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Biomedical subjects

F A Calvo

Publications and source records attributed to F A Calvo.

At least 37 records · Page 2Linked to original sources

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.

Aged↗

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.

Actuarial Analysis↗

Arteriodigestive fistula: a complication associated with intraoperative and external beam radiotherapy following surgery for gastric cancer.

Intestinal hemorrhage due to arteriodigestive fistula is described to be a rare and serious complication of radiotherapy. Three cases of this type of fistula in gastric cancer patients treated with gastrectomy, intraoperative electron boost (15 Gy), and fractionated external beam irradiation (46 Gy) are reported. Selective angiography is most helpful in the diagnosis and immediate surgery could be lifesaving. An attempt to explain the etiopathogenesis is made.

Adult↗

Clinical trials with anticoagulant and antiplatelet therapies.

Clinical trials of drugs that influence coagulation and fibrinolysis pathways have been undertaken in patients with malignancy because these pathways are capable of influencing malignant progression. The validity of this concept was originally confirmed in experimental animal models of malignancy. Earlier pilot studies in human disease have been succeeded by definitive prospective randomized clinical trials that have revealed heterogeneity of responsiveness to anticoagulant and fibrinolytic agents that may be attributable to differences in mechanisms of interaction of the tumor cells of various types of malignancy with these pathways in vivo. In certain tumor types studied thus far, increased tumor response rates and prolongation of survival have been observed that suggest the possibility that substantial benefit may be realized from this treatment approach in patients with malignancy. In addition, the availability of newer and potentially more effective therapeutic agents holds promise for even greater gains in previously tested tumor types. The ability to design treatment regimens that correspond to defined mechanisms that pertain to specific tumor types should permit future studies to be designed rationally. Current data suggest that anticoagulant and fibrinolytic agents might reasonably be tested in tumor types characterized by the existence of a tumor cell-associated coagulation pathway with thrombin generation and conversion of fibrinogen to fibrin (such as small cell carcinoma of the lung). By contrast, protease inhibitors might reasonably be tested in tumor types characterized by expression of tumor cell plasminogen activators. Expansion of current views on the possible role of antithrombic drugs in cancer therapy is justified. For example, antithrombotic drugs classified as non-steroidal anti-inflammatory agents may inhibit carcinogenesis while polyanionic drugs with anticoagulant properties, such as suramin and heparin, may inhibit growth factor interactions with cells. Intriguing new opportunities clearly exist for interactions between clinical and basic investigators that may provide both novel biologic insights and improved patient care.

Anticoagulants↗

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.

Humans↗

[Infiltrating carcinoma of the bladder: preliminary results of multidisciplinary protocols with radiotherapy and neoadjuvant chemotherapy].

Report on the evolution of a series of 64 patients with T2-4 N0-3 M0 infiltrant transitional carcinoma of the bladder, treated with TUR and radical cystectomy (28/62) or intra-operative radiotherapy (IOR) 15 Gy and external radiotherapy 40 Gy prior to cystectomy (34/62). The last group including 24 patients which received neo-adjuvant chemotherapy. Seventy percent (15 p0N-, 5 p0N+, 1 p1N-, 3 p1N+) patients treated with radiotherapy, with and without chemotherapy, had local response. Considering just the group which received IOR, external radiotherapy and co-adjuvant chemotherapy (24/34), the local response accounts for 79% (10 p0N-, 5 p0N+, 1 p1N-, 3 p1N+). Current survival of the group receiving concomitant multiple therapy is 92 +/- 5%, 75 +/- 9% and 57 +/- 11% at 1, 3 and 5 years; for equal intervals current survival of the group undergoing cystectomy is 57 +/- 9%, 46 +/- 9% and 40 +/- 10% (p = 0.02). The univariate analysis has confirmed that stage decrease is significantly more frequent in the group receiving radiotherapy with and without chemotherapy (p less than 0.001). Such a decrease significantly biased survival (p = 0.001). In the multivariate analysis, the variables with greater prognostic power were pre-surgical renal function (p less than 0.001), use of radiotherapy (p less than 0.001) and surgical complications (p less than 0.001). Preliminary results show a very high local response to multiple therapy which has been translated so far in increased survival.

Actuarial Analysis↗

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.

Adolescent↗

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.

Adult↗

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.

Adult↗

Postoperative radical radiotherapy with concurrent weekly intra-arterial cis-platinum for treatment of malignant glioma: a pilot study.

