Chemotherapy of colorectal carcinoma

The benefit of adjuvant therapy in colorectal cancer (CRC) has been provided in clinical studies that have demonstrated reduction of up to 30% in a 5-year overall mortality in patients (pts.) with TNM stage III (Dukes' stage C) carcinoma. Patients with metastatic CRC are usually in a relatively good condition despite their advanced disease. Therefore, some clinicians wished to withheld the toxicity of chemotherapy until the disease became symptomatic. Others, however, felt it appropriate to treat patients early in the course of the disease. Four clinical trials may be cited addressing this clinical uncertainty (Table 1). Patients receiving chemotherapy had a significantly longer median survival in comparison with only best supportive care. The delay of the carrying out of systemic chemotherapy in patients with metastatic disease decreases the symptom free interval (2 vs. 10 months, p < 0.001), time to disease progression (3 vs. 8 months, p < 0.001) and median survival (14 versus 9 months, p < 0.02) compared to an early start of therapy [7C. Patients with metastatic colorectal cancer benefit from early chemotherapy in terms of survival and quality of life. It is clear that survival is determined by prognostic factors, mainly the performance status, which is a highly significant predictor of therapeutic response and overall survival in advanced colorectal cancer patients. Some authors suggests that the response is a potent and independent prognostic factor of survival, and that response can be used as surrogate marker of survival. Stable disease is a category in therapy response evaluation which is not included in the overall response rate. In many studies with a response rate below 20%, chemotherapy almost doubles the survival of patients. In most chemotherapy trials in advanced colorectal cancer patients, about 30-50% had stable disease. One of the possible reasons may be that in colorectal cancer stabilization of disease is a clinically relevant effect of chemotherapy. If we accept that disease stabilization is a clinically relevant effect of chemotherapy, should we continue with chemotherapy after 3 or 4 courses, and for how long, or should we stop treatment according to rules for stable disease, i.e. following 4 courses? The results of on study, which we performed in 99 patients with advanced colorectal cancer, indicate that under category of "stable disease" there are two different subpopulations of patients with quite different symptom responses as an effect of chemotherapy, different time to progression and possible different survival (Graph 1 and Graph 2). It seems that stable disease patients with clinical benefit could be a target group for policy "to treat until disease progression". The tumour response is likely to be positively correlated with improvement in quality of life when a patient is a symptomatic from cancer before the treatment. Stable disease patients without symptom improvement have no benefit from further chemotherapy and in these patients treatment should be stopped. Such selection would spare from toxicity stable disease patients without clinical benefit. We have no data whether different number of chemotherapy cycles in the groups of patients with and without clinical benefit could lead to a bias in survival estimation. Patients who achieved also a stable disease, but who were asymptomatic from the beginning of chemotherapy, and who are still asymptomatic after 4 chemotherapy courses, make a group for which is hard to make decision either to continue or to stop chemotherapy. We have treated and followed-up these stable disease patients as patients without clinical benefit. We have no answer if they could reach better time to progression and/or survival if they had been treated for more than 4 courses. Careful studies in the evaluation of the quality of life in connection with treatment effects for all stable disease subpopulations of patients are warranted. (ABSTRACT TRUNCATED)     

Features of the lateralization of speech function in stutterers as a function of the sex of the subjects

