Mitomycin, ifosfamide, and cisplatin in unresectable non-small-cell lung cancer: effects on survival and quality of life. Survival of premenopausal women with metastatic breast cancer. Long-term follow-up of Eastern Cooperative Group and Cancer and Leukemia Group B studies. General condition of asymptomatic patients with advanced colorectal cancer receiving palliative chemotherapy. A longitudinal study. Long-term survival after chemotherapy for advanced epithelial ovarian carcinoma. Radiation therapy alone for stage I non-small cell lung cancer. Improved survival, quality of life, and quality-adjusted survival in breast cancer patients treated with efaproxiral (Efaproxyn) plus whole-brain radiation therapy for brain metastases. Randomized comparison of whole brain radiotherapy, 20 Gy in four daily fractions versus 40 Gy in 20 twice-daily fractions, for brain metastases. Surgically staged high-risk endometrial cancer: randomized study of adjuvant radiotherapy alone vs. sequential chemo-radiotherapy. The curative treatment by radiotherapy alone of stage I non-small cell carcinoma of the lung. A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III non-small-cell lung cancer. [Intensive chemotherapy and autograft of hematopoietic stem cells in the treatment of metastatic cancer: results of the national protocol Pegase 04]. Long-term effects of mammography screening: updated overview of the Swedish randomised trials. A randomized trial of alternating chemotherapy versus best supportive care in advanced non-small-cell lung cancer. Impact of follow-up testing on survival and health-related quality of life in breast cancer patients. A multicenter randomized controlled trial. The GIVIO Investigators. Earlier diagnosis and survival in lung cancer. Whole-brain radiotherapy with or without efaproxiral for the treatment of brain metastases: Determinants of response and its prognostic value for subsequent survival. The Scottish and Manchester randomised trial of neo-adjuvant chemotherapy for advanced cervical cancer. Preoperative chemotherapy followed by surgery compared with primary surgery in resectable stage I (except T1N0), II, and IIIa non-small-cell lung cancer.
Chemotherapy for non-small-cell lung cancer (NSCLC) remains controversial. We describe the two largest reported, randomized, parallel trials designed to determine whether the addition of chemotherapy influences duration and quality of life in localized, unresectable (mitomycin, ifosfamide, cisplatin [MIC]1 trial) and extensive (MIC2 trial) disease.
                Ambulatory patients with NSCLC, aged 75 years or younger, with localized disease, were randomized in MIC1 to receive up to four cycles of chemotherapy (CT: mitomycin 6 mg/m(2), ifosfamide 3 g/m(2), and cisplatin 50 mg/m(2)) every 21 days, followed by radical radiotherapy (CT + RT) or radiotherapy (RT) alone. Extensive-stage patients were randomized in MIC2 to identical chemotherapy plus palliative care (CT + PC) or palliative care (PC) alone. Short-term change in quality of life (QOL) was assessed in a subgroup of patients. Data from the two trials were combined to allow multivariate and stratified survival analyses.
                Seven hundred ninety-seven eligible patients were randomized, 446 in MIC1 and 351 in MIC2. MIC CT improved survival in both trials (significantly in MIC2). The median survival time in MIC1 was 11.7 months (CT + RT) versus 9.7 months (RT alone) (P =.14); whereas in MIC2, median survival time was 6.7 months (CT + PC) compared with 4. 8 months (PC alone) (P =.03). QOL, assessed in 134 patients from start of trial to week 6, showed improvement with chemotherapy and deterioration with standard treatment. In the combined analysis of 797 randomized patients, the positive effect of MIC on survival was significant overall (P =.01) and after adjusting for prognostic factors (P =.01).
