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.

[Use of filgrastim, granulocyte colony stimulating factor (G-CSF), in radiotherapy to reduce drop-outs because of radiogenic leukopenia]. / Impiego del filgrastim, fattore stimolante le colonie granulocitarie (G-CSF), nella radioterapia allo scopo di ridurne le interruzioni per leucopenie radioindotte.

Radiotherapy patients are at risk of developing leukopenia, which risk depends on the irradiated volume, the rate of irradiated bone marrow and the radiation dose. Radiogenic leukopenia may cause radiotherapy drop-out, with consequent effects, on local tumor control and clinical outcome. The introduction of granulocyte growth factors, such as filgrastim, has permitted to accelerate normal neutrophil count recovery in irradiation-related neutropenia both in vitro and animal models; clinical experience in humans is still lacking, relative to both indications and scheduling. In the Oncologic Radiotherapy Department of Treviso Hospital, 31 patients irradiated for Hodgkin disease, rectal cancer and other malignancies, who presented leukopenia requiring treatment discontinuation, were given filgrastim to assess its actual effect in avoiding further drop-outs and to compare two administration schedules (2 or 3 vials, 30 MIU, weekly). Filgrastim treatment was continued throughout the radiotherapy cycles, for 1 to 5 weeks. Eighteen patients had received previous chemotherapy and 11 were undergoing concurrent 5-fluorouracil chemotherapy-irradiation. A mean 203% increase in leukocyte count was observed (136% in the patients treated with 2 vials/week and 274% in those receiving 3 vials/week); this increase was more apparent in women that in men (256% versus 91%) and slightly higher in patients 50 years old and with target volumes < 5000 ml. Filgrastin treatment was well tolerated by all patients, with no discontinuations due to adverse effects; 9 patients (29%) reported skeletal pain, which was marked in 2 of them only. Eighty percent of patients completed all the radiotherapy cycles with no discontinuation, while 6 patients dropped out because leukopenia persisted. Biweekly filgrastim administration was effective to prevent unscheduled radiotherapy discontinuation in 75% of patients and triweekly administration was effective in 86% of patients. In our experience, filgrastim administration was well tolerated and effective in decreasing the irradiation drop-outs caused by treatment-related leukopenia. Since this drug is rather expensive, we decided to use routinely the lower dosage of biweekly administration (with one vial given on Friday and Saturday, to permit neutrophil recovery during the day off) and to reserve the higher dosage (3 vials a week) to the patients with large body areas, big target volumes and persistent leukopenia during previous chemotherapy.

Radiotherapy in the elderly with lung carcinoma: the experience of the Italian "Geriatric Radiation Oncology Group".

One hundred ninety-six patients aged > or = 70 years, with non small-cell lung carcinoma and no evidence of metastasis on staging, observed over a 6-month period in 20 Italian Radiotherapy Centers, were analyzed in order to assess indications for treatment, tolerance of radiotherapy (assessed in terms of completion of planned doses and toxicity), and quality of life using the Performance Status and a concise activity of life test. Of the 196 patients studied in 20 Italian Centers, 182 (98%) underwent radiotherapy, 109(60%) of whom with radical intent and 73 (40%) with palliative intent. Of 179 assessable patients undergoing radiation treatment, 163 (91%) completed the treatment as originally planned. Of the 64 assessable patients who completed palliative radiotherapy, relief of symptoms was observed in a percentage ranging from 78% to 86%. Analysis of parameters assessing the quality of life, showed no significant differences in general and functional conditions, as assessed before and upon completion of radiotherapy.

Radiation therapy of bone metastases in the elderly: a multicentric survey of the Italian "Geriatric Radiation Oncology Group".

External radiation therapy (ERT) has been reported to be the elective treatment of symptomatic bone metastases. A nationwide survey on the use of ERT in elderly patients with bone metastases has been conducted by the Italian "Geriatric Radiation Oncology Group" with a three-fold aim: define the state of the art of ERT, evaluate the analgesic efficacy and identify the optimal dosage and schedule, if any. 347 patients aged 70 or over, treated in 29 different institutions for a period of six months were analyzed. Conclusive results were: a significant pain relief achieved shortly after ERT completion; an improvement in the quality of life; a decrease in the dose of analgesics and consequently, a reduction in treatment-related costs. Unfortunately the optimal treatment schedule remains unidentified; ERT was neither aggressive nor toxic in this series of elderly patients.