BACKGROUND: To analyze the response to eradicative therapy and prognostic factors in 52 patients with primary gastrointestinal lymphoma (PGIL) diagnosed at a single institution in a 13 year period. PATIENTS AND METHODS: The main clinical, biological and evolutive data were recorded. Pathologic diagnosis of PGIL was made according to the Working Formulation. Clinical stage was determined by the Ann Arbor system modified by Mushoff. The results of therapy as well as the influence of such characteristics on complete remission (CR), disease-free survival (DFS) and overall survival (OS) were studied. RESULTS: Mean age of the series was 53 years (SD 15). Thirty patients were males. HIV infection preceded PGIL diagnosis in 10 cases. Seventeen had bad performance status (ECOG 2-4) and 30 B symptoms. The PGIL localization was gastric in 31 cases and 29 had a low grade malignant lymphoma. B phenotype was demonstrated in 98% and 22 patients presented advanced stages (IIE2-IV). Treatment was radical surgery followed by intensive chemotherapy in 32 cases, intensive chemotherapy alone in 17, and surgical resection in 3. CR was obtained in 34 patients and 6 of them relapsed. The projected DFS from CR at 9 years was 72% and OS was 26%. CR and survival were not influenced by PGIL localization and treatment type. The main unfavourable prognostic factors were advanced stage (CR and OS), B symptoms (DFS and OS) and advanced ECOG score (CR, DFS and OS). Previous HIV infection had an independent prognostic influence on both CR and OS. CONCLUSIONS: In patients with PGIL, the achievement of CR, DFS and survival have been independent of the type of eradicative treatment used. Performance status, B symptoms and clinical stage have been the main prognostic factors. HIV infection carried an independent prognostic significance.     

Prognostic factors for survival in patients with brain metastases from renal cell carcinoma

BACKGROUND: Patients presenting with brain metastases from renal cell carcinoma portend a poor prognosis, with a reported median survival of 4-6 months. Given their short life expectancy, these patients generally have been excluded from clinical trials that assess the efficacy of medical treatments. However, clinical impression suggests that some patients may achieve long term palliation. METHODS: The clinical features of 68 patients who were treated at the Institut Gustave Roussy for brain metastases from renal cell carcinoma were collected retrospectively. Using univariate and multivariate analyses, a prognostic model based on independent prognostic factors was established. An external data set of 57 patients was used to validate the model. RESULTS: The median survival was 7 months. On univariate analysis survival was related significantly to the following adverse prognostic factors: no initial nephrectomy, left side and temporal location of brain metastases, presence of fever or weight loss, erythrocyte sedimentation rate > 50 mm/h, and time from initial diagnosis to brain metastases < or = 18 months. Multivariate analyses identified the previous variable as well as the presence of other visceral metastases as independent prognostic factors. Forty-four patients (65%) with no or 1 adverse prognostic factor (average risk group) had a median survival of 8 months and a 26% 1-year survival rate. Twenty-four patients (35%) with 2 adverse prognostic factors (poor risk group) had a median survival of 3 months and a 1-year survival rate of 9%. This model proved to be discriminant in an external data set; the median survival of patients assigned to the average risk group was 11 months (46% 1-year survival rate) compared with 4 months (9% 1-year survival rate) for patients assigned to the poor risk group. CONCLUSIONS: Patients presenting with brain metastases from renal cell carcinoma and poor risk prognostic factors are highly unlikely to benefit from medical treatments except symptomatic procedures. Conversely, the enrollment of patients with average risk prognostic factors into clinical trials dealing with chemotherapy or immunotherapy may be considered.     

Practical considerations in the treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) represents one of the most common neoplasms worldwide. To date, curative treatment options include liver transplantation or resection. Unfortunately, most patients are detected with nonresectable or -transplantable HCC due to disease extension or comorbid factors, and are therefore candidates only for palliative treatments. Palliative medical treatments, including systemic chemotherapy, immunotherapy or hormonal manipulation, have a borderline activity on HCC and cannot be recommended outside clinical trials. A high response rate has been reported with local therapies such as transcatheter arterial embolisation, intra-arterial chemotherapy or percutaneous alcohol (ethanol) injection, but as there is no clear evidence of a survival advantage for these treatment modalities, further investigations are required. Multidisciplinary treatment, including preoperative cytoreduction or postoperative adjuvant therapy, is currently under investigation, with encouraging survival results. HCC patients should be evaluated within clinical trials, possibly randomised and with homogeneous prognostic factors, in order that we may find the answer to all these important questions.     