                MIC chemotherapy prolongs survival in unresectable NSCLC without compromising QOL. In premenopausal women with metastatic breast cancer, differences in survival curves early during follow-up can be misleading. The authors therefore analyzed long-term survival in 378 patients, entered in three randomized trials, started between 1973 and 1978. Combined data from the three trials were used to increase the power for identifying prognostic variables. Cancer and Leukemia Group B (CALGB) trial 7382 randomized patients to oophorectomy plus either cyclophosphamide or combination chemotherapy or observation. Eastern Cooperative Oncology Group (ECOG) 2174 randomized patients who had not progressed 3 months after oophorectomy to combination chemotherapy or combination chemotherapy or observation. Trial ECOG 2177 randomized estrogen receptor (ER) positive or ER-unknown patients to oophorectomy plus combination chemotherapy or immediate combination chemotherapy, and ER-negative patients were directly assigned to combination chemotherapy. Hence ER-negative patients need not have been healthy enough to be randomized to oophorectomy. With only 14% of the patients still alive, median survival on the three studies was 30, 24, and 28 months. The median survival of individual treatments changed noticeably in ECOG 2174 and ECOG 2177 with long-term follow-up. At this time there are no differences in survival between randomized regimens in any of the three trials. In a multivariate model, factors associated with significantly poorer survival were visceral-dominant disease, nodal metastases, breast metastases, age younger than 45 years, ER negativity, and not receiving chemotherapy immediately after oophorectomy. This treatment difference was thus not due to imbalances in the prognostic variables used in the model, but it may be due to imbalances of unknown prognostic factors or differences in patient selection. A Nordic multicenter study in asymptomatic patients with advanced colorectal cancer compared initial chemotherapy with sequential methotrexate-5-FU with leucovorin rescue (MFL) for 6 months versus primary expectancy with chemotherapy only after the appearance of symptoms. The study (183 patients randomized between January 1985 and February 1990) showed that symptom-free survival, progression-free survival and survival respectively were about 6 months longer in the group of patients randomized to initial MFL. Whether these prolongations could be achieved without an impaired 'quality of life' was studied in an associated study. Between January 1985 and March 1987, 43 patients were randomized at one of the hospitals, 36 of which were interviewed with a questionnaire at randomization. Even if all these patients were considered, by the physician, to be 'free of symptoms from their disease', 16/36 (44%) had symptoms that could be referred to the disease. In spite of this, the patients were in a good general condition, and considerably better off than patients considered to have 'symptoms from the disease' who were interviewed with the same questionnaire when randomized in a parallel study of symptomatic patients. Patients randomized to initial chemotherapy and interviewed longitudinally maintained their good condition throughout treatment. Toxicity was mild, although the patients expressed more adverse effects than the physicians recorded. Since symptom-free survival, progression-free survival and survival were statistically significantly longer in the group of patients randomized to MFL also in this associated study, it is concluded that initial chemotherapy can prolong symptom-free survival and survival without reduced 'quality of life' during the treatment period. Four hundred twenty-nine patients were entered into four prospective randomized clinical studies between January 1, 1973, and July 1, 1979. The records of 395 of these were analyzed to determine the proportion of patients surviving 48 months after therapy initiation. Ninety-six patients (24%) were living at 48 months, 89 of whom had second-look laparotomies. Of the 96 living patients, 53 (55%) were clinically free of disease and 43 (45%) had disease. Combination-agent chemotherapy produced a larger proportion of 48-month survivors than single-agent therapy (P = 0.001); 70% of these survivors were clinically free of disease. Patient characteristics, such as age, International Federation of Gynaecology and Obstetrics (FIGO) stage, histologic grade of tumor, and amount of residual tumor present prior to chemotherapy exerted a strong influence on length of survival. Long-term survival was not totally dependent on a complete response to chemotherapy; in fact, persistent treatment with drug regimens induced bone marrow disorders and death due to toxicity in five patients. The continued fall in survival curves after 48 months suggests that current therapy regimens are not dramatically changing long-term survival rates. This paper is a retrospective analysis of patients with clinical Stage I non-small cell carcinoma of the lung treated with definitive radiation therapy alone. The results of therapy, patterns of failure and the relationship of technical aspects of the delivery of radiotherapy to outcome are presented.
                From 1980 through 1990, 53 patients with Stage I non-small cell lung cancer were treated with definitive radiation therapy alone at the Radiation Oncology Center of the Mallinckrodt Institute of Radiology and its affiliated hospitals. All patients had a pathologic diagnosis of non-small cell lung cancer and were not candidates for surgical resection because of either patient refusal (10 patients), poor performance status (5 patients), or premorbid medical problems (38 patients). The median age was 73 years. Histologic cell type included squamous (32), adenocarcinoma (11), large cell (4), and unclassified non-small cell (6). Initial tumor size was < or = 3 cm in 23 patients, between 3 and 5 cm in 13 patients and > or = 5 cm in 17 patients. Diagnostic staging varied during the study period. All patients had chest X-rays and computed tomography scans of the chest. A majority had liver and bone scans, but only four underwent mediastinoscopy. The radiation therapy was of megavoltage energy in all patients, with a median primary prescription tumor dose of 63.2 Gy. Survival was measured from the date radiation therapy was initiated.
