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Biomedical subjects

S E Order

Publications and source records attributed to S E Order.

At least 19 recordsLinked to original sources
PubMed1999

Metastatic nonresectable fibrolamellar hepatoma: prognostic features and natural history.

Fibrolamellar hepatoma has a clinical course distinct from that of typical histologic hepatocellular carcinoma. The clinical behavior and prognostic features of nonresectable metastatic fibrolamellar hepatoma have not previously been fully addressed and are the focus of this report. Retrospective chart review of all patients (n = 17) with nonresectable metastatic fibrolamellar hepatoma referred to the Johns Hopkins Oncology Center from 1985 through 1990 was carried out. All patients had hepatic parenchymal involvement and regional node metastases at the time of referral. Metastases were limited to regional nodes in four patients. The remaining patients had lung metastases (n = 4), peritoneal metastases (n = 5), or both (n = 4). To assess the impact of the fibrolamellar variant, characteristic-matched control patients with typical histologic hepatocellular carcinoma were obtained from the Radiation Therapy Oncology Group database. Actuarial median survival from treatment was 14 months in the patients with fibrolamellar hepatoma and 7.7 months in the patients with hepatocellular carcinoma (p < 0.001). Karnofsky performance status and hepatic tumor volume at time of referral were important prognostic features. Multimodality treatment included radiation therapy and radiolabelled antibody, cisplatin-based chemotherapy, or both; results are discussed. Thirteen patients died, nine of liver failure, three of metastatic disease, and one of sepsis. Fibrolamellar histologic type, liver function tests, tumor volume, and patient performance status were significant predictors of survival. The cause of death in fibrolamellar hepatoma differs considerably from that observed in typical histologic hepatocellular carcinoma in the United States. The techniques of treatment of this uncommon disease were modeled after advances in the multimodality treatment of hepatocellular carcinoma and are discussed. Median survival was 14 months in patients with metastatic nonresectable fibrolamellar hepatoma.

Adult↗
PubMed1999

Complete remission of nonresectable pancreatic cancer after infusional colloidal phosphorus-32 brachytherapy, external beam radiation therapy, and 5-fluorouracil: a preliminary report.

This is a preliminary report of five patients diagnosed with locally advanced nonresectable pancreatic cancer who achieved improved quality of life, delay of local progression, and reduction of biomarker CA 19-9 after infusion of colloidal phosphorus 32 (32P) and administration of combined chemoradiotherapy. A phase II trial using intratumoral colloidal 32P delivery for nonresectable pancreatic cancer without metastases is in progress. Patients initially were given infusions of decadron followed by macroaggregated albumin and 30 mCi colloidal 32P to the interstitial space of the tumor by two infusions 1 week apart. Through this method, doses ranging from 750,000 to 1,800,000 cGy were delivered. After administration of colloidal 32P, external radiation to a dose of 6000 cGy minimum tumor dose, including regional lymph nodes, was given concomitantly with four intravenous infusions of 500 mg bolus 5-fluorouracil on alternating days within the first 2 weeks after initiation of external radiation. All five of these patients demonstrated cessation of local tumor growth or regression of disease on serial computed tomography scans for a minimum of 10 months from completion of therapy. Three of these patients have survived without local disease progression over 24 months from initiation of therapy, with one patient approaching 36 months. CA 19-9 values for all patients declined within weeks after completion of therapy. This new method of isotope delivery has resulted in reduction of tumor volume, normalization of the biomarker CA 19-9, and improved performance status in those patients who have localized nonresectable disease without dissemination.

Aged↗
PubMed1997

Objective responses after fractionated infusional brachytherapy of unresectable pancreatic adenocarcinomas.

BACKGROUND: The prognosis of unresectable pancreatic adenocarcinoma is poor. Therefore, the treatment potential of an intratumoral infusional brachytherapy using macroaggregated human albumin in combination with radioactive chromic phosphate [32P] was investigated in this group of patients. METHODS: Seventeen patients with unresectable tumors received intratumoral infusional brachytherapy. Treatment and assessment of response was performed with the aid of ultrasonography. RESULTS: Four patients had complete response with a duration ranging from 2-57 weeks and 5 patients had partial response with a duration ranging from 4-21 weeks, corresponding to an objective response of 53% (9 of 17 patients). Six of these patients were alive 33-57 weeks after treatment. Radiation necrosis was observed in 1 patient after a 19,000-gray cumulative radiation dose and a slight decrease in blood counts was observed in 2 patients. CONCLUSIONS: Intratumoral infusional brachytherapy using radioactive colloidal chromic phosphate has the potential to reduce inoperable pancreatic tumors with few side effects.

