No-chemotherapy Group Research Articles

Ototoxicity after radiotherapy for head and neck tumors

To investigate the incidence of radiation-induced ototoxicity according to the total dose delivered to specific parts of the auditory system, fractionation, and chemotherapy. Records of 325 patients treated for primary extracranial head and neck tumors with curative intent who received radiotherapy between 1964 and 2000 (median follow-up, 5.4 years) were retrospectively reviewed. Reconstructions of the treatment plans were generated to estimate the doses received by components of the auditory system. Radiotherapy-induced morbidity developed in 41.8% of patients (external ear, 33.2%; middle ear, 28.6%; and inner ear, 26.8%). Univariate/multivariate analyses indicate that total dose received by parts of the auditory system seem to be significant, though fractionation and chemoradiation may contribute to the incidence of ototoxicities. Sensorineural hearing loss (SNHL) was observed in 49 patients (15.1%). Univariate and multivariate analyses indicated that age (p = 0.0177 and p = 0.005) and dose to cochlea (p < 0.0001 and p < 0.0001) were significant, and chemoradiation (p = 0.0281 and p = 0.006) may increase the incidence of SNHL. Five-year and 10-year actuarial risk of clinically overt SNHL increased to 37% (p > 0.0001) above doses of 60.5 Gy compared to 3% at doses below 60.5 Gy. For patients treated with adjuvant chemotherapy, clinically overt SNHL increased to 30% compared to 18% in the no-chemotherapy group at 10 years (p = 0.0281). Radiotherapy toxicity was observed in all parts of the auditory system with median doses for incidence varying between 60 Gy to 66 Gy. Total dose to organ seems to be a significant factor though fractionation and chemo-radiation may contribute to ototoxicities.

Adjuvant Treatment of Stage II Colon Cancer: Is There a True No-Chemotherapy Group?

In this issue of Annals of Surgical Oncology, Andre et al. present an exhaustive review of the controversial management in the use of adjuvant chemotherapy for stage II colon cancers. The authors review the results of the most recent clinical trials and metaanalyses investigating the value of adjuvant chemotherapy for stage II patients. They emphasize that this is a heterogenous patient population that includes patients with T2, T3, and T4 lesions, tumor perforation, and tumor differentiation, all of whom are believed to be N0. This heterogeneous population is the reason that 5-year survival rates for stage II colon cancer range from a high of 70% to a low of 30%. It is because of this same heterogeneity and the relatively rare event of stage II colon carcinoma that trials attempting to evaluate the treatment efficacy of adjuvant chemotherapy have had insufficient power. Even larger trials that have included both stage II and stage III colon carcinomas have been insufficient to demonstrate a durable benefit in this rare group. It has been estimated, as the authors have pointed out, that to detect a 4% survival benefit at 5 years in stage II colon cancer by using a median of 75% 5-year survival as a baseline would require 4700 patients. The rapid expansion in chemotherapeutic options has made the care of colon cancer patients more complex and optimistic. In the past, when only 5-fluorouracil chemotherapy was an option, there was little enthusiasm for giving chemotherapy in a subset of patients with a 5-year survival rate of 75%. However, now, with a myriad of options, there is considerable enthusiasm for identifying all stages and/or subsets of patients who may receive any form of benefit from additional chemotherapy. To most, this represents an advance in treatment, as has been seen in breast and prostate therapy. The core question remains as to what is a clinically relevant benefit from additional chemotherapy? Is a 5-year increase of 4.3% for stage II colon cancers clinically relevant? If this translates into an improvement of 3 months in overall survival, which is half the duration of the treatment itself (6 months of adjuvant therapy), is it worthwhile in all stage II patients? One of the key areas in which surgery has been lacking has been established surgical criteria for colon resections in cancer. Only until recently has there been a recommendation for at least 12 lymph nodes to be evaluated in all surgically treated colon cancers. This minimum number of lymph nodes retrieved has been demonstrated to improve 5-year survival, through a stage migration effect, and to be highly predictive of survival in both lymph node–negative and lymph node–positive patients. Adequate lymph node identification has been difficult to standardize because of the variability of both surgical technique and pathologic lymph harvest. One technique that may demonstrate the ability to increase lymph node retrieval and possibly improve lymph node stage sensitivity and specificity is sentinel lymph node biopsy. The successful conclusion of this multi-institutional trial of this technique demonstrated the feasibility and possible benefit (Bilchik et al., unpublished data). Received November 29, 2005; accepted December 6, 2005; published online April 13, 2006. Address correspondence and reprint requests to: Robert C. G. Martin, MD; E-mail: robert.martin@louisville.edu.

