Association between steroid hormone receptor status and disease-free interval in breast cancer.

The possibility of an association between steroid hormone receptor status and disease-free interval was examined in 292 patients with breast cancer. Estrogen receptor positivity was associated with a prolonged disease-free interval. This association was independent of age, menopausal status, tumor size, or nodal status. There was no association between the presence or absence of progesterone, androgen, or glucocorticoid receptor and disease-free interval.     

Contemporary operative management of pulmonary metastases of colorectal origin

The management of patients with metastatic disease from primary carcinoma of the colon and rectum is still controversial. To evaluate the results of resection of pulmonary metastases from patients with colorectal primaries, a retrospective study of all patients who underwent such resection was carried out at the teaching hospitals of McGill University and Université de Montréal. A total of 345 patients admitted with pulmonary metastases; 27 of them underwent pulmonary resection with the extent of the resection varying from wedge excision of the metastatic nodule to pneumonectomy. In 25 of the 27 patients the resection was considered curative. Eight of the 27 patients had resection of two metastatic lesions while the remaining 19 patients had resection of solitary lesions. The interval between resection of the primary colorectal malignancy and the resection of the metastatic lesion (disease-free interval) varied from 2 to 77 months with a median interval of 35 months. The five-year survival following resection of pulmonary metastases was 21 percent. A prolonged interval between treatment of the primary and resection of the pulmonary metastasis was associated with a longer survival. This retrospective study demonstrates that prolonged survival can be achieved following resection of pulmonary metastases from colorectal carcinoma. Read at the meeting of the American Society of Colon and Rectal Surgeons, Washington, D.C., April 5 to 10, 1987.     

Chemotherapy in stage II testicular tumours: preliminary communication.

Twenty-six patients with stage II testicular teratomas (metastatic spread to the retroperitoneal lymph nodes only) were treated after retroperitoneal lymph node dissection (RLD) by cytostatic chemotherapy with or without radiotherapy. So far, eight patients (30.5%) have recurrent disease, with a median interval of 21 months from time of diagnosis to relapse. The 3-year survival rate for the total group (relapse-free and relapsed patients) was 85.7%. The median survival is not yet reached after 36 months. The own results and reports of the literature show an advantage of early cytostatic treatment over its institution in widespread disease only. It remains to be clarified whether chemotherapy in stage II disease prevents or only delays metastatic spread.     

Phase II study of vinblastine, methyl-CCNU, and medroxyprogesterone in advanced renal cell cancer.

One hundred and sixty-five patients with advanced renal cell cancer were evaluable for combination or single-agent therapy with methyl-CCNU, vinblastine, and medroxyprogesterone. A low order or response was observed, and these agents were not proven effective as treatment for metastatic renal cell cancer. Performance status and a relatively long symptom-free interval from primary tumor to metastatic disease were found to be the most prognostically significant factors for survival.     

Long-term follow-up of nonmyeloablative allogeneic stem cell transplantation for renal cell carcinoma: The University of Chicago Experience

Nonmyeloablative allogeneic stem cell transplantation (NST) has considerable activity in patients with metastatic renal cell carcinoma (RCC), although there are limited long-term follow-up data. Between February 1999 and May 2003, 18 patients with metastatic RCC underwent 19 matched-sibling NSTs after conditioning with fludarabine and cyclophosphamide with tacrolimus and mycophenolate mofetil as post-transplant immunosuppression. Among the four objective responses, all were partial and have relapsed with a median response duration of 609 days (range, 107-926). All responders are alive at a median of 41 months. Median overall survival for the entire cohort was 14 months. There were four early treatment-related deaths and one late treatment-related death. Eight patients died from progressive disease and five (28%) from treatment-related mortality. Stratifying transplant outcome as early death, intermediate (no response, no early death), or response, the combination of pre-treatment anemia and decreased performance status, was associated with adverse outcome (P = 0.015) and reduced survival (HR 5.4, 95% confidence interval of 1.4 to 21, P = 0.007). Responders demonstrated prolonged survival compared to nonresponders (P = 0.002). NST leads to durable responses in a minority of metastatic RCC patients. Appropriate patient selection is paramount. Anemia and decreased performance status may enable risk stratification.     

