A benchmark study on 883 nasopharyngeal cancer patients treated in two Italian centres from 1977 to 2000. Part II: Evolving technical choices and toxicity patterns.

PURPOSE: The authors sought to define toxicity patterns according to the different accrual periods and clinical-therapeutic features in a large series of nasopharyngeal cancer (NPC) patients treated in two Italian centres over more than two decades. MATERIALS AND METHODS: A total of 883 patients consecutively treated with radiotherapy from 1977 to 2000 at the Florence (FLO) and Brescia (IRA) radiation oncology centres were studied. The crude incidence of late treatment toxicity in the different subgroups of patients was calculated and compared. RESULTS: Higher total and fractional doses and the "older" treatment techniques were related with an increased incidence of the main late effects of treatment. More recently treated patients experienced less treatment-related complications. CONCLUSIONS: Results of this benchmark study may have implications for understanding and developing new radiotherapy techniques, such as three-dimensional conformal radiotherapy (3D-CRT) and, in particular, intensity-modulated radiotherapy (IMRT) for NPC patients.

Late computed tomography scan response improvement and gallium scintigraphy evaluation as on-treatment prognostic parameters to tailor treatment intensity in patients with Hodgkin's lymphoma. A prospective phase II study.

BACKGROUND: Tailoring treatment intensity is critical in Hodgkin's lymphoma (HL). Ongoing prognostic parameters may be an useful adjunct to pretreatment stratification. We used the kinetics of computed tomography (CT) scan response and residual gallium (Ga)-67 uptake to better stratify risk. MATERIALS AND METHODS: Patients received 4-8 adriamycin, bleomycin, vinblastine and dacarbazine courses according to stage. Disease was reassessed evaluating late computed tomography scan response improvement (CTRI) and Ga-67 uptake. Patients received no further treatment, radiotherapy (RT) or additional chemotherapy + RT according to the presence of none (low risk), one (intermediate risk) and both parameters (high risk). Patients with bulky mediastinum received RT anyhow. RESULTS: Among 102 assessable patients, 35 showed late CTRI and 9 residual Ga-67 uptake. In 30 patients with bulky mediastinum, the 3-year progression-free survival (PFS) was significantly better when neither parameter was present (100% versus 69%; P = 0.02). In 72 patients without bulky mediastinum, treatment was tailored according to risk assignment. Relapses occurred in 5 of 47 low-risk and 3 of 21 intermediate-risk patients, with no differences between the two groups, and in 3 of 4 high-risk patients. CONCLUSION: This study shows that two on-treatment parameters, late CTRI and residual Ga-67 uptake, can predict PFS in HL and identify patients in which RT can be spared without apparently affecting the outcome.

Postoperative radiotherapy after radical prostatectomy for prostate carcinoma: the experience of the Brescia Radium Institute.

PURPOSE: The purpose of this study was to evaluate the efficacy of postoperative radiotherapy in reducing the incidence of prostate carcinoma (PCa) recurrences after radical prostatectomy (RP), define the importance of the time interval between surgery and radiotherapy for prognosis and the toxicity of the treatment in comparison with radiotherapy or surgery alone. MATERIALS AND METHODS: We examined 97 patients who consecutively underwent postoperative radiotherapy after RP between 1980 and 2003. The treatment was considered "adjuvant" if was conducted less than 6 months after RP, if there was no macroscopic residual disease and if there was no progressive increase in serum prostate-specific antigen (PSA) and "salvage" if performed more than 6 months after RP, for the presence of macroscopic recurrence or with rising PSA. Radiotherapy was salvage in 56 patients and adjuvant in 41. Age range was 60-70 years in 80% of patients, and the Karnofsky index was over 80 in 78% of cases. Histology revealed extracapsular spread in 60% of patients. Preradiotherapy PSA was higher than 1 ng/ml in 36%. Radiotherapy was performed on the surgical bed only in 80%, and the total dose was 70 Gy in 62% of cases. RESULTS: Recurrence-free survival (RFS) at 5 years and 10 years was 53+/-8% and 32+/-14.2%, respectively, for the whole sample; 76+/-9% and 38+/-2.7% for patients treated with adjuvant radiotherapy and 36+/-10% and 28+/-10% for those treated with salvage radiotherapy (p<0.01). Moreover, the 5-year RFS was better in the group treated with adjuvant radiotherapy and PSA less than or equal to 1 ng/ml (p<0.05). Treatment toxicity was acceptable. CONCLUSIONS: Postoperative radiotherapy improves RFS and reduces the risk of local recurrence. The best results are obtained with early postoperative treatment ("adjuvant"); adjuvant radiotherapy of high-risk forms yields better results if performed with PSA less than or equal to 1 ng/ml.

