Response to thyrotropin of normal thyroid follicular cell strain FRTL5 in hypergravity.

Thyroid hormones control every cell in the organisms and, as indicated by many hormonal changes in astronauts during and shortly after space missions, its complex regulation may be influenced by gravity. To test in vitro the effects of gravity environment on thyroid, we selected a unique cultured cell system: the FRTL5, a normal follicular thyroid cell strain in continuous culture, originally derived from adult rat thyroids. To establish if modifications of the gravitational environment may interfere with post-receptorial signal transduction mechanisms in normal mammalian cultured cells, following our previous microgravity experiments, we exposed thyrotropin-stimulated and unstimulated FRTL5 cells to hypergravity (5 g and 9 g) in a special low-speed centrifuge. At all thyrotropin doses tested, we found significant increases in terms of cyclic AMP production in FRTL5 thyroid cells. The data here reported correlate well with our previous microgravity data, showing that the FRTL5 cells functionally respond to the variable gravity force in a dose-dependent manner in terms of cAMP production following TSH-stimulation.

Combined modality therapy of resectable high risk rectal cancer.

Aim of this phase I-II study was to evaluate the efficacy of preoperative concomitant radiochemotherapy in resectable high risk (TNM stage: II and III) rectal tumors, 64 patients entered the study: 37 had low rectal cancer, 27 mid-rectal cancer. 50 patients were clinically staged as stage III (Dukes C) and 14 as stage II (Dukes B). Treatment protocol included bolus mitomycin C at the dose of 10 mg/m2 on day 1 and 5FU continuous infusion at the daily dose of 1000 mg/m2 on day 1, 2, 3, 4. Concomitant external radiotherapy up to a dose of 3780 cGy was delivered at the daily dose of 180 cGy. Surgery was performed 4 to 5 weeks after radiation therapy (RT). Before surgery all patients were clinically restaged to evaluate the response to concomitant radiochemotherapy. Treatment compliance was 97%. Toxicity was 27% prevalently shown as bone marrow depletion and radiodermatitis. In 37 patients (61%) there was 50% reduction (partial response) of neoplastic volume. In 5 patients (8%) no neoplastic cells were evidenced in the surgical specimen on histology (complete response). The distance between the lower margin of the tumor and the internal anal orifice increased in 72% of cases. Postoperative morbidity was 28%. The incidence of anastomotic dehiscences was 8.7% over 46 anterior resections. Postoperative mortality was nil. Definitive staging evidenced 24 patients (39%) stage I or with no evidence of tumor. The incidence of local recurrence was 5% and that of distant metastasis 8%.

A randomized phase II study comparing sequential versus simultaneous chemo-radiotherapy in patients with unresectable locally advanced squamous cell cancer of the head and neck.

BACKGROUND: Single-modality radiotherapy is still considered standard treatment for patients with locally advanced unresectable cancer of the head and neck. As treatment outcome is poor, attempts to integrate chemotherapy into the overall management of these patients are ongoing. PATIENTS AND METHODS: A randomized study was undertaken to compare a sequential with a simultaneous chemoradiotherapy program. Between February 1986 and February 1991, 93 eligible patients with locally advanced unresectable cancer of the head and neck were stratified by WHO PS, T and N class and primary site and then randomized to receive either three courses of neoadjuvant chemotherapy with cisplatin (100 mg/m2 i.v. d 1) and 5-fluorouracil 1000 mg/m2/days 1-5 by continuous i.v. infusion every 3 weeks prior to definitive conventional radiotherapy of 65-70 Gy (sequential treatment), or cisplatin 100 mg/m2 on days 1, 22, 43 given simultaneously for the duration of the same conventional radiotherapy (simultaneous treatment). RESULTS: At the end of the entire treatment 18 complete responses (47%) in the sequential-treatment arm and 18 (41%) in the simultaneous treatment arm were obtained. No statistically significant differences in the 5-yr progression-free survival, in the median time to loco-regional and distant progression and in the 5-yr overall survival were observed. Leukopenia was more frequent in the simultaneous than in the sequential arm (p = 0.03), whereas alopecia (p = 0.008) and phlebitis (p < 0.0001) were more frequent in the sequential-treatment arm. A better compliance was associated with the concomitant treatment, with 87% of the patients completing the entire radiotherapy program versus 63% of those in the sequential arm (p = 0.01). CONCLUSIONS: In the present study, the two treatment arms showed similar activity (complete response, progression-free and overall survival rates). Compliance to treatment was better in the concomitant arm. These data suggest that concomitant chemo-radiation therapy might be considered an option in unresectable locally advanced cancer of the head and neck. Phase III studies are needed in order to establish the superiority of this combination of cisplatin and radiotherapy versus radiotherapy alone.