                The actuarial overall survival rate for the entire group was 19% at 3 years and 6% at 5 years, with a median survival time of 20.9 months. Of the 49 deaths, 35 died of lung cancer; 13 died of intercurrent illness, and one died of pancreatic cancer, which made the actuarial cause-specific survival 33% at 3 years and 13% at 5 years. The actuarial 3-year disease-free survival was 33%. Local primary tumor progression occurred in 22 patients, resulting in a 51% 3-year actuarial freedom from local progression. An additional four patients failed in regional lymph nodes that were included in the original treatment portals. Multivariate analysis found only T stage to be associated with overall survival (p = .02). However multivariate analysis showed age as a prognostic factor to be approaching statistical significance (p = .07). Patients under 70 years of age showed an increased survival rate compared to patients over 70 years. Radiation therapy doses > or = 65 Gy appeared to result in a decreased proportion of patients dying of lung cancer with no apparent increase in either acute or long-term complication rates.
                Results of definitive radiation therapy for inoperable Stage I non-small cell lung remain inferior to surgical therapy. Potential methods to improve local control with radiotherapy are discussed. To determine whether efaproxiral, an allosteric modifier of hemoglobin, improves quality of life and quality of survival in patients with primary breast cancer and brain metastases when used as an adjunct to whole-brain radiation therapy (WBRT).
                Patients with brain metastases from breast cancer were randomly assigned to receive WBRT and either efaproxiral or no efaproxiral. The primary endpoint for this analysis was quality of life and quality-adjusted survival. Quality of life was assessed prior to initiation of WBRT and periodically in follow-up using the Spitzer Quality of Life Index (SQLI).
                A subgroup of 106 eligible breast cancer patients with baseline SQLI were randomized into this study and represent the target population discussed in this report. Treatment, age, and SQLI were significant predictors of survival. The addition of efaproxiral to WBRT reduced the death rate by 46% (P = 0.0086). Quality of life was improved in the WBRT + efaproxiral arm compared with the WBRT alone arm (P = 0.019). Quality-adjusted survival was statistically significantly improved by the addition of efaproxiral to WBRT (P = 0.001).
                Survival, quality of life, and quality-adjusted survival were all improved in breast cancer patients with brain metastases receiving efaproxiral and WBRT compared with those receiving WBRT alone. The present study compared the intracranial control rate and quality of life for two radiation fractionation schemes for cerebral metastases.
                A total of 113 patients with a Eastern Cooperative Oncology Group performance status <3; and stable (>2 months), absent, or concurrent presentation of extracranial disease were randomized to 40 Gy in 20 twice-daily fractions (Arm A) or 20 Gy in four daily fractions (Arm B), stratified by resection status. The European Organization for Research and Treatment of Cancer Quality of Life 30-item questionnaire was administered monthly during Year 1, bimonthly during Year 2, and then every 6 months to Year 5.
                The patient age range was 28-83 years (mean 62). Of the 113 patients, 41 had undergone surgical resection, and 74 patients had extracranial disease (31 concurrent and 43 stable). The median survival time was 6.1 months in Arm A and 6.6 months in Arm B, and the overall 5-year survival rate was 3.5%. Intracranial progression occurred in 44% of Arm A and 64% of Arm B patients (p = .03). Salvage surgery or radiotherapy was used in 4% of Arm A patients and 21% of Arm B patients (p = .004). Death was attributed to central nervous system progression in 32% of patients in Arm A and 52% of patients in Arm B (p = .03). The toxicity was minimal, with a minor increase in short-term cutaneous reactions in Arm A. The patients' quality of life was not impaired by the more intense treatment in Arm A.
                Intracranial disease control was improved and the quality of life was maintained with 40 Gy in 20 twice-daily fractions. This schema should be considered for better prognosis subgroups of patients with cerebral metastases.