Prognosis and prediction of response in breast cancer: the current role of the main biological markers

In the medical literature there are frequently conflicting reports on the utility of biological tumour markers available in the clinical management of breast cancer. In this review we analyse current information on the relationships between the most widely investigated breast cancer biological markers including oestrogen and progesterone receptors, p53, Bcl-2, c-erbB-2, cyclin expression, proliferative activity, DNA ploidy and the urokinase plasminogen activation system, as well as their relevance to prognosis and response to clinical treatment. By biological prognostic indicator, we mean a marker that correlates with survival and disease-free survival; the term predictor marker indicates a marker that is capable of predicting tumour sensitivity or resistance to various therapies. Similarly to other authors' experiences, our analysis suggests that oestrogen receptors are weak prognostic indicators and good predictors of response to endocrine therapy. Furthermore, there are consistent data suggesting that proliferation indices are good indicators of prognosis, and that they are directly related to response to chemotherapy and closely related to response to hormonotherapy. On the contrary, there is no evidence or conflicting data for all of the other biological markers. These should be considered in the context of randomized trials in order to precisely define their prognostic and predictive roles. p53 and c-erbB-2 seem to be the most promising factors, but their use in routine practice still needs validation.     

Current guidelines for the management of aggressive non-Hodgkin's lymphoma

The prognosis of aggressive non-Hodgkin's lymphoma (NHL) has improved greatly during recent years with the use of combination chemotherapy. Planning the treatment must take into consideration the patient's age, performance status, histological subtype and disease extent and severity. Recently, a 4-part International Prognostic Index (IPI), based on 5 prognostic factors, has permitted the allocation of patients with NHL in 2 well defined prognostic groups: good prognosis (low and low-intermediate risk) and poor prognosis (intermediate-high and high risk). Conventional chemotherapy with CHOP (a chemotherapeutic regimen consisting of a combination of cyclophosphamide, doxorubicin, vincristine and prednisone) or other equivalent third-generation regimens may be considered the standard treatment for the good prognosis group. In the poor prognosis group the probability of long term survival is less than 40% with conventional chemotherapy. Therefore, an early intensification with high dose therapy following peripheral stem cell transplantation (PSCT) should be considered in the setting of randomised trials. Localised stage disease, defined as stages I-IE and II-IIE without adverse prognostic factors, has a very good prognosis with a long term survival exceeding 80% using brief conventional chemotherapy regimens plus involved field radiotherapy. Refractory or relapsing patients after the drugs of first choice are given who subsequently respond to salvage chemotherapy should be enrolled for a course of high dose consolidation chemotherapy followed by PSCT. Elderly patients without severe organ dysfunction can take advantage from specifically devised chemotherapy regimens, with a response rate similar to that of younger patients. However, despite major advances in the treatment of aggressive NHL, additional clinical trials are required to enable the clinician to define the best therapeutic programmes to treat patients with this disorder.     

Effects of systemic and regional chemotherapy after hepatic resection for colorectal metastases

BACKGROUND: Although the survival benefit of hepatic resection for colorectal metastasis has been established, some controversy remains regarding the significance of adjuvant chemotherapy after hepatic resection. METHODS: One hundred thirty-two consecutive patients who had liver resection for colorectal metastasis at our hospital between 1980 and 1997 were studied. After curative hepatic resection, 37 patients underwent systemic chemotherapy, administered orally or intravenously, and 38 patients underwent regional chemotherapy, given intra-arterially or intraportally. Forty patients had no adjuvant chemotherapy. The chemotherapeutic agents used for oral administration were uracil and Tegafur or Tegafur alone. Mitomycin C (MMC) or 5-FU was used for IV chemotherapy. Combinations of 5-FU/leucovorin or MMC/5-FU (doxorubicin) were used for regional chemotherapy. Univariate and multivariate analyses were applied to test the significance of adjuvant chemotherapy for patient survival or disease-free survival. RESULTS: Overall 5-year survival was 42.2% (95% CL: 31.2%, 53.2%). Among the possible prognostic factors studied, univariate analysis showed a significant difference in survival based on the number of tumors and lymph node metastases in the hepatic hilum. There was a significant difference in disease-free survival based on adjuvant chemotherapy and lymph node metastasis. The multivariate analysis for patient survival selected four prognostic factors (P < .05), including adjuvant chemotherapy, lymph node metastasis, disease-free interval, and tumor size. The multivariate analysis for disease-free survival selected adjuvant chemotherapy, lymph node metastasis, and disease-free interval as significant factors. The most common recurrence site was remnant liver, regardless of adjuvant chemotherapy. CONCLUSIONS: Adjuvant chemotherapy significantly improved survival and disease-free survival after hepatic resection for colorectal metastases. It did not decrease recurrence rate in the remnant liver.     

