck cancer, 8.2% had a second tumour in the lung, 10.6% had recurrent disease in the neck, 2.9% had distant metastasis, and 3.9% had local recurrence at the same site as the primary cancer. For the group without tumour-free margins, these figures were the following: second primary in the head and neck area: 17.1%, second primary in the lung: 7.0%, recurrent disease in the neck: 11.8%, distant metastasis: 8.0% and local recurrence at the primary site: 21.9%. Local recurrences were rare in patients in which the pathologist reported the resection to be complete. Although there may be tumour cells in surgical margins that evade histological detection, their clinical impact appears to be almost negligible.

Carcinoma, Squamous Cell↗
PubMed2004

Molecular diagnosis of surgical margins and local recurrence in head and neck cancer patients: a prospective study.

PURPOSE: Approximately 10-30% of surgically treated head and neck cancer patients develop local recurrences while the resection margins are histologically tumor free. These recurrences may arise from cancer cells left behind but not detected by the pathologist, or they may develop from precursor lesions adjacent to the tumor that were not completely resected. We have investigated whether TP53-mutated DNA in the surgical margins is suitable to identify patients with head and neck squamous cell carcinoma at risk for local and locoregional recurrence. EXPERIMENTAL DESIGN: In a prospective cohort study of 76 patients with histologically tumor-free margins, the presence of TP53-mutated DNA was determined in the surgical margins using the phage plaque assay and correlated to clinical outcome. Immunostaining of the molecular-positive margins for mutated p53 protein was used to identify whether unresected precursor lesions or residual tumor cells were left behind. RESULTS: The absence of TP53-mutated DNA in surgical margins was significantly associated with remaining free of local and locoregional recurrence (P = 0.027 and P = 0.028, respectively). Moreover, the presence of TP53-mutated DNA in the surgical margins was an independent prognosticator for locoregional recurrence (relative risk = 7.1; P = 0.021; 95% confidence interval, 0.9-56). In 20% of the cases, the presence of TP53-mutated DNA in the surgical margins was found to be related to the presence of tumor-related precursor lesions. CONCLUSIONS: This study shows the value of TP53-mutated DNA as a molecular marker to predict locally recurrent head and neck squamous cell carcinoma. The observation that all patients who were negative for TP53-mutated DNA in the surgical margins remained free of local recurrence raises hope that molecular analysis of histologically tumor-free surgical margins can be exploited to decide on postoperative radiotherapy. Furthermore, our data provide evidence that local recurrences originate mainly from tumor cells left behind but also originate, in part, from unresected precursor lesions.

Adult↗
PubMed1985

Patterns of metastasis and natural courses of breast carcinoma.

Breast carcinoma is known to metastatize to all organs. In order to understand the patterns of spread and natural courses, this review summarizes detailed studies of patients with various stages of the disease. After treatment of early breast carcinoma (stage I, II, and some III), the recurrent lesion can be classified as local, regional, distant, or combinations thereof. The sites of dissemination of patients presenting with stage IV disease and of those who had autopsy after diagnosis of breast cancer are presented for comparison. Clinicopathological factors that influence the relative incidence, specific site, subsequent event, and prognosis of recurrent and metastatic breast cancers are discussed.

Adult↗
PubMedDate not supplied

Pelvic recurrence following resection of rectal cancer: a multivariate predictive model.

Local recurrence of rectal cancer (LR) after "curative" surgery is a major clinical problem, with a low resectability rate and a dismal prognosis. Prediction of LR might permit more targeted postoperative surveillance with earlier diagnosis of recurrent disease and might help in selecting the patients to be assigned to the most suitable adjuvant treatment protocol. To evaluate if a simple multivariate model could predict the LR and survival probability in the single case, we retrospectively evaluated 118 consecutive patients (63 males, 55 females; mean age 62 +/- 12 years) operated on for rectal cancer and followed up for a minimum of 4 years (range 51-111 months). Local recurrence rate was 28%, with a 6% of local + distant failure. Age and sex of patients, type of surgery, location of tumour in the rectum, size, morphology and grading of the tumour were all unrelated to the event under investigation. At Cox regression, the Dukes' stage and the postoperative radiotherapy were the only independent prognostic factors for LR (p < 0.001). The multivariate model was able to correctly reclassify the patients and predict local recurrence in 86.2% of the cases. Prevention of LR by adequate surgery and adjuvant therapy as well as its early detection offer the best prospect of improving the results of surgery for rectal cancer.