                (c) 2010 Elsevier Inc. All rights reserved. Our purpose was to establish whether platinum-based chemotherapy combined with standard surgery and radiotherapy will improve overall and disease-free survival and lower the recurrence rate in patients with high-risk endometrial cancer.
                A total of 156 patients with Stage IA-B Grade 3 (n=28), or Stage IC-IIIA Grade 1-3 (n=128) were postoperatively randomized to receive radiotherapy (56 Gy) only (Group A, n=72) or radiotherapy combined with three courses of cisplatin (50 mg/m(2)), epirubicin (60 mg/m(2)) and cyclophosphamide (500 mg/m(2)) (Group B, n=84).
                The disease-specific overall five-year survival was in Group A 84.7% vs. 82.1% in Group B (p=0.148). The median disease-free survival in A was 18 (range 9-36) months and 25 (range 12-49) months in B (p=0.134), respectively. During a five-year follow-up 32 patients relapsed. Of the recurrences 5 were local and 20 distant, while 7 were combined. As calculated from the operation, the median time to recurrence was 15 (range 6-37) months in Group A, and 20 (range 8-60) months in Group B, respectively (p=0.170). Twenty-six patients died of the disease during the five-year follow-up, 11 in A and 15 in B. The patients succumbing in A lived a median 23 (range 15-44) months as compared to 37 (range 13-50) months in B (p=0.148). Chemotherapy was associated with an acceptable rate of acute toxicity. Less than 8% of the patients complained of Grade 3/4 nausea. The rate of Grade 3/4 leucopenia was at the highest at 16.6% during the third cycle but only 6.2% of the patients had Grade 3 infection. A total of 10 patients developed intestinal complications demanding surgery, 2 in Group A (2.7%) and 8 (9.5%) in Group B, respectively.
                Adjuvant chemotherapy with cisplatin, epirubicin and cyclophosphamide failed to improve overall survival or lower the recurrence rate in patients operated on and radiated for high-risk endometrial carcinoma. Chemotherapy was associated with a low rate of acute toxicity but appeared to increase the risk of bowel complications. This review was initiated to assess the outcome of treatment with radical radiotherapy with curative intent for patients diagnosed as having stage I non-small cell lung cancer. The study involved a retrospective review of 347 patients with T1 and T2N0M0 tumors treated at the Queensland Radium Institute during the period 1985 to 1992. The main reasons for not proceeding to surgery included poor performance status, old age, or refusal to submit to surgery. The median age for the group was 70 years, with the range being 34 to 90 years. Patients in this group were all treated by a standard technique involving external-beam radiotherapy to 50 Gy, minimum tumor dose, in 20 fractions over 4 weeks. The overall survival rate was 27% at 5 years with a median survival of 27.9 months. The 5-year recurrence-free survival was 23% with the median being 19.5 months. There was a strong correlation of survival to tumor size with 5-year survival rates being 32% and 21% for T1 and T2 tumors, respectively. Multivariate analysis found only T stage to be associated with overall survival (p < 0.01). In addition, the analysis showed that age younger than 70 years was a prognostic factor that approached statistical significance at the p < 0.05 level of significance. We conclude from this large series of patients with stage I non-small cell lung cancer that radical radiotherapy with curative intent may be a viable alternative to surgery in those patients who either refuse surgery or are judged to be unfit for operation. For patients with locally or regionally advanced non-small-cell lung cancer radiation is the standard treatment, but survival remains poor. We therefore conducted a randomized trial to determine whether induction chemotherapy before irradiation improves survival.
                All the patients had documented non-small-cell cancer of the lung with Stage III disease established by clinical or surgical staging. Eligibility requirements included excellent performance status, minimal weight loss, and visible disease on radiography. Patients randomly assigned to group 1 received cisplatin (100 mg per square meter of body-surface area given intravenously on days 1 and 29) and vinblastine (5 mg per square meter given intravenously on days 1, 8, 15, 22, and 29) and then began radiation therapy on day 50 (60 Gy over a 6-week period). Patients assigned to group 2 received the same radiation therapy but began it immediately and received no chemotherapy.
