Determinations of the urinary excretion of 5-S-cysteinyldopa were performed in 571 patients previously treated by surgery for melanoma or melanoma metastasis. 90% of the 161 patients with metastases showed values exceeding 0.15 mg/24 h, and 9% of the 410 patients without metastases had such values. The increase in 5-S-cysteinyldopa excretion was generally more pronounced in men with metastases than in women, 98% of the men and 77% of the women with metastases showing values exceeding 0.15 mg/24 h. High levels of 5-S-cysteinyldopa are of grave prognostic significan4% died within one month, and only 3% survived for more than a year. In Sweden, determination of 5-S-cysteinyldopa in patients operated on for melanoma gives maximum information in the winter (October--March), when sun exposure does not influence the excretion levels.
OBJECTIVE: To evaluate differences in clinical appearance and survival rates in patients operated on for adenocarcinoma in the distal esophagus with and without Barrett epithelium. DESIGN: Prospective clinical study. SETTING: University hospital, Sweden. PATIENTS: Fifty-four patients with adenocarcinoma in the distal esophagus with (n = 17) or without (n = 37) Barrett epithelium. INTERVENTION: Esophagectomy or total gastrectomy. MAIN OUTCOME MEASURES: Preoperative symptoms, endoscopic results, and histological findings; postoperative morbidity, mortality, and survival rates. RESULTS: The main indication for the endoscopic examination that revealed tumor in the group with Barrett esophagus was reflex-related symptoms in 6 patients (routine Barrett examination, n = 4; symptoms of reflux, n = 2), symptoms related to upper gastrointestinal tract bleeding in 6, and malignant symptoms in 5 (dysphagia, n = 4; weight loss, n = 1). In contrast, most patients in the cardia cancer group were admitted because of malignant symptoms (dysphagia, n = 26; epigastric pain, n = 9; and anemia, n = 2). Ten of 17 patients in the Barrett esophagus cancer group had tumors limited to the mucosa and submucosa only. In 1 patient the tumor grew into the muscular layer but not through it. In the remaining 6 patients the tumor did grow through the muscular layer and lymph node metastases were found. Wall penetration was found in 30 patients and metastases to lymph nodes in 29 patients in the cardia cancer group. The hospital mortality rate was 0 of 17 patients in the Barrett cancer group and 2 of 37 patients in the cardia cancer group. In the patients operated on for adenocarcinoma in the distal esophagus, a better long-term survival rate was seen in those with Barrett epithelium (50%) than in those without this metaplasia (10%) (log rank P = .005; X2 = 7.80). CONCLUSIONS: Concomitant Barrett epithelium improved the prognosis for patients with adenocarcinoma in the distal esophagus. Probably the reason for this was a higher rate of early-stage disease, because symptoms of gastroesophageal reflux and other benign disorders, not dysphagia, were most common in patients with adenocarcinoma without Barrett epithelium in the distal esophagus.
Capecitabine is an active agent in the treatment of breast cancer. It is not known whether integration of capecitabine into an adjuvant regimen that contains a taxane, an anthracycline, and cyclophosphamide improves outcome in early breast cancer.
Women with axillary node-positive or high-risk node-negative breast cancer were randomly assigned to receive either three cycles of docetaxel and capecitabine (TX) followed by three cycles of cyclophosphamide, epirubicin, and capecitabine (CEX; n = 753) or three cycles of docetaxel (T) followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil (CEF; n = 747). The primary end point was recurrence-free survival (RFS).
During a median follow-up time of 59 months, 214 RFS events occurred (local or distant recurrences or deaths; TX/CEX, n = 96; T/CEF, n = 118). RFS was not significantly different between the groups (hazard ratio [HR], 0.79; 95% CI, 0.60 to 1.04; P = .087; 5-year RFS, 86.6% for TX/CEX v 84.1% for T/CEF). Fifty-six patients assigned to TX/CEX died during the follow-up compared with 75 of patients assigned to T/CEF (HR, 0.73; 95% CI, 0.52 to 1.04; P = .080). In exploratory analyses, TX/CEX improved breast cancer-specific survival (HR, 0.64; 95% CI, 0.44 to 0.95; P = .027) and RFS in women with triple-negative disease and in women who had more than three metastatic axillary lymph nodes at the time of diagnosis. We detected little severe late toxicity.
Integration of capecitabine into a regimen that contains docetaxel, epirubicin, and cyclophosphamide did not improve RFS significantly compared with a similar regimen without capecitabine.
Comment In: J Clin Oncol. 2012 Jan 1;30(1):1-222105825
Clinical trials commonly mandate that adjuvant chemotherapy for colon cancer should commence within 8 weeks (56 days) of surgery.
We investigated the consequences of the timing of adjuvant chemotherapy for stage III colon cancer.
