High pathological response rate in locally advanced esophageal cancer after neoadjuvant combined modality therapy: dose finding of a weekly chemotherapy schedule with protracted venous infusion of 5-fluorouracil and dose escalation of cisplatin, docetaxel and concurrent radiotherapy.

BACKGROUND: This phase I study was aimed at defining the toxicity profile and pathological response rate of a neoadjuvant schedule including weekly docetaxel and cisplatin, protracted venous infusion (PVI) of 5-FU and concomitant radiotherapy (RT) in locally advanced esophageal cancer. PATIENTS AND METHODS: The schedule consisted of a first phase of chemotherapy alone and a second phase of concurrent chemoradiation. Initial doses were: docetaxel and cisplatin 20 mg/m2 on days 1, 8, 15, 29, 36 and 43 plus 5-FU 150 mg/m2 PVI on days 1-21 and 29-49; RT (40 Gy) started on day 29. In the following steps the doses were escalated up to docetaxel 35 mg/m2 and cisplatin 25 mg/m2 on days 1, 8, 15, 29, 36, 43, 50 and 57 plus 5-FU 180 mg/m2 PVI on days 1-21 and 150 mg/m2 PVI on days 29-63 concurrently with RT 50 Gy. RESULTS: Forty-seven patients were enrolled and 46 completed the planned treatment. During the concomitant phase, grade 3-4 hematological toxicities occurred in three patients (6.5%) (or 3/174 cycles) and non-hematological toxicities in six patients (13%) (or 7/179 cycles). A pathological downstaging was obtained in 59.6% of the cases (28/47): complete remission (pCR) in 14 patients, near pCR (residual microfoci on the primary pN0) in eight patients, pT2 pN0 in three patients and partial response on the primary with positive lymph nodes in three patients. Six (13%) and 13 (28%) patients were considered stable and non-responders, respectively. In the last dose level, eight pCR and four near-pCR were obtained out of 15 patients. The maximum tolerable dose was not formally defined because dose escalation was stopped at the last dose level. CONCLUSION: This schedule represents a feasible treatment and the high pathological response rate is extremely encouraging; the doses found in the last dose-level are the basis for an ongoing phase II study at our institution.

Pattern of recurrence after surgery in adenocarcinoma of the gastro-oesophageal junction.

AIMS: This study reports mode, timing and predictive factors of recurrence after curative surgery for cardia cancer. METHODS: A prospective study in a series of 92 curatively (R0) resected patients from 1988 to 2002. RESULTS: The 5-year recurrence rate was 71%. Lymph node involvement was the only predictor of recurrence. No patients with more than 6 metastatic nodes were free from relapse 2 years after surgery. Locoregional, peritoneal and haematogenous relapses showed a similar median recurrence time (12, 10 and 12 months, respectively), 80% occurred within 24 months. CONCLUSIONS: Few patients can be cured by surgery, lymph nodal involvement is the only predictor of recurrence.

[Radiotherapy of stage T1 carcinoma of the glottis. Analysis of prognostic factors in 154 patients]. / La radioterapia dei carcinomi della glottide nello stadio T1. Analisi dei fattori prognostici in 154 pazienti.

A retrospective study was carried out on a series of 154 patients affected with vocal cord cancer in stage T1 treated with definitive radiotherapy April, 1979, to November, 1991. According to the 1992 TNM classification (UICC), 121 patients were classified as stage T1a and 33 patients as stage T1b. All patients were treated using parallel opposed fields of a 60 cobalt unit. Field size ranged from 16 to 30 square centimeters and the dose from 4400 to 7000 cGy, but only 15 patients received less than 6400 cGy. All patients were treated with once-daily fractionation (200 cGy/day). Follow-up ranges from 25 to 123 months; the median is 63 months. We observed 14 local recurrences (9.0%), all but one within 36 months from the end of treatment. Ten of 14 patients (71.4%) were rescued by surgery (8 patients underwent total laryngectomy and 2 conservative surgery); 13 patients were lost for intercurrent deaths. The incidence of recurrences is 7.4% for T1a patients (9/121) and 15.1% for T1b patients (5/33). The total dose does not seem to be related to relapse rate since recurrences were found in 6.6% of patients after a dose < 6400 cGy and in 9.3% of patients who had received higher doses. In our experience, field size did not affect, treatment results (< 25 cm2: 7.5% recurrences, > 25 cm2: 10.7%). Besides lesion volume, the main prognostic factor was overall treatment time. The incidence of failure was 3 times lower (5.8%) in the patients who completed the treatment within 7 weeks than in the patients whose treatment lasted more than 8 weeks (16.6%).

Population density pattern and change in the city of Riyadh, Saudi Arabia.

"This paper examines and assesses the changes in the population density pattern in the city of Riyadh, the capital of Saudi Arabia where the city has undergone dramatic changes in its physical as well as its social structure. Analysis of data revealed a decline in population density at an exponential rate from the city center with variation between city sectors and zones. The city's rapid horizontal expansion and dispersal of population is the result of factors such as increases in city population and in size and number of single family dwellings, widening of streets, rise in income and residential mobility rates, mass use of automobiles, change in family size, zoning regulations, leapfrogging, and huge governmental city development projects."