Intraoperative radiotherapy during lung cancer surgery: technical description and early clinical results.

A phase I-II study of intraoperative radiotherapy (IORT) for Stage III lung cancer was performed in 34 patients during a period of 58 months. Loco-regional treatment included tumor resection if technically feasible, IORT boost of electron beams using moderate single doses (10-15 Gy) to tumor bearing areas and external photon beam irradiation (46-50 Gy in 5 weeks) using conventional fields. Indications for this study were unresectable hiliar tumors (14, 41%), and mediastinal, hiliar and/or chest wall residual disease following resection (20, 59%). Thirty-four procedures, with 40 IORT fields, have been analyzed to describe the relevant technical aspects and the toxicity. IORT was delivered using acrylic transparent cones of different diameters. Surgical approach consisted in a lateral thoracotomy in all patients (21 right side and 13 left side). Tissues included within the IORT field were: tumor or residual tumor tissues (34, 100%), collapsed lung parenchyma and main bronchus not surgically manipulated (14, 41%), bronchial stump and vascular suture following resection (19, 55%), mediastinal structures (20, 58%), and brachial plexus (1, 3%). The bronchial suture was covered with pleural or pericardial flap after IORT in 10 cases (29%). Life threatening toxicity related to IORT consisted in broncho-pleural fistula (1, 3%) and massive hemoptysis (1, 3%). Other reversible toxic events were acute pneumonitis (12, 85%) and esophagitis (10, 50%). Long term asymptomatic lung fibrosis was detected in 11 cases (32%). Median survival time for the entire group has been 12 months. With a median follow-up time of 12 months the freedom from thoracic recurrence rate is 30% (65% in cases with tumor resection). Projected actuarial survival rates at 4 years were 28% for resected group and 7% for unresected cases. This experience supports IORT as a feasible alternative modality to be used in the management of locally advanced lung cancer. Tolerance of thoracic organs to moderate doses of IORT appeared to be adequate and local control is achieved in certain patients. These results deserve further investigation and confirmation trials.

Stereotactic radiosurgery of the foramen magnum region and upper neck lesions: technique modification.

A modification of the stereotactic radiosurgical procedure to permit treatment of lesions in the foramen magnum and upper cervical regions is described. The modification consists of placing the frontal pins of the stereotactic head ring in the zigoma bone, with no changes in the position of the occipital pins, so the final BRW head ring is oblique to the orbito-meatal plane. In this new position there is room enough in the posterior part of the guide for the support scrubs. This is unhampered by the patient's shoulders and the lesion is far enough to permit setting the axial coordinate sufficiently above the head ring plane.

Intraoperative radiation therapy in malignant glioma: early clinical results.

Intraoperative radiation therapy (IORT) with high energy electron beams is a treatment modality that has been included in multimodal programs in oncology to improve local tumor control. From August 1991 to December 1993, 17 patients with primary (8) or recurrent (9) high grade malignant gliomas, anaplastic astrocytoma (4), anaplastic oligodendroglioma (6) and glioblastoma multiforme (7), underwent surgical resection and a single dose of 10-20 Gy intraoperative radiation therapy was delivered in tumor bed. Fourteen patients received either pre-operative (8) or post-operative (6) external beam radiation therapy. Primary gliomas: 18-months actuarial survival rate has been 56% (range: 1-21+ months) and the median survival time has not yet been achieved. Four patients developed tumor progression (median time to tumor progression: 9 months). Recurrent gliomas: 18-months actuarial survival rate and median survival time has been 47% and 13 months (range: 6-32+ months) respectively. The median time to tumor progression was 11 months. No IORT related mortality has been observed. IORT is an attractive, tolerable and feasible treatment modality as antitumoral intensification procedure in high grade malignant gliomas.

Intraoperative and external beam radiotherapy in invasive bladder cancer: pathological findings following cystectomy.

