Postoperative intra-abdominal infection is an independent prognostic factor of disease-free survival and disease-specific survival in patients with stage II colon cancer.

BACKGROUND: Recurrence occurs in up to 20% of patients with stage II colon cancer operated on for cure. Although postoperative intra-abdominal infection has been linked with an increased risk of recurrence, the association is controversial. The aim was to investigate the impact of postoperative intra-abdominal infection on disease-free survival and disease-specific survival in patients with stage II colon cancer. METHODS: Patients undergoing elective surgery for colon cancer stage II, between 2003 and 2014, were included. Patients with anastomotic leak or intra-abdominal abscess were included in the infection group. We used the Kaplan-Meier method to represent the distribution of survival and the Cox proportional hazards model to estimate the contribution of relevant clinicopathological factors with prognosis. RESULTS: Postoperative intra-abdominal infection was diagnosed in 37 of 363 (10.2%) patients. Perioperative blood transfusion was more frequent in patients with infection (p = 0.008). Overall 5-year disease-free survival rate was 85.1%. Disease-free survival at 5 years was lower in patients with postoperative intra-abdominal infection (52.8 vs 88.7%; p < 0.001), perineural invasion (p = 0.001), lymphovascular invasion (p = 0.001), pT4 (p = 0.013), and in patients with adjuvant chemotherapy (p = 0.013). Multivariate analysis showed that postoperative intra-abdominal infection (HR 4.275; p < 0.001), perineural invasion (HR 2.230; p = 0.007), and lymphovascular invasion (HR 2.052; p = 0.016) were all significant independent predictors of reduced disease-free survival. Regarding specific survival, independent significant prognostic factors were the number of lymph nodes, lymphovascular invasion, and postoperative intra-abdominal infection. CONCLUSION: In this series of patients with stage II colon cancer, postoperative intra-abdominal infection has an independent negative impact on disease-free survival and disease-specific survival.

Mitogen-activated protein kinase phosphatase-1 (MKP-1) impairs the response to anti-epidermal growth factor receptor (EGFR) antibody cetuximab in metastatic colorectal cancer patients.

BACKGROUND: The validation of KRAS mutations as a negative marker of response to anti-epidermal growth factor receptor (EGFR) antibodies has meant a seminal advance towards treatment individualisation of colorectal cancer (CRC) patients. However, as a KRAS wild-type status does not guarantee a response to anti-EGFR antibodies, a current challenge is the identification of other biomarkers of response. On the basis of pre-clinical evidence, we hypothesised that mitogen-activated protein kinase phosphatase-1 (MKP-1), a phosphatase that inactivates MAPKs, could be a mediator of resistance to anti-EGFR antibodies. METHODS: Tumour specimens from 48 metastatic CRC patients treated with cetuximab-based chemotherapy were evaluated for KRAS and BRAF mutational status and MKP-1 expression as assessed by immunohistochemistry. RESULTS: As expected, clinical benefit was confined to wild-type KRAS and BRAF patients. Mitogen-activated protein kinase phosphatase-1 was overexpressed in 16 patients (33%) and was not associated with patient baseline clinicopathological characteristics and KRAS mutational status. All patients with BRAF mutations (n=3) had MKP-1 overexpression. Among KRAS wild-type patients, MKP-1 overexpressors had a 7% response rate (RR), whereas patients not overexpressing MKP-1 had a 44% RR (P=0.03). Moreover, median time to progression was significantly longer in MKP-1 non-overexpressing patients (32 vs 13 weeks, P=0.009). CONCLUSION: These results support the concept of MKP-1 as a promising negative marker of response to cetuximab-based treatment in CRC patients with wild-type KRAS.

Feasiblity study of gemcitabine and cisplatin administered every two weeks in patients with advanced urothelial tumors and impaired renal function.

