Giuseppe Pani

Radical radiation alone versus radical radiation plus microwave hyperthermia for N3 (TNM-UICC) neck nodes: a prospective randomized clinical trial☆

Between September 1985 and December 1986, 44 N3 (TNM-UICC) metastatic squamous cell cervical lymph-nodes were randomized to receive conventionally fractionated radical irradiation (RT) to a total dose of 64-70 Gy, or conventionally fractionated radical irradiation plus twice a week local microwave hyperthermia (Ht). The two major end points of this study were (a) local control rates evaluated at 3 months after the end of combined therapy and (b) incidence of acute local toxicity. Thirty-six nodes (82%) were evaluable as of December 1986, at which time there was a premature closure of this study due to ethical reasons. An interim analysis had revealed a statistically significant difference in complete response rates in favor of the combined arm (p = 0.0152). The complete response rates were 82.3% (14/17) for the combined treatment arm versus 36.8% (7/19) for the control irradiation arm, leading to an iso-dose thermal enhancement ratio (TER) value of 2.23. Both arms are comparable in average total RT dose delivered (RT: 67.05 Gy; RT + Ht: 67.85 Gy) and in average maximum node diameter (RT arm: 4.81 cm; RT + Ht: 4.88 cm). Acute local toxicities were similar in irradiated and heated plus irradiated neck regions; only one skin burn was observed. As possible treatment related death, one patient in the RT + Ht arm died 2 months after completion of therapy with a carotid rupture associated with extensive tumor necrosis. These results confirm previous non-randomized reports suggesting that hyperthermia in combination with full dose conventionally fractionated irradiation significantly enhances the chance of early local control of fixed N3 neck nodes without exhibiting an increase of acute local toxicity.

Cisplatin, hyperthermia, and radiation (trimodal therapy) in patients with locally advanced head and neck tumors: A phase I–II study

PURPOSEnHyperthermia is now being widely used to treat clinical malignancies especially combined with radiotherapy and more rarely with chemotherapy. The combination of heat, radiation, and chemotherapy (trimodality) can lead to potent interaction. The present Phase I-II study was conducted to evaluate the feasibility and acute toxicity of a combination of cisplatin, hyperthermia, and irradiation in the treatment of superficial cervical nodal metastases from head and neck cancer.nnnMETHODS AND MATERIALSnEighteen patients with measurable neck metastases from previously untreated squamous cell head and neck tumors were entered into the trial. Therapy consisted of a conventional irradiation (total dose 70 Gy, 2 Gy five times a week) combined with a weekly administration of 20 mg/m2 iv of cisplatin and a total of two sessions of local external microwave hyperthermia (desired temperature of 42.5 degrees C for 30 min).nnnRESULTSnFeasibility of the treatment was demonstrated. Acute local toxicity was mild; no thermal blisters or ulcerations were reported and only two patients experienced local pain during hyperthermia. Cutaneous toxicity appeared greater than in our previous studies with irradiation plus hyperthermia and irradiation plus cisplatin. Systemic toxicity was moderate with major toxic effects observed in three patients (World Health Organization (WHO) grade 3 anaemia). Even though it was not an aim of the study to evaluate the nodal response, we observed a complete response rate of 72.2% (95% confidence interval 51-93.4%), 16.6% of partial response and 11.1% of no change.nnnCONCLUSIONnThe study confirms the feasibility of the combination of cisplatin, heat, and radiation with an acceptable toxicity profile. The trimodal therapy deserves further evaluation as a way to enhance the efficacy of irradiation in the treatment of nodal metastases from head and neck tumors.

Hyperfractionated radiation in combination with local hyperthermia in the treatment of advanced squamous cell carcinoma of the head and neck: a phase I–II study

Twenty-seven patients with cervical metastases from squamous cell head and neck tumours were treated with hyperfractionated XRT (total dose 69.60-76.80 Gy, 1.2 Gy b.i.d. five times a week) combined with a total of two to six sessions of superficial external HT. Acute local toxicity was mild; as major acute side effects, only one ulceration was recorded. No severe late side effects were observed. Late toxicity was similar to that observed in our previous studies with the combination of heat and radiation. Nodal complete response was observed in 77% of patients, partial response was observed in 15% of patients and no change was observed in 8% of patients. Five-year actuarial nodal control was 64.5 +/- 19% and 5-year actuarial survival was 24 +/- 10%. The treatment of nodal metastases from head and neck tumours with the combination of HT and hyperfractionated XRT is feasible with an acceptable acute and late toxicity profile.

STAGE I SEMINOMA OF THE TESTIS : LONG TERM RESULTS AND TOXICITY WITH ADJUVANT RADIOTHERAPY

Aims and background Pure testicular seminoma has historically been treated with post-orchidectomy radiation therapy with excellent results. Recently, several aspects of the treatment of stage I seminoma have been questioned. We assessed long-term results and toxicity of patients with pure testicular seminoma treated at the Department of Radiation Oncology of S. Chiara Hospital, Trento. Methods From 1953 to 1987, 102 patients with stage I pure testicular seminoma were given megavoltage irradiation with curative intent. All patients had a minimum follow-up of 3 years (maximum 37 years, median 13 years). They received a mean para-aortic/pelvic dose of 33.07 Gy (range 23.70-45.20 Gy) with different doses and fields reflecting the change in techniques over a long period of time. Results The cause-specific actuarial survival at 30 years was 99% and crude survival 67%. One patient had an out-field relapse (inguinal) after a few months and was cured with radiotherapy and chemotherapy. Another patient relapsed with widespared metastases and died after 1 year of progressive disease. Early toxycity was mild and the treatment was well tolerated. Late side effects were reported in 8/102 patients. Conclusion In our series adjuvant radiation therapy resulted in cure rates corresponding to those reported in the literature. The 30-year actuarial survival of 99% was extremely good and the toxicity of the treatment was mild. Post-orchidectomy radiation to the para-aortic and ipsilateral pelvic nodes is a safe and effective method of preventing recurrences and is currently to be considered the treatment of choice in stage I testicular seminoma.

