Intraoperative radiotherapy in locally advanced recurrent colorectal cancer.

PURPOSE: In an effort to promote local control and improve quality of life in patients with recurrent colorectal cancer, a multimodality approach has been used. METHODS AND MATERIALS: Twenty-seven patients were treated with moderate doses of pre/postoperative radiotherapy with/without simultaneous systemic chemotherapy, surgical re-resection and IORT electron boost over areas at high risk for local recurrence. RESULTS: The 2-year actuarial disease-free and local relapse-free survival for the entire group were 14% and 26%, respectively. The most important factor predicting a favorable outcome was the radicality of surgical procedure. The determinate local control rate and the actuarial 2-year local relapse-free, and disease-free survival for patients undergoing complete resections were 50%, 56%, and 34%, respectively, whereas for patients undergoing partial resections these figures were 16%, 13%, and 6%. The radicality of surgical procedure was influenced by both tumoral size and previous treatment with irradiation. Complete resection rate was higher in patients with tumors less than 5 cm vs. more than 5 cm (40% vs. 22%), and in patients without previous radiotherapy versus those with previous radiotherapy (40% vs. 28%). Distant metastasis rate was high (41%). The most significant toxicities attributable to the whole treatment protocol were enteritis (37%), hydronephrosis (30%), and pelvic neuropathy (52%). CONCLUSION: Currently, our policy is to recommend IORT in patients with "favorable factors" such as: absence of previous pelvic radiotherapy, single previous surgical procedure, and complete resections.

Intra-arterial hepatic treatment with carboplatin (CBDCA) and 5-fluorouracil (5-FU) in metastases from colorectal carcinoma.

Thirty-one patients with hepatic metastases from colorectal carcinoma were treated with carboplatin (CBDCA), 55 mg/m2, given in a 4-hour intra-arterial infusion daily for 5 days, and 5-fluorouracil, 900 mg/m2, given in a 20-hour intra-arterial infusion daily for 5 days. Cycles were administered every 5 weeks. Objective responses were observed in 16 (51.6%) patients (5 complete and 11 partial responses). Another 13 patients maintained stable disease, and 2 patients rapidly progressed. The overall median survival was 23.5 months. The 16 patients with objective response had a median survival of 26.5 months. In this series, no evidence of biliary sclerosis, cholecystitis, chemical hepatitis, or myelosuppression was observed. Complications of drug delivery system were observed in 14 (45.16%) patients. In conclusion, intra-arterial hepatic chemotherapy with CBDCA-5FU was associated with a modest benefit, expressed in good quality responses and extended survival of approximately 2 years in about half of the treated patients.

Intraoperative and external preoperative radiotherapy in invasive bladder cancer: effect of neoadjuvant chemotherapy in tumor downstaging.

Absence of residual cancer (pT0) in the cystectomy specimen was evaluated in patients with invasive bladder cancer treated with intraoperative (IORT) (15 Gy) and preoperative external beam radiotherapy (EBR) (46 Gy/5 weeks) with or without neoadjuvant chemotherapy. The overall pT0 rate was 68% (67% and 70% in patients with or without neoadjuvant chemotherapy, respectively). The tolerance to the program was acceptable in both groups. It is concluded that intense, combined modality treatment is feasible in bladder cancer patients, and the addition of neoadjuvant chemotherapy does not increase the morbidity. Preliminary results on disease-free survival are encouraging.

Intraoperative and external radiotherapy in resected gastric cancer: updated report of a phase II trial.

From September 1984 to August 1991, 48 evaluable patients with resected gastric cancer and apparent disease confined to locoregional area were treated with intraoperative electron beam boost to the celiac axis and peripancreatic nodal areas (15 Gy) and external irradiation (40 to 46 Gy in 4 to 5 weeks) including the gastric bed and upper abdominal nodal draining regions. At the time of evaluation for IORT, the disease was primary in 38 cases, recurrent but resectable in four (anastomosis), and unresectable in four (nodal). Post operative complications were reversible. Acute tolerance to the complete treatment program was acceptable. Late complications included life-threatening events: Six episodes of gastro intestinal bleeding (three of them had an arteriographic documentation of arterioenteric fistula) and nine with severe enteritis (five required reoperation). Other long-term treatment related complications were six cases of vertebral collapse. The median follow-up time for the entire group is 22 months. Locoregional recurrence/persistence of disease has been identified in five patients (three with residual and/or recurrent postsurgical tumor). Systemic tumor progression has been detected in 15 patients (11 in intra-abdominal sites). Overall actuarial survival for patients with positive or negative serosal involvement was 33% versus 56%. It is concluded that the treatment program described is able to induce a high locoregional tumor control rate (100%) when used strictly in an adjuvant setting and might control long term, a small portion of patients not amenable for curative surgery (2 out of 8 patients with confirmed residual post-surgical disease). Gastrointestinal bleeding and enteritis are findings that indicate treatment intensity at the upper limits of tissue tolerance. Assessment of long term tolerance of pancreatic parenchyma and large blood vessels (tissues included in the IRORT field) are pending for longer follow-up and the appropriate selective studies.

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.

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.

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.

[Multidisciplinary protocol for the treatment of epidermoid carcinoma of the esophagus: experience from 1985 to 1989]. / Protocolo multidisciplinar de tratamiento del carcinoma epidermoide de esófago: experiencia 1985-1989.

A phase II study activated in 1985 for the multidisciplinary treatment of squamous cell carcinoma of the esophagus is described. The treatment program included simultaneous neoadjuvant continuous infusion chemotherapy with cisplatinum and 5-fluorouracil, preoperative radiotherapy (46 Gy in 5 weeks) and delayed programmed surgery (or radical irradiation in selected cases). Twenty-one patients with tumor stages I (6), II (10), III (5) entered in the study and 20 patients completed the treatment program. Severe toxicity observed was: esophagitis 100%, bone marrow aplasia 30%, severe weight loss 52%. One patient developed a tracheo-esophageal fistula at the end of radiotherapy. Clinical objective tumor response rate was 85%. Pathologic complete tumor response rate was 47%. Median follow-up of the entire group is 11 months (range 2 + to 49 + months). Ten patients have been alive for more than 12 months; six are still alive without any evidence of disease (from 12 + to 49 + months). It is concluded that the protocol described is feasible, with treatment related severe but reversible toxicities, and able to induce a high rate of tumor response and long term survivors in patients with initial locally advanced tumor stages.

[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.