                The eligible patients in group 1 (n = 78) and group 2 (n = 77) were comparable in terms of age (median, 60 years), sex, performance status, histologic features, stage of disease, and completeness of radiation therapy. The median survival was greater for those in group 1-13.8 versus 9.7 months (P = 0.0066 by log-rank test). Rates of survival in group 1 were 55 percent after one year, 26 percent after two years, and 23 percent after three years, as compared with 40, 13, and 11 percent, respectively, in group 2. Those in group 1 had a higher incidence of serious infections requiring hospitalization (7 percent, vs. 3 percent in group 2) and severe weight loss (14 percent vs. 6 percent), but there were no treatment-related deaths.
                In patients with Stage III non-small-cell lung cancer, induction chemotherapy with cisplatin and vinblastine before radiation significantly improves median survival (by about four months) and doubles the number of long-term survivors, as compared with radiation therapy alone. Since three quarters of the patients still die within three years, however, further improvements in systemic and local therapy are needed. We report hereby the results of the french multicentric randomized PEGASE 04 protocol established to evaluate the impact on survival of high-dose chemotherapy over conventional chemotherapy for MBC patients.
                Inclusion criteria were: age < or = 60 year, PS < 2, adenocarcinoma initially metastatic or in first relapse, chemosensitive disease. Randomization was done after 4-6 courses of conventionnal chemotherapy between high-dose (Mitoxantrone, 45 mg/m2, Cyclophosphamide: 120 mg/kg, Melphalan: 140 mg/m2), and the pursuit of the same conventionnal chemotherapy. Between 09/92 and 12/96, 61 chemosensitive patients were enrolled: 29 were referred to standard chemotherapy, 32 to intensive therapy. At randomization, 13 pts (21.3%) were in complete response and 48 in partial response.
                The median progression-free survivals were 20 and 35.3 months in the standard and intensive groups (p=0.06). The relapse rates were respectively 79.3% vs 50.8% at 3 years and 90.8% vs 90.7% at 5 years. The median overall survivals were 20 and 43.4 months, with an overall survival rate of 18.5% vs 29.8% at 5 years (p=0.12).
                The CMA regimen could prolong the progression-free survival of MBC patients, however without any significant impact on overall survival. There has been much debate about the value of screening mammography. Here we update the overview of the Swedish randomised controlled trials on mammography screening up to and including 1996. The Kopparberg part of the Two-County trial was not available for the overview, but the continuation of the Malmö trial (MMST II) has been added. The article also contains basic data from the trials that have not been presented before. Methods The trials (n=247010, invited group 129750, control group 117260) have been followed up by record linkage to the Swedish Cancer and Cause of Death Registers. The relative risks (RR) for breast cancer death and mortality were calculated for the invited and the control groups. The trial-specific as well as the age-specific effects were analysed. RRs were calculated by the density method, with total person-time experience of the cohort by time interval of follow-up as a basis for estimating mortality rates. We calculated weighted RRs and 95% CI with the Mantel-Haenszel procedure.
                The median trial time-the time from randomisation until the first round was completed for the control group or if the control group was not invited, until end of follow-up-was 6.5 years (range 3.0-18.1). The median follow-up time, the time from randomisation, to the end of follow-up, was 15.8 years (5.8-20.2). There were 511 breast cancer deaths in 1864770 women-years in the invited groups and 584 breast cancer deaths in 1688440 women-years in the control groups, a significant 21% reduction in breast cancer mortality (RR=0.79, 95% CI 0.70-0.89). The reduction was greatest in the age group 60-69 years at entry (33%). Looking at 5-year age groups, there were statistically significant effects in the age groups 55-59, 60-64, and 65-69 years (RR=0.76, 0.68, and 0.69, respectively). There was a small effect in women 50-54 years at randomisation (RR=0.95). The benefit in terms of cumulative breast cancer mortality started to emerge at about 4 years after randomisation and continued to increase to about 10 years. Thereafter the benefit in absolute terms was maintained throughout the period of observation. The age-adjusted relative risk for the total mortality was 0.98 (0.96-1.00).