Survival Prediction Model Using Clinico-Pathologic Characteristics for Nonsmall Cell Lung Cancer Patients After Curative Resection

The current TNM staging system did not provide disease relapse information. The aim of study was try to establish a predictive survival model for disease and overall survival in nonsmall cell lung cancer patients who presented as resectable disease and to develop a reference for follow-up imaging tool selection.From January 2005 to December 2011, 442 patients who initially presented as resectable disease (stages I–IIIa) and received anatomic resection and mediastinal lymph node dissection were included in the study.Medical charts were thoroughly reviewed and clinico-pathologic factors were collected and analyzed.Visceral pleural invasion, tumor size >5 cm, and postoperative adjuvant therapy were identified as risk factors for poorer disease-free survival. The 5-year disease-free survival from score 0 to 3 was 68.7%, 46.6%, 31.9%, and 26.1%, respectively. The disease relapse percentage for scores 0 to 3 were 26.49%, 50.61%, 65.05%, and 73.81%, respectively. For analysis of overall survival, age >60 years, tumor size >3 cm, and total metastatic lymph node ratio >0.05 were correlated to worse overall survival. Because greater age may be correlated with poor general condition, we re-scored risk factors that correlated to disease severity that ranging from 0 to 2. The 5-year overall survival range from score 0 to 2 was 56.3%, 43.1%, and 13.1%, respectively.Poor prognostic factors correlated to disease-free survival were tumor size >5 cm, visceral pleural invasion, and patients needing to receive postoperative adjuvant therapy. Disease-free survival of resectable nonsmall cell lung cancer patients and disease relapse can be stratified by these 3 factors. Chest tomography may be recommended for patients with 1 or more poor disease-free survival risk factors.     

Doxorubicin versus mitomycin versus doxorubicin plus mitomycin in advanced breast cancer: a randomized study

In a randomized trial the antineoplastic and toxic effects of doxorubicin (ADR), mitomycin (MMC), and the combination of the two were evaluated in postmenopausal patients with advanced breast cancer using the following treatment regimens: ADR (75 mg/m2 by iv bolus every 3 weeks); MMC (20 mg/m2 by iv bolus every 6 weeks); and ADR (45 mg/m2 by iv bolus every 3 weeks) and MMC (10 mg/m2 by iv bolus every 6 weeks). One hundred one patients were entered in the study. Entrance to single-agent MMC therapy was stopped after allocation of 12 patients because of unacceptable side effects, especially nausea and vomiting, and the suggestion of minor efficacy. One of these patients had partial response, eight had no change, and three had progressive disease. The patients in the ADR and ADR plus MMC group were similar as to the following: age (median, 60 years); menopausal age; disease-free interval; performance status, extent of previous cytotoxic therapy (approximately 90% were pretreated) and radiation therapy; and dominant site of disease but with significantly more involved organ sites in the ADR plus MMC group. Among evaluable patients (42 in the ADR group and 39 in the ADR plus MMC group), response rates were as follows: complete response--21 versus five; partial response--26 versus 44; no change--40 versus 38; and progressive disease--12 versus 13 (P greater than 0.10). Median times to disease progression were 5.2 and 7.8 months, respectively (log-rank test, P = 0.03), but survival times were similar, 9.3 and 10.2 months, respectively (log-rank test, P greater than 0.40). For the two treatment groups suppression of wbc count was similar, while anemia, thrombopenia, and nausea and vomiting were significantly more common among the ADR plus MMC-treated group. Five treatment-induced deaths were observed in the ADR plus MMC group (one from sepsis; two from diffuse hemorrhage; and two from cardiomyopathy), compared to none in the ADR group. In conclusion, this study disclosed no major advantage of the combination of ADR plus MMC compared to ADR alone as second-line treatment of advanced breast cancer, but results from other studies may imply a possible role of MMC as part of second-line combination chemotherapy regimens.     