Adenocarcinoma↗
PubMed2005

Patterns of recurrence and long-term survival after curative resection of localized fibrous tumors of the pleura.

BACKGROUND: Localized fibrous tumors of the pleura (LFTPs) are uncommon thoracic neoplasms with variable malignant potential that were previously classified as benign presentation of mesothelioma. We investigate the clinical presentation, recurrence patterns, and long-term survival of patients undergoing curative resection of LFTPs. PATIENTS AND METHODS: Thirty-four patients underwent resection of LFTPs in the present study. There were 20 women and 14 men with a median age of 59 years (range, 35-81 years). The malignant potential of the tumor was estimated through histologic assessment of the degree of cellularity, mitotic activity, and nuclear pleomorphism. Patients' clinical outcomes were correlated to pathologic findings. RESULTS: Seventeen patients (50%) were symptomatic, and 7 tumors (21%) were considered malignant by histologic characteristics. Ipsilateral pleural recurrence remote to the original tumor site occurred in 6 of these patients with malignant microscopic characteristics at a mean of 9 months after resection. Repeated resection was accomplished in 3 of these patients (range, 3-8 repeat operations). There have been no recurrences among the other 27 patients with benign histologic features, and 31 patients remain alive at a median follow-up of 34.5 months. CONCLUSION: Histologic characteristics are helpful in estimating the risk of recurrence among patients with LFTPs. Close surveillance is recommended for patients with malignant histologic characteristics. Local recurrence is common without evidence of systemic spread among such patients. Surgical resection is definitive therapy; however, patients with tumors with histologic atypia require close postoperative observation because of the frequency of locoregional recurrence.

Adult↗
PubMed1996

Radiotherapy in the treatment of uterine sarcomas. A retrospective analysis of 54 cases.

BACKGROUND: In the general population, uterine sarcoma (US) is an uncommon tumor, which accounts for approximately 1-3% of all uterine neoplasms. Its biological behavior is characterized by hematogenous metastases and local recurrent growth including the pelvis and peritoneal cavity. In the management of US, surgery is the primary form of treatment. Up to now the role of adjuvant radiotherapy has not been clearly established. PATIENTS AND METHODS: We report about 54 patients with US treated from 1954 to 1994 by surgical resection alone (22) or a combination of surgery and irradiation (32) and evaluate the influence of histology, stage and different treatment options on survival. RESULTS AND CONCLUSIONS: Our data indicate an increased disease-free survival for patients treated with adjuvant radiotherapy, especially if poor prognostic factors are present (advanced tumor stage, histopathological grade II or III of leiomyosarcoma and mixed mesodermal sarcoma). Postoperative irradiation using doses between 50 and 60 Gy is recommended, in selected cases brachytherapy should be added. Prospective multicentric trials including a statistically evaluable number of patients are necessary to further clarify the role of multimodality treatment programs for US.

Disease-Free Survival↗
PubMed2005

Relapse patterns in WHO 2/3 nasopharyngeal cancer: is there a difference between ethnic Asian vs. non-Asian patients?

