The role of neoadjuvant therapy in surgically resectable esophageal cancer

OBJECTIVE: To determine the effect of neoadjuvant therapy (NT) (preoperative chemotherapy, radiation therapy, or both) in surgically resectable esophageal cancer. DESIGN: A retrospective review over a 20-year period. SETTING: A tertiary academic medical center. PARTICIPANTS: All patients undergoing surgical resection for esophageal cancer (N = 316) over this time period. MAIN OUTCOME MEASURES: Perioperative morbidity and mortality, local and distant recurrences, and overall survival. RESULTS: Patients undergoing NT (n = 106) had prognostic factors similar to those treated with surgery alone (n = 210). No increase was noted in surgical morbidity with NT (anastomotic leaks, reoperation rates, complications, or extended hospital stays). Overall survival was not improved by NT (median survival, 14 months) except in the subset of patients (11/83) who responded completely (100% histological necrosis) to preoperative chemotherapy (median survival, 79.2 months; P < .02). Complete response to radiation therapy alone was not associated with improved survival. Partial necrosis of the primary tumor was seen in 13 (15%) of 83 patients but conferred no survival advantage. Complete response to preoperative chemotherapy was associated with squamous cell pathological features and excellent performance status as measured by preanesthesia evaluation. CONCLUSIONS: The addition of NT did not increase perioperative morbidity or mortality. Only the subset of patients who had a complete response to preoperative chemotherapy showed a survival advantage. Excellent performance status and squamous cell pathological features were associated with an increased chance of complete pathological response following preoperative chemotherapy.     

Diet supplemented with yoghurt or milk fermented by Lactobacillus casei DN-114 001 stimulates growth and brush-border enzyme activities in mouse small intestine

Adjuvant and neoadjuvant therapeutic principles have in recent years received increasing attention in the management of patients with carcinoma of the upper gastrointestinal tract. A series of randomized prospective trials has demonstrated that adjuvant postoperative radiation or chemotherapy does not result in a convincing survival advantage after complete tumor resection in gastric or esophageal cancer. The available data on the role of neoadjuvant preoperative therapy in these patients as yet permit no conclusion. While neoadjuvant therapy may reduce the tumor mass in a substantial portion of patients, a series of randomized controlled trials has shown that, compared to primary resection, a multimodal approach does not result in a survival benefit in patients with loco-regional, i.e. potentially resectable, tumors. In contrast, in patients with locally advanced tumors, i.e. tumors for which complete removal with primary surgery appears unlikely, neoadjuvant therapy increases the chance for complete tumor resection on subsequent surgery. However, only patients with objective histopathologic response to preoperative therapy appear to benefit from this approach. Compared to preoperative chemotherapy alone, combined radio-chemotherapy increases the rate of response, particularly in squamous cell esophageal cancer, but may also increase postoperative morbidity and mortality. Neoadjuvant therapy should therefore currently only be performed in experienced centers within the context of prospective clinical trials. The identification of factors that would allow prediction of response to neoadjuvant or adjuvant therapy is the focus of ongoing studies.     

Catheter-related infection: an update on diagnosis, treatment, and prevention

PURPOSE: Neoadjuvant chemotherapy is becoming the standard of care for locally advanced breast cancer. This study was performed to determine whether pathologic primary tumor response to neoadjuvant chemotherapy might predict axillary lymph node status and so be used to identify patients in whom surgery could be effectively limited to biopsy of the previous primary tumor site without axillary dissection. PATIENTS AND METHODS: Between 1992 and 1996, 170 consecutive patients with locally advanced breast cancer were treated in a prospective trial with four preoperative cycles of 5-fluorouracil, doxorubicin, and cyclophosphamide. Disease was staged before initiation of preoperative chemotherapy and before surgery. Segmental resection with axillary lymph node dissection or modified radical mastectomy was performed first, followed by postoperative chemotherapy and radiation therapy of the breast (or chest wall) and regional lymphatics. Patient and tumor characteristics associated with complete versus incomplete pathologic primary tumor response to neoadjuvant chemotherapy and correlation between primary breast tumor pathologic response and axillary lymph node status found at surgery were analyzed. RESULTS: Of 156 evaluable patients, 30 patients (19%) had primary breast tumors that were completely eliminated after induction chemotherapy based on histologic assessment. Nineteen of those 30 patients (63%) had negative axillary lymph nodes at dissection, compared with 13 patients (33%) of the 40 who had a near-complete pathologic primary tumor response (< or = 1 cm3 remaining) and only 15 patients (17%) of the 86 who had > 1 cm3 tumor remaining in the pathology specimen of the breast primary. Of the 22 patients with a complete pathologic response in the breast and a clinically negative axilla after induction chemotherapy, axillary dissection revealed positive lymph nodes in four. These four patients had only one or two positive lymph nodes. DISCUSSION: Because initial clinical regression of primary tumor with neoadjuvant chemotherapy is considered an excellent prognostic indicator and because patients with locally advanced breast cancer routinely receive local and regional radiation treatment followed by additional chemotherapy, the role of breast and axillary surgery has been questioned. In this study, a complete pathologic response of the primary tumor to induction chemotherapy is highly predictive of negative axillary lymph node status. Therefore, axillary lymph node dissection may be omitted in certain subsets of patients who have a biopsy-proven complete pathologic response in the primary tumor and a clinical negative axillary examination. Further prospective, randomized investigation is needed to confirm this finding.     

