Biomedical subjects

C Forscher

Publications and source records attributed to C Forscher.

8 recordsLinked to original sources

PubMed2001

Treatment-induced pathologic necrosis: a predictor of local recurrence and survival in patients receiving neoadjuvant therapy for high-grade extremity soft tissue sarcomas.

PURPOSE: To determine whether treatment-induced pathologic necrosis correlates with local recurrence and overall survival in patients who receive neoadjuvant therapy for high-grade extremity soft tissue sarcomas. PATIENTS AND METHODS: Four hundred ninety-six patients with intermediate- to high-grade extremity soft tissue sarcomas received protocol neoadjuvant therapy. All patients underwent surgical resection after neoadjuvant therapy and had pathologic assessment of tumor necrosis in the resected specimens. RESULTS: The 5- and 10-year local recurrence rates for patients with > or = 95% pathologic necrosis were significantly lower (6% and 11%, respectively) than the local recurrence rates for patients with less than 95% pathologic necrosis (17% and 23%, respectively). The 5- and 10-year survival rates for the patients with > or = 95% pathologic necrosis were significantly higher (80% and 71%, respectively) than the survival rates for the patients with less than 95% pathologic necrosis (62% and 55%, respectively). Patients with less than 95% pathologic necrosis were 2.51 times more likely to develop a local recurrence and 1.86 times more likely to die of their disease as compared with patients with > or = 95% pathologic necrosis. The percentage of patients who achieved > or /= 95% pathologic necrosis increased to 48% with the addition of ifosfamide as compared with 13% of the patients in all the other protocols combined. CONCLUSION: Treatment-induced pathologic necrosis is an independent predictor of both local recurrence and overall survival in patients who receive neoadjuvant therapy for high-grade extremity soft tissue sarcomas. A complete pathologic response (> or = 95% pathologic necrosis) correlated with a significantly lower rate of local recurrence and improved overall survival.

Adolescent↗

PubMed2000

Recurrent gastrointestinal stromal sarcomas.

Gastrointestinal stromal sarcomas, formerly categorized as leiomyosarcomas of gastrointestinal origin, have a common pattern of intraperitoneal dissemination. Despite surgical resection with or without adjuvant systemic chemotherapy the vast majority of these patients succumb to intraperitoneal sarcomatosis and/or hepatic metastases. In an attempt to improve upon the morbidity and mortality associated with this disease we and several other centers have begun treating these patients with intraperitoneal chemotherapy. We have found that aggressive surgical resection with postoperative intraperitoneal chemotherapy has significantly lowered the peritoneal recurrence rate in patients with recurrent gastrointestinal stromal sarcomas as compared to those who have undergone surgical resection alone. However, this treatment approach has proven to be ineffective in preventing hepatic metastases, and thus has had little effect upon overall survival. With the treatment of primary rather than recurrent disease we hope to interrupt the disease process at an earlier stage further decreasing peritoneal recurrences and potentially improving survival.

Antineoplastic Agents↗

PubMed1999

Immunotherapy of advanced malignancy by direct gene transfer of an interleukin-2 DNA/DMRIE/DOPE lipid complex: phase I/II experience.

