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Biomedical subjects

Raphael E Pollock

Publications and source records attributed to Raphael E Pollock.

52 records · Page 3Linked to original sources

Radiographic response to neoadjuvant chemotherapy is a predictor of local control and survival in soft tissue sarcomas.

BACKGROUND: Downstaging of large soft tissue sarcomas can be accomplished by the use of neoadjuvant chemotherapy (NeoCT). The authors tested the hypothesis that radiographic response to NeoCT predicts improved local control and survival. METHODS: The authors reviewed the medical records of 65 patients with Stage II or III soft tissue sarcoma (42 extremity, 23 retroperitoneal) who were treated with doxorubicin or ifosfamide-based NeoCT from January 1991 to December 1996. Radiographic response and impact on surgical therapy were determined retrospectively by comparing imaging studies obtained before and after chemotherapy. RESULTS: The radiographic responses observed were partial response (PR; 22 patients [34%]); minor response (MR; 6 patients [9%]); stable disease (20 patients [31%]); and progressive disease (17 patients [26%]). Downstaging sufficient to decrease the scope of the operation occurred in 13% of the patients, 78% had no change, and 9% had disease progression sufficient to increase the scope of the operation. Patients having any radiographic response (PR or MR) had a higher margin-negative resection rate, a better local recurrence-free survival rate, and a better overall survival rate than did nonresponders. CONCLUSIONS: The NeoCT regimens used in this study resulted in tumor shrinkage sufficient to impact surgical therapy in a few patients. However, radiographic response predicted improved local control and overall survival rate.

Adolescent↗

Surgical management of soft tissue sarcomas of the hand and foot.

BACKGROUND: Soft tissue sarcomas of the hand and foot present unique management challenges. The purpose of the current study study was to determine oncologic outcome, particularly with respect to factors affecting local recurrence, distant recurrence, and disease-specific survival. METHODS: A retrospective study was performed on 115 patients with soft tissue sarcomas of the hand or foot who were evaluated, treated, and followed at the authors' institution between 1980 and 1998. The medical records and radiographs were reviewed. Kaplan-Meier analysis was used to assess patient survival. RESULTS: Most patients (95%) were referred after previous surgery. The majority of tumors (75%) were T1 lesions (less than 5 cm), and most tumors (81%) were high grade. Patients who were treated by definitive, wide re-excision (n = 43) had a 10 year local recurrence-free survival of 88%, which was significantly better than the corresponding rate of 58% for patients who did not have re-excision (n = 40, P = 0.05). Radiation improved local control in patients who did not undergo re-excision (n = 17, P = 0.02). However, radiation did not improve local control in patients who had definitive re-excision with negative margins (n = 13, P = 0.51). The disease-specific survival at 5 and 10 years was 76% and 65%, respectively, for patients who presented with localized disease. Disease-specific patient survival was significantly worse for patients who had regional or distant metastasis. Radical amputation as initial surgical treatment did not decrease the likelihood of regional metastasis and did not improve disease-specific patient survival. The presence of distant metastasis at presentation was an independent predictor of local recurrence. CONCLUSION: Limb sparing treatment is possible in many patients with soft tissue sarcomas of the hand and foot. Re-excision to achieve microscopically negative surgical margins is an effective method of achieving a high rate of local control in appropriately selected patients who present after unplanned excision of the primary tumor. There does not appear to be a survival benefit to immediate radical amputation, which should be reserved for cases where surgical excision or re-excision with adequate margins cannot be performed without sacrifice of functionally significant neurovascular or osseous structures.

Adolescent↗

Tumor volume as a prognostic factor for sarcomatosis.

BACKGROUND: The appropriate therapeutic interventions for sarcomatosis, or sarcoma characterized by intraabdominal dissemination, remain unclear. The authors performed a retrospective analysis of their recent experience with patients diagnosed with sarcomatosis to determine the overall survival and the effects of clinicopathologic features on survival rates at two and four years. METHODS: A query of the authors' prospective soft tissue sarcoma database identified 51 patients with a diagnosis of sarcomatosis who were evaluated at the authors' institution between June 1996 and June 1999. Clinical and pathologic factors were evaluated, and survival was calculated using a Kaplan-Meier survival analysis. Disease was categorized as low or high volume based on findings at surgical exploration or computed tomography scan evaluation. Disease was classified as low/intermediate grade or high grade based upon histologic examination. RESULTS: Twenty five patients were male and 26 were female. The median time from the initial diagnosis of sarcoma to the development of sarcomatosis was 0.9 years (range, 0-26 years). Thirty nine patients were treated with surgery, whereas 32 received primarily nonsurgical treatment. Histology revealed gastrointestinal stromal tumor (GIST) in 33 patients and other histologies in 18 patients. The two year overall survival rate of patients with GIST was similar to that of patients with other types of sarcoma (38% versus 42%, respectively, P = 0.77). Patients with low volume disease had an overall two year survival rate of 82%, compared with only 24% for patients with high volume disease (P = 0.008). There was no difference in the overall survival rates of patients with low grade (n = 18) versus high grade tumors (n = 33, P = 0.29). With a median followup of 2.7 years (range, 0.5-26.4 years), the median time from sarcomatosis to death was 13 months (range, 4-42 months). CONCLUSIONS: Evaluating volume of disease at the time of diagnosis permits stratification of patients into prognosis based subsets. We found no significant difference in two or four year survival rates in patients with GIST and those with non-GIST sarcomatosis.