Complications of craniofacial surgery for tumors involving the anterior cranial base

OBJECTIVE: To evaluate the risk factors for postoperative complications among patients undergoing craniofacial resection for the treatment of anterior cranial base tumors, a retrospective analysis of patients treated in University of Tokyo Hospital between September 1987 and November 1996 was conducted. METHODS: Twenty-nine patients underwent 33 craniofacial resections for tumors involving the anterior cranial base. Twenty-three of the 29 patients had malignant tumors and 6 patients had benign tumors. Anterior craniofacial resection was performed using a combination of intracranial and extracranial approaches. Radiotherapy and neoadjuvant chemotherapy were administrated to some patients. RESULTS: Severe intracranial infections were more common among patients who underwent partial frontal lobectomies (P < 0.03). These infections occurred only in patients who had been treated previously with a craniotomy (P < 0.02) and a total radiation dose of > or =60 Gy (P = 0.06). Neither management of the extracranial structures nor methods of reconstruction of the cranial base showed significant correlation with major postoperative complications. CONCLUSION: Compared with previous reports, craniofacial resection has become a relatively safe and effective procedure for the treatment of tumors involving the anterior cranial base. However, additional care should be taken with patients who have experienced a previous craniotomy, frontal lobe involvement, or radiotherapy with a total dose of > or =60 Gy.     

Esthesioneuroblastoma. Long-term outcome and patterns of failure--the University of Virginia experience

BACKGROUND: Esthesioneuroblastoma is a rare tumor arising from olfactory epithelium. This retrospective review analyzed the patterns of failure and long term outcome of patients with esthesioneuroblastoma evaluated at a single institution. METHODS: Forty patients with esthesioneuroblastoma were evaluated at the University of Virginia, with a median follow-up of 130 months. In most cases, treatment consisted of combined-modality therapy, including radiotherapy and surgery for Stages A and B disease and the addition of chemotherapy for Stage C disease. Fifteen patients received chemotherapy that included cyclophosphamide plus vincristine. Thirty-eight patients received radiotherapy, with a median dose of 50 Gy. Initial surgery for 23 patients included craniofacial resection, whereas the remainder had less extensive surgery (3 had no initial surgery). Five patients were salvaged with high dose chemotherapy and autologous bone marrow transplantation (CTX/BMT). RESULTS: Actuarial survivals at 5, 10, and 15 years are 78%, 71%, and 65% respectively. Fifty-five percent of patients failed therapy, and 68% of the failures were locoregional. Thirty-nine percent of recurrences occurred later than 5 years from diagnosis. Three of the five patients were successfully salvaged with CTX/BMT compared with four of seventeen patients who underwent conventional salvage therapy. CONCLUSIONS: Esthesioneuroblastoma is associated with long term survival and late recurrences. Multimodality therapy should be used initially. Durable remissions of failures can be achieved with CTX/BMT:     

Effect of EDTA on reduction of copper toxicity in Oreochromis mossambicus (Peters)

