Concomitant chemoradiotherapy versus induction docetaxel, cisplatin and 5 fluorouracil (TPF) followed by concomitant chemoradiotherapy in locally advanced head and neck cancer: a phase II randomized study.

BACKGROUND: Concomitant chemoradiotherapy (CT/RT) is the standard treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN). We evaluated the efficacy of induction docetaxel (Taxotere), cisplatin, and 5-fluorouracil (TPF) before CT/RT versus CT/RT alone. PATIENTS AND METHODS: Patients with stage III-IVM0 SCCHN, Eastern Cooperative Oncology Group performance status of zero to one, were randomly assigned to receive CT/RT alone (arm A: two cycles of cisplatin 20 mg/m(2), days1-4, plus 5-fluorouracil 800 mg/m(2)/day 96 h continuous infusion, during weeks 1 and 6 of radiotherapy) or three cycles of TPF (arm B: docetaxel 75 mg/m(2) and cisplatin 80 mg/m(2), day 1, and 5-fluorouracil 800 mg/m(2)/day 96 h continuous infusion, every 3 weeks) followed by the same CT/RT. The primary end point was the rate of radiologic complete response (CR) at 6-8 weeks after the end of CT/RT. RESULTS: A total of 101 patients were randomly allocated to the study (51 arm A; 50 arm B). CR rates were 21.2% (arm A) versus 50% (arm B). Median progression-free survival and overall survival were, respectively, 19.7 and 33.3 months (arm A) and 30.4 and 39.6 months (arm B). Hematologic and non-hematologic toxic effects during CT/RT were similar in the two arms. CONCLUSION: Induction TPF followed by CT/RT was associated with higher radiologic CR in patients with locally advanced SCCHN with no negative impact on CT/RT feasibility.

Effects of fluconazole in the prophylaxis of oropharyngeal candidiasis in patients undergoing radiotherapy for head and neck tumour: results from a double-blind placebo-controlled trial.

Fluconazole is recommended in the prophylaxis of oropharyngeal candidiasis (OPC) in patients undergoing radiotherapy for head-neck tumours; however, the actual effectiveness of fluconazole in this setting remains unclear. Adult patients with cervico-cephalic carcinoma submitted to radical or adjuvant radiotherapy were randomized to 100 mg fluconazole (n = 138) or matched placebo (n = 132) oral suspension once daily from the sixth session of radiotherapy up to the end of treatment. The final analysis of the investigation showed a higher rate of the OPC outbreak-free survival in the fluconazole compared with placebo (P = 0.008 in the log-rank test). The mean time (95% CI) to OPC outbreak was 56 (53-59) days in the fluconazole group and 47 (43-51) days with placebo. The mean duration of radiotherapy was 43.5 and 39.9 days, respectively in the two groups (P = 0.027). Adverse effects were reported in 70.3% of patients in the fluconazole group and in 67.4% with placebo. The results showed prophylaxis with fluconazole given in irradiated patients with head-neck tumours significantly reduces the rate and the time to development of OPC compared with placebo.

Preoperative chemoradiotherapy in cancer of the thoracic esophagus.

Surgery with or without adjuvant radiotherapy (RT) is the standard treatment of esophageal cancer. Preoperative radio- and chemotherapy (CT) have been introduced to improve prognosis. We report a phase II prospective non-randomized trial of preoperative RT (42 Gy/25) plus CT (cisplatin 20 mg/mq/day plus 5-fluorouracil 600 mg/mq/day, 1-5 weeks) for the treatment of thoracic esophageal cancer. From 1993, 50 patients were enrolled (40 men and 10 women, mean age 57 years, range 30-75 years). Squamous cell carcinoma accounted for 90% of cases; 10% were adenocarcinoma. Downstaging of the disease was obtained in 77.3% of cases; there were 13 (29.5%) complete responses (CR) and 21 (47.7%) partial responses (PR). Median survival was 28 and 25 months, respectively, for CR and partial response (PR) plus stable disease (SD) and progressive disease (PD) (P = 0.05). Progressive-free median survival was 22 and 17 months, respectively, for CR and PR + SD + PD (P = 0.08). Multimodal treatment of esophageal cancer showed promising results, although not significant, in terms of survival and disease progression for patients achieving a complete pathologic response.

Primary systemic CD30 (Ki-1)-positive anaplastic large cell lymphoma of the adult: sequential intensive treatment with the F-MACHOP regimen (+/- radiotherapy) and autologous bone marrow transplantation.