[Conservative surgery in the environment of a screening program for breast carcinoma: evaluation of the results in terms of local recurrence]. / Chirurgia conservativa nell'ambito di un programma di screening per il carcinoma della mammella: valutazione dei risultati in termini di recidiva locale.

This report evaluates the results of conservative surgery plus radiotherapy (QUART) in a group of 123 patients from the screening programme of the District Health Board USSL 41 in Brescia, Italy (over 250 tumours diagnosed in two screening rounds, between 1987 and 1993). To date no recurrence of neoplasms in the operated breast have been diagnosed in either of the two QUART groups (64 patients from the first round, average follow-up 28 months, median 66 months; 59 patients from the second round, average follow-up 28 months, median 30 months). A new carcinoma in the contralateral breast occurred in 3 patients (2 from the first and 1 from the second round), while in 3 cases there was a recurrence in another site (2 from the first and 1 from the second round). These results confirm both the proven effectiveness of conservative treatment in the local control of breast tumours, and the importance of the correct choice of conservative treatment in optimising aesthetic and therapeutic results.

[Exclusive radiotherapy in the treatment of carcinoma of the portio cervicis, stage IIB FIGO]. / La radioterapia esclusiva nel trattamento dei carcinomi della portio allo stadio IIB FIGO.

From January 1970 through December 1987, 135 patients with cervical cancer in stage IIB (FIGO criteria) were treated by means of exclusive radiotherapy in the Istituto del Radio of the Brescia University. Thirty cases were treated by exclusive external-beam radiotherapy (RTT), 39 by brachytherapy (CU) plus external-beam radiotherapy, 24 by combined RTT and CU, 41 by RTT + CU + RTT, and 1 case by CU alone. Crude survival at 5 years is 52.4%, and NED survival is 50%. The differences between the values of crude and NED survival by radiotherapy technique were statistically significant (p 0.05), ranging from 69.8% in the RTT + CU group to 35.5% in the RTT alone group. Twenty-four cases (18%) failed to obtain complete remission, and 24 more cases recurred in the pelvis. Sequelae were evaluated by the French-Italian glossary; they were present in 62 cases (46%), but in 12 cases only (9%) they were severe. The incidence of sequelae was highest in the groups of patients treated with the combined techniques (RTT and CU) which allowed best disease control.

[Chemo-radiotherapy in advanced head and neck tumors. Personal experience]. / La chemio-radioterapia nei tumori avanzati del capo-collo. Esperienza personale.

From January 1981 through December 1983, 49 untreated patients with locally advanced head and neck cancers were randomized in two groups to receive different radiochemotherapy regimens. Group A, including 29 cases, received 4 cycles of induction chemotherapy with Bleomycin, Methotrexate and Hydroxyurea before definitive external radiotherapy (60 Gy); group B, including 20 patients, received the same total dose of radiotherapy but the 4 cycles of chemotherapy, as described above, were administered between the 20- and the 40-Gy doses. Both groups were compared with a control group treated in the same period with radiotherapy (60 Gy) alone. The response to treatment was evaluated at the end of chemotherapy or radiotherapy alone and at the end of combined regimens. Long-term survival rates were analyzed for all groups relative to complete tumor response, disease-free interval and time to disease progression. In our experience the radio-chemotherapy combination, according to the described schedules, failed to improve both local control and overall survival; the comparison with the control group does not suggest that induction or intercalated chemotherapy can increase long-term survival even if initial complete and partial response rates are high.