PURPOSE: The purpose of this study was to assess whether ethnicity is an independent prognostic factor in patients with World Health Organization (WHO) type 2 or 3 nasopharyngeal carcinoma (NPC). Specifically, we examined the patterns of relapse observed in patients classified as "Asian" (born in southern China or southeast Asia) or "non-Asian" (born in Australia, Europe, the Middle East, or the Pacific Islands). METHODS AND MATERIALS: All patients planned for radical treatment at the Peter MacCallum Cancer Centre from April 1985 to December 1999 were included in this study. Pathology was reviewed to confirm WHO type 2 or 3 NPC. Patients were staged using the 1997 International Union Against Cancer (UICC) criteria. Mean potential follow-up time was 9.6 years (range, 1.0-18.5 years) RESULTS: There were 158 patients: 86 Asian and 72 non-Asian. Stage groupings were: I--12 patients; II--32 patients; III--59 patients; and IV--55 patients. A staging computerized tomography was performed in 121 patients, and 53 (34%) also had a staging magnetic resonance imaging (MRI). The Asian patients had significantly more women, more patients aged <45, and more with performance status 0 than the non-Asians. Other putative prognostic factors were not significantly different between the groups. The 5-year rates for freedom from local recurrence (FLR), failure-free survival (FFS), and overall survival (OS) for Asian and non-Asian patients were 74% vs. 82%, 61% vs. 55%, and 75% vs. 63%, respectively. Corresponding 10-year figures were: 62% vs. 82%, 43% vs. 48%, and 58% vs. 49%, respectively. Multifactor analysis showed stage and the use of MRI for staging to be significant prognostic factors for all three endpoints. Age was also significant for FFS and OS. There were no significant differences in FFS or OS between Asian and non-Asian patients. However, the FLR interval was significantly worse in the Asian group (hazard ratio [HR], 2.37; 95% confidence interval [CI], 1.11-5.06), whereas duration of freedom from distant metastasis tended to be better (HR, 0.71; 95% CI, 0.33-1.53). CONCLUSIONS: Although this study provides no evidence that race is an independent prognostic factor for overall survival in patients with WHO 2/3 NPC, it does suggest that relapse patterns may vary, with a higher rate of late primary failures (offset by a lower rate of distant failure) in the Asian population. Further confirmatory studies with larger patient cohorts are indicated.

Adolescent↗
PubMed2002

[Cystic pancreatic tumors--differential diagnosis, surgical therapy. Prognosis of cystic pancreatic tumors].

From 1986-2001 we treated 31 patients with cystic neoplasms of the pancreas. 13 patients showed a cystadenocarcinoma including one rare case of a serous cystadenocarcinoma. A curative resection (R0) was possible in 10 patients (resection rate: 76.9%). After median 61 months (range 29-144 months) 8 patients are alive without evidence of tumour. 2 patients died 2 months (pneumonia) and 36 months (local recurrence) respectively after operation. The latter case of tumour recurrence showed nodal involvement (pN1) in the Whipple specimen. One patient died 44 months after Whipple procedure with tumour-positive resection margin (R1 Situation) from local recurrence and hepatic spread. Our data reflect the good prognosis of cystic neoplasms of the pancreas reported in literature after curative resection--a result of the different biological behaviour compared with ductal adenocarcinome.

Adenocarcinoma↗
PubMed1982

Autoradiographic evidence of a loss of iodination within hormone-dependent GR mouse mammary tumors as they progress to independence.

The purpose of this study was to determine by use of light- and electron-microscope autoradiography whether or not iodination occurred in mammary tumors of female GR mice. Of the sixty tumors studied it was found that pregnancy-dependent and hormone-induced tumors possessed iodinating ability. Although mammary glands from nonpregnant GR mice lacked the ability to iodinate, by the 16th day of pregnancy in response to hormonal stimulation the glands readily iodinated casein, and some epithelial cells contained ultrastructural cytochemical evidence of mammary peroxidase. Preneoplastic mammary gland lesions known as hyperplastic alveolar nodules were also able to iodinate, as were plaques, the disc-shaped lesions which give rise to the hormone-responsive mammary tumors in this strain. Plaques also contained epithelial cells with mammary peroxidase activity. When hormone-induced mammary tumors were transplanted into syngeneic mice they retained the ability to iodinate for several generations. However, as the tumors progressed to hormone independence, the ability to iodinate was gradually lost. Hormone-independent mammary tumors from GR mice lacked both iodinating ability and cytochemical evidence of mammary peroxidase. These findings suggest that iodination depends upon hormone-responsive cells within the mammary tumors and that as these cells become hormone unresponsive, the ability to iodinate is lost.

Animals↗
PubMed1988

The incidence, multiple presentation and recurrence of aggressive cysts of the jaws.

The incidence, multiple presentation and recurrence rate of aggressive cysts of the jaws is discussed, based on a study of 677 cysts in 651 patients. Cysts that are considered aggressive include: cysts in which carcinoma develops, unicystic ameloblastoma, keratocysts and calcifying odontogenic cysts. Based on literature studies and on our own material, the incidence and multiplicity of these lesions is calculated. Recommendations for treatment include careful preoperative assessment and treatment of suspicious lesions with excision of the overlying mucosa and fixation of the defect with Carnoy's solution. The cyst in which carcinoma develops should be treated as a true malignancy i.e. by resection. Long term follow-up is necessary to eliminate the possibility of recurrence.