The pathological findings observed following intraoperative radiotherapy (IORT) boost (15Gy) to the whole bladder, external beam fractionated irradiation (46Gy in 5 weeks), and planned radical cystectomy in patients with deep invasive bladder carcinoma are analyzed. Clinical pretreatment stage of disease was T3 (16 cases) and T4 (two cases). No evidence of residual tumor (pT0) was demonstrated in 11 cystectomy specimens (61%) and residual tumor (pT+) was observed in seven (39%). Toxicity and complications related to the treatment approaches were minor and reversible. It is concluded that IORT is a feasible boosting modality in the management of invasive bladder cancer, able to induce high rates of pT0 cystectomy specimens, and might be considered as a valuable technique for organ preservation treatment programs.

[Changes in radiation lesions using platinum derivatives. Biological bases and clinical experience]. / Modificación de la lesión por radiación con derivados de platino. Bases biológicas y experiencias clínicas.

The biological basis of radiation damage modulation with platinum derivatives are reviewed. Cisplatin and Carboplatin are cytostatic agents used increasingly in the treatment of different human tumours. In vitro and in vivo studies have established the interest of the simultaneous combination of platinum compounds and radiation in tumor cells and neoplastic tissue, describing potentiation, sensitization, and inhibition of sublethal damage repair effects from radiation. Clinical trials have been recently activated in order to explore a possible benefit from the biological modulation with platinum compounds of radiotherapy. In the frame of developmental therapeutic protocols in modern oncology, this approach might explore a positive effect on the therapeutic index of radiotherapy for malignant tumors. The initial clinical results reported indicate that the available platinum derivatives used in human oncology behave as radiopotentiating and radiosensitizing agents.

[Intraoperative radiotherapy with accelerated electrons for urinary bladder carcinoma: principles and results]. / Radioterapia intraoperatoria con electrones acelerados en el carcinoma de vejiga urinaria: fundamentos y resultados.

OBJECTIVE: To describe intraoperative radiotherapy with accelerated electrons, a highly selective method of administering irradiation for radical treatment of bladder cancer. METHODS: We reviewed the experience reported in the literature since this treatment modality was utilized in Japan and its application extended to the western countries. RESULTS: Animal experiments have shown an acceptable clinicopathological tolerance to 20 Gy intraoperative irradiation of partial bladder volume. The local recurrence rate was 9% for early solitary tumor (> T2) and 27% for early multicentric tumor, according to the Japanese clinical experience. In the western countries, intraoperative radiotherapy plus external irradiation with or without systemic chemotherapy achieves a pT0 of about 65% (in total cystectomy specimens) and an intravesical tumor control rate of 88% in organ-sparing protocols. CONCLUSIONS: The results achieved by the groups with wider experience demonstrate that highly selective intraoperative radiotherapy is feasible, well-tolerated and effective in terms of inducing complete pathological remissions and definitive control of intravesical tumor. These selected clinical experiences must be corroborated by multicenter studies.

Urokinase combination chemotherapy in small cell lung cancer. A phase II study.

BACKGROUND AND METHODS: Fifty-one patients with small cell lung cancer (SCLC) were treated with alternating urokinase (UK)-cyclophosphamide-doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH)-vincristine and cisplatin-etoposide-vincristine. UK was given as a loading dose of 3000 micrograms/kg body weight, followed by 3000 micrograms/kg/h for 6 hours. Thoracic irradiation with split technique (46 Gy) and prophylactic cranial irradiation (25 Gy) were administered to responding patients. A second staging was performed in patients exhibiting a clinical complete response (CR) after 1 year. RESULTS: In 27 patients with limited disease, there were 23 CR and 8 partial responses (PR) (CR, 85.1%; 66.2-95.8% at 95% confidence intervals); in 24 patients with extensive disease, there were 17 CR, 4 PR, and 3 cases with progression. Pathologically proven CR were observed in 59.2% patients with limited disease and 33.3% patients with extensive disease. Survival rates were as follows: in patients with limited disease, 1 year, 85.1%; 2 years, 55.5%; and 3 years, 25.9%; in patients with extensive disease, 1 year, 54.1; and 2 years, 16.9%. Median survival times were 26.3 months (patients with limited disease) and 13.3 months (patients with extensive disease). UK-related toxic effects included four episodes of mild to moderate bleeding, one allergic reaction, and one cerebrovascular accident. Myelotoxicity was severe, with a median of two episodes of Grade III-IV (World Health Organization classification) aplasia per patient. CONCLUSIONS: These results are consistent with a potential benefit of fibrinolytic therapy in combination with chemotherapy in patients with SCLC with limited disease. Additional trials are indicated.

