Important Predictor Of Local Recurrence Research Articles

Histopathologic Examination and Reporting of Esophageal Carcinomas Following Preoperative Neoadjuvant Therapy

Neoadjuvant chemoradiotherapy is being increasingly offered to patients with invasive esophageal carcinoma in an effort to downstage the tumor and consequently increase the rate of curative resection. A substantial amount of data has suggested that pathologic tumor regression following neoadjuvant therapy is an important predictor of local recurrence and long-term survival in esophageal cancer. Therefore, it is important that these posttreatment resection specimens are handled in a standardized manner and a reproducible method of tumor regression grading is used. Pathologic examination of such specimens is not straightforward, and, in fact, it presents a particular challenge to pathologists, especially when a good response to neoadjuvant therapy has been achieved and little or no residual tumor remains. We provide some guidelines for handling and reporting such specimens and outline the commonly used tumor regression grading systems for posttreatment esophagectomy specimens.

Clinic study of lateral lymph node metastasis in advanced lower rectal cancer

To evaluate the risk factors of lateral lymph node metastasis in advanced lower rectal cancer and its correlation with local recurrence and prognosis. Data from 96 consecutive patients with advanced lower rectal cancer underwent curative surgery with lateral dissection were retrospectively analyzed. The correlations of lateral lymph node metastasis with clinicopathologic characteristics, local recurrence and prognosis were investigated. Lateral lymph node metastasis was observed in 14.6 (14/96) of the cases. In 40 patients with tumor diameter > or = 5 cm, 10 (25.0%) patients were found with lateral lymph node metastasis; while in the other 56 patients, only 4 (7.1%) cases were found with lateral lymph node metastasis (P < 0.05). Lateral lymph node metastasis was more frequent in patients whose tumor infiltrated full range of the intestinal wall (70%) than patients with 3/4, 2/4 and 1/4 intestinal wall was infiltrated (12.0%, 6.7% and 6.3%, respectively) (P < 0.05). Lateral lymph node metastasis rate of poorly differentiated carcinomas was significantly higher than those of moderate and well-differentiated ones (30% vs. 9.1% and 4.5%, P < 0.05). Local recurrence occurred in 18.8% (18 of 96 cases) of patients. Local recurrence in patients with positive lateral lymph node metastasis was 64.3%, while 11.0% in those without lateral lymph node metastasis (P < 0.05). Kaplan-Meier survival analysis showed significant improvements in median survival for patients with negative lateral lymph node metastasis over patients with lateral lymph node metastasis (80.9 +/- 2.1 vs. 38 +/- 6.7 months, log-rank P < 0.05). Tumor diameter, degree of tumor infiltration and histological differentiation are significant risk factors of lateral lymph node metastasis in advanced lower rectal cancer. Lateral lymph node metastasis is an important predictor of local recurrence and prognosis of patients.

Determination of Immunohistochemical Markers for Oral Squamous Cell Carcinoma Invasions