PURPOSE: We have completed a phase I study, followed by three phase I/II studies, in patients with metastatic melanoma, renal cell carcinoma (RCC), and sarcoma in order to evaluate the safety, toxicity, and antitumor activity of Leuvectin (Vical Inc, San Diego, CA), a gene transfer product containing a plasmid encoding human interleukin (IL)-2 formulated with the cationic lipid 1, 2-dimyristyloxypropyl-3-dimethyl-hydroxyethyl ammonium bromide/dioleyl-phosphatidyl-ethanolamine (DMRIE/DOPE) and administered intratumorally. PATIENTS AND METHODS: Twenty-four patients were treated in the phase I study. Leuvectin doses were 10 microg, 30 microg, or 300 microg weekly for 6 weeks. In three subsequent phase I/II studies, a total of 52 patients (18 with melanoma, 17 with RCC, and 17 with sarcoma) were treated with further escalating doses of Leuvectin: 300 microg twice a week for 3 weeks, 750 microg weekly for 6 weeks, and 1,500 microg weekly for 6 weeks. RESULTS: There were no drug-related grade 4 toxicities and only one grade 3 toxicity, but the majority of patients experienced mild constitutional symptoms after treatment. In the phase I/II studies, 45 patients were assessable for response (14 with RCC, 16 with melanoma, and 15 with sarcoma). Two patients with RCC and one with melanoma have achieved partial responses lasting from 16 to 19 months and continuing. In addition, two RCC, three melanoma, and six sarcoma patients had stable disease lasting from 3 to 18 months and continuing. The plasmid was detected by polymerase chain reaction assay in the posttreatment samples of 29 of 46 evaluated patients. Immunohistochemistry studies on serial biopsy specimens showed increased IL-2 expression and CD8(+) infiltration after treatment in the tumor samples of several patients (12 and 16, respectively). CONCLUSION: Direct intratumoral injection of Leuvectin is a safe and possibly effective immunotherapeutic approach in the treatment of certain tumor types.

Adult↗

PubMed1997

Tumor quantitation and monitoring in whole-body planar technetium-99m-sestamibi imaging.

UNLABELLED: We have developed a completely automatic software package to normalize, rigidly register and elastically match serial whole-body planar images from patients with limb tumors. Variations in tumor uptake and size are analyzed and quantitated by the software. METHODS: The software consists of a chain of modules incorporating several automatic algorithms. A rigid registration algorithm aligns images by translation and rotation based on feature points corresponding to the patient's neck and bladder. An elastic matching algorithm generates a grid for each image in a sequence by combining thresholding and local feature analysis in the head, torso and leg regions. A linear warping algorithm then interpolates pixel values and locations to make the grid points in all images coincide with the grid points of one of them (the reference image). All images in a sequence are normalized based on brain uptake. Quantitation of tumor uptake and size is performed in all images using an ROI automatically determined from a single user-selected seed point. RESULTS: The software was tested on four 2-image and one 3-image sequences from five patients (11 images). Quantitative measurements of body contour overlap show an average intrasequence agreement of 73.4%, 78.7% and 91.5% for unregistered, rigidly registered and rigidly registered + matched images, respectively. CONCLUSION: Our method represents an objective, quantitative tool to measure tumor activity in sequential whole-body scintigraphic images, and may help assess tumor response to chemotherapy or radiation therapy.

Algorithms↗

PubMed1995

Preoperative therapy for soft tissue sarcoma.

Soft tissue sarcomas appear to be an ideal tumor type for delivering preoperative therapy. The rationale for preoperative therapy is that it is delivered to undisturbed tissue planes with well-oxygenated tissue. This is of great benefit for radiation therapy, because with new computed tomography scan treatment planning it is possible to completely delineate the tumor without surgical clips or postoperative hematoma (or both) obscuring the tumor margin.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1994

Synovial sarcoma. Uniform response of metastases to high dose ifosfamide.

BACKGROUND: This report describes the unusually high response rate of metastatic synovial sarcoma to high dose ifosfamide (14-18 g/m2) when that drug was used to treat 13 consecutive patients with recurrent metastatic synovial sarcoma before surgery (or thoracotomies) to provide optimal salvage therapy for these patients. PATIENTS AND METHODS: Thirteen patients with recurrent or pulmonary metastatic synovial sarcoma seen at the Cedars-Sinai Comprehensive Cancer Center (Los Angeles, CA) from April, 1989 through January, 1993 were treated with high dose ifosfamide (14-18 g/m2). Ifosfamide was infused at the dose of 2 g/m2 over a 4-hour bolus infusion, followed by 2-g/m2 24-hour continuous infusions of ifosfamide, for a total of 14 or 18 g/m2 (6-8 days). Mesna (Mesnex, Bristol-Myers Oncology, Princeton, NJ) was infused with the ifosfamide at equimolar doses. Supplemental sodium bicarbonate (180 mEq) was given daily to prevent severe acidosis. Nine of the thirteen patients were treated with prior chemotherapy for their primary tumors. Prior chemotherapy consisted of doxorubicin (Adriamycin, Adria Labs, Dublin, OH) in all patients and doxorubicin combined with cisplatin in eight of them. RESULTS: All 13 patients had objective responses to high dose ifosfamide chemotherapy. There were nine partial responses and four complete responses. Five of the patients died of disease at 20-40 months (median, 27 months) from initial therapy. Eight patients have survived from 2 to 43 months (median, 20 months) from initial therapy, and three of these patients are disease free. Those patients surviving disease free had successful surgical removal of their residual metastatic disease after chemotherapy. CONCLUSION: Metastatic synovial sarcoma appears to be particularly sensitive to high dose ifosfamide chemotherapy. This experience suggests that there is a role for high dose ifosfamide chemotherapy in preoperative and postoperative adjuvant chemotherapy for primary synovial sarcoma, which is usually always a high grade malignant lesion with a poor prognosis after surgery alone.