Postoperative radiotherapy and chemotherapy in the management of oligodendroglioma: single institutional review of 88 patients

We retrospectively evaluate the prognostic factors affecting the local control, survival and the potential role of chemotherapy in the management of patients with oligodendroglioma. The medical records of 88 patients treated by postoperative external beam radiotherapy +/- chemotherapy at our institution between December 1993 and December 2002 were analyzed. Nine patients (10%) were treated with an accelerated fractionation scheme, while 79 patients were treated with conventional doses. The median RT dose was 54.8 +/- 2.58 Gy for low-grade tumors, and 58.7 +/- 2.46 Gy for high-grade tumors. PCV chemotherapy regimen was given to 18 patients; temozolamide was administered in three patients. Chemotherapy was not given concomitantly in any patients. The median follow-up was 56 months (range 7-134 months). The 5-year overall and progression-free survival rates for entire group were 86% and 79%, respectively. Patients with epilepsy at presentation had better 5-year overall survival (93% vs. 74%, P=0.04). High grade tumors had significantly lower overall survival rate. Age, presence of motor deficit at diagnosis and histological grade were found have a significant impact on progression-free survival. The 5-year overall and progression free survival rates of patients with high-grade tumors were 69%, 51% and 74%, 68% for chemotherapy and no-chemotherapy group, respectively (P=0.9 for OS, P=0.3 for PFS). In multivariate analysis no significant factor affecting the overall survival and progression-free survival was found. Chemotherapy given after postoperative radiotherapy in patients with oligodendroglioma did not improve survival in this retrospective study.

Is postoperative adjuvant chemotherapy necessary in locally advanced rectal cancers after preoperative chemoradiation