                The advantageous effect of breast screening on breast cancer mortality persists after long-term follow-up. The recent criticism against the Swedish randomised controlled trials is misleading and scientifically unfounded. From April 1985 to September 1988, 128 patients with advanced non-small-cell lung cancer (NSCLC) were enrolled in a prospective randomized trial evaluating chemotherapy (arm A) versus best supportive care (arm B). Chemotherapy consisted of cyclophosphamide 500 mg/m2 intravenously (IV) day 1, epirubicin 50 mg/m2 IV day 1, and cisplatin 80 mg/m2 IV day 1 (CE'P regimen) alternating every 4 weeks with methotrexate 30 mg/m2 IV day 1, etoposide 200 mg/m2 IV day 1, and lomustine (CCNU) 70 mg/m2 orally day 1 (MEC' regimen) until progression. Of the 123 patients (62 treated and 61 controls) eligible for survival, 115 were fully evaluable for response (58 treated and 57 controls). Response rates were 21% partial response, 53% stable disease, and 26% progressive disease in arm A, and 47% stable disease and 53% progressive disease in arm B. Median survival was 34.3 weeks (range, 4.3 to 218.6+ weeks) in arm A versus 21.1 weeks (range, 4.3 to 188.6 weeks) in arm B; the difference was not significant at P = .153 (Mantel-Cox). Subgroups of patients retrospectively analyzed by age, performance status, stage M0/M1, and weight loss or not showed no significant difference in survival. Poor-risk patients (at least two of the following: poor performance status, stage M1, weight loss) of arm A survived significantly longer than poor-risk patients of arm B (23.6 weeks v 12.4 weeks, Mantel-Cox P = .008); a significant difference in survival was also observed between nonsquamous cell patients of arm A and those of arm B (median survival, 38.6 weeks v 16.7 weeks; Mantel-Cox P = .041). Toxicity on the chemotherapy arm was hematologic (World Health Organization [WHO] grade greater than 3) in 12% of CE'P and in 13% of MEC' courses and gastroenteric (WHO grade greater than 3) in 24% of CE'P courses and in 8% of MEC' courses. Our alternating treatment was not significantly superior to supportive care. It is likely that certain subgroups of the NSCLC category may have an advantage with chemotherapy. To assess prospectively the impact on survival and health-related quality of life of two follow-up protocols in patients with early breast cancer.
                Randomized controlled clinical trial.
                Multicenter study involving 26 general hospitals in Italy.
                A consecutive sample of 1320 women younger than 70 years with stage I, II, and III unilateral primary breast cancer.
                Patients were randomly assigned to an intensive surveillance, which included physician visits and performance of bone scan, liver echography, chest roentgenography, and laboratory tests at predefined intervals (n = 655), or to a control regimen (n = 665), in which patients were seen by their physicians at the same frequency but only clinically indicated tests were performed. Both groups received a yearly mammogram aimed at detecting contralateral breast cancer.
                Primary end points were overall survival and health-related quality of life.
                Compliance to the two follow-up protocols was more than 80%. At a median follow-up of 71 months, no difference was apparent in overall survival with 132 deaths (20%) in the intensive group and 122 deaths (18%) in the control group. No significant differences were apparent in time to detection of recurrence between the two groups. Measurements of health-related quality of life (ie, overall health and quality-of-life perception, emotional well-being, body image, social functioning, symptoms, and satisfaction with care) at 6, 12, 24, and 60 months of follow-up did not show differences by type of care received.
                Results of this trial support the view that a protocol of frequent laboratory tests and roentgenography after primary treatment for breast cancer does not improve survival or influence health-related quality of life. Routine use of these tests should be discouraged. In a controlled investigation the survival prospects of lung cancer in a population of men aged 40 and over who had been offered six-monthly chest radiographs over a period of three years were compared with lung cancer in a similar population without such x-ray facilities. The five-year survival rate of lung cancer in the study series was 15%, and in cases discovered by six-monthly examination 23%, compared with 6% in the control series. The average expectation of life after diagnosis was 2.5 years for the test cases and 1.2 for the control cases. Survival declined with age. Of resected lung cancer, 32% survived five years in the test series and 23% in the control series. The five-year survival rate for squamous carcinoma and adenocarcinoma in the test series was 28% and 25% respectively, compared with 15% and nil in the control series.On the basis of these results it is concluded that through earlier radiological detection a modest improvement in the prognosis of lung cancer can be achieved. To determine the prognostic factors for radiographic response and its prognostic value for subsequent survival in patients undergoing whole-brain radiotherapy (WBRT) for brain metastases.