Carcinomas are characterized by invasion of malignant cells into the underlying connective tissue and migration of malignant cells. The cellular differentiation of the invasion site as well as the pattern of invasion is crucial for the tumor behavior. Both resection margins and the pattern of invasions are important predictors of local recurrence and survival in surgically treated patients. Therefore, surgical margins should be free from carcinoma or dysplasia after surgical intervention and the accepted definition of a close margin is tumor within 5 mm of the inked resection margin, but has not so clear yet. Others use less than 2 mm or 3 mm within one high power field or a variable definition related to the pattern of invasion at the tumor host interface. The aim of this study was to determine the immunohistochemical markers for identification of invasion pattern of oral squamous cell carcinoma (OSCC) and detection of epithelial cells of surgical margins. The study analyzed the immunohistochemical characteristics of 32 cases : 8 cases each of carcinoma in situ (CIS), OSCC border, OSCC early invasion and OSCC front using Ki-67, p53, CK 17, CK 13, laminin -5γ2 and type IV collagen. The correlation between the morphological pattern on invasive sites and immunohistochemical staining were studied. The results were obtained as follows :1)The average number of Ki-67 positive basal cells was 22.7% in CIS, 57.5% in OSCC border, 62.0% in OSCC early invasion and 60.2% in OSCC front, respectively. The percentage of immuno-positive cells in OSCC border, OSCC early invasion and OSCC front are significantly higher than those of CIS (p<0.05). p53 appeared in almost all tumor cells and highest in OSCC front.2)CK 17 was positive and strong in superficial cells of OSCC border, parabasal cells of OSCC early invasion and pearl nests of OSCC front, although the degree of positivity was variable. It was negative to discrete positive in CIS.3)CK 13 was positive in superficial and parabasal cells of CIS and pearl nests of OSCC front, negative in basal cells of CIS and OSCC early invasion, and weakly present in variable distribution in OSCC border.4)The cytoplasmic accumulation of laminin -5γ2 expression was intense in OSCC border, moderate in OSCC early invasion and OSCC front, and discrete in CIS.5)Type IV collagen was strong in both OSCC border and OSCC early invasion and weak in CIS and OSCC front.These results suggested that the combined expression of Ki-67 and p53 confirmed the proliferative and mutational activities of these OSCC invasions in contrast to CIS. CK 17 and CK 13 biomarkers detected their histological differentiation and variation in epithelial cells. The migration-promoting activity and role in cancer invasion were regulated by laminin -5γ2 and type IV collagen, and was clearly observed in OSCC border. The present study also revealed high proliferative activity and high invasiveness of epithelial cells in OSCC border similar to cancer and the combined used of the markers for safety margins should be considered important by surgeon.

Case Report: Laparoscopic Removal of 10-cm Retroperitoneal Liposarcoma

Liposarcomas are the second most frequent tumors in the retroperitoneal space and classically present as a large mass with minimal symptoms and a high local recurrence rate. The gold standard of treatment remains surgical excision. We describe the first successful removal of a well-differentiated retroperitoneal liposarcoma using a laparoscopic approach. An asymptomatic patient presented a large fatty mass in the retroperitoneal space on CT imaging. A transperitoneal laparoscopic approach was planned. A well-capsulated mass was exposed under Gerota's fascia that was dissected easily and removed completely without complications. Histologic examination revealed a well-differentiated liposarcoma. No recurrence was found at 12 months' followup. Resecting the mass completely remains the most important predictor of local recurrence and overall survival in liposarcoma. Thus, the success of radical surgical treatment is very important. The laparoscopic approach is technically safe and successful in maintaining oncologic principles and avoiding recurrences in retroperitoneal liposarcomas, representing a feasible alternative to open surgery.

Chemotherapy response is an important predictor of local recurrence in ewing sarcoma

Local recurrence in Ewing sarcoma is associated with a poor prognosis. The purpose of the study was to determine the factors that predict local recurrence after surgical treatment of the primary tumor. Between 1990 and 2001, 64 patients underwent surgical resection of Ewing sarcoma. Surgical margins were assessed histologically and radiologically. Response to preoperative chemotherapy was determined by detailed specimen mapping. Local recurrence-free survival (LRFS) was calculated by Kaplan-Meier analysis. Multivariate analysis was performed with the Cox proportional hazards model. A number of factors were found to be associated with local recurrence on univariate analysis. Patients with a good response to chemotherapy (> or = 90% tumor necrosis), had superior LRFS at 5 years (86% vs 51%, P = .015). Central site of disease was associated with an increased rate of recurrence. The LRFS at 5 years was 50% for the chest wall, 74% for pelvic/scapular, and 86% for extremity tumors (P = .083). Positive surgical margin was not a strong predictor of recurrence (P = .72). A critical analysis of minimal surgical margin based on preoperative magnetic resonance imaging (MRI) and computed tomography (CT) scans also failed to reveal an association between margin and local recurrence. In multivariate analysis, the 2 independent predictors of local recurrence were histological response to chemotherapy and central site of disease. Local recurrence after surgical resection is a complex phenomenon. An important predictive factor is the response to chemotherapy. In the current study, this seems to have the largest impact. Central site of disease may be a second independent predictive factor.

