Research opportunities in intraoperative radiation therapy: the next decade 2013-2023

The reality of intraoperative radiation therapy (IORT) practice is consistent with an efficient and highly precise radiation therapy technique to safely boost areas at risk for local recurrence. Long-term clinical experience has shown that IORT-containing multi-modality regimens appear to improve local disease control, if not survival in many diseases. Research with IORT is a multidisciplinary scenario that covers knowledge from radiation beam adapted development to advance molecular biology for bio-predictability of outcome. The technical parameters employed in IORT procedures are important information to be recorded for quality assurance and clinical results analysis. In addition, specific treatment planning systems for IORT procedures are available, to help in the treatment decision-making process. A systematic revision of opportunities for research and innovation in IORT is reported including radiation beam modulation, delivery, dosimetry and planning; infrastructure and treatment factors; experimental and clinical radiobiology; clinical trials, innovation and translational research development (AU)

Research opportunities in intraoperative radiation therapy: the next decade 2013-2023.

The reality of intraoperative radiation therapy (IORT) practice is consistent with an efficient and highly precise radiation therapy technique to safely boost areas at risk for local recurrence. Long-term clinical experience has shown that IORT-containing multi-modality regimens appear to improve local disease control, if not survival in many diseases. Research with IORT is a multidisciplinary scenario that covers knowledge from radiation beam adapted development to advance molecular biology for bio-predictability of outcome. The technical parameters employed in IORT procedures are important information to be recorded for quality assurance and clinical results analysis. In addition, specific treatment planning systems for IORT procedures are available, to help in the treatment decision-making process. A systematic revision of opportunities for research and innovation in IORT is reported including radiation beam modulation, delivery, dosimetry and planning; infrastructure and treatment factors; experimental and clinical radiobiology; clinical trials, innovation and translational research development.

Intraoperative radiotherapy in recurrent gynecological cancer.

A retrospective analysis to assess the feasibility and clinical tolerance of intraoperative radiotherapy (IORT) in the treatment of recurrent gynecologic cancer is reported. From February 1985 to September 1992, 26 patients with recurrent gynecologic tumors entered this trial. The clinical experience comprises two different categories of disease situations: tumors relapsing after full dose radiation therapy (group I) and recurrent disease to previous surgery (group II). Cervical carcinoma was the initial tumor site of involvement in 18 patients (69%). Treatment consisted in maximal surgical resection + IORT boost (10-25 Gy) to the high-risk areas for recurrence. Non previously irradiated patients also received external beam irradiation (EBRT) (+/- chemotherapy) pre- or postoperatively. IORT-related toxicity was one episode of motor neuropathy. Local control rates have been 33% and 77%, respectively in groups I and II. The 4-year actuarial overall survival in Group I is 7% and 6-year actuarial overall survival in Group II is 33%. The addition of IORT to surgical debulking achieves modest local control and long-term survival rates if tumor-free margins cannot be obtained in previously irradiated patients. Combined EBRT (+/- chemotherapy) maximal surgical resection plus IORT could render some long-term survivors among those surgical recurrent patients not candidates for radical surgery with curative intent.

Phase II evaluation of doxorubicin, ifosfamide, and dacarbazine plus amphotericin B in the treatment of metastatic soft tissue sarcomas. A pilot study.

Amphotericin B enhances the cytotoxicity of certain antineoplastic agents in vitro and in vivo. A phase II study was designed to evaluate whether this effect can be produced in the treatment of metastatic soft-tissue sarcomas (STS). The program AIDAB consisted of ADM 50 mg/m2 i.v. bolus at day 1; ifosfamide (IFX) 1.5 g/m2 in 1 hour i.v. infusion/day x 3 days; mesna 300 mg/m2 i.v. bolus before and 4 and 8 hours after IFX; dacarbazine (DTIC) 400 mg/m2 i.v. in 6 hours infusion/day x 3 days; and amphotericin B 25 mg/m2 i.v. in 6 hours infusion/day x 3 days; repeated every 4 weeks. There were 25 patients evaluable for response and toxicity, 22 with no previous chemotherapy. The median age was 44, (range: 16-64); 14 males, 11 females with a Karnofsky range of 40 to 90%. The response rate was 48% (4% complete response and 44% partial response). The median duration of response was 6.6 months. Of these 25 patients, 17 (68%) have died; the median survival was 12 months (range: 3-51 months). A total of 175 cycles were given to the 25 patients, with a mean of 7 cycles per patient. Toxicities encountered were leukopenia and/or thrombocytopenia, grade IV (WHO), in 9 patients (36%); fever and chills during amphotericin B infusion in 40%; vomiting, grade III (WHO), in 56%; mild mucositis in 12%, and a symptomatic decrease in cardiac ejection fraction in one patient. There was one toxic death due to severe thrombocytopenia. We can conclude that AIDAB is effective in the treatment of metastatic soft-tissue sarcoma. The addition of amphotericin B did not improve the response rate or survival above what is expected from chemotherapy alone.

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.

Carboplatin (CBDCA), 5-fluorouracil (5-FU) and mitoxantrone (DHAD): an effective and well tolerated regimen for metastatic breast cancer.

Fifty-five women with metastatic breast cancer were treated with carboplatin (CBDCA), 55 mg/m2 i.v. bolus, daily for 3 days, 5-fluorouracil (5-FU) 900 mg/m2, (max. dose 1,500 mg/day in 24-h infusion (Travenol system) daily for 3 days, and mitoxantrone (DHAD) 8 mg/m2, i.v. bolus on day 1. Cycles were administered every 5 weeks. Objective responses were observed in 25 (44%) patients (95% confidence interval: 28%-60%) with a median duration of remission of 11.5+ months (range 6.5(+)-31+). Toxicity was mild. These results reflect the fact that combination of CBDCA, 5-FU and DHAD is effective and very well tolerated as an outpatient regimen.