Few series of adult patients with primary systemic CD30 (Ki-1)-positive anaplastic large cell lymphoma (ALCL) are reported in the literature; most of them have been treated with combination chemotherapy (CHT), with only an occasional patient being autotransplanted, mainly after relapsing. The remission rate ranges from 60% to 90%, but relapses are frequent (up to 60%) and precocious (mainly in the first 24 months). The aim of our study was to analyze the outcome of a series of adult patients affected by primary systemic ALCL that were treated at our institution with a sequential intensive therapeutic program including CHT, radiotherapy (RT), and autologous bone marrow transplantation (ABMT). Sixteen consecutive, unselected patients with ALCL were identified. All of them were treated with the 5-fluorouracil, methotrexate, cytosine arabinoside, cyclophosphamide, doxorubicin, vincristine, and prednisone (F-MACHOP) regimen; 9 of 16 (56.2%) reached a complete remission (CR). In six cases with residual mediastinal disease, involved-field RT was performed, allowing three additional patients to become free of disease. All 16 were then autotransplanted with bone marrow stem cells after conditioning with the cytosine arabinoside, etoposide, cyclophasphamide, and carmustine (BAVC) regimen. A present, 16 of 16 patients are alive and in CR. The actuarial overall survival is 100% at a median of 45.5 months, and the actuarial disease-free survival is 100% at a median of 33.5 months. These data suggest that ALCL can be successfully managed with a sequential intensive treatment (CHT +/- RT + ABMT) that prevents early relapses and projects these patients as long-term survivors.

The role of radiotherapy in the treatment of stage III non-small cell lung cancer: a survey of clinical practices in Lombardy, Italy, by the Airo*-Lombardia Cooperative Group.

AIMS AND BACKGROUND: The role of radiotherapy in the treatment of stage III non-small cell lung cancer is controversial. The aim of this survey was to investigate the use of this modality in current clinical practice in Lombardy, a highly industrialized region of northern Italy. METHODS: A questionnaire was sent to all 13 radiotherapy centers in Lombardy, covering statistical, clinical, technical and strategical aspects, and the responses were analyzed. RESULTS: A wide range of attitudes was observed among participating radiation oncologists; the percentage of cases treated with curative intent varied largely between centers (4-100%), as did the proportion of patients given to radiation only rather than combined modality treatment (5-100% vs 0-90%). CONCLUSIONS: An urgent need exists for better cooperation between all clinicians involved in lung cancer treatment, pursuing the goals of a more uniform clinical practice and a more aggressive clinical research attitude.

[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.

Total lymphoid irradiation in chronic progressive multiple sclerosis.

6 patients with severe chronic progressive multiple sclerosis were subjected to total lymphoid irradiation (TLI) to assess clinical efficacy and side effects. During a 4 year follow-up the disability progression was continuous. Side effects during TLI were well tolerated; side effects after TLI brought about a worsening of the quality of life. One patient died of pneumonia. In this preliminary study TLI did not reduce the worsening of disability in MS patients.

[Progressive multiple sclerosis. Evaluation of the effectiveness of total lymph node irradiation]. / Sclerosi multipla progressiva. Valutazione dell'efficacia dell'irradiazione linfonodale totale.

A long-lasting immunological suppression action seems to be produced by total lymphoid irradiation; some authors emphasize the favorable effect of this treatment on chronic progressive multiple sclerosis. In order to evaluate the actual role of TLI, 6 patients affected with chronic progressive multiple sclerosis were submitted to TLI with shaped and personalized fields at the Instituto del Radio, University of Brescia, Italy. The total dose delivered was 19.8 Gy in 4 weeks, 1.8 Gy/day, 5d/w; a week elapsed between the first and the second irradiation course. Disability according to Kurtzke scale was evaluated, together with blood lymphocyte count and irradiation side-effects, over a mean follow-up period of 20.8 months (range: 13-24). Our findings indicate that: a) disease progression was not markedly reduced by TLI; b) steroid hormones responsivity was restored after irradiation, and c) side-effects were mild and tolerable.

[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.

[The use of high energy electrons in the field of oncology. Experience of the O. Alberti Radio Institute of Brescia]. / L'impiego di elettroni di alta energia in campo oncologico. L'esperienza dell'Istituto del Radio "O. Alberti" di Brescia.