OBJECTIVES: To determine the best therapeutic approach for treatment of patients with urethral cancer according to tumor location and clinical-pathologic stage. METHODS: A retrospective review of 21 consecutive patients diagnosed with primary urethral carcinoma was performed. Clinical-pathologic staging, treatment modality, and outcome were analyzed. RESULTS: The overall survival rate was 62%. In patients with clinical Stage Ta-2N0M0 tumors, 8 of 9 patients (89%) are free of disease compared to 5 of 12 patients (42%) with Stage T3-4N0-2M0 tumors (P = 0.03). Best treatment outcome for patients with Stage T3 disease or higher was obtained when multimodality therapy (neoadjuvant chemotherapy and radiation therapy with or without surgery) was administered, with a disease-free survival rate of 60%. CONCLUSIONS: Clinical-pathologic stage was a strong predictor of disease-free survival rate. For patients with Ta-2N0M0 tumors, multimodality therapy may not be required. Conversely, best treatment outcomes in patients with T3-4N0-2M0 tumors are obtained by administering a multimodal therapy combining chemotherapy and radiation therapy with surgical resection.     

Outcome of large-bowel perforation in patients with colorectal cancer

PURPOSE: Perforation of the colon is seldom associated with malignant disease. Operative mortality varies widely in published studies and little is known about patterns of failure and long-term outcome. An observational study was undertaken to assess the outcome of colorectal cancer complicated by perforation. METHOD: We reviewed a series of 83 consecutive patients treated during a 14-year period at one institution. RESULTS: Fifty-four (65 percent) patients had perforation of the tumor itself, and 29 (35 percent) had diastatic perforation proximal to an obstructing tumor. Twenty-six (31.5 percent) patients had metastatic disease at laparotomy. Primary resection of the diseased segment was performed in 47 (87 percent) patients with perforation of the tumor itself and in 21 (72.4 percent) patients with diastatic perforation proximal to an obstructing tumor. However, only 57 patients (39 (72.2 percent) with perforation of the tumor itself; 18 (62 percent) with diastatic perforation proximal to an obstructing tumor; P = not significant) were potentially cured. Operative mortality was 16.7 and 48.3 percent, respectively (P < 0.01) and correlated significantly with Hinchey's stage (P < 0.001) and advanced disease (P = 0.023). At a mean follow-up of 43 (median 31) months, 21 (46 percent) of the 46 potentially cured survivors were alive. The local recurrence rate was 22.9 percent in patients with perforation of the tumor itself and 18.2 percent in patients with diastatic perforation proximal to an obstructing tumor (P = not significant). Peritoneal seeding occurred in 17 and 0 percent (P = not significant); the mean disease-free interval was 33.9 and 49.9 months (P = not significant); and five-year cumulative disease-related survival probability was 0.51 and 0.90 (P = 0.049), respectively. CONCLUSIONS: Diastatic perforation proximal to an obstructing tumor is associated with higher operative mortality and better cancer-related survival than a tumor perforating through the bowel wall. Early diagnosis in diastatic perforation and aggressive management of sepsis associated with radical surgical resection is recommended.     

Effect of preoperative chemotherapy on the outcome of women with operable breast cancer

PURPOSE: To determine, in women with primary operable breast cancer, if preoperative doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan; AC) therapy yields a better outcome than postoperative AC therapy, if a relationship exists between outcome and tumor response to preoperative chemotherapy, and if such therapy results in the performance of more lumpectomies. PATIENTS AND METHODS: Women (1,523) enrolled onto National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 were randomly assigned to preoperative or postoperative AC therapy. Clinical tumor response to preoperative therapy was graded as complete (cCR), partial (cPR), or no response (cNR). Tumors with a cCR were further categorized as either pathologic complete response (pCR) or invasive cells (pINV). Disease-free survival (DFS), distant disease-free survival (DDFS), and survival were estimated through 5 years and compared between treatment groups. In the preoperative arm, proportional-hazards models were used to investigate the relationship between outcome and tumor response. RESULTS: There was no significant difference in DFS, DDFS, or survival (P = .99, .70, and .83, respectively) among patients in either group. More patients treated preoperatively than postoperatively underwent lumpectomy and radiation therapy (67.8% v 59.8%, respectively). Rates of ipsilateral breast tumor recurrence (IBTR) after lumpectomy were similar in both groups (7.9% and 5.8%, respectively; P = .23). Outcome was better in women whose tumors showed a pCR than in those with a pINV, cPR, or cNR (relapse-free survival [RFS] rates, 85.7%, 76.9%, 68.1%, and 63.9%, respectively; P < .0001), even when baseline prognostic variables were controlled. When prognostic models were compared for each treatment group, the preoperative model, which included breast tumor response as a variable, discriminated outcome among patients to about the same degree as the postoperative model. CONCLUSION: Preoperative chemotherapy is as effective as postoperative chemotherapy, permits more lumpectomies, is appropriate for the treatment of certain patients with stages I and II disease, and can be used to study breast cancer biology. Tumor response to preoperative chemotherapy correlates with outcome and could be a surrogate for evaluating the effect of chemotherapy on micrometastases; however, knowledge of such a response provided little prognostic information beyond that which resulted from postoperative therapy.     