Mutational activation of the K-ras oncogene and the effect of chemotherapy in advanced adenocarcinoma of the lung: a prospective study

PURPOSE: To determine whether the clinical course and the response to chemotherapy of patients with advanced adenocarcinoma of the lung depends on the presence or absence of a ras mutation in the tumor. Mutational activation of K-ras is a strong adverse prognostic factor in stage I or II lung cancer and laboratory studies have suggested that ras mutations lead to resistance against ionizing radiation and chemotherapy. PATIENTS AND METHODS: Patients with advanced adenocarcinoma of the lung with measurable or assessable disease received chemotherapy with mesna, ifosfamide, carboplatin, and etoposide (MICE). Archival biopsies, fresh biopsies, or fine-needle aspirations were tested for the presence of ras gene mutations. Associations of ras mutations with clinical characteristics, response to chemotherapy, and survival were studied. RESULTS: The presence or absence of ras gene mutations could be established in 69 of 83 patients (83%). A total of 261 courses of MICE were administered to 62 informative patients, 16 of whom were shown to have a K-ras mutation-positive tumor. The frequency of mutations (26%) and the type of mutations closely matched the pattern we have previously reported in operable disease. Patients with a ras mutation in their tumor were more likely to have a close relative with lung cancer, but other clinical characteristics, such as pattern of metastases, response, and survival, were similar between the ras mutation-positive and ras mutation-negative groups. CONCLUSION: Patients with advanced lung adenocarcinoma who harbor a ras mutation may have major responses to chemotherapy and have similar progression-free and overall survival as patients with ras mutation-negative tumors. K-ras mutations may represent one of several ways in which early tumors are enabled to metastasize to distant sites.     

Prediction of recurrence for advanced breast cancer. Traditional and contemporary pathologic and molecular markers

Approximately 50% of patient with breast cancer ultimately develop metastases, among which only 10% to 15% of patients live 5 years or more. Patients with locally advanced (stage III) breast cancer have a 5-year survival rate of approximately 20% to 30%. Thus, despite high remission rates obtained with current therapies, the poor long-term results associated with the apparent plateau of response achievable with systemic therapies emphasize the necessity of identifying accurate prognostic factors for this group of patients. This will allow an informed discussion with the individual patient. In addition, prognostic information could be used to guide the therapy and also to identify those subgroups of patients who may benefit with less-aggressive therapies. Furthermore, in the context of randomized studies, prognostic factors can be used to stratify patients. Prognostic factors have been extensively studied in early-stage breast cancer. In comparison, only a few studies exist on biologic prognostic factors in advanced breast cancer. Based on the limited information available, it appears that the biologic factors prognostic for locally advanced breast cancer are similar to those reported for early-stage breast cancer. Apparently, certain factors have a prognostic value irrespective of the stage of the disease at the time of presentation. This would then suggest that certain factors maintain their significance as the breast cancer progresses from an overtly local to a systemic disease. It is already well recognized that histologic grade is a significant prognostic factor for early-stage as well as metastatic breast disease. Hormone receptors have been reported to be of prognostic value at all stages of disease. Proliferation rate assessed by a variety of techniques as well as determination of the Nottingham Primary Prognostic Index provides important information about the rate of the growth of the tumor. Thymidine labeling index and S-phase fraction also provide information in regard to response to chemotherapy. DNA ploidy has been reported to be of significance in prediction of response to adjuvant chemotherapy and to a lesser extent to hormone therapy. The value of DNA ploidy in relation to survival in advanced breast cancer, however, remains controversial. Other prognostic factors such as oncogenes, tumor suppressor genes, and growth factors have also shown some predictive value in advanced breast cancer. Similar to what has also been suggested in early breast cancer, much research still needs to be done to clarify the role of currently available prognostic factors and to identify new, more powerful discriminants.(ABSTRACT TRUNCATED AT 400 WORDS)     