Twelve patients with histologically proven malignant glioma have been treated with a combination of intra-arterial (IA) cis-platinum (CDDP) and radical radiation therapy (RT). Chemotherapy consisted of intracarotid (IC) CDDP, 40-60 mg/m2, weekly, repeated for 3-5 treatments. Radiation therapy consisted of whole-brain irradiation 5000 cGy in 5 weeks, plus a cone-down boost (1000 cGy in one week) to the primary tumour lesion. Ocular toxicity derived from IC chemotherapy was observed in 3 out of 41 procedures analyzed (7%). Results in tumour response assessed by computed tomography (CT) showed 5 complete remissions, 6 partial remissions and one patient was not evaluable. The median survival time for the entire group was 10 months. Median survival time in patients with complete response is 17 months, and 10 months in patients with partial response. Four patients are still alive with a follow-up ranging from 6+ to 27+ months.

Adult↗

Intraoperative radiotherapy for recurrent and/or residual colorectal cancer.

Intraoperative radiotherapy (IORT) is an attractive boosting modality in the combined treatment of recurrent and/or residual colorectal cancer. Twenty seven patients treated with IORT are analysed. Residual disease following resection of the primary tumor was treated in 11 cases (group I). Localized recurrent disease without previous radiotherapy was treated in 11 cases (group II). IORT was used in five additional patients with local recurrences in previously irradiated areas (group III). The treatment program consisted of maximal tumor resection, IORT (10-30 Gy) to the area of residual disease and external beam radiotherapy (46-50 Gy). The median follow-up time for the entire series of patients is 11 months. Local tumor control rates are 90% in group I, 63% in group II and 60% in group III. Toxicity and complications related to IORT observed in this initial experience have been pelvic pain (29%) and lower extremity neuropathy (3%). These early clinical results suggest that the IORT combined with surgery and external beam radiotherapy is feasible in primary and recurrent disease. Local control rates obtained in patients not suitable for curative surgery are encouraging.

Adenocarcinoma↗

Intraoperative and external beam radiotherapy in advanced resectable gastric cancer: technical description and preliminary results.

Twenty-two patients with resectable gastric cancer treated with intraoperative radiotherapy and external beam irradiation, in a Phase I-II oriented study, were analyzed. Tumor Stages were III & IV in 18 cases (82%). Tumor histology was described as diffuse undifferentiated type in 14 cases (63%). Following surgical resection of the primary tumor, IORT 15 Gy was delivered in the celiac axis area, using high energy electron beams ranging from 9 to 20 MeV. External beam irradiation fields covered the draining nodal areas of the upper abdomen and the gastric bed. There were no postoperative deaths. Reversible postoperative complications were recorded in 14 patients (63%). Long term complications observed were vertebral collapse and liver hemangiomas. First sites of recurrence have been: hepatic hilum (three cases), peritoneum combined with central axis nodes (two cases), liver metastasis (one case), and lung metastasis (one case). Survival data shows a follow-up period ranging from 1+ to 33+ months, with a median survival time for the entire group of 13+ months. At the time of this report, 16 patients (72%) are still alive and six have died (four from progressive malignant disease and two from intercurrent disease). From this preliminary data, it can be concluded that a combined approach with surgical resection, intraoperative radiotherapy, and external beam irradiation is feasible in advanced gastric carcinoma, and is not limited by toxicity or any complications observed. Despite this intense loco-regional therapeutic approach, the upper abdominal failure rate has been demonstrated in 22% of the cases.

Adult↗

Intraoperative radiotherapy in the multidisciplinary treatment of pediatric tumors. A preliminary report on initial results.

From September 1984 to July 1987, 33 children received intraoperative radiotherapy as part of a multidisciplinary tumor treatment. Their age ranged from 2 to 17 years. Tumors types: Ewing's sarcoma (n = 11), osteosarcoma (n = 8), soft tissue sarcomas (n = 5), Wilms' tumor (n = 3), neuroblastoma (n = 3), malignant pheochromocytoma (n = 1), Hodgkin's disease (n = 1), and optic nerve glioma (n = 1). In 25 patients the disease was localized while 8 had distant metastases. Intraoperative radiotherapy was used in 26 previously untreated patients as part of a radical treatment program and in 7 cases as an effort to rescue local failures (5 in previously irradiated areas). The intraoperative radiation field included the surgically exposed tumor or tumor bed, and the single doses ranged from 10 to 20 Gy, with 6-20 MeV electrons. Patients with osteosarcoma and recurrent tumor in a previously irradiated area did not receive postoperative external beam radiotherapy. With a median follow-up time of 10 months (1 to 31 + months) 24 out of 33 patients are alive without local recurrence and 9 have died from tumor (5 with local disease progression). Intraoperative radiotherapy seems to be a feasible treatment which might promote local control in pediatric tumors.

Adolescent↗