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 electron boost followed by moderate doses of external beam radiotherapy in resected soft-tissue sarcoma of the extremities

To analyze the patterns of failure and the toxicity profile of intraoperative electron beam radiotherapy (IOERT) after resection of soft tissue sarcomas of the extremities (STS). PATIENTS AND METHODS: Forty-five patients with extremity STS were treated with IOERT and moderate-dose postoperative radiotherapy (45-50 Gy). Twenty-six patients were treated for primary disease (PD) and 19 patients for an isolated recurrence (ILR). Tumor size was >5 cm (maximum diameter) in 36 patients (80%), and high-grade histology in PD patients was present in 14 patients (54%). In nine patients, IOERT was used alone, due to previous irradiation or patient refusal. Chemotherapy (neoadjuvant and/or adjuvant) was mainly given to high-grade tumors. RESULTS: Nine patients relapsed in the extremity (20%), and 12 patients in distant sites (28%). Actuarial local control at 5 years was 88% for patients with negative/close margins and 57% for patients presenting positive margins (P=0.04). Five patients (11%) developed neuropathy associated with the treatment. Extremity preservation was achieved in 40 patients (88%). With a median follow-up of 93 months (range: 27-143 months) for the patients at risk, 25 patients remain alive (a 7-year actuarial survival rate of 75% for PD and 47% for ILR; P=0.01). CONCLUSIONS: IOERT combined with moderate doses of external beam irradiation yields high local control and extremity preservation rates in resected extremity STS. Peripheral nerves in the IOERT field are dose-limiting structures requiring a dose compromise in the IOERT component to avoid severe neurological damage

Multiple cycles of dose-intensive chemotherapy with repeated stem cell support as induction treatment in metastatic breast cancer: a feasibility study

The purpose of this trial was to study feasibility and tolerance of a dose-intensive multicyclic alternating induction chemotherapy with repeated stem cell support in a series of 43 metastatic breast cancer patients. Anthracycline-naive patients (n = 21) received cyclophosphamide 2.5 g/m2 plus doxorubicin 80 mg/m2 alternating every 14 days with paclitaxel 200-350 mg/m2 plus cisplatin 120 mg/m2. Patients who had previously received anthracyclines (n = 22) received cisplatin 120 mg/m2 plus etoposide 600 mg/m2 alternating with paclitaxel 200-350 mg/m2 plus ifosfamide 8 g/m2. Peripheral blood stem cells were infused after every course except the first, with a median CD34+ dose of 2.1 ´ 106/kg per cycle. Positive selection of CD34+ cells was performed in good mobilizers. The median number of cycles administered was six (4-8), and the time interval between them was 17 days. Median summation dose intensities (SDI) actually administered for the CA-TP and PE-TI protocol were 4.95 and 4.69, respectively (87% of scheduled SDI). There were 15 complete (35%) and 21 partial responses (49%), for an overall response rate of 84% (95% CI, 73%-95%). Infection or neutropenic fever occurred in 50% of the cycles. There was one treatment-related death. After a median follow-up of 26 months, the median event-free-survival was 12 months (95% CI: 10-14) and overall survival was 31 months. These high dose-intensity induction treatments seem to be feasible with sequential stem cell support

Quimioterapia complementaria del cáncer de mama; experiencia de la Clínica Universitaria de Navarra

Desde 1982 a 1989 se han tratado 68 pacientes con carcinoma de mama. 57 han sido premenopáusicas y 11 postmenopáusicas. El estadio tumoral más frecuente ha sido T2N1 (44,1 %) seguido de T1N1 (20,6 %). La dosis media de quimioterapia recibida ha sido de 91,2 %, 88 % y 94 % para la ciclofosfamida, metotrexate y 5-fluorouracilo respectivamente. El tratamiento ha sido bien tolerado, siendo la toxicidad más frecuente la hematológica (leucopenia). Las pacientes premenopáusicas han presentado un intervalo libre de enfermedad de 89,4 % a 96 meses y las postmenopáusicas de 63,3 % a 68 meses. No se han observado diferencias en el intervalo libre de enfermedad según el tamaño del primario o la positividad del tumor a receptores de estrógeno o progesterona. Los factores pronósticos más importantes de esta serie han sido el número de ganglios axilares afectos y la dosis de quimioterapia recibid