                Five hundred fifteen eligible patients were randomized in a phase III trial evaluating WBRT and supplemental oxygen with or without efaproxiral, an allosteric modifier of hemoglobin that reduces hemoglobin oxygen-binding affinity and enhances tumor oxygenation, potentially increasing tumor radiosensitivity. Brain images were obtained at baseline and at scheduled follow-up visits after WBRT. Landmark analysis was used to assess the ability of response at selected time points to predict subsequent survival. Logistic regression was used to assess determinants of response at 3 months.
                Treatment arm, Karnofsky Performance Status, presence or absence of liver metastases, and primary site were all determinants of response at the 3-month follow-up visit, with patients in the efaproxiral arm experiencing a 67% greater odds of response at this visit (p = 0.02). Response at 3 and 6 months was a significant prognostic factor for longer subsequent survival.
                The 3-month scan is a valuable prognostic factor for subsequent survival in patients with brain metastases treated with WBRT. Patients in the efaproxiral arm had a higher response rate at 3 and 6 months than those in the control arm. 204 eligible patients were entered into a multicentre randomised trial of neo-adjuvant chemotherapy prior to radical radiotherapy. The aim of this study was to assess whether there was any survival advantage in patients undergoing chemotherapy and radiotherapy compared with those given radiotherapy alone. Patients were aged up to 70 years, performance status 0-1/2, with bulky stage IIb, stage III or stage IVa squamous or adenosquamous carcinoma. Three cycles of methotrexate 100 mg/m2 and cisplatin 50 mg/m2 were given at 2-weekly intervals before radical radiotherapy. 104 eligible patients received the combination treatment and 100 radiotherapy only. The two arms of the study were well balanced for tumour and patient characteristics. The response rate to chemotherapy was 49%, 33% of patients in the radiotherapy (XRT) alone arm and 45% of the combination arm were clinically free of tumour at the end of treatment. The median follow-up for surviving patients is 5.4 years (range: 11 months-8 years) and 84% have been followed-up for more than 4 years. 134 patients have died (68 XRT only, 66 combined arm). The median survival RT alone was 111 weeks (95% confidence interval (CI) 72-151 weeks), combination arm 125 weeks (95% CI 79-170 weeks). The estimated death ratio is 0.79 (P = 0.19, 95% CI 0.56-1.12). The estimated 3-year survival is 40% (95% CI 30-50%) RT only compared with 47% (95% CI 37-57%) in the combination arm. Acute and late toxicity of radiotherapy was not increased by the addition of chemotherapy. To evaluate whether preoperative chemotherapy (PCT) could improve survival in resectable stage I (except T1N0), II, and IIIA non-small-cell lung cancer (NSCLC).
                A randomized trial compared PCT to primary surgery (PRS). PCT consisted of two cycles of mitomycin (6 mg/m(2), day 1), ifosfamide (1.5 g/m(2), days 1 to 3) and cisplatin (30 mg/m(2), days 1 to 3), and two additional postoperative cycles for responding patients. In both arms, patients with pT3 or pN2 disease received thoracic radiotherapy.
                Three hundred fifty-five eligible patients were randomized. Overall response to PCT was 64%. There were two preoperative toxic deaths. Postoperative mortality was 6.7% in the PCT arm and 4.5% in the PRS arm (P =.38). Median survival was 37 months (95% confidence interval [CI], 26.7 to 48.3) for PCT and 26.0 months (95% CI, 19.8 to 33.6) for PRS (P =.15). Survival differences between both arms increased from 3.8% (95% CI, 1.3% to 25.1%) at 1 year to 8.6% (95% CI, 2.64% to 24.4%) at 4 years. A quantitative interaction between N status and treatment was observed, with benefit confined to N0 to N1 disease (relative risk [RR], 0.68; 95% CI, 0.49 to 0.96; P =.027). After a nonsignificant excess of deaths during treatment, the effect of PCT was significantly favorable on survival (RR, 0.74; 95% CI, 0.56 to 0.99; P =.044). Disease-free survival time was significantly longer in the PCT arm (P =.033).
                Although impressive differences in median, 3-year, and 4-year survival were observed, they were not statistically significant, except for stage I and II disease.
MAB produces a modest overall and cancer-specific survival at five years but is associated with increased adverse events and reduced quality of life.