To evaluate the impact of postoperative adjuvant chemotherapy in patients with locally advanced rectal cancers who have received preoperative chemoradiation, and to determine which post-chemoradiation TNM stages will benefit from postoperative chemotherapy. Between 1986 and 2000, 209 patients with tethered or fixed rectal cancers were treated with preoperative chemoradiation according to 3 different schedules. In schedule I, 54 patients were treated with 40 Gy RT plus concurrent 5FU infusion and mitomycin C. In schedule II, 27 patients were treated with “sandwich” chemoradiation: 40 Gy preoperative RT with concurrent 5FU infusion, leucovorin and mitomycin C, and 18 Gy postoperative RT with similar concurrent chemotherapy. The design of both schedules I and II did not include any postoperative adjuvant chemotherapy. In schedule III, 128 patients were treated with 50 Gy preoperative RT concurrent with 5FU infusion, leucovorin and mitomycin C, followed by 5 cycles of postoperative bolus 5FU/leucovorin chemotherapy. After excluding patients with M1 disease and patients in schedules I and II who have received some postoperative chemotherapy off-protocol, 184 patients were available for the analysis. There were 134 males and 50 females. The median age was 62 years (range: 30–82 years). There were 141 tethered and 43 fixed rectal cancers. There were 91 low- (3–5 cm from the anus), 82 mid- (6–10 cm) and 11 high- (> 10 cm) rectal cancers. 97 patients had an abdominoperineal resection, 84 patients had an anterior resection, 2 patients had a Hartman’s resection and one patient had an exenteration. The post-chemoradiation TNM stage distribution was as follow: 36 stage 0 (T0N0M0), 52 stage I, 58 stage II, and 38 stage III. 99 patients (in schedule III) received postoperative bolus 5FU/leucovorin chemotherapy and 85 patients did not. 65% (55/88) of stages 0 and I, and 46% (44/96) of stages II and III had received postoperative adjuvant chemotherapy. As of January 1, 2004, 100 patients are alive, 78 patients were dead and 6 patients were lost to follow-up. 120 patients (65%) were free of relapse, 9 patients (5%) had local recurrence alone, 44 patients (24%) had distant metastases, and 11 patients (6%) had both local and distant failures. The 5-year overall survival was 65% for all 184 patients, 77% for those who received postoperative chemotherapy versus 52% for those who did not (logrank p = 0.0001). The 5-year relapse-free survival was 65%, 76% for the chemotherapy group and 57% for the no-chemotherapy group (p = 0.00017). The 5-year actuarial distant failure rate was 23% for those who received postoperative chemotherapy and 42% for those who did not. For stages 0-I, the 5-year overall survival was 85% for the chemotherapy group and 78% for the no-chemotherapy group (p = 0.34), and the 5-year relapse-free survival was 87% for the chemotherapy group and 77% for the no-chemotherapy group (p = 0.18). For stages II and III, there were statistically significant differences in the outcome with the addition of postoperative chemotherapy. The 5-year overall survival was 66% for those who received chemotherapy and 37% for those who did not (p = 0.00079), and the respective 5-year relapse-free survival was 62% versus 35% (p = 0.0033). The 5-year actuarial distant failure rate was 38% for the chemotherapy group and 58% for the no-chemotherapy group (p = 0.02). In the multivariate analysis of prognostic factors (post-chemoradiation stage, postoperative bolus chemotherapy, fixed versus tethered tumors, different treatment schedules, lymphovascular/ perineural invasion, pT4 and positive nodal disease), postoperative chemotherapy was an independent prognosticator for the relapse-free survival (hazard ratio = 0.4, p = 0.01). For locally advanced rectal cancer, the administration of postoperative adjuvant 5FU/leucovorin chemotherapy after preoperative chemoradiation appeared to reduce recurrences, and improve the overall survival and the relapse-free survival, especially in high risk groups with post-chemoradiation stages II and III disease

Outcome of children with cystic partially differentiated nephroblastoma treated with or without chemotherapy

Background/purpose Cystic partially differentiated nephroblastoma (CPDN) is a rare variant of Wilms’ tumor thought to be more favorable than standard nephroblastoma. The purpose of this report is to examine the outcome of children with CPDN, after nephrectomy, treated with vincristine and dactinomycin based chemotherapy (+/− doxorubicin) or no chemotherapy. Methods Patients were registered with the National Wilms’ Tumor Study Group (NWTSG) and data were collected prospectively. All patients had central review by the NWTSG Pathology Center to confirm the diagnosis of CPDN. Results Twenty-one patients were identified with a diagnosis of CPDN. Thirteen patients received chemotherapy, and 8 patients did not. In the chemotherapy group the stage distribution was as follows: stage I (n = 10), stage II (n = 2), stage V (n = 1). In the no-chemotherapy group, all 8 patients were stage I. All patients had complete tumor resection. There were no cases of disease progression or recurrence in any patient. In patients receiving chemotherapy, 30% (n = 4) had toxicities causing dose reduction. Conclusions The outcome of patients with CPDN is favorable with 100% survival rate and no recurrences. For stage I patients, treatment with complete tumor resection appears to be as efficacious as nephrectomy plus chemotherapy. Stage II patients also have excellent outcome when treated with tumor resection and postoperative vincristine and dactinomycin.

The Incidence and Cost of Hospitalization for 5-FU Toxicity among Medicare Beneficiaries with Metastatic Colorectal Cancer

