Tadeusz Popiela

Benefit of adjuvant chemotherapy for resectable gastric cancer: A meta-analysis

CONTEXT Despite potentially curative resection of stomach cancer, 50% to 90% of patients die of disease relapse. Numerous randomized clinical trials (RCTs) have compared surgery alone with adjuvant chemotherapy, but definitive evidence is lacking. OBJECTIVES To perform an individual patient-level meta-analysis of all RCTs to quantify the potential benefit of chemotherapy after complete resection over surgery alone in terms of overall survival and disease-free survival, and to further study the role of regimens, including monochemotherapy; combined chemotherapy with fluorouracil derivatives, mitomycin C, and other therapies but no anthracyclines; combined chemotherapy with fluorouracil derivatives, mitomycin C, and anthracyclines; and other treatments. DATA SOURCES Data from all RCTs comparing adjuvant chemotherapy with surgery alone in patients with resectable gastric cancer. We searched MEDLINE (up to 2009), the Cochrane Central Register of Controlled Trials, the National Institutes of Health trial registry, and published proceedings from major oncologic and gastrointestinal cancer meetings. STUDY SELECTION All RCTs closed to patient recruitment before 2004 were eligible. Trials testing radiotherapy; neoadjuvant, perioperative, or intraperitoneal chemotherapy; or immunotherapy were excluded. Thirty-one eligible trials (6390 patients) were identified. DATA EXTRACTION As of 2010, individual patient data were available from 17 trials (3838 patients representing 60% of the targeted data) with a median follow-up exceeding 7 years. RESULTS There were 1000 deaths among 1924 patients assigned to chemotherapy groups and 1067 deaths among 1857 patients assigned to surgery-only groups. Adjuvant chemotherapy was associated with a statistically significant benefit in terms of overall survival (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.76-0.90; P < .001) and disease-free survival (HR, 0.82; 95% CI, 0.75-0.90; P < .001). There was no significant heterogeneity for overall survival across RCTs (P = .52) or the 4 regimen groups (P = .13). Five-year overall survival increased from 49.6% to 55.3% with chemotherapy. CONCLUSION Among the RCTs included, postoperative adjuvant chemotherapy based on fluorouracil regimens was associated with reduced risk of death in gastric cancer compared with surgery alone.

The ratio of metastatic/resected lymph nodes is an independent prognostic factor in patients with node-positive pancreatic head cancer.

Objectives: The aim of this study was to evaluate the prognostic value of nodal involvement in resected adenocarcinoma of the pancreatic head. Methods: For the period between 1980 and 2002, 96 patients underwent pancreaticoduodenectomy for pancreatic cancer. Lymph nodes were numbered and classified into groups according to the Japan Pancreatic Society rules. Metastatic lymph nodes were identified based on hematoxylin and eosin staining. Results: Sixty-four (66.7%) patients had positive lymph nodes. The median number of metastatic nodes was 2 (95% confidence interval [CI], 1.0-3.0) and the median ratio of metastatic/resected nodes was 9.7% (95% CI, 7.1%-14.4%). The median survival was 14.2 months (95% CI, 10.7-17.7) and was significantly higher for node-negative than node-positive patients (27.9; 95% CI, 20.9-34.9 vs. 10.6; 95% CI, 8.7-12.5; P < 0.001). The Cox proportional hazards model, including all patients, demonstrated that nodal involvement (hazard ratio [HR], 1.461; 95% CI, 1.177-12.024), moderate or poor tumor differentiation (HR, 2.330; 95% CI, 1.181-6.949), and positive resection margins (HR, 3.838; 95% CI, 1.390-10.597) were independent negative prognostic factors. If the analysis was limited to node-positive patients, lymph node ratio of more than 20% (HR, 1.364; 95% CI, 1.116-2.599), moderate or poor tumor differentiation (HR, 3.393; 95% CI, 1.041-11.061), and positive resection margins (HR, 9.400; 95% CI, 2.235-39.536) significantly correlated with a poorer survival. Conclusions: Lymph node ratio seems to be a new promising prognostic factor in patients with respectable node-positive pancreatic head cancer.

Preoperative radiotherapy and local excision of rectal cancer with immediate radical re-operation for poor responders

BACKGROUND AND PURPOSE To report an early analysis of prospective study exploring preoperative radiotherapy and local excision in rectal cancer. MATERIALS AND METHODS Mucosa at tumour edges was tattooed. Patients with cT1-3N0 tumour <3-4 cm were treated with either 5x5Gy+4Gy boost (N=31) or chemoradiation (50.4Gy+5.4Gy boost, 1.8Gy per fraction+5-fluorouracyl and leucovorin; N=13). Thirteen patients from the short-course group were unfit for chemotherapy. The interval from radiation to full-thickness local excision was 6 weeks. The protocol called for conversion to a transabdominal surgery in case of ypT2-3 disease or positive margin. RESULTS The postoperative complications requiring hospitalization were recorded in 9% of patients. The rate of pathological complete response was 41%. The rate of patients requiring conversion was 34%; however, 18% actually underwent conversion and the remaining 16% refused or were unfit. During the 14 months of median follow-up, local recurrence was detected in 7% of patients and all underwent salvage surgery. Of 19 patients in whom initially anterior resection was likely, 16% had abdominoperineal resection performed for a conversion or as a rescue procedure. CONCLUSION Our study suggests that the short-course radiation prior to local excision is a treatment option for high-risk patients.