Results of interleukin-2-based treatment in advanced melanoma: a case record-based analysis of 631 patients

PURPOSE: In patients with stage IV melanoma, durable responses have been reported with treatment regimens that involve high-dose interleukin-2 (IL-2). We analyze long-term results of 631 melanoma patients from 12 institutions who had received IL-2 alone, in combination with interferon alfa 2a or 2b (IFNalpha), or with cytotoxic drugs. METHODS: Case records that contained pretreatment parameters, response data, and updated survival information were collected. After univariate analysis, the multivariate evaluation of the impact of pretreatment parameters on response and survival was performed by logistic regression and Cox's regression, respectively. RESULTS: Patients were divided into four groups according to treatment: IL-2 alone (n=117), IL-2 and chemotherapy (n=49), IL-2 and IFNalpha (n=153), and IL-2, chemotherapy, and IFNalpha (n=312). The median survival of all patients was 10.5 months and the 2- and 5-year survival rates were 19.9% and 10.4%, respectively. Independent prognostic factors for response and survival were entirely different, treatment group being the only significant factor for response, and serum lactate dehydrogenase (LDH), metastatic site, and performance predicting survival. The addition of IFNalpha to IL-2 was associated with prolonged survival, but the effect of additional chemotherapy was less obvious. CONCLUSION: Serum LDH, metastatic site, and performance status are useful stratification factors for randomized trials in metastatic melanoma. The improved long-term survival rates observed in melanoma patients treated with IL-2/IFNalpha-containing regimens are notable in contrast to the reported 5-year survival rates of 2% to 6% achieved with chemotherapy, but because selection bias cannot be ruled out, the impact of IL-2, as well as all other components of the treatment regimens, on survival needs to be confirmed in prospective randomized trials.     

Role of biological indicators in the therapeutic decision in breast carcinoma

Before planning therapeutic strategies for patients at different risks of relapse, it is essential to identify prognostic factors. In addition to important anatomo-pathological prognostic factors such as lymph node status and tumour size, certain biological indicators, such as receptor status and proliferative kinetics, are now regarded as useful tools for prognosis. Tumour cell kinetics is an important prognostic variable in different stages of breast cancer. It is also a useful index for identifying subjects of aggressive tumours in node-negative patients. As far as the relationship between TLI estrogen receptor status and tumor size is concerned, it has been observed that only TLI retains its prognostic significance as regards both time to relapse and overall survival. Lymph node status, receptor status, cell kinetics and c-erbB-2 expression were examined as predictive factors of response. It emerged that not all chemotherapeutic regimens have the same impact in a situation where the disease is evaluated exclusively on the basis of lymph node status. Moreover, receptor status and receptor level significantly condition the response to endocrine therapy. Response rates to chemotherapy increase in highly proliferating tumours, whereas endocrine therapy achieves a better response in ER+ tumours with a low TLI index. Further studies are needed to clarify the role of c-erbB-2 as a predictive factor of response.     

Adult acute leukemia. The Rochester (NY) Experience

A ten-year retrospective study of adult acute leukemia was performed in nonieukemia-specialized centers to determine prognostic factors, length and quality of survival, cause of death, and response to different modes of therapy. Of 200 patients, 9.5% achieved complete remission, 14.0% obtained partial remission, and no response was present in 76.5%. Patients who were 50 years old or more (64.5%) had a significantly lower response rate (P less than .005) and survival (P less than .05) than the younger age group. Aggressive chemotherapy significantly improved the response rate, as well as survival (P less than .001). Quality of life was similar for responders and nonresponders, both spending only one fourth of their survival time in the hospital. Infection as the leading cause of death. The overall ten-year response rate of 23.5% represents a realistic rate in nonleukemia-specialized centers in which the treatment of adult acute leukemia is variable.     