Adenocarcinoma↗
PubMed1996

Selective tumor irradiation by infusional brachytherapy in nonresectable pancreatic cancer: a phase I study.

PURPOSE: Selective high-dose radiation of solid tumors has been a goal of radiation oncology. The physiological barriers of solid tumors (high interstitial tumor pressure, reduced tumor vascularity, and poor perfusion) have been major barriers in achieving significant tumor dose of systemically infused radioconjugates. Direct tumor infusional brachytherapy overcomes these barriers and leads to selective high tumor doses. METHODS AND MATERIALS: The development of interstitial tumor infusion of macroaggregated albumin (MAA) followed by colloidal chromic phosphate 32P has overcome solid tumor obstacles in 47 patients with nonresectable pancreatic cancer in a Phase I dose escalation study. The colloidal 32P infusion was followed by external radiation and five fluorouracil. RESULTS: Of the 28 patients with cancer limited to the pancreas, 15 of 16 patients retained 86-100% (mean 96%) of the infused colloidal 32P isotope. While the other 12 patients had partial shunting to the liver, shunting to the liver was due to high interstitial resistance with tumor dose deposition of 17-88% (mean 52 %). Of the 19 patients with metastatic pancreas cancer, colloidal 32P tumor deposition ranged from 22 to 100% of the infused dose (mean 79%). The less than optimal tumor deposition led to our increasing the MAA from 600,000 to 1.5-2.5 million particles. Interstitial dexamethasone 2 mg and later 4 mg was infused first and prevented liver shunting by somehow reducing tumor resistance. The median survival in 28 Phase I patients with nonresectable pancreas cancer without metastasis, was 12 months. No significant toxicity occurred when treatment was limited to two infusions with as much as 30 mCi each. The maximum tumor dose was 17,000 Gy (1.700,000 cGy). In 19 nonresectable pancreatic cancer patients with metastasis, a 6.9 months median survival was observed. CONCLUSIONS: Infusional brachytherapy is an outpatient procedure that delivers high-dose radiation selectively to pancreatic cancer. Results of the Phase I study in nonresectable pancreas cancer has led to a national multiinstitutional Phase II trial.

Adult↗
PubMed1996

Preliminary experience of infusional brachytherapy using colloidal 32P.

In the past, we have clinically evaluated radiolabelled antibodies in Hodgkin's disease and hepatocellular cancer. Increased tumour pressure, reduced vascularity and poor diffusion has limited significant radiolabelled antibody tumour dose deposition. Using intratumoural infusion of macroaggregated albumin to blockade exiting vasculature followed by colloidal chromic 32Phosphorous, we have been able to achieve 75% to 100% tumour dose deposition by interstitial tumour infusion under computerised tomographic guidance. Phase I studies in a variety of solid tumours indicate extremely high doses may be achieved without toxicity (i.e. non-resectable pancreas 900,000 cGy to 1.7 million cGy) with tumour control and remission. This is a review of those studies and how the technique was applied.

Astrocytoma↗
PubMed1995

Quantitative bremsstrahlung single photon emission computed tomographic imaging: use for volume, activity, and absorbed dose calculations.

PURPOSE: To perform bremsstrahlung single photon emission computed tomographic (SPECT) imaging using 32P chronic phosphate for volume and activity quantitation to calculate absorbed dose estimates. METHODS AND MATERIALS: Seven cancer patients enrolled in clinical Phase I therapeutic protocols were injected with 2.5 million particles of macroaggregated albumin, followed by colloidal 32P chromic phosphate by direct interstitial injection into the tumor-bearing region under computed tomographic (CT) guidance. SPECT images were obtained in these patients. The patient body contour was defined through the use of two externally placed Compton backscatter 99mTc sources. A computer algorithm was written to facilitate region-of-interest volume and activity determination on the reconstructed SPECT slices based on a fixed threshold method. Three sequential SPECT studies were acquired in two of these patients, to determine the accuracy of activity quantitation for bremsstrahlung SPECT studies using Chang's postprocessing method of attenuation compensation with a computer-generated body contour based on the Compton backscatter sources, and an experimentally measured effective linear attenuation coefficient for 32P. The serial data in these two patients were used to calculate absorbed dose estimates. RESULTS: The 99mTc backscatter sources enabled the patient body outline to be clearly visualized in all the transaxial reconstructed slices and did not contribute significant counts to the patient 32P counts. The calculated activities from the SPECT studies were within 7.8% of the administered 32P activity. The two calculated patient absorbed doses were 4.2 x 10(3) Gy and 5.9 x 10(3) Gy for injected activities of 736 MBq and 920 MBq, respectively. CONCLUSION: We conclude that accurate quantitative bremsstrahlung SPECT imaging, for the case of high contrast well-localized activity distributions, with a commercially available postprocessing attenuation correction algorithm, can be performed in a clinical setting. Entirely SPECT-based measurements can be used to generate absorbed dose estimates.