Peritoneal recurrence of gastric adenocarcinoma after curative resection

BACKGROUND/AIMS: Death from gastric carcinoma after curative resection is mostly due to recurrence. The most common recurrence is peritoneal dissemination, which represents 33 to 50% of total recurrence after curative gastrectomy. Since survival after peritoneal dissemination is very poor, selection of high-risk patients for further management after resection may contribute to better survival. METHODOLOGY: Based on a prospective database, a total of 1,092 patients with gastric carcinoma who underwent curative resection were included in this study. The incidence of peritoneal recurrence, disease-free interval and survival after peritoneal recurrence were determined. The clinicopathological factors including sex, age, tumor location, size, gross appearance, histological findings, depth of tumor invasion, lymph node status, tumor cell infiltration pattern were analyzed to see if there is any relationship with peritoneal dissemination. RESULTS: The incidence of peritoneal recurrence after curative resection was 13.46%. The mean disease-free interval was 14.2 months and the survival after peritoneal recurrence was 4.9 months in average. Almost all the clinicopathological factors were related with peritoneal recurrence, but only depth of tumor invasion, gross appearance and tumor infiltration pattern are closely associated with peritoneal tumor dissemination after multivariate analyses. CONCLUSIONS: Since the prognosis after peritoneal recurrence is so poor, selection of high-risk patients for further management after gastrectomy may be based on these three factors.     

Resection of liver metastasis from gastric adenocarcinoma

BACKGROUND/AIMS: To determine the factors influencing the prognosis of patients undergoing resection of liver metastases from gastric adenocarcinoma. METHODOLOGY: Over a 10-year period, at Kiryu Kousei General Hospital, 12 patients underwent potentially curative hepatectomy for metastatic adenocarcinoma of gastric origin. Two patients were excluded from this study, one because of postoperative death and one due to insufficient follow-up. We retrospectively examined the following factors: including TNM classification of the primary tumor, disease-free interval between gastric and hepatic resection, number and maximum diameter of the metastases, histological differentiation of the metastases, and the presence of lymphocyte aggregation enclosing the metastatic lesions. Survival rates were estimated by the Kaplan-Meier method and the weighting of each factor was compared by the log-rank test. RESULTS: The overall 5-year survival rate of the 10 patients was 10%. The median survival time after hepatectomy was 16.3 months, ranging from 3.1 to 245.7 months. Eight patients died of recurrent cancer and 1 died of unrelated septic shock with no evidence of cancer recurrence. Only one patient was alive without recurrence at the time of maximum follow-up. A significant survival advantage was noted in patients with disease-free interval > or = 1 year, and those with metastatic tumors < 5 cm in maximum diameter and/or enclosed by the aggregated lymphocytes, when compared with patients with disease-free interval < 1 year and those with metastatic tumors > or = 5 cm and/or directly infiltrated hepatic parenchyma. CONCLUSIONS: It was suggested that hepatectomy should be attempted in patients where the disease-free interval was > or = 1 year and with metastatic nodules < 5 cm. Lymphocyte aggregation around the metastatic tumor is a good prognostic sign for long-term survival.     

Inflammatory carcinoma of the breast. Clinical review and summary of the Vanderbilt experience with multi-modality therapy

Inflammatory breast cancer is a distinct clinicopathologic entity that accounts for 1 percent of all cases of breast cancer. The diagnosis should be strongly suspected on the basis of the distinctive clinical findings, which include edema of the breast, inflammation, wheals, and a typical reddish-purple color of the overlying skin. Pathologic examination usually shows infiltration of the dermal lymphatics with carcinoma. Evidence of distant metastatic spread is more frequent than with other types of breast cancer and is seen in approximately 30 percent of patients. The five-year disease-free survival rate is less than 5 percent when local therapy alone (mastectomy and/or local radiotherapy) is used. The addition of combination chemotherapy to high-dose local radiotherapy has improved the five-year survival rate to approximately 30 percent. The potential for long-term survival is limited to the subgroup of patients with only local-regional disease at the time of diagnosis. Patients with inflammatory breast cancer should be treated with combined-modality therapy using combination chemotherapy and high-dose radiotherapy to the breast, since this approach is potentially curative. The fatalism formerly associated with this diagnosis is no longer warranted, particularly in patients with local-regional disease. Failure to employ intensive combined-modality treatment will deny some patients a chance for long-term survival.     

