Biological effective dose evaluation in gynaecological brachytherapy: LDR and HDR treatments, dependence on radiobiological parameters, and treatment optimisation.

PURPOSE: This study was undertaken to compare the biological efficacy of different high-dose-rate (HDR) and low-dose-rate (LDR) treatments of gynaecological lesions, to identify the causes of possible nonuniformity and to optimise treatment through customised calculation. MATERIALS AND METHODS: The study considered 110 patients treated between 2001 and 2006 with external beam radiation therapy and/or brachytherapy with either LDR (afterloader Selectron, (137)Cs) or HDR (afterloader microSelectron Classic, (192)Ir). The treatments were compared in terms of biologically effective dose (BED) to the tumour and to the rectum (linear-quadratic model) by using statistical tests for comparisons between independent samples. RESULTS: The difference between the two treatments was statistically significant in one case only. However, within each technique, we identified considerable nonuniformity in therapeutic efficacy due to differences in fractionation schemes and overall treatment time. To solve this problem, we created a Microsoft Excel spreadsheet allowing calculation of the optimal treatment for each patient: best efficacy (BED(tumour)) without exceeding toxicity threshold (BED(rectum)). CONCLUSIONS: The efficacy of a treatment may vary as a result of several factors. Customised radiobiological evaluation is a useful adjunct to clinical evaluation in planning equivalent treatments that satisfy all dosimetric constraints.

Five years survival in metastatic non-small cell lung cancer patients treated with chemotherapy alone or chemotherapy and melatonin: a randomized trial.

Numerous experimental data have documented the oncostatic properties of melatonin. In addition to its potential direct antitumor activity, melatonin has proved to modulate the effects of cancer chemotherapy, by enhancing its therapeutic efficacy and reducing its toxicity. The increase in chemotherapeutic efficacy by melatonin may depend on two main mechanisms, namely prevention of chemotherapy-induced lymphocyte damage and its antioxidant effect, which has been proved to amplify cytotoxic actions of the chemotherapeutic agents against cancer cells. However, the clinical results available at present with melatonin and chemotherapy in the treatment of human neoplasms are generally limited to the evaluation of 1-year survival in patients with very advanced disease. Thus, the present study was performed to assess the 5-year survival results in metastatic non-small cell lung cancer patients obtained with a chemotherapeutic regimen consisting of cisplatin and etoposide, with or without the concomitant administration of melatonin (20 mg/day orally in the evening). The study included 100 consecutive patients who were randomized to receive chemotherapy alone or chemotherapy and melatonin. Both the overall tumor regression rate and the 5-year survival results were significantly higher in patients concomitantly treated with melatonin. In particular, no patient treated with chemotherapy alone was alive after 2 years, whereas a 5-year survival was achieved in three of 49 (6%) patients treated with chemotherapy and melatonin. Moreover, chemotherapy was better tolerated in patients treated with melatonin. This study confirms, in a considerable number of patients and for a long follow-up period, the possibility to improve the efficacy of chemotherapy in terms of both survival and quality of life by a concomitant administration of melatonin. This suggests a new biochemotherapeutic strategy in the treatment of human neoplasms.

Antiprolactinemic approach in the treatment of metastatic breast cancer: a phase II study of polyneuroendocrine therapy with LHRH-analogue, tamoxifen and the long-acting antiprolactinemic drug cabergoline.