Breast cancer Multiple cycles of dose-intensive chemotherapy with repeated stem cell support as induction treatment in metastatic breast cancer: a feasibility study

Summary: The purpose of this trial was to study feasibility and tolerance of a dose-intensive multicyclic alternating induction chemotherapy with repeated stem cell support in a series of 43 metastatic breast cancer patients. ades. Extensive literature reviews by Hryniuk et al 1,2 have found dose intensity to be correlated with response rate and survival. This effect has been considered in the rationale of many clinical trials that attempted to improve long-term survival in metastatic BC by delivering single courses of high-dose chemotherapy (HDC). Despite some promising data derived from phase II trials, results of the randomized studies published thus far have failed to show a sound clinical benefit for single autografts. 8 Multicyclic treatment schemes appear to take advantage of the inherent time-dependant responsiveness of most cancer tissues. Autologous peripheral blood stem cell infusions have been extensively used to support single courses of HDC. Nonetheless, their possible use in programs of multicyclic non-myeloablative dose-intense chemotherapy has been little explored. Materials and methods Women with histologically proven metastatic BC were evaluated for study entry. An ECOG performance status of 0-1, age less than 65 years, and no evidence of cardiac, pulmonary, liver or renal impairment were required. All patients gave written informed consent according to institutional policy before entering the study. Patients presenting with brain metastases, leptomeningeal disease, or bone marrow involvement, as well as patients previousl

Intraoperative radiotherapy electron boost in advanced and recurrent epithelial ovarian carcinoma: a retrospective study

<p>Abstract</p> <p>Background</p> <p>Relapses of epithelial ovarian carcinoma (EOC) have a poor prognosis and are almost always fatal. The aim of this study was to evaluate the clinical outcome and toxicity of intraoperative electron beam radiation therapy (IOERT) in advanced and recurrent EOC.</p> <p>Methods</p> <p>Forty-five women with EOC were treated with IOERT. Twenty-five patients had primary disease (PD) without distant metastasis at IOERT, and 20 patients had an isolated local recurrence (ILR) after surgery. All 45 patients in this series underwent optimal cytoreductive (≤ 1 cm) surgery. The whole pelvic (WP) radiotherapy was intraoperatively delivered using 12 Mev electron beam; 43 patients received 18-20 Gy and two patients received 10 Gy. Thirty-three patients received postoperateive intraperitoneal (IP) chemotherapy, while seven patients received intravenous (IV) chemotherapy. Five patients refused concurrent chemotherapy. Overall survival (OS) rates were analyzed using the Kaplan-Meier method.</p> <p>Results</p> <p>Tumor recurrence and metastasis were observed in 16 patients (35.6%). Of those, 14 patients (31.1%) relapsed and two patients (4.4%) had distant metastasis alone. Eight of 25 (32%) local failures were observed in the PD group, as compared to 6/20 (30%) in the ILR group (<it>P </it>= 0.885). Actuarial local control at five year follow-up was 31/45 (68.9%). Seventeen of the total 45 (37.8%) patients died. Nine of 25 (36%) in the PD group died, as compared to 8 of 20 (40%) in the ILR group. The 5-year OS and disease-free survival (DFS) rates were 28/45 (62.2%) and 25/45 (55.6%), respectively. In the PD group, the 5-year OS and DFS rates were 16/25 (64%) and 14/25 (56%) (<it>P </it>> 0.05, <it>vs</it>. the ILR group at 12/20 and 11/20, respectively). The OS and DFS in the IOERT plus IP group were 25/33 (75.8%) and 23/33 (69.7%), respectively, which were superior to the rates achieved with IOERT plus IV chemotherapy (<it>P </it>< 0.05, 2/7 and 1/7, respectively). The major complication of IOERT was neuropathy. Five (11.1%) patients developed peripheral neurotoxicity.</p> <p>Conclusions</p> <p>IOERT may be feasible and effective as a boosting technique for advanced and recurrent ovarian cancer. IOERT plus IP chemotherapy may achieve high locoregional disease control and survival benefit with a low risk of toxicity. Peripheral nerves in the IOERT field are dose-limiting structures requiring nerve protection policies or a dose compromise to ensure against severe neurological damage.</p

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