[Can the prophylactic treatment of mycotic mucositis improve the time of performing radiotherapy in head and neck tumors?]. / Può il trattamento profilattico delle mucositi micotiche migliorare il rispetto dei tempi di esecuzione della radioterapia nei tumori del capo e del collo?

Radiotherapy-related mucositis is the most frequent complication in the patients submitted to irradiation for head and neck cancers. Many such patients may develop mycotic infections which may lead to treatment discontinuation, with possible consequences on the local control of these cancers. In this study, we investigated the efficacy of fluconazole in preventing mycotic mucositis in 80 patients undergoing radiation therapy for head and neck cancers. The patients were randomized to two groups: 41 patients in group A received the supporting treatment we usually administer, plus fluconazole (50 mg/day) starting from the 6th irradiation session throughout the treatment; 39 patients in group B received the same baseline treatment, but were given the drug only when mycotic infections appeared. The clinical characteristics, treated sites, treatment doses and volumes were similar in the two groups of patients. Fluconazole was well tolerated and no early or late toxicity was observed. We had 1 mycotic mucositis and 14 non-scheduled treatment discontinuations in group A, vs. 19 and 30, respectively, in group B. Radiation therapy lasted 52.3 days (mean) in group A and 55.6 days (mean) in group B; the differences were statistically significant. In our experience, fluconazole, used prophylactically from the 6th radiotherapy session on, reduced the number of mycotic infections and improved radiotherapy schedule in our head and neck cancer patients.

Phase III trial of initial chemotherapy in stage III or IV head and neck cancers: a study by the Gruppo di Studio sui Tumori della Testa e del Collo.

BACKGROUND: The standard treatment for advanced (stage III and IV) head and neck squamous cell carcinoma (i.e., surgery with postoperative radiotherapy in operable patients and radiotherapy alone in inoperable patients) has had poor results. A series of randomized trials of induction chemotherapy have up to now failed to demonstrate an improvement in survival. PURPOSE: This trial was designed to determine whether intensive induction chemotherapy administered before loco-regional treatment would improve survival of patients with advanced disease. METHODS: Patients had previously untreated, advanced nonmetastatic (stages III and IV) squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and paranasal sinuses. The study design was a randomized, multi-institutional, phase III trial. Eligible patients (n = 237) were randomly assigned to receive either initial chemotherapy (cisplatin and infusional fluorouracil) followed by loco-regional treatment (group A, n = 118) or loco-regional treatment alone (group B, n = 119). For operable patients (group A, n = 34; group B, n = 32), loco-regional treatment included resection followed by adjuvant radiotherapy. For inoperable patients, radical irradiation was performed with a planned dose of 65-70 Gy to involved areas. A dose of 45-50 Gy was also planned to the uninvolved neck or postoperatively. The statistical (log-rank) test was performed no earlier than 2 years after the randomization of the last patient. RESULTS: Seventy-one patients (60%) in group A and 67 patients (56%) in group B were considered free of disease after they completed the treatment sequence. The analysis of time to distant metastases showed an advantage for group A patients. (Respective 2- and 3-year values for inoperable patients were 15% and 24% for group A versus 36% and 42% for group B, P = .04; only one operable group A patient had distant metastases after 49 months versus 26% [2 years] and 31% [3 years] for operable group B patients, P = .01.) For inoperable patients, the combined treatment was significantly associated with an increase in complete remission rate (group A, 44%) as compared with radiotherapy alone (group B, 30%) (P = .037). Inoperable patients also benefitted from induction chemotherapy in terms of disease-free survival (49% and 34% for group A versus 28% and 26% for group B; P = .06) and of overall survival (30% and 24% for group A versus 19% and 10% for group B; P = .04). CONCLUSIONS: When all 237 randomly assigned patients were analyzed, there were no significant differences in the two treatment strategies in loco-regional failure or in disease-free or overall survival, although the development of distant metastases was reduced. For operable patients, the only benefit from neoadjuvant chemotherapy was a significant reduction in the incidence of distant metastases. For inoperable patients, neoadjuvant chemotherapy improved local control, decreased the incidence of distant metastases, and improved the complete remission rate and overall survival. IMPLICATIONS: Confirmatory studies with effective chemotherapy regimens delivered for an adequate number of cycles are required.

[Teleradiotherapy in the treatment of thyroid neoplasms]. / La teleradioterapia (RTE) nel trattamento delle neoplasie tiroidee.