Multinomial-sampling models for random genetic drift

OBJECTIVE: The aim of this study was to determine the usefulness of endosonography for evaluating the effect of neoadjuvant therapy for advanced esophageal carcinoma. MATERIALS AND METHODS: Thirty-four patients with esophageal carcinoma (stage II, 16 patients; stage III, 18 patients) underwent various preoperative treatment. In all patients, endosonography was performed before and after treatment, and the percentage reduction in tumor size was calculated from the maximum area of the tumor. In the 27 patients who underwent surgery, the percentage reduction was compared with the pathologic response. Also, the overall survival rates were compared with the percentage reduction in tumor area. RESULTS: Reduction in tumor area ranged from 0% to 47%. The patients were divided into three groups according to the percentage reduction in tumor area. Pathologic response was graded according to the number of viable cells in the entire lesion. Correlation between pathologic response and percentage reduction in tumor area was strong. We found a significant difference in survival rates among the three groups. CONCLUSION: The percentage reduction in tumor area estimated by means of endosonography reflects the histologic effectiveness of neoadjuvant therapy in patients with advanced esophageal carcinoma and may enable clinicians to predict the prognosis of the disease.     

Quantitative imaging study of extent of surgical resection and prognosis of malignant astrocytomas

OBJECTIVE: This study used quantitative radiological imaging to determine the effect of surgical resection on postoperative survival of patients with malignant astrocytomas. Previous studies relied on the surgeons' impressions of the amount of tumor removed, which is a less reliable measure of the extent of resection. METHODS: Information concerning possible prognostic factors was collected for 75 patients undergoing magnetic resonance imaging or computed tomography preoperatively and within 10 days postoperatively. Image analysis of the neuroradiological studies was conducted to quantify pre- and postoperative total tumor volumes and enhancing volumes. Univariate and multivariate proportional hazards models were used to analyze the regression of survival regarding 22 covariates that might affect survival. The covariates that were entered included age, gender, tumor grade, cumulative radiation dose, chemotherapy, seizures as a first symptom, Karnofsky performance status at presentation, pre- and postoperative total and enhancing tumor volumes, ratio of pre- to postoperative total and enhancing tumor volumes, tumor location, surgeon's impression of the degree of resection, and subsequent surgery. RESULTS: There were 23 patients with anaplastic astrocytomas and 52 with glioblastomas multiforme. The estimated mean survival time was 27 months for patients undergoing gross total resection, 33 months for subtotal resection, and 13 months for open or stereotactic biopsy. Five factors that were significant predictors of survival in multivariate analysis were tumor grade, age, Karnofsky performance status, radiation dose, and postoperative complications (P < 0.05). In univariate analysis, tumor grade, radiation dose, age, Karnofsky status, complications, presence of enhancing tumor in postoperative imaging, and postoperative volume of enhancing tumor were significantly associated with survival (P < 0.05). CONCLUSION: We conclude that the most important prognostic factors affecting survival of patients with anaplastic astrocytomas and glioblastomas multiforme are tumor grade, age, preoperative performance status, and radiation therapy. Postoperative complications adversely affect survival. Aggressive surgical resection did not impart a significant increase in survival time. Surgical resection may improve survival, but its importance is less than that of other factors and may be demonstrable only by larger studies.     