Humans↗
PubMed1994

A new method for delivering radioactive cytotoxic agents in solid cancers.

PURPOSE: Therapeutic agents such as monoclonal antibodies, radiopharmaceuticals, and radioactive growth factors are limited in effectiveness due to the inability to deposit significant quantities of the agents and for limited periods of time in solid cancer. A new technique based on knowledge of the pathophysiology of solid tumors allows for significant concentration of these agents to accumulate and for a prolonged period of time, thus allowing interaction with the tumor for potentially increased effectiveness. METHODS AND MATERIALS: Three agents have been studied: 131I antiferritin monoclonal antibody, colloidal 32P chromic phosphate, and 131I transferrin. The time required for maximal tumor uptake was determined in vitro in tissue culture and was 10 min, 25 min, and 40 min, respectively. The new method of in vivo tumor infusion consisted of a direct intratumoral injection of macroaggregated albumin (MAA) 10,000 particles, followed by the radioactive agents under study. Tumors were infused in vivo using the new technique and compared to intratumoral infused controls. In the instance of radiolabeled antiferritin antibody, intraperitoneal administration and intratumoral infusion were compared to the new technique. In the other two instances, intratumoral infusion was compared to the new method. RESULTS: In all instances the direct vascular blockade caused by MAA led to greater deposition of the agent under study for at least 24 h. These results were clinically applied with MAA followed by 32P colloidal chromic phosphate and were consistent with the experimental findings. CONCLUSION: A new technique is described that may be carried out in the experimental laboratory and clinic by direct tumor infusion of macroaggregated albumin (MAA), followed by other radioactive agents that will remain localized in solid cancers and will allow for high tumor dose deposition for potentially increased therapeutic efficacy.

Animals↗
PubMed1991

Whole-abdominal irradiation for the management of gastrointestinal and abdominal manifestations of agnogenic myeloid metaplasia.

A patient with a long-standing history of agnogenic myeloid metaplasia developed weight loss and ascites secondary to gastric/small bowel infiltration and peritoneal implants of myeloid tissue. Moderate doses of radiation were very effective in controlling her gastrointestinal symptoms. In contrast to previous reports, clinical improvement after irradiation was a slow, gradual process, requiring 5 months for complete resolution of the patient's ascites. Hematologic suppression may be profound and careful attention to the rate of change in leukocyte and platelet counts is necessary to avoid severe toxicity.

Ascites↗
PubMed1991

Multimodality cisplatin treatment in nonresectable alpha-fetoprotein-positive hepatoma.

Twenty-eight patients with alpha-fetoprotein-positive (AFP+) nonresectable hepatoma have been enrolled in a new multimodality Phase I, II program. Induction therapy consisted of 50 mg/m2 intravenous cisplatin followed by 2100 cGy irradiation to the tumor volume in seven fractions over 10 days. Hepatic arterial infusion of 50 mg/m2 cisplatin (IA-CDDP) was then administered at monthly intervals. Twenty-one patients have completed induction and at least two cycles of IA-CDDP. Twelve-month cumulative survival was 52% for all 28 patients and 69% for the 21 patients completing induction and IA-CDDP. Median survival has not yet been reached. Response rate (complete and partial) was 36% overall and 48% among the 21 patients who completed treatment. The improved survival of the present series of patients as well as the minimal hematologic toxicity suggests possible further integration of new modalities for therapy.

Adult↗
PubMed1991

Delayed split whole abdominal irradiation in the combined modality treatment of ovarian cancer.