Long-term results of intraoperative presacral electron boost radiotherapy (IOERT) in combination with total mesorectal excision (TME) and chemoradiation in patients with locally advanced rectal cancer

We analyzed the long-term results of patients with locally advanced rectal cancer using a multimodal approach consisting of total mesorectal excision (TME), intraoperative electron-beam radiation therapy (IOERT), and pre- or postoperative chemoradiation (CRT). Between 1991 and 2003, 210 patients with locally advanced rectal cancer (65 International Union Against Cancer [UICC] Stage II, 116 UICC Stage III, and 29 UICC Stage IV cancers) were treated with TME, IOERT, and preoperative or postoperative CHT. A total of 122 patients were treated postoperatively; 88 patients preoperatively. Preoperative or postoperative fluoropyrimidine-based CRT was applied in 93% of these patients. Median age was 61 years (range, 26-81). Median follow-up was 61 months. The 5-year actuarial overall survival (OS), disease-free survival (DFS), local control rate (LC), and distant relapse free survival (DRS) of all patients was 69%, 66%, 93%, and 67%, respectively. Multivariate analysis revealed that UICC stage and resection status were the most important independent prognostic factors for OS, DFS, and DRS. The resection status was the only significant factor for local control. T-stage, tumor localization, type of resection, and type of chemotherapy had no significant impact on OS, DFS, DRS, and LC. Acute and late complications > or =Grade 3 were seen in 17% and 13% of patients, respectively. Multimodality treatment with TME and IOERT boost in combination with moderate dose pre- or postoperative CRT is feasible and results in excellent long-term local control rates in patients with intermediate to high-risk locally advanced rectal cancer.

Quality and completeness of histopathology reports of rectal cancer resections: Results of an audit in Brittany

Few data are available in France about implementation of guidelines for pathology reports of rectal cancer resections. The purpose of this study was to audit quality and completeness of histopathology reports of rectal cancer resections in Brittany by comparing results with French guidelines published in 1998. All inhabitants in Brittany who were beneficiaries of the general health insurance system and who underwent surgery for rectal cancer between February 1999 and January 2000 were included in the study. Twenty-one pathology laboratories, including 14 private laboratories, participated in this study. All pathology reports were examined by two physician-consultants of the health insurance system trained in the analysis of pathology reports (search for consigned or missing data). Results were compared with guidelines published in 1998. Of 234 pathology reports, 204 (84%) mentioned the number of examined lymph nodes and 217 (93%) the number of those found positive. The criterion of at least 8 examined lymph nodes was noted in 53.4% of reports. Longitudinal margin involvement was recorded in 92% of reports and circumferential margin involvement in 27% only. Venous and/or lymphatic and neural invasion were recorded in 34% and 18% of reports, respectively. Tumor staging was made by using UICC (pTNM) in 67% of reports. This study shows that the quality and completeness of histopathology reports of rectal cancer resections could be improved in Brittany. Despite its documented value as an important predictor of local recurrence, circumferential margin involvement is too frequently omitted. Standardisation of the examination procedures and exhaustive reporting would be useful to improve practice quality.

Local control in ductal carcinoma in situ treated by excision alone: incremental benefit of larger margins

Background Margin width has been shown previously to be the most important predictor of local treatment failure after breast conservation for ductal carcinoma in situ (DCIS). Methods Five variables thought to be associated with local recurrence were evaluated by univariate and multivariate analysis in 455 nonrandomized patients with DCIS treated with excision alone. Results Multivariate analysis showed that margin width, age, nuclear grade, and tumor size all were independent predictors of local recurrence, with margin width as the single most important predictor. After adjusting for all other predictors the likelihood of local recurrence for patients with margins less than 10 mm was 5.39 times as much as that for patients with margins of 10 mm or more (95% confidence interval, 2.68–10.64). Conclusions Margin width, the distance between DCIS and the closest inked margin, was the single most important predictor of local recurrence. As margin width increases, the risk for local recurrence decreases.