Cisplatin-based neoadjuvant chemotherapy and combined resection for ethmoid sinus adenocarcinoma reaching and/or invading the skull base

OBJECTIVE: To review our experience with cisplatin-based neoadjuvant chemotherapy before en bloc resection via a combined neurosurgical and transfacial approach for ethmoid sinus adenocarcinoma reaching and/or invading the skull base. DESIGN: Case series. SETTING: A tertiary care center and university teaching hospital. PATIENTS: Twenty-two patients with primary untreated ethmoid sinus adenocarcinoma reaching and/or invading the skull base consecutively treated between 1984 and 1992 with cisplatin-based neoadjuvant chemotherapy and combined neurosurgical and transfacial approach. MAIN OUTCOME MEASURES: Statistical analysis of survival, local control, nodal recurrence, distant metastasis, and metachronous second primary tumor incidence based on the Kaplan-Meier actuarial method. Univariate analysis was performed to analyze the relationships between various factors, survival, and local recurrence. Clinical response, histological response, toxic effects of chemotherapy, and postoperative course were also reported. RESULTS: The Kaplan-Meier 3-year survival, local control, nodal recurrence, and distant metastasis estimates were 68.1%, 65.7%, 5.3%, and 10%, respectively. Metachronous second primary tumor was not encountered in our series. Survival was statistically more likely to be reduced in patients with intrasphenoidal tumor extent (P = .04) and local recurrence (P = .01). Local recurrence was statistically more likely in patients with intrasphenoidal tumor extent (P = .002) and no response to cisplatin-based neoadjuvant chemotherapy (P = .03). CONCLUSIONS: The results achieved suggest that cisplatin-based neoadjuvant chemotherapy before combined neurosurgical and transfacial approach should be further investigated for the treatment of ethmoid sinus adenocarcinoma reaching and/or invading the skull base.     

The role of chemotherapy in the management of nasopharyngeal carcinoma

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a radiosensitive tumor for which there is a high local control rate after radical radiotherapy (RT). However, for patients with locoregionally advanced disease, the rate of distant metastasis is high and the 5-year overall survival rate is poor. METHODS: A review of retrospective and prospective clinical studies was performed to assess the role of chemotherapy in three settings: metastatic disease; neoadjuvant and/or adjuvant; and concurrent chemotherapy with radiotherapy. RESULTS: Cisplatin-based combination chemotherapy results in a high response rate in patients with metastatic NPC, and a subgroup may achieve long term disease free survival. The use of neoadjuvant and adjuvant chemotherapy to treat locoregionally advanced disease has resulted in consistently high response rates, but no randomized trial to date has demonstrated an improvement in overall survival. A recent Head and Neck Intergroup study randomized patients in the United States to receive concurrent chemotherapy (cisplatin) and radiotherapy or radiotherapy only. Although this approach demonstrated significant benefit in overall survival favoring the use of concurrent chemotherapy and radiotherapy, its applicability in geographic areas of high NPC incidence remains to be proven. CONCLUSIONS: NPC is a chemosensitive tumor, and patients with metastatic disease have a high response rate. Further prospective studies will define the standard approach to treating locoregionally advanced NPC, which is likely to incorporate into the primary treatment some form of systemic chemotherapy.     

Residual metastatic axillary lymph nodes following neoadjuvant chemotherapy predict disease-free survival in patients with locally advanced breast cancer

BACKGROUND: This study was performed to validate the prognostic significance of residual axillary lymph node metastases in patients with locally advanced breast cancer (LABC) treated with neoadjuvant chemotherapy and to analyze other clinicopathologic factors that might be independent predictors of disease-free survival (DFS) in an attempt to identify patients in whom axillary dissection might be omitted. METHODS: One hundred sixty-five assessable patients with LABC were treated in a prospective trial of neoadjuvant chemotherapy utilizing four cycles of 5-fluorouracil, doxorubicin, and cyclophosphamide. Responding patients were treated with segmental mastectomy and axillary dissection or modified radical mastectomy. Patients subsequently received additional chemotherapy followed by irradiation of the breast or chest wall and draining lymphatics. The median follow-up was 35 months. RESULTS: Clinical tumor response to neoadjuvant chemotherapy (P = 0.046) and the number of residual metastatic axillary lymph nodes found at axillary dissection (P = 0.05) were the only independent predictors of DFS. Patients with a complete clinical response had a predictably excellent DFS and those with no change or progressive disease had a poor DFS. In patients with a partial response, the number of residual metastatic lymph nodes further stratified patients with respect to DFS (P = 0.006). CONCLUSIONS: Clinical response and residual metastatic axillary lymph nodes following neoadjuvant chemotherapy are important predictors of DFS. Patients with a clinically positive axilla following neoadjuvant chemotherapy should undergo axillary dissection to ensure local control. However, the benefit of axillary dissection in patients with a clinically negative axilla may be minimal if the axilla will be irradiated, and histologic staging does not affect subsequent systemic treatment. A prospective randomized trial of axillary dissection versus axillary radiotherapy in patients with a clinically negative axilla following neoadjuvant chemotherapy is presently under way to evaluate this hypothesis.     