Despite the well-demonstrated stimulatory role of prolactin (PRL) on breast cancer cell growth and the possible existence of a PRL-dependency in estrogen-independent mammary tumors, the therapeutic role of the antiprolactinemic drugs in the treatment of human breast cancer has still to be investigated and defined. Previous preliminary studies have already shown that the concomitant administration of antiprolactinemic agents may enhance the efficacy of cancer chemotherapy for breast carcinoma, whereas their impact on the efficacy of the endocrine therapy is still unknown. At present, the classic endocrine therapy for breast cancer consists of anti-estrogens plus LHRH-analogue. The concomitant administration of antiprolactinemic drugs could enhance the efficacy of treatment by blocking not only the action of estrogens, but also that of another growth factor for breast cancer, such as PRL. The present phase II study was performed to evaluate the efficacy and tolerability of a polyneuroendocrine approach for breast cancer, consisting of LHRH-analogue plus the anti-estrogen tamoxifen plus a long-acting antiprolactinemic agent, cabergoline. The study included 14 consecutive metastatic breast cancer women, heavily pretreated with the standard anticancer therapies and for whom no other conventional treatment was available. The LHRH-analogue, triptorelin, was given intramuscularly at a dose of 3.75 mg every 28 days, tamoxifen was given orally at 20 mg/day and cabergoline was given orally at 0.5 mg once/week. The clinical response consisted of partial response (PR) in 4 out of 14 (29%) patients, including one who had progressed on a previous treatment with triptorelin plus tamoxifen alone. A stable disease (SD) was achieved in another 5 patients, whereas the other 5 patients had a progressive disease (PD). Mean serum levels of PRL significantly decreased on treatment within the first month of therapy, and its decline was significantly more evident in patients with PR or SD than in those with PD. The treatment was well-tolerated in all patients, and in particular no cabergoline-related toxicity occurred. This preliminary study would suggest that the association of the long-acting antiprolactinemic drug cabergoline may further enhance the efficacy of the classical endocrine therapy for advanced breast cancer with anti-estrogens plus LHRH-analogues.

Conservative management of T1-T2N0 supraglottic cancer: a retrospective study.

PURPOSE: Evaluate the results of conservative management of early-stage supraglottic cancer. PATIENTS AND METHODS: A retrospective analysis of 166 consecutive T1-T2N0 cases of squamous cell carcinoma of the supraglottic larynx, treated conservatively between 1983 and 1992, was performed. Sixty-six patients received conservative surgery (CS), whereas 100 patients received definitive radiation therapy (RT). Surgical procedures included horizontal supraglottic laryngectomy in 38 patients, extended supraglottic laryngectomy in 16 patients, and reconstructive laryngectomy with cricohyoidopexy in 12 patients. Elective bilateral neck dissection was always performed. Radiotherapy was delivered with 60Co or 6 MV photons to the primary laryngeal tumor and the upper and mid neck nodes (level II and III), whereas supraclavicular nodes (level IV) were electively irradiated only in 54 patients with T2N0 tumors. Fifty-two patients received conventional fractionation, whereas 31 patients were irradiated according to a twice-a-day fractionation regimen. The median total tumor dose was 67 Gy (range, 64 to 72 Gy). RESULTS: The 5-year overall survival of the whole series was 72.7% +/- 4.5. In patients treated with CS, the 5-year disease-free survival was 88.4% +/- 4.5 versus 76.4% +/- 6.1 for patients who received RT. Salvage surgery was effective in rescuing 2 of 3 CS failures and 12 of 25 RT failures. The overall incidence of secondary tumors (11%) and distant metastases (5%) was relatively low, although together they account for 15% of all deaths. Complications of CS were significantly correlated to the extent of surgical procedure. A multivariate analysis performed in the RT group showed that performance status, tumor grade, and fractionation regimen significantly influenced disease-free survival. CONCLUSION: Conservative management of T1-T2N0 supraglottic cancer, either by CS or RT, can achieve good cure rates with larynx preservation for the majority of the patients (82% overall; 95% in the CS group and 72% in the RT group). The decision between different conservative treatment modalities may be influenced by the patient's conditions, tumor characteristics, treatment modalities, and also economic costs.

Hyperfractionated radiotherapy and concomitant cisplatin in stage III non-small cell lung cancer: a phase II study by the AIRO-Lombardia Cooperative Group.

A multicenter Phase II study was performed by the AIRO-Lombardia Cooperative Group on 36 patients with Stage III non-small cell lung cancer. The treatment schedule included hyperfractionated radiotherapy, 1.2 Gy twice daily (5 days/week) up to a total dose of 69.6 Gy, and concomitant cisplatin by continuous infusion using a portable pump, 16 mg/m2/week for 6 weeks. Overall, adequate treatment (defined as a total dose > 66 Gy in < 46 days and 6 weeks of infusional cisplatin) was received by 56% of accrued patients. Response was complete in 6% and partial in 56% of patients; median survival was 8 months and 1-year survival rate was 37%. Site of first failure was local in 43%, distant in 43%, local and distant in 10% and unknown in 3% of failing patients. Grade 3 esophagitis was recorded in 14% of patients and a fatal case of late pulmonary toxicity was reported. On the basis of feasibility, toxicity and survival results, the planned extension to Phase III was abandoned by the Group.