Elevated serum levels of C-reactive protein are indicative of a poor prognosis in patients with esophageal cancer

SUMMARY: Despite improved results gained by the combination of neoadjuvant chemotherapy and radiotherapy with surgery, the prognosis for the esophageal carcinoma patient remains poor. There is a need for prognostic markers that can help improve patient selection. The aim of this study was to evaluate whether serum levels of C-reactive protein (CRP) have any influence on the patient prognosis in terms of prediction of chemoradiosensibility, and overall and disease-free survival. Blood samples were obtained at the time of diagnosis in 67 patients with biopsy-proven primary carcinoma of the esophagus. Although not significantly, the mean CRP level was higher than that of 20 patients with benign esophageal pathology who served as controls. No significant correlation could be found between CRP levels and baseline characteristics such as age, gender, histology, cancer localization, tumor depth, lymph node status or metastatic spread. However, patients with CRP levels higher than 6 mg/L were more frequently non-responders to chemoradiotherapy (P = 0.035), had a shorter overall survival (P = 0.061) and a shorter disease-free survival (P = 0.016). It is concluded from these results that pretreatment measurement of serum CRP levels in patients with esophageal cancer could to be used in routine practice as indicators of chemoradiosensibility and prognosis.     

Tumor volume is a better prognostic factor than greatest tumor diameter in stage Ia non-small cell lung cancer

OBJECTIVE: The objective was to determine whether tumor volume, calculated by multiplying 3-dimensional diameters recorded from surgical specimens, could represent tumor size more precisely than the currently used greatest tumor diameter (T status) as a prognostic factor in early-stage non-small cell lung cancer (NSCLC). METHODS: From 1991 to 2001, a total of 236 stage Ia NSCLC patients underwent curative resection in our institution. Their clinicopathological factors were retrospectively reviewed. The cases were grouped according to stereographic tumor size. Group 1 included tumor volumes less than 0.5236 (1(3) x pi/6) cm3, Group 2 included tumor volumes between 0.5236 - 4.1888 (2(3) x pi/6) cm3, while Group 3 included tumor volumes between 4.188 - 14.1372 (3(3) x pi/6) cm3. Overall survival and disease-free interval analyses were performed with the Kaplan-Meier method and multivariable Cox's proportional hazard model. Tumor volume and other clinico-pathological factors were included for analysis. RESULTS: Median follow-up was 55.5 months. The overall 5- and 10-year survival rates were 78 % and 71 %, and the 5- and 10-year disease-free intervals were 68 % and 64 %, respectively. The overall survival ( P = 0.0075) and disease-free interval ( P = 0.0025) showed significant differences between tumor volume groups. Smoking history, presence of symptoms and the number of resected lymph nodes were also significantly related to overall survival and disease-free interval. CONCLUSION: The products of 3-D diameters (tumor volume) more precisely evaluated tumor size as well as survival of patients with stage Ia NSCLC.     

Survival and clinical evaluation of salvage operation for cervical lymph node recurrence in esophageal cancer

BACKGROUND/AIMS: Although extended lymphadenectomy for thoracic esophageal cancer is widely practiced in Japan, solitary supraclavicular lymph node recurrence (SCLR) has often become a problem. This study was designed to evaluate the survival and clinical benefit of salvage cervical lymphadenectomy. METHODOLOGY: Between 1989 and 2001, 153 patients underwent esophagectomy for esophageal cancers. SCLR was identified in 5 (3.7%) patients and these five patients were examined retrospectively. RESULTS: Surgical treatment was performed intensively for all patients. Two patients showed longterm survival for 7 years 3 months and 4 years, respectively. Four patients belonged to the good prognostic group but the other patient had poor prognosis from the viewpoint of both the pathological metastatic lymph node number and disease-free interval (DFI). There were no local recurrences but were a recurrent laryngeal nerve palsy in three patients associated with treatment. CONCLUSIONS: Salvage cervical lymphadenectomy for SCLR should be performed positively by selecting each case carefully. Indication must be weighed against increased morbidity considering such indicators as the extent of metastatic lymph node numbers and DFI.     