Adult↗

Soft tissue sarcoma of the upper extremity: a 5-year experience at two institutions emphasizing the role of soft tissue flap reconstruction.

BACKGROUND: The objective of this study was to define the impact of soft tissue flap reconstruction on multimodality therapy for patients with soft tissue sarcomas of the upper extremity. Treatment standards continue to evolve for these patients, and, with multimodality therapy, most of them are candidates for limb-preserving surgery. Consequently, the role of soft tissue flap reconstruction is expanding. METHODS: A review was conducted of 100 consecutive patients with soft tissue sarcomas of the upper extremity who underwent surgery at several institutions between 1992 and 1997. RESULTS: Seventy-one patients underwent direct closure of defects after tumor resection, and 29 patients required soft tissue reconstruction with flaps. These groups were similar in most respects, except that 52% of the patients who required soft tissue reconstruction presented with recurrent disease (P = 0.0004), and 79% of them had tumors measuring > 5 cm in greatest dimension (P = 0.0003). The patients who required flap reconstruction had larger skin deficits after undergoing tumor resection (140 cm2) compared with the patients who had wounds that were managed by direct closure (40 cm2; P < 0.00001). Margins around the resected tumors were larger (1.62 cm) when flaps were employed compared with margins when defects were closed directly (0.87 cm; P = 0.0005). However, the number of patients with intralesional, marginal, wide, and radical resections was the same regardless of wound management. Major complications occurred in 14% of patients, but none led to death or amputation. The median follow-up was 31 months, and 66% of patients had no evidence of disease at that time. Rates of local recurrence and survival were similar for patients who underwent flap reconstruction compared with patients who underwent direct closure. CONCLUSIONS: Soft tissue flap reconstruction facilitates therapy for patients with soft tissue sarcomas of the upper extremity, so that patients with larger tumors can undergo resection, limiting complications and limb sacrifice.

Adolescent↗

Combined anti-fetal liver kinase 1 monoclonal antibody and continuous low-dose doxorubicin inhibits angiogenesis and growth of human soft tissue sarcoma xenografts by induction of endothelial cell apoptosis.

Vascular endothelial growth factor (VEGF) and VEGF receptor 2 [fetal liver kinase 1 (Flk-1)/kinase insert domain-containing receptor] have been shown to play a major role in tumor angiogenesis. In this study, we investigated whether anti-Flk-1 monoclonal antibody DC101 could therapeutically inhibit growth and angiogenesis of human soft tissue sarcoma, and we explored its capacity to enhance the tumoricidal effects of doxorubicin. Treatment of well-established leiomyosarcoma SKLMS-1 and rhabdomyosarcoma RD xenografts in severe combined immunodeficient mice with DC101 resulted in significant antitumor activity. In a parallel study, we compared tumor inhibition with continuous low-dose "antiangiogenic" schedule versus once-every-2-weeks high-dose standard schedule of doxorubicin. We found that continuous low-dose treatment inhibited the tumor growth of RD xenografts about 46.5% of that with standard-schedule treatment, but that continuous low-dose treatment did not inhibit the tumor growth of SKLMS-1 xenografts. Notably, combined DC101 and continuous low-dose doxorubicin resulted in more effective growth inhibition of SKLMS-1 and RD xenografts than has been observed with any agent alone in a long-term s.c. tumor xenograft model. The combination therapy was associated with no additional toxicity to the host animal compared with low-dose doxorubicin alone. Histological examination of xenografts showed significantly reduced microvessel counts in the tumors given combined therapy compared with the tumors given either agent alone. These results are consistent with an enhanced inhibition of angiogenesis in vivo by combined DC101 and doxorubicin using Matrigel plug assay. Additionally, DC101 plus doxorubicin directly exerted enhanced inhibitory effects on endothelial cell migration, proliferation, and tube-like formation in vitro. Furthermore, the combination induced an enhanced apoptosis of endothelial cells that was associated with an increase of capase-3 activity. Thus, the inhibition of angiogenesis and induction of endothelial cell apoptosis are likely important mechanisms for the antitumor activity of combined DC101 and doxorubicin. Collectively, our data suggested that anti-VEGF receptor 2 in combination with continuous low-dose doxorubicin may provide a new therapeutic approach for human soft tissue sarcoma in the clinic.

Animals↗

Breast cancer on the world wide web: cross sectional survey of quality of information and popularity of websites.