OBJECTIVES: Cisplatin-based combination chemotherapy is the mainstay of treatment for advanced bladder cancer. However, full doses of cisplatin cannot be delivered in patients with impaired renal function. Our aim was to prove the feasibility of a gemcitabine and low-dose cisplatin regimen, delivered every two weeks in patients with impaired renal function. MATERIAL AND METHODS: Patients with locally advanced or metastatic bladder cancer with creatinine clearance between 35-60 ml/min received gemcitabine 2500 mg/m2 and cisplatin 35 mg/m2 on day 1, every 14 days. RESULTS: Between January 2004 and March 2005, 17 patients were treated. Mean creatinine clearance was 47.8 ml/min (range: 37-59 ml/min). Four patients had previously received chemotherapy with gemcitabine and/ or platinum. Median number of cycles per patient was 5 (1-13). No patient developed renal toxicity or worsening of renal function. Main toxicities were (grade 3/4): Anemia 2/1; leucopenia: 1/2; trombopenia 1/1. There was one toxic death related to metabolic acidosis, secondary to vomiting. Among 16 patients evaluable for response, we observed one complete response, 7 partial responses (ORR: 53.3%; IC 95%: 28.1-78.5%), 6 stabilizations (37.5%) and 2 progressions (12.5%). CONCLUSIONS: Gemcitabine and low-dose cisplatin is a safe and feasible combination in patients with poor renal function. Response rates seem similar to those previously described with standard schedules of this combination.

[Helicobacter pylori and gastric cancer: relationship with histological subtype and tumor location]. / Helicobacter pylori y cáncer gástrico: relación entre el subtipo histológico y la localización del tumor.

INTRODUCTION: Helicobacter pylori (HP) has been implicated in the pathogenesis of gastric adenocarcinoma. Published data on HP infection and its association with both histological subtype and tumor localization are contradictory and few data are available on this topic in Spain. The aim of the present study was to evaluate the association of HP infection with histological subtype and tumor localization in a series of patients with gastric adenocarcinoma. MATERIAL AND METHOD: We retrospectively reviewed all the patients diagnosed with gastric neoplasms in Hospital del Mar in Barcelona between 1995 and 2001. The histological subtype was established using Lauren's classification. Tissue samples were obtained from the surgical specimen or from endoscopic biopsies. HP infection was histologically determined through hematoxylin-eosin, Masson's trichromic, and Giemsa staining. RESULTS: During the study period, 304 gastric neoplasms, 275 (90.4%) adenocarcinomas, 22 (7.2%) lymphomas, 3 (1.0%) leiomyosarcomas, 2 (0.7%) degenerated gastrointestinal stromal tumors (GIST) and 2 (0.7%) Kaposi's sarcomas were diagnosed. In patients with adenocarcinoma, the mean age at diagnosis was 69 years and most patients were male (62%). A total of 48.1% of the neoplasms were located in the gastric antrum, 23.7% in the body and 19.1% in the fundus (13.6% in the period 1994-1997 and 25.4% in the period 1998-2001, p = 0.018). Intestinal-type gastric carcinoma was observed in 56% of the patients, diffuse-type in 28% and indeterminate-type in 16%. HP infection was confirmed in 69% of the patients (68% in intestinal subtype, 69% in diffuse subtype, and 69% in indeterminate subtype, p = 0.84), and was significantly associated with distal adenocarcinomas vs. proximal adenocarcinomas (73.6% vs 48.6%, p < 0.05). CONCLUSIONS: No differences were observed between the histological type of adenocarcinoma and HP infection. In the last few years, the incidence of fundic adenocarcinomas has increased. These tumors show a lower association with HP infection.

Role of Helicobacter pylori in stomach cancer after partial gastrectomy for benign ulcer disease.

OBJECTIVE: To determine the prevalence of Helicobacter pylori infection in patients having undergone gastrectomy for non-neoplastic disease who later developed gastric stump cancer. MATERIAL AND METHODS: Retrospective study of all patients with partial gastrectomy for non-malignant peptic disease who were submitted to an endoscopic exploration between 1995 and 2001. A comparison was made of major clinical and histological characteristics, and the presence of Helicobacter pylori among patients with and without gastric cancer in the stomach remnant. RESULTS: A total of 73 patients were studied in this period. Fifteen patients (20.5%) had remnant-stump gastric cancer. All but one were adenocarcinomas (71% intestinal and 29% diffuse, respectively). The average time between diagnosis of gastric cancer and previous gastrectomy was 32 (14-48) years. There was a higher detection rate of Helicobacter pylori in patients with cancer in the gastric remnant (100 vs. 81.5%, respectively, p < 0.07). No relationship was seen between type of gastric reconstruction (Billroth I or II) and rate of Helicobacter pylori detection. CONCLUSIONS: Helicobacter pylori infection is frequent in patients with previous gastrectomy for non-neoplastic disease. The results of the study suggest that Helicobacter pylori infection may play a role in gastric stump cancer.

Irinotecan (CPT-11) in metastatic colorectal cancer patients resistant to 5-fluorouracil (5-FU): a phase II study.