The role of external radiotherapy in the treatment of thyroid neoplasms is not yet well defined. The indications for loco-regional treatment in the case of: anaplastic carcinomas (alone or in combination with surgery or chemotherapy); differentiated and medullary carcinomas at diagnosis or relapse; nodes or osseous metastases not otherwise curable (surgery, hormones, brachytherapy); cerebral metastases; are accepted by everyone. Results, from the various clinical reports published, are positive. The use of this methodology is not accepted by everyone as "adjuvant" in cases "at risk" for micro or macroscopic residuals after surgery for papillary, follicular or medullary carcinomas. From the analysis of the literature, even a recent publication in relation to an apparent growing local control, we have no data in favour of increased survival. Even from our experience we cannot give definitive data (78.5% of local control in case of papillary or follicular carcinoma, survival of 57% in 5 years and 36% in 10 years). The question could be solved only by randomised trials but the difficulties due to the need for a sufficient number of cases and to the long "natural" survival, even in presence of disease, appear to be insuperable. We suggest a prudent approach, in controversial cases, because of the difficulties linked to the optimal loco-regional treatment (high doses, proximity of organs "at risk").

A pilot study of concomitant radiation and chemotherapy in patients with locally advanced head and neck cancer.

Cisplatin and 5-fluorouracil act as radiosensitizers and are active cytotoxic drugs in head and neck cancer. Therefore, from May 1987 to June 1990, we gave a continuous course of radiotherapy (70 Gy/35 fractions/7 weeks) combined with the simultaneous administration, once a week, of cisplatin (40 mg/m2, i.v. bolus) and 5-fluorouracil (400 mg/m2, i.v. bolus) to 21 patients with locally advanced or recurrent tumors of the head and neck. The complete and partial response rates were 65% and 15%, respectively. With a median follow-up of 17 months (range: 4-42) and with 19/21 patients having stages III and IV tumors, 12 patients are NED (no evidence of disease), 8 died with tumor, and 1 died of bronchopneumonia during the treatment. The main toxicity was mucositis and the median length of therapy was higher than with irradiation alone. This regimen appears very encouraging and could be an improvement over radiation alone for patients with locally advanced head and neck cancer.

Extramedullary plasmacytoma: clinical behaviour and response to treatment.

The clinical features and response to treatment of 35 patients (pts) with extramedullary plasmacytoma (EMP) were retrospectively analysed. The median age at diagnosis was 49 years (28-72). Twenty-two pts (63%) had stage I disease (localized to the primary site) 12 of whom (34%) had stage I-E (locally extended). Three pts (9%) had stage II (regional lymph nodes involved) and 10 (29%) stage III (disseminated disease). In locoregional disease (stages I, I-E, II) complete local control was achieved in 22 of 25 pts (88%), while in diffuse disease (stage III) complete remission (CR) was obtained in 5 of 10 pts (50%) (p = 0.05). In 9 of 18 pts treated with surgery, local control was achieved, and in 8 of the 9 patients with incomplete resection local control was obtained with additional radiation and/or chemotherapy. In 8 (66%) of the 12 pts treated with radiation complete local control was achieved. In 11 (58%) of 19 pts evaluable for initial chemotherapy CR was obtained. Three of these pts were treated with chemotherapy only and were alive and disease-free after a minimum follow-up of 8 years. The median time to relapse in local disease was 48 months versus 13 in disseminated disease. For pts with local disease the median survival time was 114 months and for disseminated disease 16 months (p = 0.0000). We conclude that in stage I chemotherapy is curative per se. In local stages (I, I-E and II) adjuvant chemotherapy should be considered, while in stage III only palliative therapy is feasible.

[Neoplasms of the gallbladder and the extrahepatic bile ducts: radio-chemotherapeutic combined treatment. Results in 18 treated cases]. / Neoplasie della colecisti e delle vie biliari extraepatiche: trattamento integrato radio-chemioterapico. Risultati in 18 casi trattati.