Adolescent↗

PubMed1993

Synovial sarcoma. A study of intensive chemotherapy in 14 patients with localized disease.

BACKGROUND: The effectiveness of adjuvant chemotherapy in soft tissue sarcomas remains a matter of controversy. The authors reviewed their experience with 14 patients with localized disease treated with intensive doxorubicin-cisplatin-ifosfamide-based chemotherapy. METHODS: Fourteen patients with newly diagnosed nonmetastatic synovial sarcoma seen between 1985 and 1992 received intensive chemotherapy and local radiation therapy before surgical resection, followed in most patients by intensive postoperative chemotherapy. Chemotherapy included high-dose cisplatin and doxorubicin or high-dose ifosfamide (14 g/m2) and cisplatin with doxorubicin. RESULTS: One (7%) patient had a local recurrence during the study interval and remains free of disease 35 months after re-excision and a second course of intensive chemotherapy. All other 13 (93%) patients remained continuously free of disease after a median follow-up of 37 months (range, 6-85 months). There were no deaths. General toxicity was the reason cited by seven patients who elected not to receive postoperative chemotherapy. For the remaining seven patients who elected to continue treatment, there were only two hospitalization admissions for neutropenia and fever. There was no significant cardiotoxicity, nephrotoxicity, or neurotoxicity. CONCLUSION: Additional studies using new intensive systemic adjuvant therapies are needed to determine whether the encouraging results of this experience can be translated into prolonged disease-free and overall survival.

Adolescent↗

PubMedDate not supplied

Surgical resection and intraperitoneal chemotherapy for recurrent abdominal sarcomas.

BACKGROUND: Recurrent abdominal sarcomas have an extremely high rate of recurrence and poor overall survival. A prospective study was initiated to assess the feasibility, toxicity, and benefit of surgical resection and intraperitoneal chemotherapy for improving local control of disease and overall survival. METHODS: Fifty-four patients underwent surgical excision of all gross disease and postoperative intraperitoneal chemotherapy with mitoxantrone. Thirty-five patients had peritoneal disease only (stage II), and 19 patients had peritoneal disease with hepatic metastases (stage III). RESULTS: Nine (17%) patients remain free of disease with a mean follow-up of 37 months. The remaining 45 patients (83%) have had recurrence, with a mean interval to recurrence of 11 months. Stage (P = .001) and grade (P = .005) were the only two variables found to significantly affect recurrence. There was an overall peritoneal recurrence rate of 48% and an overall hepatic failure rate of 69%. Nineteen (35%) of the patients are alive, with a mean follow-up of 46 months. The overall 5-year survival was 31%. The 5-year survival for stage II patients was 46%; for stage III patients, it was only 5%. Stage (P = .001) and grade (P = .056) were the only two variables found to significantly affect survival. There were no treatment-related deaths, and only 5 patients (9%) developed local complications. CONCLUSIONS: Aggressive surgical resection and intraperitoneal chemotherapy for recurrent abdominal sarcomas is a feasible treatment approach with minimal toxicity. Although this treatment had little effect on the hepatic spread of this disease and thus overall survival, it appears to have significantly lowered the rate of peritoneal recurrence and may provide a survival benefit for patients with disease limited to the peritoneum.

Abdominal Neoplasms↗