The vast clinical experience of the "Istituto del Radio" (Brescia) in electron beam therapy (2-18 MeV Betatron, 1964-1974; 5-21 MeV Microtron accelerator, 1974 onwards) leads to underline three possible risks: the underestimation of the lesion thickness, the underestimation of the field dimensions, the exclusive use of electrons to give the whole tumour dose. Both in ENT tumours and in breast cancer electrons must be associated with high energy photons, in order to improving the clinical results with reduced risks of severe late effects. The exclusive use of fast electrons in cancer therapy is only indicated in "particular and rare" cases.

[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.

Bladder cancer prognostic indices: analysis of 286 patients treated with radical radiation therapy.

From 1974 through 1982, 286 patients with histologically proven bladder cancer (Tis 8, T1 62, T2 109, T3 86, T4 21 NXMO) were treated with external irradiation after transurethral resection. Irradiation was given with 260 degrees arc technique photon beam from a Cobalt Unit; the tumor doses ranged from 52.5 to 65 Gy in 21-50 days, with a TDF between 75 and 110. The analysis was conducted with the log rank test on the cumulative percent survival (CPS) at 5 years. The study pointed out the importance of risk factors other than clinical stage on cumulative survival in bladder cancer. Prognostic factors associated with a relatively successful outcome (p less than 0.001) were the Karnofsky performance status (100 vs others) (CPS 75% vs 30%), the absence of ureteral obstruction on the initial intravenous pyelogram (CPS 50% vs 35%), a negative urine culture (CPS 60% vs 30%), normal bladder capacity (CPS 50% vs 35%), low-grade histology (CPS 65% vs 35%), and grossly complete resection (55% vs 40%). The data from this analysis should be taken into consideration when radical radiotherapy is considered in new clinical trials.

[Local-regional recurrence after mastectomy. CT as a tool of diagnosis and treatment planning]. / Recidive loco regionali in pazienti mastectomizzate. Accertamento diagnostico e programmazione terapeutica con TC.

In 19 out of 25 patients with local-regional recurrence of breast cancer, CT provided significant information better than any other procedure; in 15 patients CT contributed to a change in the treatment chosen on the basis of physical examination and routine studies. CT should be considered as part of the diagnostic work-up in patients with locally recurrent breast cancer who are being planned for comprehensive radiotherapy.

Multifactorial analysis of NOC lung carcinoma radiotherapy.

In order to evaluate survival of non-oat-cell lung carcinoma patients treated exclusively with radiotherapy, the authors analyzed a series of 791 cases irradiated at the Istituto del Radio "O. Alberti" from 1978 to 1982. The authors selected a homogeneous group of 131 patients, treated with high energy photons and with a fractionation course of a dose ranging from 1.75 to 2.00 Gy per fraction, 5 fractions per week, total dose ranging from 40 to 65 Gy within 4 to 8 weeks and with a time dose factor (TDF) ranging from 60 to 108. The survival curve was computed according to several prognostic factors by means of the Kaplan and Meier approach; a multifactorial analysis was carried out according to Cox's model. No factor significantly affected survival at the level P less than 0.05, except complications: anyway, TDF and tumor size seem to play a particular role. The non-oat-cell lung carcinoma patient who can profit from radiotherapy may be only partially featured: an improved survival and quality of life may be achieved if there are correct criteria to include the patient in the radiotherapy program, if the tumor is small, heavy complications are absent and treatment TDF ranges from 82 to 92.

[Tangential pendular cobalt-therapy in the management of malignant testis tumors: a clinical evaluation after 14 years' experience]. / La telecobaltoterapia pendolare tangenziale nella radioterapia dei tumori del testicolo. Valutazione clinica dopo oltre 14 anni.

129 cases of malignant testis tumors (88 seminoma and 41 carcinomas) treated at Istituto del Radio "O. Alberti" from 1966 to 1979 were statistically reviewed. All patients had inguinal orchiectomy followed by irradiation to iliac and lumbar para-aortic lymph nodes, with an original technique, tangential pendular cobalt therapy, worked out at our Institute in 1966. Results are very good: there is calculated with actuarial method, a 92% of patients with seminoma alive at 5 years and 84% of patients with carcinoma. Earlier or later iatrogenic sequences did not happened. The worth and actuality of tangential pendular cobalt therapy to post-operative irradiation in patients with stage I or II malignant testis tumors is confirmed.