Presenting features and prognosis in 72 patients with multiple myeloma who were younger than 40 years

The purpose of this study was to analyse the presenting clinical and laboratory features and the outcome of 72 patients with multiple myeloma (MM) who were younger than 40 years. The records of all Mayo Clinic patients with MM younger than 40 years who were seen between 1 January 1956 and 31 December 1992 were reviewed. Survival was measured from the date when treatment was required to the date of last follow-up or death. The frequency of MM in patients younger than 40 and 30 years in 3278 Mayo Clinic patients was 2.2% and 0.3%, respectively. The main presenting clinical features were bone pain (66%), fatigue (26%), extramedullary plasmacytomas (19%) and bacterial infection (11%). Renal function impairment (creatinine level > or = 177 micromol/l) and hypercalcaemia (serum calcium value > or = 2.75 mmol/l) occurred in 29% and 30% of patients, respectively. Among the 57 patients evaluable for response the objective response rate was 54%. 14/35 patients treated with a single alkylating agent achieved an objective response, whereas 17/22 patients given combination chemotherapy had an objective response (P=0.013). However, this higher response rate did not result in a significantly longer survival. The median survival for the 72 patients was 54 months. Patients with good prognostic features (normal renal function or low beta 2-microglobulin level) had a median survival of 8 years. The actuarial survival at 5 and 10 years after initiation of therapy was 43% and 13%, respectively. In summary, survival in very young patients with myeloma is longer than that observed in series of patients of all ages, especially in those with good prognostic factors.     

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.     

Seminal vesicle cysts associated with ipsilateral renal agenesis. Diagnosis, and long-term clinical course

PURPOSE: This report focuses on the prognostic factors of the renal pelvic and ureteral cancer and on the treatment for advanced and/or recurrent cases. METHODS: We reviewed the forty-nine patients with transitional cell carcinoma of the renal pelvis and/or ureter who underwent surgery at the Department of Urology, Osaka National Hospital from April, 1986 to October, 1996. Univariate and multivariate analysis was done on the pathological features from these patients. RESULTS: The patients consisted of 34 males and 15 females and the mean age was 64.9, ranging from 27 to 83. Overall the 1, 3 and 5-year disease specific survival rates were 93.5%, 70.2% and 61.3% respectively by the Kaplan-Meier's method. The prognostic significance of the 6 pathological factors (pT, Grade, INF, pL, pV and pR) were evaluated statistically in terms of generalized Wilcoxon test and/or Cox-Mantel test. All the 6 factors effected on survival rates significantly. However, the grade, INF, pL, pV and pR factors were closely related to the pT factor. Moreover the pT factor was confirmed to be the most important and independent factor according to a multivariate analysis by the Cox's proportional hazard model. And the grade 3 factor with pT2 or higher stage was a high risk factor in recurrences significantly, in spite of curatively operated cases. Thirteen patients with high stage, metastasis or recurrences were treated after operation with the M-VAC or modified M-VAC regimen as preventive, adjuvant and/or salvage chemotherapy. The overall response rate was 72.7% in eleven cases with evaluable lesions, while these regimens could not be expected to improve long-term survival rate. The response rate of combined chemoradiation therapy was 66.7% for six cases with the localized recurrent cancer. CONCLUSIONS: The pT factor was the independent predictor of disease-specific survival. Adjuvant chemotherapy for prevention of cancer recurrence should be considered in the case of pT2 or higher stage plus grade 3 factor, even if curatively operated cases. The M-VAC or modified M-VAC regimen was reconfirmed to be useful as first line chemotherapy of advanced renal pelvic and ureteral cancer. Combined chemoradiation therapy was useful for the localized cancer recurrences, especially as a second line therapy for relapsed cases after M-VAC chemotherapy in this series.     