Predictors of reexcision findings and recurrence after breast conservation

Purpose To identify predictors of reexcision findings and local recurrence in the setting of breast-conserving therapy with radiation. Methods The records of 535 patients who underwent breast-conserving surgery followed by radiation for Stage I or II cancer between 1972 and 1996 were reviewed. The mean follow-up period for surviving patients without evidence of recurrence is 6 years. Various clinical and pathologic prognostic factors were examined for significance with regard to reexcision findings and recurrence rates. Pathologic margin status was classified as negative, close (≤2 mm), positive, or indeterminate. Results The pathologic margin status was the most important predictor of local recurrence. The freedom from local relapse (FFLR) at 6 years was 97% for patients with negative pathologic margins and 86% for all others ( p < 0.0001). There was no significant difference in recurrence rates among patients with close, positive, or indeterminate margins. However, the use and sequencing of systemic therapy affected recurrence rates among these patients. For patients with close, positive, or indeterminate margins, the crude risk of local recurrence was 4% among patients who received tamoxifen or received chemotherapy integrated with or after radiation. The risk of local recurrence was 16–29% among the patients with close, positive, or indeterminate margins who did not receive systemic therapy or who received radiation after completion of chemotherapy. Local recurrence rates were low in patients with negative margins (2–8%) regardless of the use of systemic therapy or its timing. The presence or absence of residual disease at reexcision did not predict recurrence as long as the final margins were negative. Among patients who underwent reexcision before radiation, extensive intraductal component (EIC) ( p = 0.0001) and young patient age ( p = 0.03) were predictive of residual disease in the specimen. Patients with initially close margins and no EIC had a low risk of residual disease at the time of reexcision, as did patients older than age 65 without EIC. Conclusion Pathologic margin status is the most important predictor of local recurrence after breast conservation with radiation. Patient age and EIC were significant predictors of residual disease at reexcision. The use and timing of systemic therapy appear to influence the risk of local recurrence in patients who do not have negative lumpectomy margins.

Value of the Van Nuys Prognostic Index in prediction of recurrence of ductal carcinoma in situ after breast-conserving surgery.

The Van Nuys Prognostic Index (VNPI), an algorithm based on tumour size, tumour grade, presence of necrosis and excision margin width, is claimed to predict local recurrence after breast-conserving surgery for ductal carcinoma in situ (DCIS). The aim of this study was to examine the validity of the VNPI in a UK population. Clinicopathological data, including VNPI subgroups, for 237 patients who had breast-conserving operations for DCIS were examined. Multivariate data analysis was performed using a Cox regression model to examine the independence and relative importance of different variables in predicting recurrence, and to compare the data with those used in derivation of the VNPI. The median follow-up was 47 months. There were 37 ipsilateral local recurrences. Excision margin width (P < 0.001) and tumour grade (by Van Nuys grading (P = 0.014) or simple nuclear grading (P = 0.004)) were the only independent risk factors for local recurrence. Excision margin width had three times more power than grade in predicting local recurrence. Subgrouping data by VNPI score predicted recurrence-free survival (P < 0.001), but stratified 78 per cent of patients into a group with a moderate risk of local recurrence. Excision margin width is the most important predictor of local recurrence after breast-conserving surgery for DCIS. The VNPI lacked discriminatory power for guiding further patient management.

Curative resection for rectal carcinoma: definition influences outcome in terms of local recurrence.

There are wide variations in local recurrence rate following curative surgery for rectal cancer and there are substantial inconsistencies among surgeons regarding the method of defining curative resection. This paper seeks to explore whether defining criteria is one of the important factors driving the variations in outcome. A literature review was undertaken to find all UK-based studies that had data on curative resection and local recurrence rates. The studies were divided into groups with distinct definitions of curative resection for rectal cancer. Meta-analyses were performed to pool the risks of local recurrence by group definition. Statistical tests were used to explore the variation in local recurrence by group. Confounding relationships of age, sex, Dukes stage, length of follow-up and year of study were explored as far as possible given the limitations of the available data. For rectal cancers significant differences were found between the pooled local recurrence risks by group definition (P < 0.01). Meta-regression tests including all the studies indicate that the definition of curative resection is an important predictor of local recurrence. It is suggested that a standardized approach towards defining curative resection and local recurrence may have a significant effect on outcomes in colorectal cancer surgery and would enable comparisons to be made between different series.