The efficacy and toxicity of irinotecan (CPT-11) 350 mg/m(2) i.v. once every 3 weeks was assessed in 60 patients with advanced colorectal cancer (CRC) showing failure to 5-fluorouracil (5-FU) treatment. The overall objective response rate was 13.6% (1 complete response and 4 partial responses) and 25 patients (42.4%) showed stable disease; the median time to disease progression was 4.4 months and the median survival was 10.5 months. The main non-hematological toxicities were alopecia (80.3% of patients), diarrhea (75.0%), and nausea/vomiting (71.7%); neutropenia was the main hematological toxicity. Grade 3 or 4 diarrhea appeared in 21 of 131 cycles (16.1%), whereas grade 3 or 4 neutropenia appeared in 78 cycles (25.0%). In conclusion, the present phase II study confirms that CPT-11 350 mg/m(2) every 3 weeks is active and well tolerated as second-line chemotherapy for CRC in 5-FU resistant patients.

Treatment of oesophageal cancer with preoperative chemoradiotherapy may increase operative mortality.

AIMS: This phase II multicentric study evaluates a modified preoperative chemoradiotherapy schedule. METHODS: Patients <75 years with potentially resectable neoplasm were eligible. Treatment included an initial course of CDDP 100 mg/m2 (Day 1) and 5-FU CI 5000 mg/m2 (Days 1-5) followed by 45 Gy (Days 28-63) and 5-FU CI 5000 mg/m2 (Days 28-33), CDDP 75 mg/m2 (Day 56) and 5-FU CI 3750 mg/m2 (Days 56-61). Regional lymph nodes were irradiated. RESULTS: Nineteen patients were studied. Oesophagectomy was performed in 17. Clear margins were achieved in 16 of these. Eight patients showed a pathologic complete response (pCR). One patient died of infection during the preoperative treatment and four died due to acute surgical complications. The study was closed prematurely because of excessive mortality. Median follow-up was 19 months. Local and regional relapse occurred in one and three patients, respectively. Median time and actuarial 3-year of overall survival and progression free rates were 18.6 months and 28%, and 12.7 months and 10.4%, respectively. CONCLUSIONS: This schedule showed a high pCR, resectability and local control rate. Treatment-related mortality limits its clinical applicability, but further investigations are warranted.

Retrospective evaluation of toxicity in three different schedules of adjuvant chemotherapy for patients with resected colorectal cancer. TTD Spanish Cooperative Group.

Adjuvant chemotherapy has been established since 1990 as standard treatment for patients with colon cancer stage III (Dukes' C). Chemotherapeutic schemes combining 5-fluorouracil with levamisole or leucovorin have shown significant advantage over surgery alone. Adjuvant trials are being currently implemented to investigate some relevant questions, such as which is the optimal duration of chemotherapy, as well as the possible advantage of levamisol versus leucovorin schedules, and of high-dose versus low-dose leucovorin. While these trials are ongoing, a retrospective evaluation of the toxicity associated with the different chemotherapeutic schemes might be of help when choosing the most appropriate regimen for individual patients not involved in clinical trials. A total of 519 patients subjected to three different schedules of adjuvant chemotherapy between 1993 and 1996, were evaluated for toxicity according to the NCI-CTC criteria. Chemotherapeutic regimens were: 5-fluorouracil plus levamisole (5-Fu+Lev; Moertel schedule), 5-fluorouracil plus low-dose leucovorin (5-Fu+LVLD; NCCTG schedule) and 5-fluorouracil plus high-dose leucovorin (5-Fu+LVHD; IMPACT-modified schedule). 5-Fu+LVLD is significantly more toxic than the other two regimens in terms of neutropenia, mucositis and diarrhea. delay in chemotherapy and dose reduction of 5-fluorouracil were also more frequent in the 5-Fu+LVLD group. However, the percentage of prematurely discontinued treatments was significantly higher in the 5-Fu+Lev group. Information on toxicity of adjuvant chemotherapy for colon cancer may help medical oncologists to choose the most appropriate regimen for individual patients not involved in clinical trials.

UFT plus or minus calcium folinate for metastatic colorectal cancer in older patients.

