Long-course oxaliplatin-based preoperative chemoradiation versus 5 × 5 Gy and consolidation chemotherapy for cT4 or fixed cT3 rectal cancer: results of a randomized phase III study.

BACKGROUND: Improvements in local control are required when using preoperative chemoradiation for cT4 or advanced cT3 rectal cancer. There is therefore a need to explore more effective schedules. PATIENTS AND METHODS: Patients with fixed cT3 or cT4 cancer were randomized either to 5 × 5 Gy and three cycles of FOLFOX4 (group A) or to 50.4 Gy in 28 fractions combined with two 5-day cycles of bolus 5-Fu 325 mg/m(2)/day and leucovorin 20 mg/m(2)/day during the first and fifth week of irradiation along with five infusions of oxaliplatin 50 mg/m(2) once weekly (group B). The protocol was amended in 2012 to allow oxaliplatin to be then foregone in both groups. RESULTS: Of 541 entered patients, 515 were eligible for analysis; 261 in group A and 254 in group B. Preoperative treatment acute toxicity was lower in group A than group B, P = 0.006; any toxicity being, respectively, 75% versus 83%, grade III-IV 23% versus 21% and toxic deaths 1% versus 3%. R0 resection rates (primary end point) and pathological complete response rates in groups A and B were, respectively, 77% versus 71%, P = 0.07, and 16% versus 12%, P = 0.17. The median follow-up was 35 months. At 3 years, the rates of overall survival and disease-free survival in groups A and B were, respectively, 73% versus 65%, P = 0.046, and 53% versus 52%, P = 0.85, together with the cumulative incidence of local failure and distant metastases being, respectively, 22% versus 21%, P = 0.82, and 30% versus 27%, P = 0.26. Postoperative and late complications rates in group A and group B were, respectively, 29% versus 25%, P = 0.18, and 20% versus 22%, P = 0.54. CONCLUSIONS: No differences were observed in local efficacy between 5 × 5 Gy with consolidation chemotherapy and long-course chemoradiation. Nevertheless, an improved overall survival and lower acute toxicity favours the 5 × 5 Gy schedule with consolidation chemotherapy. CLINICAL TRIAL NUMBER: The trial is registered as ClinicalTrials.gov number NCT00833131.

Risk of chemotherapy-induced pulmonary fibrosis is associated with polymorphic tumour necrosis factor-a2 gene.

In some patients, chemotherapy (CHT) of cancer can result in pulmonary inflammation and fibrosis, eventually leading to respiratory insufficiency. As animal studies have underlined the importance of major histocompatibility complex (MHC) genes in the susceptibility to bleomycin (BLM)-induced pulmonary fibrosis, the authors typed human leukocyte antigen-DR (HLA-DR) and tumor necrosis factor (TNF) genes in patients treated for Hodgkin's disease by a therapy including bleomycin. Patients were divided into pulmonary responders (PR) (n=21) or nonresponders (PNR) (n=20) on the basis of pulmonary alterations detected on chest radiography and the cumulated amount of BLM injected. The incidence of TNFa2, a microsatellite allele in the promoter region of the TNFB gene reported to be associated with increased TNF-a production, was significantly higher in PR than PNR (65% versus 19%). HLA-DRB1*15 showed a weak but nonsignificant association with the PR phenotype (50% versus 14%), as well as HLA-DRB1*03 (30% versus 19%) and TNFA-308*2 (30% versus 14%). TNFa2 and DR15 were independent risk factors and the occurrence of either genetic marker was 85% versus 29% in the PR and PNR groups respectively. Thus, the polymorphic TNFa2 microsatellite is associated with a risk of chemotherapy-induced pulmonary fibrosis.

CYFRA 21-1, TPA-M, TPS, SCC-Ag and CEA in patients with squamous cell lung cancer and in chemical industry workers as a reference group.