Fifty-eight patients with ovarian malignancies have been treated using a delayed split whole abdominal irradiation technique (DSA) allowing the entire tumor volume to be irradiated with tumoricidal fractional doses without undue toxicity. The lower hemiabdomen was irradiated with 2 Gy per fraction to a total dose of 40 Gy. A 2-6 hour delay was used between the irradiation of each half of the abdomen to avoid excessive acute gastrointestinal toxicity. The upper hemiabdomen was irradiated with 1.5 Gy per fraction to a total dose of 30 Gy. The acute toxicity was acceptable, with 53 of 58 patients able to complete the prescribed course of treatment. Three patients (5%) experienced grade 3 or greater acute gastrointestinal toxicity. Fourteen of 60 patients (24%) required treatment breaks because of thrombocytopenia. Nadir platelet counts were lower in patients who had received previous chemotherapy than in previously untreated patients (80,000 vs 118,000; p = .02). However, only 4 out of 60 patients were unable to complete DSA because of prolonged thrombocytopenia. In addition to DSA, patients were also treated with intraperitoneal 32P (52 patients), intraperitoneal human ovarian antitumor serum (14 patients), and prior (14 patients) or subsequent (32 patients) chemotherapy. Granulocytopenia was more severe among patients who had received prior chemotherapy (mean nadir 900 vs 2200). Seven patients (11.5%) developed delayed bowel obstruction in the absence of recurrence. There was one death caused by hepatitis, presumably related to colloidal 32P and DSA. Twenty-five percent of Stage III optimally cytoreduced patients were disease-free at 5 years; these patients had a median survival of 45 months. DSA irradiation is an acceptable technique for delivering a high fractional dose of radiation to the entire peritoneal cavity. Shielding of the iliac crests spares bone marrow allowing DSA irradiation to be integrated into an aggressive combined modality treatment plan.

Combined Modality Therapy↗
PubMed1991

Prognostic factors in unresectable hepatocellular cancer: Radiation Therapy Oncology Group Study 83-01.

The Radiation Therapy Oncology Group (RTOG) conducted a Phase I/II study in hepatocellular cancer that closed on September 9, 1987 and some results presented previously. Here, 17 patient characteristics are evaluated to identify any of prognostic significance. Two hundred sixteen patients were entered and 198 (74% with metastases and/or previous chemotherapy) were evaluable. Treatment began with an induction regimen of external beam radiotherapy to the liver (21.0 Gy, 3.0 Gy/Fx, 10 MV photons, 4 days per week) with low-dose chemotherapy (5-Fluorouracil (FU), 500 mg, i.v.; Doxorubicin, 15 mg, i.v.) on treatment Days 1, 3, 5 and 7. In the later stages of these studies, 56 patients received external beam radiotherapy as hyperfractionated treatment (1.2 Gy twice daily, 4 hours separation, 5 days per week, 24.0 Gy total) with similar chemotherapy. One month following induction therapy, cycles of radiolabeled antibody therapy were given every 2 months. Each cycle was derived from a different species of animal and consisted of 30 mCi I-131 antiferritin, Day 0, and 20 mCi, Day 5. On Day -1, 5-FU, 500 mg, and Adriamycin, 15 mg, were administered. The overall median survival for the entire group, including previously treated patients, was 4.9 months. The median survival for alpha-fetoprotein (AFP) - patients not previously treated was 10.5 months. Median survival for all AFP - patients was 8.5 months and for all AFP + patients was 4.6 months (p = 0.006). Of the 17 pretreatment characteristics investigated for prognostic value Karnofsky Performance Score (KPS) (80-100 vs. less than 80) (p = 0.0001), presence/absence of ascites (p = 0.0002), bilirubin level (less than 1.5 vs. greater than or equal to 1.5) (p = 0.018), SGOT (less than or equal to 35 vs. greater than 35) (p = 0.001); alkaline phosphatase (less than or equal to 95 vs. greater than 95) (p = 0.008) were found to be significant independently using a multivariant regression model. The relative risk of dying for the unfavorable component of each of these characteristics was 2.2, 2.0, 1.5, 1.9 and 1.7, respectively. Good and poor prognostic groups were then defined and compared to a similar patient population (RTOG study 83-19) with confirmation of the validity of the model. When stratification for these overpowering clinical factors was incorporated, AFP status was again significant with a relative death rate 1.80 times higher for AFP+ patients. Our recommendations for structuring future prospective randomized trials are discussed and include stratification by AFP status.

Antibodies↗
PubMed1991

The Radiation Therapy Oncology Group: an update of clinical research activities.

This paper provides an introduction into the clinical activities of the RTOG (Radiation Therapy Oncology Group), its goals, its organization, its format for protocol development, and presents major areas of achievement. It provides an organizational chart of the group, a disease site modality cross-reference for protocols, and appendices which provide the key published results of the Group's clinical activities. This paper presents an important overview of the RTOG clinical research activities, which are designed to improve the role of radiation therapy.

Clinical Protocols↗