Case-control study of lifetime occupational and recreational physical activity and risks of colon and rectal cancer.

Important aspects of the inverse relation between physical activity and colon cancer risk are still under discussion. In 2000–2003, 239 incident cases of colorectal cancer confirmed by histopathology and 239 hospital-based controls, matched by age and gender, were enrolled. In standardized interviews, data on occupational and recreational physical activity for ages 20, 30, 40, 50 and 60 years were collected from 98 colon cancer cases, 141 rectal cancer cases, and from 193 controls. Besides lifestyle and sociodemographic characteristics, a detailed food frequency questionnaire was assessed. In multivariate logistic regression for colon cancer, significant risk reductions for the highest quartile of total physical activity were found for almost all ages. For lifetime mean physical activity, the multivariate odds ratio for the highest quartile was 0.37 [95% confidence interval (CI) 0.17, 0.83]. For lifelong constantly high-exercisers compared with lifelong non-exercisers an odds ratio of 0.26 (95% CI 0.08, 0.84) was estimated. For rectal cancer, no consistent association with physical activity was found. No confounding effects were observed but the authors found effect modification with total energy intake. These data support an inverse association of colon cancer risk and physical activity which is most expressed if activity is kept up throughout life.

Ratio of metastatic to resected lymph nodes for prediction of survival in patients with inadequately staged gastric cancer

Staging is inadequate in up to 70 per cent of patients with gastric cancer in Western countries owing to the small number of lymph nodes dissected during surgery. The aim was to determine whether using the ratio of metastatic to resected lymph nodes (LNR) might improve accuracy.

Adjuvant Chemotherapy with Etoposide, Adriamycin and Cisplatin Compared with Surgery Alone in the Treatment of Gastric Cancer: A Phase III Randomized, Multicenter, Clinical Trial

Objective: The aim of this study was to evaluate the efficacy of adjuvant chemotherapy with etoposide, Adriamycin and cisplatin (EAP) after potentially curative resections for gastric cancer. Methods: After surgery, patients were randomly assigned to the EAP or control arm. Chemotherapy included 3 courses, administered every 28 days. Each cycle consisted of doxorubicin (20 mg/m2) on days 1 and 7, cisplatin (40 mg/m2) on days 2 and 8, and etoposide (120 mg/m2) on days 4, 5, and 6. Results: Of 309 eligible patients, 141 were allocated to chemotherapy and 154 to the supportive care group. Four (2.8%) treatment-related deaths were recorded, including 3 due to septic complications of myelosuppression and 1 due to cardiocirculatory failure. Grade 3 or 4 toxicities were found in 17 (22%) patients. According to the intention-to-treat analysis, the median survival was 41.3 months (95% confidence interval, 24.5–58.2) and 35.9 months (95% confidence interval, 25.5–46.3) in the chemotherapy and control group, respectively (p = 0.398). Subgroup analysis revealed survival benefit from chemotherapy in patients with tumors infiltrating the serosa and in those with 7–15 metastatic lymph nodes. Conclusion: Three cycles of EAP regimen postoperatively offer no survival advantage in gastric cancer patients.

Efficiency of adjuvant immunochemotherapy following curative resection in patients with locally advanced gastric cancer

BackgroundDespite curative resection, 50%–90% of gastric cancer patients die of disease relapse. Although some clinical trials have indicated that chemotherapy and immunochemotherapy may be effective modalities, more recent studies have not been able to define the standard treatment for advanced gastric cancer. The present study evaluated the effect of adjuvant immunochemotherapy with the use of BCG (bacille Calmette-Guérin) and FAM (5-fluorouracil, adriamycin, mitomycin C) chemotherapy on the survival of patients with locally advanced resectable gastric cancer.MethodsA total of 156 patients with stage III or IV gastric cancer who had undergone curative resection were randomly assigned to three treatment groups: BCG + FAM (immunochemotherapy), FAM (chemotherapy), and control (surgery only). Treatment was continued for 2 years or until death. Further postsurgical follow up was carried on for up to 10 years.ResultsOverall 10-year survival was 47.1% for the immunochemotherapy group (P < 0.037 vs FAM and P < 0.0006 vs control), 30% for the chemotherapy group (vs control, NS), and 15.2% for the control group. In patients with pT2/T3 primary tumors, 10-year survival was 55.3% for BCG + FAM vs 28.2% for FAM (P < 0.01) and 14.6% for the control group (P < 0.00018). BCG + FAM signifi-cantly improved the survival of patients with intestinal-type but not diffuse-type cancer. Immunochemotherapy was well tolerated.ConclusionThis study, based on a limited number of patients, indicates that adjuvant immunochemotherapy (BCG + FAM) may prolong the survival of gastric cancer patients after curative gastrectomy; in particular, in patients with pT2/T3 tumors and intestinal-type primary tumors. There was no survival benefit from FAM adjuvant chemotherapy.