Results of Aggressive Resection of Lung Metastases from Colorectal Carcinoma Detected by Intensive Follow-Up

PURPOSE: Although outcome of resection for colorectal carcinoma has improved, about 30 percent of patients develop metastatic lesions. Small pulmonary metastases 1 cm or less in diameter now can be detected by diagnostic tests including chest radiography and computed tomography. We evaluated results of our strategy for intensive follow-up after resection of colorectal cancer and aggressive resection of lung metastases disclosed by these periodic examinations. METHODS: Our follow-up program for lung metastasis includes a serum carcinoembryonic antigen assay every two months and chest radiography every six months. Surgical resection of lung metastases was performed if the primary and any nonpulmonary metastases had been controlled, lung metastases numbered four or fewer, and pulmonary functional reserve was adequate. Standard operation for lung metastasis was lobectomy, and lymph node dissection was added in cases of tumor size over 3 cm. Forty-two patients underwent 50 lung resections for metastatic colorectal cancer between 1992 and 1999. Long-term survival was assessed in terms of clinical variables. RESULTS: Overall five-year survival rate after resection of lung metastases from colorectal cancer was 63.7 percent. Variables significantly affecting postthoracotomy survival were primary tumor histology, number of nodules, and disease-free interval up to appearance of the lung metastases, and primary tumor histology was an independent prognostic factor. CONCLUSION: Intensive follow-up for lung metastases after resection of colorectal cancer and aggressive resection improved postoperative survival rate. Patients with well-differentiated adenocarcinoma of primary tumor, a solitary metastatic nodule, and disease-free interval of at least two years after initial surgery are likely to be long-term survivors.     

Complete remission of disease for 5 years following initial and repeat resection of the liver for the removal of 22 metastases of colorectal origin

Although liver resection is accepted as the only available treatment that regularly produces long-term survival with possible cure in patients with colorectal carcinoma metastatic to the liver, controversy appears to exist regarding the surgical indication for patients with more than four nodules. Similarly, it may be arguable to perform a repeated hepatic resection for a patient who developed multiple recurrent liver metastases with a short disease-free period after the initial liver resection. During the last 7 years, we have adopted constantly the aggressive surgical approach to patients with colorectal carcinoma metastatic to the liver if the number of tumor nodules identified preoperatively were less than ten and irrespective of the length of disease-free period after the previous resection. Here we report on a patient who underwent hepatic resection twice at an interval of 3 months and in whom a total of 22 metastatic nodules (6 in the initial hepatic resection and 22 in the repeated resection) were removed. The patient is now alive and remains disease-free, 5 years after the first liver resection.     

Prognosis in hormon receptor negative breast cancer patients according to ERBB2 status

Breast carcinomas represent a heterogenous group of tumors and recent studies have demonstrated several subtypes of breast cancer by gene expression profiles. This study aimed to compare hormon receptor negative (ER-/PR-/ERBB2+) and triple negative (ER-/PR-/ERBB2-) patients in terms of prognosis and to show that molecularly defined subtypes can be distinguished by conventional laboratory methods. Patients treated between 2001-2007 for hormon receptor negative breast cancer were retrospectively studied. In addition to the conventional prognostic factors, effect of ERBB2 status of the patients on disease-free and overall survival was evaluated. Hormon receptor and ERBB2 status were determined by immunuhistochemistry and fluorescence in-situ hybridization. 141 patients were eligible for the study. Number of patients with ERBB2 positive and triple negative tumors was 70 and 71, respectively, and two groups were comparable in terms of study parameters. Tumor size, grade, axillary status, patient groups, and adjuvant chemotherapy and radiotherapy showed significant impact on disease-free survival and overall survival was significantly dependent on axillary status, type of surgery, and patient groups in univariate analysis. In multivariate analysis, patient groups, tumor grade, and axillary status were independent prognostic factors for disease-free survival whereas patient groups, extent of surgery, and axillary status were independent prognostic factors for overall survival. This study has indicated that ERBB2 negative patients had worse survival among hormon receptor negative breast cancer patients and showed that molecularly defined subtypes of breast cancer can be differentiated by immunuhistochemistry in terms of prognosis.     

Estrogen receptors and the pattern of relapse in breast cancer

To determine if the pattern of relapse in patients with breast cancer was influenced by the presence or absence of hormonal receptors, we examined 300 patients with breast cancer who had estrogen receptor (ER) assays performed on their primary tumors. A multivariate discriminant analysis of the initial site of recurrence was performed, and we included in the analysis such factors as ER status, menopausal status, axillary lymph node involvement, and the interaction between menopausal status and ER status. Estrogen receptor status was found to be the single most important independent variable associated with the pattern of recurrence. There was significantly higher likelihood of visceral metastasis with ER-negative tumors, 52.1% as opposed to 5.38% for ER-positive tumors. Conversely, there was a high frequency of osseous relapse with ER-positive tumors, 60.4%, as opposed to 13.4% for ER-negative tumors. We also found that postmenopausal women tended to be ER positive more often than premenopausal women, and progesterone receptor status appears to be a good indicator for five-year disease-free survival in patients without axillary node involvement. With the progression of disease, there was a loss of receptors, even without therapeutic intervention.     