Objective To estimate the incidence and associated cost of hospitalizations for toxicities associated with 5-fluorouracil (5-FU) among patients with metastatic colorectal cancer. Methods Using the 1994 Medicare 5% sample, we identified all patients with metastatic colorectal cancer who had undergone colorectal surgery. We then stratified them into those who received 5-FU therapy within 90 days of their surgery (5-FU group) and those who did not receive chemotherapy (no-chemotherapy group); patients who received chemotherapeutic agents other than 5-FU were excluded from the sample. Using techniques of survival analysis, we then compared the incidence and associated cost of all hospital admissions with listed International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic codes (primary or secondary) for conditions possibly related to 5-FU toxicity (e.g., volume depletion, stomatitis, nausea, and vomiting). Results A total of 441 patients met all study entry criteria, including 192 who received 5-FU and 249 who did not receive chemotherapy following surgery. Patients in the 5-FU group were younger than those in the no-chemotherapy group ( p < .001). Mean (± SD) follow-up time was slightly longer in the 5-FU group (137 ± 96 days vs. 117 ± 88 days for no chemotherapy). The incidence of toxicity-related hospitalizations at 10.5 months (principally volume depletion, agranulocytosis, gastroenteritis, and nausea and vomiting) was 31% among patients who received 5-FU and 8% among those who did not receive chemotherapy. The cost of inpatient care at 10.5 months was $2716 higher among 5-FU patients. Conclusions Hospitalization for toxicity of Medicare patients with metastatic colorectal cancer receiving 5-FU is frequent and costly.

Polychemotherapy for early breast cancer: an overview of the randomised clinical trials with quality-adjusted survival analysis

Overview analysis involving 18000 women with breast cancer in 47 randomised trials showed that prolonged chemotherapy significantly reduces the risk of relapse and death compared with no chemotherapy. Here we express the size of the benefit in terms of quality-adjusted survival time gained. We used the Q-TWiST method (Quality-adjusted Time Without Symptoms of disease and Toxicity of treatment) to provide treatment comparisons within 10 years' follow-up, incorporating differences in quality of life associated with times patients spend with chemotherapy toxic effects, after relapse, and without symptoms of relapse or toxicity. Within 10 years' follow-up the benefit of increased relapse-free and overall survival for younger women (<50 years old) who received polychemotherapy balanced the burdens in terms of acute toxic side-effects, especially among women enrolled in trials that did not include tamoxifen. Overall, chemotherapy-treated younger women gained an average of 10.3 months of relapse-free survival and 5.4 months of overall survival within 10 years (p<0.0001 for both) compared with the no-chemotherapy group. Polychemotherapy provided more quality-adjusted time than control across nearly all values of utility weights for time spent undergoing chemotherapy and time after relapse. The range of benefit was from -0.6 to 10.3 months. For older women (50-69 years) overall, polychemotherapy also provided significant benefit compared with no chemotherapy but, compared with younger women, the size of benefit was less and the range of utility-weight values favouring polychemotherapy was smaller. Average gains for older women treated with polychemotherapy (with or without tamoxifen) were 6.8 months of relapse-free survival (p<0.0001) and 2.9 months of overall survival (p=0.0001) within 10 years. The range of quality-adjusted benefit was -3.1 to 6.8 months. For older women with oestrogen-receptor-poor tumours who did not receive tamoxifen (9% of the total), the benefit of polychemotherapy was significant and similar to that observed for younger women. The benefits of adjuvant chemotherapy within 10 years outweigh the burdens especially for younger women (<50 years old) and among older women (50-69 years) to a lesser degree. Additional studies to compare the quality-adjusted survival of chemotherapy plus endocrine therapy versus endocrine therapy alone are required for younger patients with tumours that express steroid-hormone receptors.

Patients' preferences for adjuvant chemotherapy in early-stage breast cancer: is treatment worthwhile?

When making decisions about adjuvant chemotherapy for early-stage breast cancer, costs and benefits of treatment should be carefully weighed. In this process, patients' preferences are of major importance. The objectives of the present study were: (1) to determine the minimum benefits that patients need to find chemotherapy acceptable, and (2) to explore potential preference determinants, namely: positive experience of the treatment, reconciliation with the treatment decision, and demographic variables. Preferences were elicited from patients scheduled for adjuvant chemotherapy (chemotherapy group: n = 38) before (T 1), during (T 2), and 1 month after chemotherapy (T 3), and were compared to responses from patients not scheduled for chemotherapy (no-chemotherapy group: n = 38). The patients were asked, for a hypothetical situation, to indicate the minimum benefit (in terms of improved 5-year disease-free survival) to find adjuvant chemotherapy acceptable. In the chemotherapy group, the median benefit was 1% at all 3 measurement points. In the no-chemotherapy group the attitude towards chemotherapy became more negative over time, although not statistically significantly so (T 1: 12%, T 2: 15%, T 3: 15%;P = 0.10). At all measurement points, the patients in the chemotherapy group indicated that they would accept chemotherapy for significantly (P< 0.01) less benefit than the patients in the no-chemotherapy group. Of the demographic variables, age was related to preferences, but only at T 2 and only in the no-chemotherapy group. The more positive attitude towards chemotherapy and the stability of preferences in the chemotherapy group indicated that reconciliation with the treatment decision was a more important determinant of patients' preferences than positive experience of the treatment. © 2001 Cancer Research Campaign http://www.bjcancer.com