[Evaluation of the accuracy of the study on diverse techniques of planning radiotherapy of breast tumors]. / Valutazione dell'accuratezza nello studio con diverse metodiche del piano di trattamento radioterapico per tumori mammari.

The authors report the results of the analysis of several factors contributing to the accuracy of treatment planning in the radiation therapy of breast cancer. Different techniques (non-radiological vs CT-based) were used for the acquisition of patients' data; different methods (manual vs computerized) were employed for dose calculation. As for geometric parameters describing the external outline and target volume, mean differences were lower than 4%. Switching from a completely manual method to a CT-based one with computerized calculation, a 3.56% mean decrease in the value of reference isodose (p less than 0.01) was observed, together with a 3.87% mean increase in the estimated inhomogeneity (p less than 0.001). The non-CT-based outline of target volume exhibited geographic missing of inner portions of the target in 8/16 patients. Our results demonstrate that treatment planning procedures can be a significant source of clinically relevant inaccuracy, which may affect treatment outcome and tumor control.

[Rhinopharyngeal carcinoma. Clinical prognostic factors]. / Carcinoma rinofaringeo. Fattori prognostici clinici.

The authors report the results of the retrospective analysis of 306 patients with nasopharyngeal carcinoma. All patients had received high-dose radiation therapy. First, overall results were analyzed, and then the prognostic value of the patients' data (age and sex) and of tumor features (histology, local spread, lymph node involvement). Crude actuarial survival rate is 42.9% (+/- 2.9) at 5 years; loco-regional control at the end of treatment was obtained in 16.8% of cases; 53.6% of them (126 patients) had relapses, especially on T and M. Cumulative relapse rate was 51.1% (+/- 3.3) at 5 years. Mean relapse-free interval was 10 months. All the clinical factors we examined had prognostic value; especially local tumor spread, with a worse prognosis for tumors with extra-nasopharyngeal spread (5-year survival: 38.3% +/- 6.9 for T3 and 33.9% +/- 4.8 for T4), and especially for tumors with neurological deficits (5-year survival: 19.9% +/- 6.3). Regional lymph node metastases were an important factor too, with a special emphasis on size (5-year survival: 26.4% +/- 6.5 in the cases with adenopathies with phi greater than 6 cm), and fixed adenopathies (5-year survival: 23.9% +/- 4.6). These prognostic factors are considered only in part in the current TNM 1987 staging system, which calls for its partial revision.

[Exclusive radiotherapy of stage Ib cervix carcinoma]. / La radioterapia esclusiva del cervicocarcinoma stadio Ib.

From January 1st 1970 to December 31 1987, 178 consecutive cervical cancer Ib patients were treated at the Istituto del Radio, University of Brescia, by means of radiotherapy alone. In spite of the negative selection of the patients (advanced age, poor general conditions, associated pathologies) the results were good: 5-year cumulative survival was 86.5%, with a total failure rate of 13.5% (24 failures: 18 in the pelvis, 3 metastases and 3 both). The incidence of major complications (G2-G3-G4 of the Italian-French glossary) was 20% (36 patients): 19 G2, 15 G3 and 2 G4. The results in terms of survival and complications were related to the prognostic factors of the tumor (histology, grading, tumor size), of the patient (age, Karnofsky scale, associated pathologies, number of erythrocytes and hemoglobin rate) and treatment modalities (total dose, fractionation, combination of intracavitary brachytherapy and external beam).

[Radiotherapy of locally advanced tumors of the mouth floor and the tongue]. / La radioterapia dei tumori localmente avanzati del pavimento orale e della lingua.