Case-control study on beneficial effect of regular consumption of apples on colorectal cancer risk in a population with relatively low intake of fruits and vegetables.

Laboratory in-vitro studies and animal experiments showing the potential health benefits from apples raises the question to what extent the regular consumption of apples in humans may have a beneficial effect on colorectal cancer risk. A total of 592 incident cases of colorectal cancer have been enrolled in a hospital-based case–control study. The comparison group included 765 controls chosen from the patients of the same hospital without history of cancer and admitted for treatment of nonneoplastic conditions. Interviews of both cases and controls were conducted in the hospital setting by trained interviewers. The median intake of fruits among cases was lower than in controls (9.5 vs. 11 servings/week) and the difference was statistically significant. Apples were the most frequent fruit consumed by the study participants and about 80% of variability in the total fruit consumption resulted from the intake of apples. We did not observe any significant statistical differences in consumption of berries, citrus, or stone fruits and other kinds of fruits across cases and controls. The adjusted estimates of colorectal cancer risk related to the daily consumption of apples (in quintiles) were based on the unconditional multivariate logistic model, which considered the set of potential confounding variables such as demographic characteristics of participants (age, gender, place of residency, marital status, tobacco smoking), total energy intake, intake of vegetables and fruits without apples. The results of the logistic analysis showed that the adjusted risk of colorectal cancer inversely correlated with daily number of apple servings. The reduced risk of colorectal cancer of border significance level was already observed at the consumption of at least one apple a day (odds ratio=0.65, 95% CI: 0.39–1.09), but at the intake of more than one apple a day the risk was reduced by about 50% (odds ratio=0.53, 95% CI: 0.35–0.79). Neither the consumption of vegetables nor other fruits have shown beneficial effects on the risk of colorectal cancer. The observed protective effect of apple consumption on colorectal risk may result from their rich content of flavonoid and other polyphenols, which can inhibit cancer onset and cell proliferation.

The value of imaging techniques in the staging of pancreatic cancer

BackgroundThe aim of this study was to assess the clinical value of endoscopic ultrasound (EUS) in the staging of pancreatic carcinoma and to compare it to ultrasonography (US) and CT.MethodsWe evaluated 45 patients (21 women and 24 men with a mean age of 62.1 years) who had undergone surgical treatment for pancreatic cancer between 1994 and 2004. Out analysis focused on the overall accuracy, sensitivity, and specificity of routine and Doppler US, CT, and EUS.ResultsEndoscopic ultrasound was the most accurate modality for local tumor staging (93.1%), vascular infiltration (90%), and lymph node assessment (87.5%). Routine US was the least accurate (82.5%, 67.5%, and 72.5%, respectively). The accuracy rates for CT and Doppler US were similar (88.1%, 82.5% and 80.0%, respectively).ConclusionsEndoscopic ultrasound is the most accurate method available to stage pancreatic cancer in the preoperative period. However, the advantage of EUS over CT and US does not justify its routine use due to its high cost, low availability, and invasiveness.

Dietary practices in households as risk factors for stomach cancer: a familial study in Poland

In the framework of a nationwide case-control study of risk factors for stomach cancer, a household survey was conducted on those food habits at the family level which were considered relevant for stomach cancer. The practices of 741 case and 741 control households were compared and relative risks calculated by the unconditional maximum likelihood method. For each household, the person responsible for cooking completed the survey. Respondents to the household survey were 35% of the cases and 40% of the controls of the case-control study and otherwise other household members. Case households relied more frequently on their own gardens as a major source of vegetables and fruit, and they cooked their vegetables more often than control households. The vegetable and fruit consumption during the summer period per family member was significantly less in case households compared to control households. The difference in per capita vegetable and fruit consumption between case and control households persisted, but was considerably less pronounced when the consumption of the index person (case or control) was subtracted from the household consumption. The consumption of mainly wholemeal bread showed a relative risk (RR) of 0.18 (95% CI 0.07–0.44) compared with mainly white bread consumption, whereas frequent frying and stewing of meat was associated with an increased risk compared to boiling of meat (RR = 2.06, 95% CI 1.48–2.87). No association with risk was found for long-term refrigerator use or other storage modalities. This study confirmed previous findings that consumption of raw vegetables and fresh fruit is inversely related to risk for stomach cancer in Poland. In addition, the study showed that the family as a whole is affected by many risk factors for stomach cancer. Families in which stomach cancer has occurred are therefore targets for preventive measures.