According to current literature, the main cause of death in patients with gallbladder (GB) and extrahepatic biliary ducts (EHBD) neoplasms is related to local and locoregional tumor spread rather than to distant metastases. Surgery, even when radical, is followed by a high number of relapses. That is why postoperative radiation therapy (RT) is usually combined with surgery. Alone, however, RT is not effective enough to markedly improve loco-regional control, considering that the adjacent organs would be damaged by higher doses. Referring to experimental studies published in the 1960s and relative to the biological effect of ionizing radiation with 5-Fluorouracil (5-FU) in slowing the pace of tumor growth, the Department of Radiotherapy, together with the Department of Medical Oncology in Padua General Hospital, began administering a combined surgical-chemo-radiotherapeutic protocol in January 1982, to January 1989. The protocol included 5-FU administration both 3 days before and during RT, after a surgical intervention as radical as possible. Eighteen patients were given this treatment. By the end of December 1989, 7 patients were alive--6 of them disease-free with a 26-month mean survival. Eleven patients died--7 due to local/loco-regional relapse, 1 from a distant metastasis, 1 from gastric hemorrhage, with no disease, and 2 from unknown causes. Overall mean survival in the two groups was 16 months. The combined treatment proved to be tolerable and feasible, even though severe complications were observed in 2 patients, 1 case of toxic death (gastric hemorrhage) and another with complete duodenal stenosis which required further surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Oesophageal cancer treated by photodynamic therapy alone or followed by radiation therapy.

Photodynamic therapy (PDT) with porphyrins and red light is receiving increasing attention in the management of malignant tumours. At present PDT is primarily indicated for the treatment of superficial or early-stage lesions. At the Department of Radiotherapy and the First Institute of Surgery in Padova (Italy) more than 150 cases of tumours of different types have been treated using this technique. This paper briefly describes 21 cases of superficial oesophageal cancer. A complete response was observed in 11 of 21 cases. Radiation therapy appeared to be very effective as a salvage treatment of non-response patients.

Radiation-associated cerebral gliomas. A report of two cases and review of the literature.

Two cases are reported in which a cerebral glioma developed after radiation therapy for a different primary tumor. The first case was a boy, who presented a right thalamic anaplastic astrocytoma 7 years after irradiation for a left temporal polymorphic cell sarcoma. The second case was a woman, with a right temporal anaplastic astrocytoma occurring 8 years after irradiation for a GH-secreting pituitary adenoma. Thirty-five other cases of radiation-associated cerebral gliomas had already been reported in the literature. The possible causal role of radiation therapy in inducing cerebral gliomas is discussed on the basis of these observations.

Pineal germinoma: diagnosis, treatment and tumor response.

We report the case of pineal germinoma in a 25 year old man. The neurological signs and symptoms were insidious in onset; Parinaud syndrome allowed a topical diagnosis, confirmed by CT scan. Computerized Tomography and CSF cytological examination were of the utmost importance to diagnosis and treatment and it confirmed the success of radiotherapy.

[Laser-photo-radiotherapy in the treatment malignant tumors]. / La laserfotoradioterapia nel trattamento dei tumori maligni.

Photoradiation therapy or, as more recently defined, photodynamic therapy (PDT) has been effective in the treatment of several kinds of cancers, above all of the skin, lung, esophagus and bladder. It is based on the preferential retention by tumor and photosensitizing properties of certain porphyrins. We began to investigate this technique experimentally in 1978 and clinically in september 1982, with report of the initial results in 38 patients in 1985. In this paper we describe our more recent experience of PDT in 18 patients affected by different tumors and treated with a new double argon-dye laser system. These tumors included 8 carcinomas of the esophagus, 5 basal cell skin cancers, 2 carcinomas of the lung, 2 squamous cell carcinomas of the oral cavity and 1 early gastric cancer. Clinical results and technical problems of PDT are discussed.

Retinopathy following radiation therapy of paranasal sinus and nasopharyngeal carcinoma.

Radiation retinopathy is a complication of the therapeutic irradiation of orbital and periorbital structures. The authors studied two groups of patients who had orbital (group 1) and periorbital (group 2) external irradiation. Radiation retinopathy occurred in 63.6% of patients in group 1 and 36.3% group 2. Retinal radiation damage showed a different clinical evaluation in the two groups, appearing earlier (mean, 11 versus 55 months) and with greater involvement of the peripheral retina in group 1 (with three cases of neovascular glaucoma). This study demonstrates that radiation retinopathy occurs in a significant number of cases when the eye is not totally involved in the irradiation field and shows at least two different clinical aspects in relation to the radiation treatment. It also suggests that portal design and choroidal circulation damage may represent important factors in the development of radiation retinopathy.

A rarely observed case of primary multiple carcinomas of the head and neck.

We report a 71-year-old male patient with five separate primary metachronous squamous cell carcinomas of the head and neck (parotid, tongue, soft palate, larynx and hypopharynx) that occurred over a period of 8 years. The long survival of the patient after discovery of his first neoplasm (parotid) is the result of careful vigilance during the follow-up period and diligently planned therapies for each of his multiple primary tumors after radical surgery had been performed on his first neoplasm.