[Radiotherapy of cutaneous cervical-facial carcinomas]. / La radioterapia dei carcinomi cutanei cervico-facciali.

The main goal of therapy for epithelial skin cancer is cure with the best functional and cosmetic outcome. Both surgery and radiotherapy give similar results for early stage lesions with 5-year local control rates ranging from 85% to 95%. Remarkable technological progress has been made yielding well defined indications to radiotherapy as a single treatment or in the context of a multidisciplinary approach. Selection of treatment should be tailored considering anatomic site, surface conformation, size, histology, grading and characteristics of tumours (new occurrence, relapse), number of localizations, age and medical conditions of the single patient. Surgery, guided by intraoperative control of resection margins, is undoubtedly the therapy of choice for most of early stage lesions. Radiation therapy plays an important role in specific anatomic situations in which the functional or cosmetic result is better than for a surgical modality, electively for the treatment of multiple lesions and for large deep- infiltrating carcinomas that generally are not suitable to excision. Exclusive radiotherapy is also indicated as rescue treatment of surgical relapses no more amenable to reexcision as well as for palliation of advanced cases, mainly for elderly or medically compromised patients. Postoperative irradiation should be considered for macro or microscopic residual disease. Merkel cell or adnexal carcinomas and for highly recurrent lesions after repeated surgery. Treatment results and complications of radiotherapy are discussed, emphasizing high local control rates and good functional and cosmetic outcomes. The main irradiation techniques referred to specific anatomic sites are also presented.

Role of postoperative radiation therapy in the management of early stage primary gastric non-Hodgkin's lymphomas: a retrospective analysis.

BACKGROUND: Clinical approaches to early primary gastric non-Hodgkin's lymphomas have not yet been clearly defined, and the role of postoperative radiotherapy remains a matter of discussion. METHODS: Twenty-seven patients with early primary gastric non-Hodgkin's lymphoma were observed from December 1978 to December 1990 at our Institution. They were staged according to Musshoff and Schmidt-Volmer (19) as I E (n = 16), II E 1 (n = 7) and II E 2 (n = 4). All of them underwent local combined treatment, consisting of surgery and postoperative radiotherapy; chemotherapy was also administered to 10 patients, mainly with the CHOP regimen, for 4-6 cycles before radiotherapy. Irradiation was delivered using 10 MV photons from a linear accelerator. Large abdominal fields were employed in 21 cases with daily fractions of 1.5-2 Gy up to a median total dose of 30 Gy (range: 27-36 Gy). Six patients were irradiated only on the surgical bed up to 40.5 Gy (range: 39-40.5 Gy). RESULTS: The 5-year overall and disease-free survivals were respectively 92.4% and 89.8%. The main known prognostic indicators, stage of disease, type of surgery as well as age and sex, were not found to be statistically significant in our series. No clear difference emerged between patients sequentially treated with the combination surgery-chemotherapy-radiotherapy and those who did not receive adjuvant chemotherapy. Two patients recurred at distant sites, but no local failure was seen during the follow-up. CONCLUSIONS: Although no firm conclusion can be drawn, our experience, in agreement with recent published reports, points out that the use of postoperative radiotherapy is associated not only to favorable results in terms of local control and survival, but also, and moreover, to a negligible incidence of side effects and sequelae. However, in the absence of multi-institutional prospective randomized studies, whose activation is nowadays strongly warranted, the exact role of adjuvant therapies remains a matter of discussion, and the optimal treatment of early primary gastric non-Hodgkin's lymphoma still depends on individual experience and the physician's philosophy.

Postoperative radiation therapy for adult soft tissue sarcomas: a retrospective study.

From 1977 to 1988, 81 adult patients with localized soft tissue sarcomas at different sites received postoperative external beam radiotherapy (55 Gy median dose) following primary conservative surgery. Sixty were new referrals after primary surgery and 21 were irradiated after excision of recurrent disease. With a median follow-up of 4 years (range: 2-13) the 5-year overall survival (Kaplan-Meier) and local control were 55.5% and 56% respectively, while 5-year disease-free survival is 49%. There were 26 (32%) local relapses and 22 (27%) distant failures. Local recurrence was the sole pattern of failure in 16 patients (20%). Functional and cosmetic results were good to excellent in most cases. In our series local control is the main prognostic variable influencing survival (P less than 0.0001), and its probability seems to show a link with the type of surgical procedure, with a trend (P less than 0.13) in favor of wide total excision. Postoperative radiation therapy represents an acceptable treatment strategy for ASTS, but further improvements are expected from future controlled clinical trials, aiming at the achievement of the definitive cure of these tumors.