Neoadjuvant cisplatin,methotrexate,and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial

<h2>Summary</h2><h3>Background</h3> Several non-randomised trials have shown that transitional-cell carcinoma of the bladder is a moderately chemosensitive tumour. We investigated whether the addition of neoadjuvant cisplatin-based chemotherapy to radical surgery or radiotherapy would improve survival. <h3>Methods</h3> Patients with T2 G3, T3, T4a, N0-NX, or MO transitional-cell carcinoma of the bladder undergoing curative cystectomy or full-dose external-beam radiotherapy were randomly assigned three cycles of neoadjuvant chemotherapy (cisplatin, methotrexate, and vinblastine, with folinic acid rescue, n=491) or no chemotherapy (n=485). When possible, clinical tumour response was assessed cytoscopically after completion of chemotherapy but before cystectomy or radiotherapy; histopathologically assessed response was on cystectomy samples. We recorded every 6 months locoregional persistence or relapse of tumour, appearance of distant metastases, survival, and cause of death. <h3>Findings</h3> Median follow-up of patients still alive was 4·0 years. 485 patients died, and 78·6% of deaths were due to transitional-cell carcinoma. Chemotherapy mortality was 1% and operative (cystectomy) mortality was 3·7%. Kaplan-Meier curves compared by means of the log-rank test gave a calculated absolute difference between groups in 3-year survival of 5·5% (95% CI _0·5 to 11·0, p=0·075; 55·5% for chemotherapy, 50·0% for no chemotherapy). Median survival in the chemotherapy group was 44 months compared with 37·5 months for the no-chemotherapy group. 32·5% of cystectomy samples contained no tumour after neoadjuvant chemotherapy. <h3>Interpretation</h3> Three cycles of neoadjuvant chemotherapy before cystectomy or radiotherapy did not give the 10% improvement in 3-year survival that was judged to be necessary for introduction into routine use. The chemotherapy regimen was associated with a higher pathological complete-response rate in primary tumours, but there was no clear evidence that it would increase survival.

Recombinant Human Erythropoietin (rHuEPO) for the Treatment of the Anemia of Cancer

Advanced cancer is frequently associated with a significant anemia that may be due to the disease itself or the effect of concomitantly administered chemotherapeutic agents. In a series of double-blind, placebo-controlled trials, three populations of anemic cancer patients were randomized to rHuEPO or placebo. The three populations were: A) patients not receiving concomitant chemotherapy, B) patients receiving chemotherapeutic regimens which did not contain cisplatin, and C) patients receiving chemotherapeutic regimens which contained cisplatin. In the no-chemotherapy trials, patients were treated with rHuEPO (100 U/kg) or placebo s.c. three times a week for up to eight weeks. In the two types of chemotherapy trials, patients were treated with rHuEPO (150 U/kg) or placebo SC three times a week for 12 weeks. A total of 413 patients were enrolled in these trials (124 in the no-chemotherapy group, 157 in the no-cisplatin chemotherapy group and 132 in the cisplatin chemotherapy group). In each trial, patients randomized to rHuEPO had a significantly greater (p <.004) increase in hematocrit than placebo-treated patients. In the two types of chemotherapy trials combined, utilizing an rHuEPO dose of 150 U/kg, rHuEPO-treated patients had significantly lower (p </=.009) transfusion requirements (percentage of patients transfused and mean units of blood transfused per patient) than placebo-treated patients during months two and three, but not during month one. Quality-of-life parameters measured on a 100 mm visual analog scale significantly improved (p<.05) in rHuEPO-treated patients whose hematocrit increased >/= 6 percentage points, compared to corresponding quality-of-life changes in placebo-treated patients. rHuEPO was well tolerated compared to placebo. The above results suggest that rHuEPO may be a useful agent to palliate the morbid consequences of the anemia that is often found in association with advanced cancer.