The role of brachytherapy in the management of oropharyngeal carcinomas: the Trento experience.

Aims This study was undertaken to determine the outcome of patients with oropharyngeal cancer treated at the Radiotherapy Department of the Santa Chiara Hospital (Trento, Italy) with brachytherapy alone or combined with external beam radiotherapy (EBRT). Material and methods We retrospectively reviewed the medical records of 87 patients with squamous cell carcinoma of the oropharynx treated by radiation therapy between January 1986 and September 1999. The median age was 59 years and all patients had a minimum follow-up of one year. Tumor locations were 46 tonsillar region, 31 soft palate and 10 base of the tongue. The patients were staged as follows: 41 T1, 35 T2, 11 T3 with 70 N0, 9 N1 and 8 N2. They received either brachytherapy alone (14 patients) or a combination of external beam irradiation and brachytherapy (73 patients) using an afterloading iridium technique in a plastic tube. Results Overall primary tumor control, including salvage surgery, was 81/87 (93%). Control of metastatic cervical adenopathy was as follows: clinical stage N1, 5/9 patients; N2, 2/8 patients. The estimated five-year cause-specific survival and overall survival rates were 81% and 47%, respectively. After interstitial irradiation severe complications were limited to one case of osteoradionecrosis of the mandible and seven cases of mucosal ulcer. Conclusion This study confirms that iridium-192 interstitial implant alone or as a boost after external beam irradiation is a safe and effective therapy in the management of oropharyngeal carcinomas.

Adjuvant chemoradiotherapy in gastric cancer: a pooled analysis of the AIRO gastrointestinal group experience.

Background Given the poor compliance with adjuvant chemoradiotherapy (CRT) in gastric cancer reported in previous studies, a survey was conducted among 18 Italian institutions within the AIRO Gastrointestinal Group to investigate current treatment modalities, toxicities, and compliance with adjuvant CRT. Patients and Methods Data from 348 patients operated on for gastric cancer were collected retrospectively from September 2000 to June 2008 and analyzed. The adjuvant treatments included CRT according to center guidelines. In multivariate analysis, acute hematological, gastrointestinal, and renal toxicity (according to the RTOG Acute Radiation Morbidity Scoring Criteria) and compliance with treatment were studied, as well as risk factors for local control, metastasis-free survival, disease-free survival, and overall survival. Results Compliance with treatment was excellent: 95.7% of patients completed CRT. During CRT, acute G3-G4 hematological toxicity was 3.7% and acute G3-G4 gastrointestinal toxicity 4%. 78.4% of patients completed chemotherapy (CT), either before or after CRT. During CT acute G3-G4 hematological toxicity was 5.4% and acute G3-G4 gastrointestinal toxicity 6%. Overall, 74.1% of patients completed the prescribed treatment (CRT and CT). Doses greater than 4500 cGy did not compensate for more aggressive disease. The 5-year overall survival was 51%. Conclusions The adjuvant treatment of gastric cancer within the AIRO group was diverse, but radiotherapy treatment was homogeneous (in terms of technique) and well tolerated. Toxicity was low and compliance with treatment was good during CRT; these results may be due to the radiotherapy technique applied. This survey could be used as a benchmark for further studies.

Assessment of clinical outcomes and prognostic factors in patients (pts) with non-small cell lung carcinoma (NSCLC) and brain metastases (BM): Results from a single institution.

e20594Background: BM development, which is frequently observed in pts with NSCLC, is usually associated with a poor outcome. Systemic treatments and whole brain radiotherapy (WBRT) are widely used ...

LA RADIOTERAPIA INTRAOPERATORIA NEL TRATTAMENTO INTEGRATO DEL CARCINOMA PANCREATICO

Pancreatic cancer is a highly lethal disease either for the high incidence of distant metastases or for the frequent local recidive also after potentially curative resection. For this reason new multimodality approaches have to be investigated. Intraoperative radiotherapy (IORT) permits to administer a high dose to the tumor or to the retropancreatic tissues and to the regional lymphnodes. Literature data suggest it is possible a better local control and pheraps a better survival than the surgery alone or the palliative treatments by the use of schedules with IORT. Anyway they are retrospective data and IORT is an investigational method which has to be indagate in the combined modality approaches to this disease.

Neoadjuvant Chemotherapy with Vincristine, Bleomycin and Methotrexate Combined with Radiotherapy in Advanced Head and neck Squamous Cell Carcinoma

From September 1980 to August 1981, 25 patients with advanced head and neck squamous cell carcinoma were treated at the Centro Oncologico, Trento, by a chemo-radiotherapeutic combination. The treatment protocol consisted of 4–6 courses of VBM (vincristine, bleomycin and methotrexate) followed by conventional radiotherapy (65 Gy). Only to VBM responders (15 patients) were administered 10 cycles of vincristine-methotrexate. At the end of induction chemotherapy an overall response of 60 % (12 % complete, 48 % partial) was obtained. At the end of radiotherapy the responses were 52.5 % complete and 35.5 % partial, for an overall response of 88 %. The overall survival at 60 months was 8 %. This combined approach, in spite of the satisfactory immediate local response rate, does not offer advantages for survival in comparison to conventional treatment modalities.