Pattern of invasion and margin assessment in patients with oral tongue cancer.

Involvement of resection margins and the pattern of tumor invasion are reported to be important predictors of local recurrence and survival in surgically treated patients. In this study we have retrospectively assessed the significance of these two prognostic factors in a relatively homogeneous patient population. Patients and Methods This study was confined to 150 previously untreated patients who had surgery for squamous carcinoma of the oral tongue between 1987 and 1993. There were 82 men and 68 women who ranged in age from 25 to 89 years (median 60 years). Glossectomy was peroral in 129, whereas 8 and 13, respectively, had a cheek flap or mandibulotomy approach. Some form of lymphadenectomy was performed in 109 (73%), and 51 patients (34%) received postoperative radiotherapy. Histologic slides from each primary tumor were reviewed to verify the margin status. In addition, the pattern of invasion was evaluated and graded from 1 to 4, varying from a consistently well-defined, "pushing" border (Grade 1) to diffuse infiltration and cellular dissociation (Grade 4). Intraoperative frozen section assessment of margins was accurate, whether positive or negative, in 118 of 133 patients (89%). Positive or close margins (within one high-power field) and an endophytic growth pattern were associated with a significant increase in local recurrence (p <0.003 and <0.04, respectively). With higher grades of infiltration (Grade 3 or 4; 82 patients), the tumors tended to be larger and the patients younger. Although the likelihood of nodal involvement and subsequent distant metastasis was significantly greater in those with Grade 3 or grade 4 patterns (p <0.0003 and <0. 01, respectively), there was no impact on local recurrence. Cumulative survival was similar whether or not the surgical margins were involved, but was significantly reduced when the pattern of tumor invasion was of higher grade (p <0.01). Frozen section provided reasonably accurate information about margins in our patients, whether taken from the patient or the surgical specimen. Positive margins increased the likelihood of local recurrence, but did not impact on survival because subsequent surgery and/or irradiation controlled tumor recurrence in some patients. Grade 3 or 4 patterns at the tumor/host interface were associated with an increased incidence of nodal and distant metastasis, as well as a significant decrease in survival.

Primary chondrosarcoma of long bones and limb girdles

Chondrosarcomas are common solid malignant tumors of bone, second in incidence only to osteosarcomas. The biologic evolution of chondrosarcomas is slow, requiring long follow-up intervals for meaningful survival analysis. This study describes the clinicopathologic profiles of 344 patients, 194 male and 150 female (M:F, 1.3:1.0), with primary chondrosarcoma of long bones and limb girdles seen at 1 institution over a period of 80 years. The average age at presentation was 46 years (range, 5-82 years). The pelvis was the most common location (1.7% of all patients). Local pain was the most frequently reported initial symptom (81.4%). Survival analysis was limited to 233 patients whose primary treatment was given at the Mayo Clinic. All 233 patients had potential follow-up of at least 5 years. The overall 5-year survival rate was 77% (the expected rate was 96%). Local recurrence developed in 19.7% of patients and metastatic lesions in 13.7%. The recurrence rate was higher for tumors of the shoulder and pelvis than for tumors of long bones. Radiographically, chondrosarcomas had a characteristic appearance, including a combination of bone expansion and cortical thickening. Entering the tumor at surgery increased the risk of local recurrence. Histologic tumor grade was an important predictor of local recurrence and metastasis. With adequate initial surgical intervention, chondrosarcoma is primarily a local disease with a low metastatic rate.

Prognostic factors in surgically treated stage IB-IIB carcinoma of the cervix with negative lymph nodes.