At Istituto Radio "O. Alberti" in Brescia 312 patients with locally advanced cancers (T3-4N0 and T1-4N1-3) of the tongue or floor of the mouth were treated between 1970 and 1985. All underwent high energy radiotherapy associated, in 93 cases, with surgery on the T and/or on the N. The cases were divided by T and N in order to evaluate the prognostic importance of these parameters. Total remission (TR) at the end of treatment was achieved in 52% of the cases (163 patients). A relationship was found between tumor size, degree of lymph node involvement and the likelihood of response. Of the 163 cases in TR, 89 (55%) showed recurrence; 80% taking place within the first two years. After correction for natural death, the actuarial 5 year survival rate for the entire case study proved to be 27% while NED was 22%. The group undergoing radiotherapy in association with surgery showed a better survival rate than the group which only underwent radiotherapy (45% vs. 20% at 5 years). In the cases of advanced T (T3-4) lymph node involvement did not appear to affect prognosis.

Statistical evaluation of a total dose-dose rate relationship in oral tongue cancer 192 Ir implants.

A statistical tool has been made by us on 55 patients treated for oral tongue cancer with unique 192 Ir interstitial curietherapy in Brescia from 1973 to 1981. Our aim was to verify a simple analytical relationship proposed and adopted by us for oral tongue cancer implants in order to reduce the total dose with increasing dose rates and to calculate the equivalent total dose when referred to 0.357 Gy/hr. Recurrences and radionecroses are studied in a variance analysis, distinguishing according to stage and total dose; within the dose rate range used, a highly significant difference in radionecrosis rate (P less than 0.005) confirms our isoeffect relationship.

[The management of particle accelerators in radiotherapy]. / La gestione di acceleratori di particelle per radioterapia.

In this multicentric survey, the management costs and the technical problems connected with the use of electron accelerators in Radiotherapy are studied. The data were collected by a proper questionnaire and concern 11/35 accelerators in use in Italy, in public hospitals, during the period 1982-1983. The average purchase cost of an accelerator was 1113 milions lire and the amortization cost is 111 milions lire per year. The expenses for the amortization of the cost of the bunker, for ordinary and extraordinary maintenance, for the employed staff and for the electric power respectively, represent the 22%, 5%, 43% and 2% of the total management cost (395 milions lire per year). In 1983 the load per machine was 400 patients and the cost per patient was 1 milion lire. On the average, 4 years are needed from the order to the beginning of the treatments with large differences among centers. The machines average use is 7.1 hours a day and keep 2.8 technicians busy per week. The time wasted by repairs or maintenances increases (+7%) the average duration of stay in hospital of patients. An attentive evaluation of the studied parameters allows us to single out the most significant variables on which is possible to work to increase the efficiency and to reduce the management costs of an accelerator.

Radiotherapy of oral tongue cancer.

The results in the treatment of oral tongue cancer are analysed to suggest a highly specified therapeutic program. Two hundred and thirty-two cases, radiologically treated at the Istituto del Radio Alberti, Brescia, Italy, from 1964 to 1978 are considered. Depending on the staging, exclusive interstitial curietherapy, exclusive external radiotherapy, or external plus interstitial therapy were applied. The therapy of locoregional lymph nodes was surgical and/or radiological. The statistical analysis deals with actuarial survival, local remission, recurrences and radionecroses. Particular attention is paid to N0 cases that became N positive. The suggested therapeutic program depends strictly on the staging and defines also the optimal doses.

[Clinical dosimetry in radium 226 and iridium 192 interstitial therapy of oral tongue cancer (author's transl)]. / Considerazioni clinico-dosimetriche nella curieterapia interstiziale con radio 226 e iridio 192 dei carcinomi della parte mobile della lingua.

On 96 patients with carcinoma of the floating part of the tongue in the early stage treated by interstitial curietherapy alone have been effect both a comparison between the obtainable results with the 192Ir and with the 226Ra and a total valuation of some able factors (dose-rate, total dose, tumor volume) to influence the curietherapy after loading with 192Ir.