Interstitial hyperthermia and iridium-192 treatment alone vs. interstitial iridium-192 treatment/hyperthermia and low dose cisplatinum infusion in the treatment of locally advanced head and neck malignancies

Purpose : To determine whether the addition of low dose platinum infusional chemotherapy adds to the effectiveness of interstitial hyperthermia/iridium-192 management of locally advanced head and neck malignancies. Methods and Materials : From 1987 to 1993, 36 patients with locally advanced head and neck malignancies were treated locally with interstitial hyperthermia and iridium-192 as part of all of their management. Twenty-two of the above-mentioned patients also received low dose infusional cisplatinum chemotherapy at 20 mg/M 2 per day during the time of the implant. No patient received greater than 100 mg/M 2 total dose. Implant times ranges from 38.5 to 134h and total doses delivered with the radiation implants ranges from 15 to 39.9 Gy. Average implant volume was 50 cc. Twenty-three patients received external beam irradiation supplementation in a dose range from 25.2 to 64 Gy. Results : Median follow-up for the entire group was 8, months with 7 months for the chemotherapy group vs. 12 months for the no-chemotherapy group. Freedom from relapse rates for the chemotherapy group vs. the no-chemotherapy group were 70% at 41 months vs. 63% at 60 months, p = not significant ( p = NS). Overall survival by Life Table Analysis was 28% for the chemotherapy group at 41 months vs. 31% for the no-chemotherapy group at 60 months ( p = NS). Complete response (CR) rates were 93% for the chemotherapy group vs. 86% for the no-chemotherapy group. Seven patients in the chemotherapy group had recurrent disease and four patients in the no-chemotherapy group were being treated for recurrent disease. Complication rates were similar in both group, with two patients in the chemotherapy arm requiring hyperbaric oxygen treatments and one patient in the no-chemotherapy arm requiring hyperbaric oxygen treatments (for soft tissue necrosis). Conclusions : It appears that low dose platinum infusional chemotherapy can be added safely to patients receiving interstitial iridium-192 implants along with interstitial hyperthermia for head and neck malignancies. Although there appears to be a trend toward better freedom from relapse by adding chemotherapy, a larger trial and longer follow-up will be necessary to prove statistical significance. Further research in these areas is recommended in the form of a randomized prospective study.

Recombinant human erythropoietin (r-HuEPO) for the treatment of the anemia of cancer

Advanced cancer is frequently associated with a significant anemia that may be due to the disease itself or the effect of concomitantly administered chemotherapeutic agents. In a series of double-blind, placebo-controlled trials, three populations of anemic cancer patients were randomized to rHuEPO or placebo. The three populations were: A) patients not receiving concomitant chemotherapy, B) patients receiving chemotherapeutic regimens which did not contain cisplatin, and C) patients receiving chemotherapeutic regimens which contained cisplatin. In the no-chemotherapy trials, patients were treated with rHuEPO (100 U/kg) or placebo s.c. three times a week for up to eight weeks. In the two types of chemotherapy trials, patients were treated with rHuEPO (150 U/kg) or placebo SC three times a week for 12 weeks. A total of 413 patients were enrolled in these trials (124 in the no-chemotherapy group, 157 in the no-cisplatin chemotherapy group and 132 in the cisplatin chemotherapy group). In each trial, patients randomized to rHuEPO had a significantly greater (p <.004) increase in hematocrit than placebo-treated patients. In the two types of chemotherapy trials combined, utilizing an rHuEPO dose of 150 U/kg, rHuEPO-treated patients had significantly lower (p </=.009) transfusion requirements (percentage of patients transfused and mean units of blood transfused per patient) than placebo-treated patients during months two and three, but not during month one. Quality-of-life parameters measured on a 100 mm visual analog scale significantly improved (p<.05) in rHuEPO-treated patients whose hematocrit increased >/= 6 percentage points, compared to corresponding quality-of-life changes in placebo-treated patients. rHuEPO was well tolerated compared to placebo. The above results suggest that rHuEPO may be a useful agent to palliate the morbid consequences of the anemia that is often found in association with advanced cancer.