Two studies were carried out to determine the activity and evaluate the toxicity of oral chemotherapy with uracil and tegafur in a 4:1 molar ratio (UFT) plus or minus calcium folinate in elderly patients with advanced colorectal cancer. In one study, 106 patients received a fixed dose of UFT 400 mg/day in two daily doses every 12 hours continuously, plus calcium folinate 45 mg/day administered in three divided doses every 8 hours continuously. In study 2, calcium folinate was omitted, and the dose of UFT was increased to 400 mg/m2/day in two daily doses administered every 12 hours continuously to 95 patients. Treatments for both studies were administered until grade 3 or grade 4 toxicity occurred or disease progressed. The response rate among the 96 available patients in study 1 was 17.7% (95% confidence interval [CI], 10% to 27%); 41 patients (43%) achieved an objective response or stable disease. Overall survival was 13.7 months with a statistically significant difference between patients with no progressive disease and patients with progressive disease (P < .01). In study 2, 62 of 95 patients have now been evaluated for response. The response rate was 21% (95% CI, 13% to 30%); 38 patients (61%) experienced an objective response or stable disease. The overall survival for study 2 has not yet been evaluated. Toxicity was generally mild, consisting of grade 3 nausea/vomiting (6% in study 1 and 2% in study 2), grade 3 or grade 4 diarrhea (11% in study 1 and 7% in study 2), plus one case of grade 3 mucositis in study 1. These findings suggest that chemotherapy with UFT (with or without modulation with calcium folinate) is feasible for elderly patients with advanced colorectal carcinoma.

Nuclear beta-catenin in colorectal tumors: to freeze or not to freeze? Colon Cancer Team at IMAS.

beta-Catenin mediates the interaction of E-cadherin with alpha-catenin and the actin cytoskeleton. Recent evidence indicates that when the tumor suppressor gene APC is inactivated, beta-catenin can translocate to the nucleus, where it acts as a transcriptional regulator. Because APC is inactivated in most colorectal cancers, beta-catenin nuclear localization would be expected in these tumors. In a study of adhesion molecule expression in frozen colorectal cancer tissues, we were surprised by failure to detect nuclear beta-catenin. Here we compared the reactivity of an anti-beta-catenin monoclonal antibody with 11 colorectal cancers using immunohistochemistry on sections of frozen or paraffin-embedded samples. beta-Catenin was never detected in the nuclei of normal or tumor cells in frozen tissue sections. By contrast, in 8/11 cases it was detected in the nuclei of tumor cells but not of normal cells in paraffin-embedded tissue sections. These results were confirmed with an independent rabbit polyclonal anti-beta-catenin serum. We also examined beta-catenin distribution in SW480 colon cancer cells, in which its nuclear accumulation has been reported. As in tissues, nuclear beta-catenin was detected in paraffin-embedded but not in frozen samples. These findings are relevant because of the increasing interest in the study of beta-catenin in tumors, based on its dual role in cell adhesion and transcriptional regulation.

Emergency admission for cancer: a matter of survival?

The objective of this study was to compare the pre-hospital health care process, clinical characteristics at admission and survival of patients with a digestive tract cancer first admitted to hospital either electively or via the emergency department. The study involved cross-sectional analysis of information elicited through personal interview and prospective follow-up. The setting was a 450-bed public teaching hospital primarily serving a low-income area of Barcelona, Catalonia, Spain. Two hundred and forty-eight symptomatic patients were studied, who had cancer of the oesophagus (n = 31), stomach (n = 70), colon (n = 82) and rectum (n = 65). The main outcome measures were stage, type and intention of treatment and time elapsed from admission to surgery; the relative risk of death was calculated using Cox's regression. There were 161 (65%) patients admitted via the emergency department and 87 (35%) electively. The type of physician seen at the first pre-hospital visit had more often been a general practitioner in the emergency than in the elective group (89% vs 75%, P < 0.01). Emergency patients had seen a lower number of physicians from symptom onset until admission, but two-thirds had made repeated visits to a primary care physician. Emergency patients were less likely to have a localized tumour and a diagnosis of cancer at admission, and surgery as the initial treatment. Median survival was 30 months for elective patients and 8 months for emergency patients (P < 0.001), and the relative risk of death (RR) was 1.83 (95% confidence interval, CI, 1.32-2.54). After adjustment for strong prognostic factors, emergency patients continued to experience a significant excess risk (RR = 1.58; CI 1.10-2.27). In conclusion, in digestive tract cancers, admission to hospital via the emergency department is a clinically important marker of a poorer prognosis. Emergency departments can only partly counterbalance deficiencies in the effectiveness of and integration among the different levels of the health system.

Anal carcinoma: a 14 year experience.