Intraoperative radiotherapy in the multidisciplinary treatment of bone sarcomas in children and adolescents.

From September 1984 to December 1989, 38 patients of pediatric age with localized bone sarcomas received intraoperative radiotherapy (IORT) as part of a multidisciplinary treatment program. The age ranged from 6 to 21 years. The tumor histologies were 22 osteosarcomas and 16 Ewing's sarcomas. Thirty-four had initial primary disease (90%) and 4 were treated for local recurrence (10%). IORT was used on 32 untreated patients and in 6 previously treated with external beam radiotherapy (EBR). The IORT field included the surgically exposed tumor bed area. Single radiation doses ranging from 10 to 20 Gy were delivered, using 6-20 MeV electron beams. The median follow-up time for the entire group is 25 months (2-65+ months). The projected 5-year disease-free and overall survival rates are 65% and 69%, respectively. One patient developed a local recurrence in each histological group: one chondroblastic osteosarcoma and one cervical Ewing's sarcoma. Six patients died from metastatic progression: 3 initially recurrent tumors and three primary disease cases. Severe neuropathy and soft tissue necrosis were seen in some patients as IORT related complications. IORT is a feasible technique to be integrated in multidisciplinary programs that may promote local control in pediatric and adolescent patients with bone sarcomas. Peripheral nerves are dose-limiting tissue structures for IORT.

Induction chemotherapy with paclitaxel, cisplatin and 5-fluorouracil for squamous cell carcinoma of the head and neck: long-term results of a phase II trial.

BACKGROUND: The aim of this study was to evaluate the efficacy and toxicity of a combination of paclitaxel, cisplatin and 5-fluorouracil (PPF) as induction chemotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). METHODS: Seventy patients with previously untreated stage III-IV SCCHN were included in this phase II trial. Induction treatment consisted of a maximum of three outpatient courses of paclitaxel 175 mg/m(2) as a 3-h infusion on day 1, cisplatin 100 mg/m(2) on day 2, and 5-fluorouracil (5-FU) 500-750 mg/m(2)/day as a 24-h continuous infusion on days 2-6, repeated every 3 weeks. The 5-FU dose was reduced from 750 mg/m(2)/day to 500 mg/m(2)/day due to the excessive toxicity observed in the first 14 patients enrolled. Local treatment consisted of radiotherapy and/or surgery. RESULTS: Two-hundred-and-one cycles were administered to 70 patients. The main toxicities of PPF were neutropenia (grade 4, 14%; febrile neutropenia, 4%), peripheral neuropathy (grade 2-3, 14%) and catheter-associated venous thrombosis (7%). There were three early deaths (two from neutropenic sepsis and one from pulmonary embolism), and 13 patients required hospitalization due to toxicity. Other side effects included mucositis, anorexia, diarrhea, myalgias and alopecia. The overall response rate to PPF was 88%, including 59% complete responses (CR) and 29% partial responses. The CR rates at the primary tumor and neck lymph nodes were 74% and 62%, respectively. With a median follow-up of 51 months (range 40-63 months), the estimated 5-year time-to-disease progression and overall survival rates were 56% and 44%, respectively. CONCLUSIONS: The PPF regimen has major antitumor activity and is associated with manageable toxicity as induction treatment in SCCHN patients. The high complete response rate and favorable long-term outcome justify further evaluation of this chemotherapy combination.