Brief preoperative radiotherapy in surgical therapy of rectal carcinoma. Long-term results of a prospective randomized study

To ascertain whether preoperative short-term radiotherapy can improve local tumor control and the long-term survival of patients with operable rectal cancer, a prospective randomised trial was performed from 1988 to 1993. Ninety-three patients with rectal cancer were either directly treated with surgery (n = 46) or underwent preoperative radiotherapy with 5 x 3.3 Gy irradiation and operation within 48 h (n = 47). If indicated (T4, UICC stage III) patients also received postoperative irradiation. Comparison of the methods of operation (abdominoperineal amputation versus anterior resection) revealed no significant difference in 5-year survival rate (P = 0.393). Local control of R0-resected tumors was improved after preoperative irradiation (P = 0.08). The 5-year survival rate was significantly higher after preoperative short-term radiotherapy (P = 0.027). Preoperative radiotherapy is not an independent factor according to overall survival (P = 0.078) and local recurrence (P = 0.07). In agreement with the results of other authors the present study indicates improved local tumor control of rectal cancer after preoperative radiation therapy. The 5-year survival rate was significantly better after preoperative radiotherapy than after surgery alone.     

Supratentorial malignant gliomas in childhood: a single institution perspective

BACKGROUND: A retrospective study evaluated the clinical characteristics, prognostic factors, and outcome of patients with newly diagnosed supratentorial malignant gliomas treated with preirradiation chemotherapy. METHODS: Of 41 patients with supratentorial malignant gliomas accrued between 1984-1994, all had neuroimaging documentation of the extent of resection and 37 had complete neuraxis staging prior to treatment; 80% were treated with one of a variety of neoadjuvant chemotherapy regimens. RESULTS: Thirteen patients had anaplastic astrocytoma (AA), 25 had glioblastoma multiforme (GBM), and 3 had anaplastic oligodendroglioma. Gross total resection (GTR) was performed in 10 patients, subtotal resection (STR) in 22 patients, and biopsy (Bx) alone in 9 patients. For the entire group the 3-year overall and progression free survivals were 35 +/- 8% and 18 +/- 6%, respectively. Tumor recurrence was dominantly local. However, 9 patients with initially local disease failed at a distant neuraxis site, giving a 26 +/- 7% actuarial risk of dissemination at 3 years. The only significant prognostic factor was extent of tumor resection: patients who underwent GTR survived longer than those who underwent STR or Bx (P = 0.004). Histology (GBM vs. AA), age, and the use of enhanced local dose radiation therapy (brachytherapy or stereotactic irradiation) did not affect survival. CONCLUSIONS: Neoadjuvant chemotherapy was not associated with a survival rate significantly different from that observed in adjuvant chemotherapy studies. Systematic neuraxis staging at diagnosis and recurrence revealed a rate of neuraxis dissemination as a component of recurrence that was higher than previously reported; the utility of craniospinal irradiation in preventing isolated dissemination remains uncertain.     

Race, treatment, and survival among colorectal carcinoma patients in an equal-access medical system

BACKGROUND: The aim of this study was to assess the influence of race on the treatment and survival of patients with colorectal carcinoma. METHODS: This retrospective cohort study included all white or black male veterans given a new diagnosis of colorectal carcinoma in 1989 at Veterans Affairs Medical Centers nationwide. After adjusting for patient demographics, comorbidity, distant metastases, and tumor location, the authors determined the likelihood of surgical resection, chemotherapy, radiation therapy, and death in each case. RESULTS: Of the 3176 veterans identified, 569 (17.9%) were black. Bivariate analyses and logistic regression revealed no significant differences in the proportions of patients undergoing surgical resection (70% vs. 73%, odds ratio 0.92, 95% confidence interval 0.74-1.15), chemotherapy (23% vs. 23%, odds ratio 0.99, 95% confidence interval 0.78-1.24), or radiation therapy (17% vs. 16%, odds ratio 1.10, 95% confidence interval 0.85-1.43) for black versus white patients. Five-year relative survival rates were similar for black and white patients (42% vs. 39%, respectively; P=0.16), though the adjusted mortality risk ratio was modestly increased (risk ratio 1.13, 95% confidence interval 1.01-1.28). CONCLUSIONS: Overall, race was not associated with the use of surgery, chemotherapy, or radiation therapy in the treatment of colorectal carcinoma among veterans seeking health care at Veterans Affairs Medical Centers. Although mortality from all causes was higher among black veterans with colorectal carcinoma, this finding may be attributed to underlying racial differences associated with survival. This study suggests that when there is equal access to care, there are no differences with regard to race.     