Importance of investigating high-risk human papillomavirus in lymph node metastasis of esophageal adenocarcinoma

High-risk human papillomavirus has been suggested as a risk factor for esophageal adenocarcinoma. Tumor human papillomavirus status has been reported to confer a favorable prognosis in esophageal adenocarcinoma. The size of the primary tumor and degree of lymphatic spread determines the prognosis of esophageal carcinomas. Lymph node status has been found to be a predictor of recurrent disease as well as 5-year survival in esophageal malignancies. In human papillomavirus driven cancers, e.g. cervical, anogenital, head and neck cancers,associated lymph nodes with a high viral load suggest metastatic lymph node involvement. Thus, human papillomavirus could potentially be useful as a marker of micro-metastases. To date, there have been no reported studies regarding human papillomavirus involvement in lymph nodes of metastatic esophageal adenocarcinoma. This review highlights the importance of investigating human papillomavirus in lymph node metastasis of esophageal adenocarcinoma based on data derived from other human papillomavirus driven cancers.     

Pathologic response to preoperative transarte-rial chemoembolization for resectable hepato-cellular carcinoma may not predict recurrence after liver resection

BACKGROUND: Pathologic response(PR) predicts survival after preoperative chemotherapy and resection of a malignancy. Occasionally, transarterial chemoembolization(TACE)may be selected for preoperative management of resectable hepatocellular carcinoma(HCC). This study investigated whether PR to preoperative TACE can predict recurrence after resection for resectable HCC.METHODS: We conducted analysis of 106 HCC patients who underwent TACE followed by liver resection with a curative intent. The PR was evaluated as the mean percentage of nonviable tumor area within each tumor. We divided the patients into three groups according to response rate: complete PR(CPR), major response(MJR: PR≥50%) and minor response(MNR: PR50%). The primary endpoint was disease-free survival, and the secondary endpoints were predicting factors for tumor recurrence and MJR+CPR.RESULTS: Among the 121 TACE patients, PR could be measured in 106(87.6%). The mean interval between TACE and liver resection was 33.1 days. The 5-year disease-free survival rates by PR status were as follows: 40.6% CPR, 43.7% MJR, and 49.0% MNR(P=0.815). There were also no significant differences in overall survival between the three groups. Multivariate analyses revealed that microvascular invasion and capsular invasion(hazard ratio [HR]=11.224, P=0.002 and HR=2.220P=0.043) were independent predictors of disease-free survival.Multivariate analysis of the predictors of above 50% PR revealed that only hepatitis B was an independent factor.CONCLUSION: These data could reflect that the PR after TACE for resectable HCC may not be useful for predicting recurrence of HCC after resection.     

Determination of proliferative activity in colorectal carcinoma using monoclonal antibody Ki67

PURPOSE: In the search for a prognostic discriminant, Ki67 immunoreactivity of colorectal carcinoma was used to see whether this marker correlated with clinical and pathologic parameters and the ultimate prognosis of the patient. METHODS: Fresh specimens from 30 surgically resected adenocarcinomas were obtained and frozen in liquid nitrogen. Slides were immunohistochemically stained with Ki67. Ten randomly chosen fields were examined, and 1,000 nuclei per specimen were counted. The percent positive stained nuclei determined the Ki67 score. Correlation was made with the parameters of Dukes stage, location within the colon, size of malignancy, gender, age, and survival. RESULTS: There was a positive correlation of the Ki67 score for patients with metastatic disease, but no correlation was found to Dukes B and C cases. There was no correlation between Ki67 immunoreactivity and size or location of lesion, patient's age, patient's gender, or whether patient died of disease or developed a recurrence compared with those who survived five years disease-free. CONCLUSION: Ki67 immunoreactivity could not be correlated with clinical and pathologic parameters except for metastatic disease in this study and was of limited use as a prognostic discriminant.Supported by a grant from the Foundation of the Sir Mortimer B. Davis-Jewish General Hospital and the American Physician Fellow-ship.