Comerci G, Bolger BS, Flannelly G, Maini M, de Barros Lopes A, Monaghan JM. Prognostic factors in surgically treated stage IB-IIB carcinoma of the cervix with negative lymph nodes. Int J Gynecol Cancer 1998; 8: 23-26. Two hundred and seventy-five females with stage IB-IIB negative lymph node cervical cancer, treated between January 1988 and December 1994 by radical hysterectomy and pelvic lymph node dissection, form the basis of this analysis. The clinical records were reviewed for all patients including histopathology, clinical features at presentation, and follow-up. Tumors were re-staged according to the 1995 FIGO classification. Median follow-up was 55 months and 85.8% were followed for longer than two years. There were 21 recurrences, 12 of which were true central recurrence (disease-free survival at 5 years: 91.66%). Fifteen of 25 deaths were due to cervical cancer (crude survival at 5 years: 93.27%). In univariate log-rank analysis, stage (P = 0.005), tumor size (P = 0.0002), and lymph-vascular space involvement (LVSI) (P = 0.01) appeared to be statistically significant factors for tumor recurrence. Other factors including age, histology type, differentiation, adjacent cervical intraepithelial neoplasia or cervical glandular intraepithelial neoplasia, and presence of intraepithelial disease at resection margin were not found to be statistically significant. In multivariate analysis (Cox regression) tumor size (P = 0.02) and LVSI (P = 0.03) were the only independent variables. In the presence of negative lymph nodes and complete surgical excision, tumor size and LVSI are important predictors of local recurrence.

The role of adjuvant radiotherapy in the treatment of resectable desmoid tumors

Desmoid tumors have a high propensity for local recurrence with surgical resection. There are many reports describing good responses of desmoid tumors to irradiation, but none have clearly established the indications for adjuvant radiotherapy in treating resectable desmoid tumors. A retrospective analysis was performed on 61 patients with resectable desmoid tumor(s) who were treated at our institution from 1965 to February of 1992. Five patients had multifocal disease and are analyzed separately. Fifty-six patients had unifocal disease, of which 34 had positive surgical margins. Forty-five of the 56 patients with unifocal disease were treated with surgery alone, while 11 were treated with surgery plus adjuvant radiotherapy. Median follow-up was 6 years. Local control was measured from the last day of treatment, and all cases were reviewed by our Department of Pathology. Multivariate analysis of the 56 patients with unifocal disease revealed that positive margins independently predicted for local recurrence (p < or = 0.01). Only 3 of 22 patients with clear margins experienced a local recurrence, with a 6-year actuarial local control of 85%. Multivariate analysis of the 34 patients with positive margins revealed that adjuvant radiotherapy independently predicted for improved local control (p = 0.01), and patients with recurrent disease had a slightly higher risk of local recurrence (p = 0.08). The 6-year actuarial local control determined by Kaplan-Meier for patients with unifocal disease and positive margins was 32% (+/-12%) with surgery alone, and 78% (+/-14%) with surgery plus adjuvant radiotherapy (p = 0.02). Subgroup analysis of the patients with positive margins and recurrent disease revealed that those treated with surgery alone had a 6-year actuarial local control of 0% vs. 80% for those treated with surgery plus radiotherapy (p < or = 0.01). Patients with positive margins and primary disease had a trend towards improved local control with adjuvant radiotherapy, but this was not statistically significant. None of the patients treated with radiotherapy developed serious complications or a secondary malignancy. Margin status is the most important predictor of local recurrence for patients with resectable, unifocal desmoid tumor. Adjuvant radiotherapy is indicated in the treatment of patients with positive margins following wide excision of recurrent disease. The role of adjuvant radiotherapy in patients with positive margins following resection of primary disease is controversial, and should be based on a balanced discussion of the potential morbidity from radiotherapy compared to the potential morbidity of another local recurrence. Adjuvant radiotherapy is less likely to benefit those with clear margins due to the excellent results for these patients treated with surgery alone. The local control of desmoid tumor in the adjuvant setting is excellent with total doses ranging from 50-60 Gy, with acceptable morbidity. Field sizes should be generous to prevent marginal recurrences, and large volume MRIs of patients with extremity lesions should be used to identify those patients with multifocal disease.