A retrospective analysis of 20 patients with anal carcinoma treated at Hospital del Mar (Barcelona) from 1982 to 1995 was performed to evaluate clinical and pathological characteristics. This subset represents 2.1% of all the colon and rectum cancers registered in the same period. The mean age was 74 years (42-92), the female to male ratio was 1.5:1. The most frequent site was anal canal (80%) and the histological type was squamous cell and basaloid carcinomas in all cases. Five aged patients were not treated. Twelve patients were primary treated by abdominal perineal resection, 2 patients by radiotherapy and one by a local excision. The prognosis of 8 patients treated with palliative surgery was poor and none survived 30 months after surgery. In contrast, 4 of 5 patients are alive after radical surgery with a minimum 5 year follow-up. Two patients treated with radiotherapy are disease free at 7 and 13 months after treatment. The incidence of anal carcinoma is low, but our experience shows that it is diagnosed at an advanced stage and surgery is not always successful. Radiotherapy with or without chemotherapy, is an effective alternative.

A preliminary report of a phase II trial. UFT plus oral folinic acid as therapy for metastatic colorectal cancer in older patients. Spanish Group for the Treatment of Gastrointestinal Tumors (TTd Group).

The oral fluoropyrimidines have proved to be active in colorectal cancer in Japan and, recently, in the United States and Europe. Continuous oral administration simulates protracted fluorouracil (5-FU) continuous intravenous infusion. The purpose of this trial was to evaluate the tolerability and potential advantages of oral treatment for colorectal cancer in the elderly. The main inclusion criterion was age over 72 years. Patients were treated with UFT (tegafur plus uracil) 400 mg/24 hours (fixed doses) continuously plus folinic acid 45 mg/24 hours until toxicity. If grade 3 or 4 toxicity appeared, treatment was stopped until recovery. From September 1994 to November 1996, 126 patients were included. For the analysis in November 1996, 77 patients were evaluable for response, toxicity, and survival. The patients, including 34 women and 43 men, had a median age of 74 years (range, 72 to 82 years of age). The Karnofsky performance status was 60% to 80% for 41 patients and 90% to 100% for 36 patients. Liver metastasis was present in 48% of the cases, and 42% were locoregional and peritoneal. Toxicity was mild, with only one patient having grade 3 thrombocytopenia, 11 (14%) grade 3 or 4 nausea/vomiting, seven (9%) grade 3 or 4 diarrhea, and one grade 3 mucositis. Four patients (5%) had complete responses and nine (11.6%) partial responses, for an objective response rate of 16.9% (95% confidence interval, 9% to 27%). Twenty-two patients (28.6%) showed no change. The number of patients in whom disease did not progress (ie, patients with complete plus partial responses plus those with stable disease) was 35 (45.4%) (95% confidence interval, 34% to 57%). With a maximum follow-up of 24 months, the median actuarial survival is 14.4 months. The number without disease progression and the median survival in this preliminary analysis suggests that this schedule is a moderately effective, comfortable, treatment with only mild toxicity, that can be recommended for use in the elderly, and it warrants further study.

Do we believe what patients say about their neoplastic symptoms? An analysis of factors that influence the interviewer's judgement.

In order to analyze factors that influence an interviewer's judgement of the validity of responses given by patients on the duration of their neoplastic signs and symptoms, 183 consecutive symptomatic patients hospitalized for a digestive tract neoplasm were personally interviewed. The validity of the answers was judged by the interviewers to be high in 156 cases (85%), and low in 27 (15%). The subjective validity of the interview (SVI) was inversely related to the time elapsed from first medical symptom to interview (TFMSI), even after adjusting for the duration of the interview (p < 0.05). SVI was not influenced by whether patient and interviewer agreed on the first symptom. SVI was inversely related to educational level (p < 0.01) and to occupational class (p = 0.04). Patients whose Karnofsky's Index (KI) was > or = 80 were over twice as likely to yield valid responses (TFMSI-adjusted odds ratio [OR] = 2.82, p = 0.037). Multivariate analyses selected education, TFMSI and KI as independent predictors of the interviewer assessment. The SVI of patients admitted to the hospital through the Emergency Department was lower than that of subjects whose admission was planned (OR = 6.49, p = 0.005). In this study SVI related in a logical manner to the characteristics of the interview, of the subjects and of their clinical course. It hence appeared to reasonably estimate the validity of data collected. Identifying factors that affect the reliability of patients' responses would help increase the validity of studies on the duration of cancer symptoms.

Predictors of the interval between onset of symptoms and first medical visit in patients with digestive tract cancer.