Prognostic factors in osteosarcoma: a critical review

PURPOSE: The purpose of this critical appraisal was to determine the prognostic factors that influence survival in patients with nonmetastatic, high-grade osteosarcoma of the extremities. DESIGN: A computerized literature search of reports published from January 1973 to March 1992 was conducted to determine those eligible for inclusion in the review. Reports were reviewed blindly by two of the authors; inclusion and scoring were determined according to preestablished criteria. RESULTS: Eight reports were included in the appraisal. The prognostic variables evaluated were age, sex, anatomic tumor location, tumor size, and tumor necrosis. Tumor size and necrosis following preoperative chemotherapy were significant prognostic variables in relation to survival in univariate analysis. However, only tumor necrosis maintained its significance in multivariate modeling. CONCLUSION: The most important prognostic variable for patients with osteosarcoma of the extremity was tumor necrosis evident following preoperative chemotherapy. There is no consensus as to any prognostic variable that might be used to stratify patients before the onset of therapy.     

The role of chemotherapy in the treatment of non-small cell carcinoma of the lung

Within the past 10 years, the role of chemotherapy in the treatment of patients with non-small cell lung cancer has expanded greatly. Previously chemotherapy was used only for patients with disseminated disease and, despite advances in combination therapy with new agents, response rates remained low, response duration was short, and cures were rare. Performance status is an important prognostic indicator both from the standpoint of response and duration of survival. Patients with locally advanced disease who are otherwise candidates for operation have a significantly higher response rate to chemotherapy and tolerate the treatment reasonably well. Combination chemotherapy given preoperatively seems to be associated with improved survival, especially in those patients able to undergo complete resection. Radiation therapy and chemotherapy given preoperatively may be even more efficacious than either modality alone. The question as to whether surgical resection improves on what can be accomplished with radiation therapy and chemotherapy in patients with mediastinal lymph node involvement remains an open one and is currently being evaluated.     

Central nervous system metastasis in breast cancer

BACKGROUND AND PURPOSE: Central nervous system (CNS) metastasis occurs in at least 30% of patients with breast cancer. Standard treatment is the same as in other solid tumors, though clinical behavior, and sensitivity to radiation therapy (RT) and to chemotherapy may differ considerably. Most of these patients die within a few months, but a substantial subgroup may survive a year or more. The last decade has given rise to new diagnostic methods, new surgical and radiotherapeutic techniques, and the clinical evidence of a chemotherapy permissive blood-brain barrier in CNS metastases. The literature was reviewed to assess the clinical impact of early diagnosis, recognition of prognostic factors, and of the recently developed therapeutic approaches. MATERIAL AND METHODS: Review of the literature on CNS involvement in breast cancer focusing on clinical studies on early diagnosis, new modes of treatment, and factors influencing outcome. RESULTS: Although randomized studies are still awaited, systemic chemotherapy seems a valuable alternative for RT of brain metastases in selected cases. In meningeal carcinomatosis, long survival may be independent of intraventricular chemotherapy. Neurotoxicity of intensive intraventricular treatment is considerable. In epidural metastasis, early diagnosis with prompt start of treatment remains the crucial factor for outcome. Radiation therapy is the mainstay of treatment of epidural metastasis, but new surgical techniques and even systemic chemotherapy should be considered in selected cases. CONCLUSIONS: Recognition of prognostic factors combined with appropriate use of various recently developed therapeutic possibilities will improve the clinical outcome including better local tumor control and less treatment-induced neurotoxicity in a considerable number of patients with CNS metastasis from breast cancer.     

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.     

Chemotherapy of advanced malignant lymphomas comparative evaluation of results with single agent and combination therapy

86 patients with advanced malignant lymphomas (stage III and IV) were treated either with Vinblastine given as a single agent (49 cases) or with combination chemotherapy MOPP or COP (37 cases). In both, Hodgkin's disease and non-Hodgkin's lymphomas, induction of remission, relaps-free survival and prognostic significance of initial clinical stage were evaluated, in relation to the therapeutic modality. In patients with Hodgkin's disease, combination chemotherapy was found to produce significantly more durable remissions, when compared with single agent therapy. However, difference in the response rate, which was found to be more effective following the combination chemotherapy, was not statistically significant. In patients with non-Hodgkin's lymphomas overall lower response was recorded, regardless of the therapy applied. In all patients, better response rate and longer lasting remissions correlated with initial stage III.