Adolescent↗
PubMed2001

Genomic imbalances in 61 renal cancers from the proximal tubulus detected by comparative genomic hybridization.

Comparative genomic hybridization (CGH) has been applied to characterize 61 primary renal cell carcinomas derived histogenetically from the proximal tubulus. The tumor samples comprised 46 clear-cell renal cell carcinomas (ccRCCs) and 15 papillary renal cell carcinomas (pRCCs). Changes in the copy number of entire chromosomes or subregions were detected in 56 tumors (92%). In ccRCCs, losses of chromosome 3 or 3p (63%); 14q (30%); 9 (26%); 1 and 6 or 6q (17% each); 4 and 8 or 8p (15% each); 22 (11%); 2 or 2q and 19 (9% each); 7q, 10, 16, 17p, 18, and Y (7% each); and 5, 11, 13, 15, and 21 (4% each) were detected. Most frequent genomic gains in ccRCC were found on chromosome 5 (63%); 7 (35%); 1 or 1q (33%); 2q (24%); 8 or 8q, 12, and 20 (20% each); 3q (17%); 16 (15%); 19 (13%); 6 and 17 or 17q (11% each); and 4, 10, 11, 21, and Y (9% each). In pRCCs, gains in the copy number of chromosomes 7 and 17 (7/15, each) and 16 and 20 (6/15, each) were frequent. One pRCC showed amplification of subchromosome regions 2q22-->q33, 16q, 17q and the entire X chromosome. In pRCC, losses were less frequently seen than gains. Losses of chromosomes 1, 14, 15, and Y (3/15 each) and 2, 4, 6, and 13 (2/15 each) were observed. In ccRCCs, statistical evaluation revealed significant correlations of chromosomal imbalances with tumor stage and grade, i.e., a gain in copy number of chromosome 5 correlated positively with low tumor grade, whereas a gain of chromosomes 10 and 17 correlated positively with high tumor grade. Furthermore, loss of chromosome 4 correlated positively with high tumor stage.

Adenocarcinoma, Clear Cell↗
PubMed1994

An analysis on the effect of blood transfusion on recurrence and survival in patients undergoing extended lymphadenectomy for colorectal cancer.

In a retrospective study data were collected from 644 patients with cancer of the colon or rectum undergoing curative surgery with extended lymphadenectomy to evaluate a possible effect of blood transfusion, given perioperatively, on tumor recurrence and patient survival. Univariate analysis showed depth of bowel wall invasion, number and level of lymph node metastases to be of highly significant prognostic factors. After 5 years the overall recurrence rate was 16.6% for the non-transfused (n = 223) and 26.1% for the transfused (n = 421; p < .01) patients, and survival rates showed borderline significance favoring the non-transfused patients (90.5% vs. 80.0% after 5 years; p < 0.05). However, after stratification for the prognostically important factors, in a multivariate analysis a possible detrimental effect of perioperative blood transfusions could not be demonstrated.

Adenocarcinoma↗
PubMed1977

Surveillance, initial assessment, and subsequent progress of patients with superficial bladder cancer in a prospective longitudinal study. National Bladder Cancer Collaborative Group A (NBCCGA).

Through a bladder cancer surveillance protocol, a sizable population of patients suitable for characterizing the dynamics and patterns of recurrent superficial transitional cell carcinoma has been identified. One hundred thirty-three patients have been followed after their first occurrence of transitional cell carcinoma (Stage O or A). Only patients whose tumors were considered to be completely removed by transurethral resection and who were not treated by any other means were included. Although a full year of follow-up is not yet complete, recurrent bladder carcinoma has been noted in 44 (33%). Most of these recurrences were identified at the first follow-up cystoscopy and the majority were present at the site of the initial lesion. Tumor size, grade, and stage did not appear to influence recurrence, whereas multiplicity did. The relevance of these findings to various theories about the mechanism of recurrence is discussed.

Carcinoma, Transitional Cell↗