This is a retrospective review of all patients with newly diagnosed stage III colon cancer who received adjuvant chemotherapy in 2 provincial centers in 1999 and 2000. The impact of time to adjuvant chemotherapy on overall survival and relapse-free survival was analyzed by the use of univariate and multivariate Cox modeling, adjusting for prognostic factors.
Three hundred forty-five subjects were included. Median time to adjuvant chemotherapy was 50 days (range, 20-242 days); in 111 (32.2%) patients, it was beyond 56 days. On univariate analysis, time >56 days was nonsignificantly associated with a hazard ratio of death of 1.31 (P = .12). Similar results were seen for relapse-free survival. Planned exploratory analysis suggests that the commencement of adjuvant chemotherapy up to 10 weeks postsurgery still confers a benefit.
Delaying adjuvant chemotherapy in stage III colon cancer beyond 8 to 10 weeks postsurgery appears to be associated with diminished benefit.
Adjuvant Nutritional Intervention in Cancer (ANICA) was a clinical study carried out in Denmark in the 1990s with 32 typical patients with breast cancer, aged 32-81 yr and classified high risk because of tumor spread to the lymph nodes. The patients received standard therapy for their breast cancer, but got from the start additionally an adjuvant therapy in form of a cocktail consisting of vitamin C (2,850 mg/day), vitamin E (2,500 IU/day), beta-carotene (32.5 IU/day), selenium (Se; 387 micrograms/day), various other vitamins and essential trace elements, essential fatty acids (1.2 g gamma-linolenic acid/day and 3.5 g omega-3 PUFAs/day), and coenzyme Q10 (CoQ10, 90 mg/day). The protocol was later changed, with reduction of the Se intake and more coenzyme Q10 than when the study was started. The average survival of high-risk breast patients in the study was 50% after 5 yr, whereas for low-risk breast cancer patients (without metastases in the axilla when treatment was started), the average survival was 90% after ten years. The main investigator died, and the final report from the ANICA study was therefore never written. However, the published preliminary results from the trial were very promising; it seems, therefore, important to follow-up this study.
BACKGROUND: The recently published, widely publicized adjuvant radiation trials from Denmark and Canada concluded that the addition of postoperative radiotherapy (XRT) to modified radical mastectomy (MRM) and adjuvant chemotherapy reduces locoregional recurrences and prolongs survival in high-risk premenopausal patients with breast cancer. Our thesis is that adequate lymphadenectomies were not performed in either study. Consequently, the conclusion to these studies is not applicable to those patients who have undergone adequate surgery. METHODS: To better assess adequate lymph node yield from an MRM, a retrospective review was performed on 215 consecutive patients treated surgically for invasive breast cancer. Data from this review were compared with the surgical data from the above-mentioned radiotherapy trials. RESULTS: In a group of 131 patients who had MRM, the average number of nodes removed was 26 (median, 25), and 75.5% of the specimens had 20 or more lymph nodes. In 73 patients who underwent segmental mastectomy with axillary lymph node dissection, both the average and the median number of lymph nodes removed were 24, and 68.9% had 20 or more nodes. These data compare to the Danish radiation trial in which a median of 7 lymph nodes were removed (with 76% of the patients having 9 or fewer lymph nodes in the specimen) and to the Canadian radiation trial in which a median of 11 lymph nodes were removed. In addition, in our breast cancer patients with positive nodes (84 of 204; 41.2%), 45.2.% (38 of 84) had more than three positive nodes compared with 29.8% in the Danish study and 35% in the Canadian study. CONCLUSIONS: Our surgical data are sufficiently different from those of the Danish and Canadian studies to indicate that, in those studies, incomplete lymph node dissections were performed and that residual disease was left behind in the axilla in some or all of the patients. The addition of XRT in the setting of residual axillary disease may compensate for an inadequate operation and yield an acceptable oncological result; however, these studies did not provide an adequate comparison with a well-performed MRM without XRT. In the absence of documented benefit, XRT should not be routinely added if a complete lymph node dissection has been performed.
We assessed changes in advanced cancer incidence and cancer mortality in eight randomized trials of breast cancer screening.
Depending on published data, advanced cancer was defined as cancer > or = 20 mm in size (four trials), stage II+ (four trials), and > or = one positive lymph node (one trial). For each trial, we obtained the estimated relative risk (RR) and 95% CI between the intervention and control groups, for both breast cancer mortality and diagnosis of advanced breast cancer. Using a meta-regression approach, log(RR-mortality) was regressed on log(RR-advanced cancer), weighting each trial by the reciprocal of the square of the standard error of log(RR) for mortality.
RR for advanced breast cancer ranged from 0.69 (95% CI, 0.61 to 0.78) in the Swedish Two-County Trial to 0.97 (95% CI, 0.97 to 1.25) in the Canadian National Breast Screening Study-1 (NBSS-1) trial. Log(RR)s for advanced cancer were highly predictive of log(RR)s for mortality (R(2) = 0.95; P