Improved local control and survival with the "sandwich" technique of pelvic radiotherapy for resectable rectal cancer. A retrospective, multivariate analysis.

PURPOSE: The following study was done to evaluate the therapeutic value of radiotherapy as an adjunct to surgery for rectal cancer patients. METHODS: One-hundred twenty-four patients underwent curative resection by one surgeon (RC) from 1982 to 1991. Forty patients received combined preoperative and postoperative (sandwich) radiotherapy, 30 patients received postoperative radiotherapy, and 54 patients were treated by surgery alone. During the study period sandwich radiotherapy was primarily offered as a free treatment option for patients with tumors which were believed to be transmurally invasive, whereas postoperative radiotherapy was an alternative therapeutic option offered to patients with tumor classified as Dukes B and C at histopathologic examination. RESULTS: Operative mortality was 2 percent in the sandwich radiotherapy group vs. 7 percent in the surgery alone group. After a median follow-up of 60 months, the actuarial locoregional recurrence rate at five years was 3 percent for the sandwich radiotherapy group compared with 18 and 30 percent for the postoperative radiotherapy and surgery alone groups, respectively (P = 0.019). A multivariate analysis using the Cox model confirmed the favorable independent influence of sandwich radiotherapy on local tumor control, especially in distal tumors. The therapeutic benefit of sandwich radiotherapy translated into increased survival in the low-rectum Dukes B subgroup of patients. The actuarial five-year survival rates were 86 percent, 50 percent, and 28 percent in the sandwich radiotherapy, postoperative radiotherapy and surgery alone groups, respectively (P = 0.05). CONCLUSIONS: Preoperative radiotherapy has a significant effect on the prognosis of rectal cancer patients.

Prognostic factors for chemotherapy response and survival using combination chemotherapy as initial treatment of advanced head and neck squamous cell cancer.

Between May 1981 and December 1987, 152 consecutive patients with locally advanced and previously untreated head and neck squamous cell cancer (HNSCC) received two or three courses of neoadjuvant chemotherapy (NAC) prior to surgery and/or radiotherapy. Eighteen percent of patients achieved a complete response and 45% a partial response (PR), for an overall response rate of 63%. A variety of pretreatment patient and tumor characteristics were analyzed for both the tumor response to NAC and survival rate. Significantly higher CR rates were found in patients with a World Health Organization (WHO) performance status (PS) of 0 to 1 than in those patients with a PS of 2 (P = .03). Patients with stage III disease were significantly more likely to respond than those with stage IV (P = .006). Evaluation of all parameters through multivariate analysis identifies the tumor classification (P = .001) and the primary site (P = .006) as the most significant in predicting CR. The overall 5-year survival rate of the entire group of patients was 18% (median survival, 14.3 months). Analysis by PS (P = .001), stage (P = .002), and tumor (P = .001), and node (P = .01) classes showed significant differences. Patients achieving a CR after NAC had a significantly improved survival rate as compared with those with residual disease at assessment (P = .0003). With the multistep regression analysis, the tumor (P = .005) and node (P = .007) classifications, and the sex (P = .03) were significant factors, but CR (P = .0004) remained the most important and independent predictive factor. Randomized prospective trials are requested to clearly establish the role of NAC on survival rates.