Lack of effective population screening programmes for digestive tract cancer makes a prompt diagnosis of symptomatic patients the primary option for early detection. The objective of the study was to analyze the characteristics and determinants of the interval between the first medical symptom and the first medical visit (ISV) in a sample of symptomatic patients of mid-low socioeconomic level admitted to hospital for a digestive tract cancer. During two years, 183 patients were personally interviewed with a structured questionnaire designed to elicit initial symptoms of digestive cancer. Fifty-seven percent consulted a physician during the first month after onset of symptoms, and over two-thirds did so within the first 2 months, but it took more than 3 months for 22.4% of the patients. In univariate analyses, the ISV was longer among patients illiterate, unemployed and in the lower social classes. The interval was also significantly longer when the physician-interviewer judged that the patient did not correctly identify the first symptom (p<0.05). In multivariate analyses, the chance of a longer ISV was 2.8 times higher in men; 16 times higher in unemployed patients; 9 times higher in patients with a first symptom of the lower digestive tract; and it increased 8-fold in subjects who attributed no importance to the first manifestation (all p<0.05). In spite of virtually universal health coverage, social factors seemed to act as barriers to seeking medical help in a subgroup of patients. Their procrastination was also related to the nature of the initial symptoms. Achieving an early clinical detection of digestive cancers may be difficult in some segments of the population, and may require substantial improvements in access to and the efficiency of the health system.

Disagreement between hospital medical records and a structured patient interview on the type and date of the first symptom in cancers of the digestive tract.

Medical records have often been found to be less reliable than interviews to patients when data on the initial signs and symptoms of cancer, and the out-of-hospital diagnostic process are sought; in spite of this, a large body of research on "diagnostic delay" in cancer is based on clinical records. As part of a study on delay in neoplasms of the digestive tract we analyzed the agreement on the type and date of the initial symptom between hospital records and a structured personal interview. Records were abstracted for a random sample (N = 60) of 183 patients interviewed. Concordance on the date of the first symptom was deemed to exist if the difference was +/- 30 days. The Kappa index (kappa) and the overall proportion of agreement (with its corresponding 95% confidence interval) were used. Medical records and structured personal interviews were concordant on the type of the first neoplastic symptom in only 61% of cases (kappa = 0.50): 67% in esophagus cancer (kappa = 0.49), 60% in stomach cancer (kappa = 0.52), and 61% in colorectal cancer (kappa = 0.50). Records underestimated the occurrence of anorexia as first symptom and overestimated weight loss and dysphagia. Only 56% of cases were date-concordant, the agreement being lower in colorectal cancer (46%) than in esophageal (67%) and stomach cancer (75%). Records indicated the first symptom to have occurred at a later date than interviews in 33% of cases; overall, a study based on hospital records would have underestimated the symptom to diagnosis interval by 2.2 months per patient. Only 40% of cases were totally (symptom and date) concordant. Marked discrepancies may exist between the information contained in medical records and what patients report during a structured interview. The quality of medical records data on the duration and nature of cancer symptoms should be assessed before its use in etiologic and evaluative research.

Cancer survival and the duration of symptoms. An analysis of possible forms of the risk function. ISDS II Project Investigators.

The time interval between onset of symptoms and the diagnosis of cancer [symptom to diagnosis interval (SDI), or duration of symptoms] is a highly complex variable reflecting patient behaviour, the clinical course, the functioning of the health system and tumour biology. In order to assess possible forms of the risk function of SDI upon cancer survival whilst taking into account the effects of age, sex, tumour site and stage at diagnosis, 1887 symptomatic cases of lung, breast, stomach, colon, rectal, bladder cancer and lymphomas registered in the Tumour Registry of the Hospital del Mar (Barcelona) were analysed by means of survival curves and Cox proportional hazards regression. Subjects (mean age 64 years) were followed for a median length of 15 months after diagnosis (follow-up rate 93.5%). SDI showed a weak relationship with tumour stage at diagnosis and with survival: out of the seven sites studied, only in breast cancer was tumour extension at diagnosis significantly influenced by duration of symptoms, and only lung and rectal cancers showed a detectable form of the risk function of SDI upon survival; neither was linear, and for rectal cancer the relationship was complexly related with tumour stage. Hence, results show that forms of the risk function of duration of symptoms on cancer survival are specific to tumour sites, and that the interval should not be represented as a linear, continuous term. Studies analysing more complex sets of factors, processes and forms of the SDI function are needed.