[Exclusive radiotherapy of carcinoma of the hypopharynx. Retrospective study of a series of 100 patients]. / La radioterapia esclusiva del carcinoma dell'ipofaringe. Analisi retrospettiva di una casistica di 100 pazienti.

From January 1980 to December 1987, 100 patients with carcinoma of the hypopharynx, staged according to TNM (UICC-1978) criteria, received exclusive radiation therapy at the Radiotherapy Department of the General Hospital of Varese. The median follow-up is 9 months (range: 1-97). Irradiation was delivered with 60Co or with 10 MV photons and tissue-equivalent bolus. Two opposed parallel lateral fields or rotational technique were used, with progressive shrinking of treated volume in order to spare the spinal cord after 45 Gy. Direct fields of electron beams (6-15 MeV) were employed as boosts on the residual nodes. Median total doses: 64.5 Gy to T and N1-3, 45 Gy to N0. A conventional fractionation (2 Gy once a day, 5 times a week) was used in 37 outpatients, while an accelerated hyperfractionated regimen (1.5 Gy twice a day, 5 times a week, with a six hours' interval between each fraction) was employed in 63 inpatients, in order to shorten hospitalization. The five-year overall survival (Kaplan-Meier) of the 100 treated patients is 10%, while the five-year disease-free survival of the 40 patients in complete clinical remission at the end of radiation therapy is 19.8%. The five-year loco-regional control rate after exclusive radiotherapy is 19.1%. Complete remission at the end of treatment seems to represent the only significant prognostic variable affecting survival: five-year overall survival is 32% for the 40 patients achieving complete remission and only 4.4% for the others (p less than 0.05). On the contrary, tumor extension (T class) seems to affect only the two-year local control rate: 35.2% and 10.9% for T1 + T2 and T3 + T4 respectively (p less than 0.1). The main cause of failure after radiation therapy is represented by the lack of control at the primary site (T) alone or associated with regional adenopathies (N). The analysis of isoeffect parameters, according to CRE model, has not shown any evident dose-response relationship for local control. Late effects were observed in 7% of the patients and were similar to those reported in the literature. The occurrence of both distant metastases, 3% in our experience, and secondary tumors (9%) is lower than those previously reported. The present retrospective study strongly reconfirms the inadequacy of exclusive radiation therapy as the sole treatment modality for carcinoma of the hypopharynx and suggests the need of combination therapy (surgery and radiation) as primary treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

[Radiotherapy in the combined therapy of limited stage pulmonary microcytoma. The experience of the Department of Oncologic Therapy at the Multiregional Hospital of Varese (1980-1989)]. / La radioterapia nel trattamento integrato del microcitoma polmonare a malattia limitata. L'esperienza della Divisione di Radioterapia Oncologica dell'Ospedale Multizonale di Varese (1980-1989).

From January 1980 to December 1989, 86 patients with limited small cell lung carcinoma (SCLC) were treated in our Institution. Sixty-eight of them were males, 18 females; mean age was 58 years (range: 40-74); Karnofsky index was 80 or higher. All patients received induction multiagent chemotherapy (CAV or CAVE), usually fractionated into 3/4 cycles. Radiotherapy was administered by means of a 10 MV Linear Accelerator, 2-3 Gy/day, 5 days/week. Radiation dose was 60 Gy for 39 patients, 50 Gy for 25 patients, and 30 Gy for 22 patients. Parallel opposed fields (AP and PA) were used for administering the 30-Gy dose, while higher doses were delivered by multiportal arrangement (3/4 fields). Overall survival (corrected Kaplan-Meier) was 21.3% and 13.4% at 2 and 3 years, respectively; 2 years' survival according to dose was 24.5% for 60 Gy, 19.9% and 11% for 50 and 30 Gy, respectively. Mean survival time (MST) was 14 months for 60 Gy, 13 months and 10 months, respectively, for 50 and 30 Gy. Survival and disease-free survival rates were similar in patients who received 50 and 60 Gy. No major complications related to irradiation were observed, not even in the group receiving the highest dose. Our data are similar to those reported in the literature.