Adjuvant chemotherapy enhances long‐term survival of patients with advanced gastric cancer following curative resection

We examined the effectiveness of postoperative adjuvant chemotherapy with mitomycin C (MMC), 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur), plus PSK, an immunomodulator, for patients with advanced gastric cancer who underwent histological curative resection. The effect of chemotherapy on prognostic serosal (ps) invasion [ps(-) or ps(+)] and lymph node metastasis [n(-) or N(+)] was examined. One hundred eighteen patients were in the no-chemotherapy group and 137 were on the drugs. The median follow-up time for the 86 survivors at the time of analysis was 13.8 years. With regard to prognostic factors, there were no differences between the two groups. Generalized Wilcoxon test of the two survival patterns revealed a P value of .0351, and the survival rate for 15 years was 45.7% for patients in the no-chemotherapy group and 56.9% for those of the chemotherapy group. In particular, adjuvant chemotherapy was effective for patients with ps(-)n(+) (P less than .05) and ps(+)n(-) (P less than .05), but not for those with ps(-)n(-) and ps(+)n(+). Our findings show that the concomitant prescription of MMC, tegafur, and PSK improves the 15-year survival rate for patients with advanced gastric cancer, following curative resection. As the survival rate is low for the patients with ps(+)n(+), an even more aggressive postoperative chemotherapy is recommended.

The Nigerian patent system and the new industrial policy

Acute leukemia of ambiguous lineage (ALAL) is a rare leukemia with sparse data availability about the survival and management strategies in elderly patients.We used the Surveillance Epidemiology and End Results (SEER)-Medicare database to describe the overall survival (OS) and treatment pattern of elderly patients (age > 65 years) with ALAL. OS analysis was done using the Kaplan-Meier method, and its determinants were analyzed using the Cox proportional hazard regression method with a significant P < .05.We included 705 patients with ALAL and a median age of 80 years. The 2-year OS was 16.4% for patients aged 66 to 70 years, 8.1% for patients aged 71 to 75 years, 5.5% for patients aged 76 to 80 years, and 3.7% for patients aged > 80 years (P < .01). Two-year OS did not significantly vary by race or gender. Among the study cohort, 151 patients received chemotherapy. Two-year OS was 17% in the chemotherapy group and 3% in the no-chemotherapy group (P < .001). On multivariate analysis, age less than 80 years (Age 66-70 years: hazard ratio [HR]; 0.66, 95% confidence interval [CI], 0.52-0.85; age 71-75 years: HR, 0.80; 95% CI, 0.65-0.99; age 76-80 years: HR, 0.80; 95% CI, 0.66-0.98; P = .004) and chemotherapy (HR, 0.51; 95% CI, 0.42-0.62; P = .001) significantly reduced the hazard for mortality.Our study suggests that the OS of elderly patients with ALAL remains poor. Although treatment improved the OS, only 21.5% of patients received therapy. The optimal choice of therapy needs to be determined by prospective studies.