In etiology of lung cancer chemical carcinogenesis seems to be a very important factor. In the studies presented here the diagnostic usefulness of tumor markers in lung cancer was evaluated, using as a reference group workers of a chemical plant producing chromite and chromate pigments. The investigations of CYFRA 21-1, TPA-M, TPS, CEA and SCC-Ag were performed before treatment in a group of 76 squamous cell lung cancer patients in different stages of disease and in a reference group of 75 workers of the chemical company, who had been exposed to hexavalent chromium for longer than 1 year and had no clinical or radiological symptoms of lung diseases. In the squamous cell lung cancer group concentrations of all analyzed tumor markers were considered to be significantly higher than in the reference group. TPA assay demonstrated higher diagnostic performance than CYFRA 21-1 and the remaining tumor markers. At 0.95 specificity, the sensitivity of TPA was 0.79, CYFRA 21-1 -0.76, of TPS -0.29 whilst of CEA and SCC-Ag -0.31. The univariate analysis showed a significant prognostic value for clinical stages, only for CYFRA 21-1 and SCC-Ag. A significant relationship between marker level and survival was observed for CYFRA 21-1 as well as SCC-Ag levels. In a multivariate analysis CYFRA 21-1 and/or TPS remained significant predictors of survival.

Prognostic and predictive evaluation of DNA content, S-phase fraction and immunophenotyping in non-Hodgkin's lymphomas in adults. A prospective study.

In non-Hodgkin's lymphoma (NHL) patients, prognostic significance of S-phase fraction (SPF) is well known, however the significance of DNA ploidy status and antigen expressions is still unclear. The purpose of the present study is to evaluate the prognostic and predictive impact of SPF, immunophenotype and DNA ploidy in prospectively analysed NHL patients. The study was performed on lymph node biopsies of 117 nodal NHL patients. The median follow-up of patients was 25 months (range 1-64 months). All histologically verified lesions were considered according to the Working Formulation and Kiel classification. SPF, immunophenotype and ploidy were determined by flow cytometry. The rate of 2-year overall survival was 56%. SPF and DNA ploidy status were found to be independent prognostic factors in low and high grade lymphomas, respectively. Patients with near-tetraploid lymphomas were characterised by unfavourable clinical outcome, whereas hypertetraploidy was a favourable prognostic indicator. Among B-cell lymphomas CD5 expression seems to be of prognostic significance.

[Chordomas. Analysis of 24 cases]. / Struniaki. Analiza 24 przypadków.

Chordoma is a relatively rare neoplasm originating from the remnants of the embryonic notochord. We analysed 24 cases of chordoma. The patients were divided into groups depending on the localisation. We analysed the results of different methods of therapy: surgical treatment, radiation therapy and combined surgical and radiological treatment. The results were compared with the data from the references.

Poorly differentiated naso- and oropharyngeal carcinoma. A retrospective comparison between the results of radiotherapy alone and radiotherapy plus adjuvant methotrexate.

One hundred and forty-one patients with poorly differentiated naso- and oropharyngeal carcinoma were treated at the Center of Oncology in Kraków 1970-1985. Ninety-eight patients, treated from 1970 to 1980, received radiation therapy alone and forty-three patients, treated from 1981 to 1985, received adjuvant monochemotherapy with methotrexate 60 mg/m2 i.v. administered every 6 weeks, starting 6 weeks after completion of radiotherapy. The two groups were comparable in patients' characteristics such as stage of the disease, sex, age, localization and histology. The three-year survival rate in the total group of 141 patients was 46.8%. Important prognostic factors were: stage (UICC 1987), extent of local tumour and nodal involvement. Three-year survival rates according to stage were as follows: stage I, 100%; stage II, 95%; stage III, 75% stage IV, 4.4%. There was no significant survival difference between the two groups, and the adjuvant methotrexate therapy did not alter the pattern of failures. The results do not support the hypothesis that adjuvant methotrexate treatment is beneficial in this type of patient.