Factors determining the weaning outcome

OBJECTIVE: To identify the clinicopathological and chemoresistant factors predicting the response to neoadjuvant chemotherapy and the patient prognosis in high-risk cervical carcinomas. METHODS: We retrospectively reviewed 47 patients with locally advanced or bulky cervical carcinoma treated with two courses of intraarterial infusion of cisplatin, doxorubicin, mitomycin C, and 5-fluorouracil (5-FU), followed by radical hysterectomy at our hospital between 1988 and 1995. Expressions of the chemoresistance-related proteins, such as P-glycoprotein, glutathione S-transferase pi (GST-pi), and proliferating cell nuclear antigen (PCNA) in the tumor cells, were examined by immunohistochemistry using pretreatment biopsy specimens. These results were compared with the chemotherapeutic response, which was evaluated by magnetic resonance imaging (MRI) and histopathology. Outcome of the patients was also studied. RESULTS: Chemotherapeutic effect of either complete (CR) or partial (PR) response on MRI was obtained in 36 of the 47 (86%) patients. Poor response to chemotherapy was significantly correlated with P-glycoprotein expression (P < 0.005) and low PCNA labeling (P < 0. 05), but not GST-pi expression in the tumor cells. Independent prognostic factors for patient survival were parametrial involvement and lymph node metastasis. Neither the expression of GST-pi nor PCNA was correlated with the patient survival. CONCLUSION: Assessment of the expression of P-glycoprotein and PCNA is potentially useful for the prediction of tumor response to neoadjuvant chemotherapy for cervical carcinomas.     

Breast conservation and prolonged chemotherapy for locally advanced breast cancer: the University of Michigan experience

PURPOSE: To determine whether breast conservation and prolonged neoadjuvant chemotherapy have efficacy in locally advanced breast cancer (LABC), as measured by survival and rate of breast conservation. MATERIALS AND METHODS: Eighty-nine patients with stage III disease were enrolled at the University of Michigan (UM) onto a prospective nonrandomized trial. Patients received nine 21-day cycles of neoadjuvant chemohormonal therapy that consisted of doxorubicin 30 mg/m2 and cyclophosphamide 750 mg/m2 intravenously on day 1, conjugated estrogens 0.625 mg orally twice daily on days 6 to 8, methotrexate 40 mg/m2 and fluorouracil 500 mg/m2 intravenously on day 8, and tamoxifen 10 mg orally twice daily on days 9 to 14. Patients with a negative biopsy received radiation only, while those with residual disease underwent mastectomy and postoperative radiotherapy. Eight more cycles of chemohormonal therapy were administered after local-regional therapy. RESULTS: The clinical response rate to neoadjuvant therapy was 97%, 28% of patients had a complete pathologic response evaluated at biopsy. Five-year overall and disease-free survival probabilities were 54% and 44%, respectively. The median disease-free survival time was 2.4 years. The 5-year actuarial rates of local-regional control with local failure as only first failure were 82% and 78% following radiotherapy, and mastectomy and radiotherapy, respectively (P = .99). CONCLUSION: Prolonged neoadjuvant chemohormonal therapy and biopsy-driven local therapy have efficacy in LABC, with 28% of patients being candidates for breast conservation and a 5-year overall survival rate of 54%.     

Geographic variations in breast cancer mortality: do higher rates imply elevated incidence or poorer survival?

A 46-year-old women presented with an inoperable low-grade endometrial stromal sarcoma. Two doses of Depo-Lupron, 7.5 mg, and Megace, 160 mg/day, were given to control uterine bleeding and shrink the tumor mass. In 9 weeks, significant reduction in the tumor occurred allowing for surgical resection. Total abdominal hysterectomy with bilateral salpingo-oophorectomy is the mainstay for primary treatment. The role of chemotherapy, radiation therapy, and hormonal therapy is poorly defined. This is a case report of neoadjuvant hormonal therapy which may improve outcomes in patients with endometrial stromal sarcomas. Additional research is needed to define the exact role of these agents.