The importance of the technological activities of the world's largest firms

Acute leukemia of ambiguous lineage (ALAL) is a rare leukemia with sparse data availability about the survival and management strategies in elderly patients.We used the Surveillance Epidemiology and End Results (SEER)-Medicare database to describe the overall survival (OS) and treatment pattern of elderly patients (age > 65 years) with ALAL. OS analysis was done using the Kaplan-Meier method, and its determinants were analyzed using the Cox proportional hazard regression method with a significant P < .05.We included 705 patients with ALAL and a median age of 80 years. The 2-year OS was 16.4% for patients aged 66 to 70 years, 8.1% for patients aged 71 to 75 years, 5.5% for patients aged 76 to 80 years, and 3.7% for patients aged > 80 years (P < .01). Two-year OS did not significantly vary by race or gender. Among the study cohort, 151 patients received chemotherapy. Two-year OS was 17% in the chemotherapy group and 3% in the no-chemotherapy group (P < .001). On multivariate analysis, age less than 80 years (Age 66-70 years: hazard ratio [HR]; 0.66, 95% confidence interval [CI], 0.52-0.85; age 71-75 years: HR, 0.80; 95% CI, 0.65-0.99; age 76-80 years: HR, 0.80; 95% CI, 0.66-0.98; P = .004) and chemotherapy (HR, 0.51; 95% CI, 0.42-0.62; P = .001) significantly reduced the hazard for mortality.Our study suggests that the OS of elderly patients with ALAL remains poor. Although treatment improved the OS, only 21.5% of patients received therapy. The optimal choice of therapy needs to be determined by prospective studies.

A giant step for mankind?

Acute leukemia of ambiguous lineage (ALAL) is a rare leukemia with sparse data availability about the survival and management strategies in elderly patients.We used the Surveillance Epidemiology and End Results (SEER)-Medicare database to describe the overall survival (OS) and treatment pattern of elderly patients (age > 65 years) with ALAL. OS analysis was done using the Kaplan-Meier method, and its determinants were analyzed using the Cox proportional hazard regression method with a significant P < .05.We included 705 patients with ALAL and a median age of 80 years. The 2-year OS was 16.4% for patients aged 66 to 70 years, 8.1% for patients aged 71 to 75 years, 5.5% for patients aged 76 to 80 years, and 3.7% for patients aged > 80 years (P < .01). Two-year OS did not significantly vary by race or gender. Among the study cohort, 151 patients received chemotherapy. Two-year OS was 17% in the chemotherapy group and 3% in the no-chemotherapy group (P < .001). On multivariate analysis, age less than 80 years (Age 66-70 years: hazard ratio [HR]; 0.66, 95% confidence interval [CI], 0.52-0.85; age 71-75 years: HR, 0.80; 95% CI, 0.65-0.99; age 76-80 years: HR, 0.80; 95% CI, 0.66-0.98; P = .004) and chemotherapy (HR, 0.51; 95% CI, 0.42-0.62; P = .001) significantly reduced the hazard for mortality.Our study suggests that the OS of elderly patients with ALAL remains poor. Although treatment improved the OS, only 21.5% of patients received therapy. The optimal choice of therapy needs to be determined by prospective studies.

The perceived impediments to effective technology transfer from the higher education sector. The educational and training needs for their removal

Acute leukemia of ambiguous lineage (ALAL) is a rare leukemia with sparse data availability about the survival and management strategies in elderly patients.We used the Surveillance Epidemiology and End Results (SEER)-Medicare database to describe the overall survival (OS) and treatment pattern of elderly patients (age > 65 years) with ALAL. OS analysis was done using the Kaplan-Meier method, and its determinants were analyzed using the Cox proportional hazard regression method with a significant P < .05.We included 705 patients with ALAL and a median age of 80 years. The 2-year OS was 16.4% for patients aged 66 to 70 years, 8.1% for patients aged 71 to 75 years, 5.5% for patients aged 76 to 80 years, and 3.7% for patients aged > 80 years (P < .01). Two-year OS did not significantly vary by race or gender. Among the study cohort, 151 patients received chemotherapy. Two-year OS was 17% in the chemotherapy group and 3% in the no-chemotherapy group (P < .001). On multivariate analysis, age less than 80 years (Age 66-70 years: hazard ratio [HR]; 0.66, 95% confidence interval [CI], 0.52-0.85; age 71-75 years: HR, 0.80; 95% CI, 0.65-0.99; age 76-80 years: HR, 0.80; 95% CI, 0.66-0.98; P = .004) and chemotherapy (HR, 0.51; 95% CI, 0.42-0.62; P = .001) significantly reduced the hazard for mortality.Our study suggests that the OS of elderly patients with ALAL remains poor. Although treatment improved the OS, only 21.5% of patients received therapy. The optimal choice of therapy needs to be determined by prospective studies.