OBJECTIVES: To determine the characteristics of popular breast cancer related websites and whether more popular sites are of higher quality. DESIGN: The search engine Google was used to generate a list of websites about breast cancer. Google ranks search results by measures of link popularity---the number of links to a site from other sites. The top 200 sites returned in response to the query "breast cancer" were divided into "more popular" and "less popular" subgroups by three different measures of link popularity: Google rank and number of links reported independently by Google and by AltaVista (another search engine). MAIN OUTCOME MEASURES: Type and quality of content. RESULTS: More popular sites according to Google rank were more likely than less popular ones to contain information on ongoing clinical trials (27% v 12%, P=0.01 ), results of trials (12% v 3%, P=0.02), and opportunities for psychosocial adjustment (48% v 23%, P<0.01). These characteristics were also associated with higher number of links as reported by Google and AltaVista. More popular sites by number of linking sites were also more likely to provide updates on other breast cancer research, information on legislation and advocacy, and a message board service. Measures of quality such as display of authorship, attribution or references, currency of information, and disclosure did not differ between groups. CONCLUSIONS: Popularity of websites is associated with type rather than quality of content. Sites that include content correlated with popularity may best meet the public's desire for information about breast cancer.

Breast Neoplasms↗

Extraosseous osteosarcoma: response to treatment and long-term outcome.

PURPOSE: To evaluate the clinicopathologic features of extraosseous osteosarcoma (EOO), a rare soft tissue form of osteosarcoma, and to examine its response to multimodality therapy. PATIENTS AND METHODS: The medical records of all patients with EOO evaluated at The University of Texas M.D. Anderson Cancer Center between 1960 and 1999 were reviewed for clinicopathologic factors, treatment, and outcome. RESULTS: Sixty consecutive patients with EOO were identified, including 38 patients with localized (American Joint Committee on Cancer stages I to III) disease. The majority of patients presented with T2 tumors (n = 35, 58%), and 90% of tumors were located beneath the investing fascia. Twenty-seven patients with measurable and assessable disease were treated with doxorubicin-based chemotherapy (median doxorubicin starting dose, 75 mg/m(2); median number of cycles, four). The overall response rate was 19%, with two complete and three partial responses; one (6%) of 18 doxorubicin-treated patients who underwent subsequent surgery had a pathologic complete response. For the subset of 30 patients with localized disease treated at M.D. Anderson, the 5-year actuarial local recurrence-free, distant recurrence-free, event-free, and disease-specific survival rates were 82% (95% confidence interval [CI], 70% to 98%), 64% (95% CI, 43% to 93%), 47% (95% CI, 30% to 70%), and 46% (95% CI, 26% to 80%), respectively. CONCLUSION: EOO should be considered clinically and therapeutically distinct from osseous osteosarcoma. Radiographic response rates and pathologic complete response rates to doxorubicin-based systemic therapy are low.

Adolescent↗

Cost-effectiveness of staging computed tomography of the chest in patients with T2 soft tissue sarcomas.

BACKGROUND: Published practice guidelines recommend routine chest computed tomography (CT) scanning as part of the staging evaluation for patients with T2 soft tissue sarcomas (STS), although there is no direct evidence to support this practice. The objective of this study was to determine the yield and cost-effectiveness of routine versus selective chest CT scanning for the staging of patients with T2 STS and to identify any subgroups for whom a more selective approach to chest CT scanning could be considered. METHODS: Six hundred consecutive patients with primary, nonthoracic, T2 (> 5 cm) STS underwent both chest X-ray (CXR) and chest CT scanning to evaluate the presence of pulmonary metastatic disease (M1). The authors constructed a decision tree that modeled the outcomes of diagnostic testing for two hypothetical diagnostic strategies: 1) routine chest CT (rCT) or 2) CXR and selective chest CT (sCT). The yield and cost of each strategy were determined; the incremental cost-effectiveness ratio (ICER) was calculated as the cost per additional patient with pulmonary metastases identified by rCT versus sCT. RESULTS: The yield of rCT was higher than that of sCT (M1 disease identified in 19.2% vs. 16.0% of patients, respectively), but rCT was more costly ($1301 vs. $418 per patient, respectively). The ICER of rCT compared with sCT was $27,594 per patient identified with pulmonary metastasis. The expected yields, costs, and ICERs of the diagnostic strategies varied across patient subgroups based on grade, anatomic site, and tumor size. CONCLUSIONS: For patients with T2 STS, rCT was most cost-effective in patients with high-grade lesions or extremity lesions. The findings of this study do not support the routine use of chest CT scanning in all patients with T2 STS.

Adolescent↗

Predictors of locoregional recurrence among patients with early-stage breast cancer treated with breast-conserving therapy.

BACKGROUND: Our aim was to identify predictors of locoregional recurrence (LRR) in patients with early-stage breast cancer treated with breast-conserving therapy (BCT) and long-term follow-up. METHODS: From 1970 to 1994, 1153 patients with stage I to II breast cancer underwent BCT and radiotherapy at our institution. Patients with prior breast cancer or other primary malignancies were excluded. Clinical and pathologic characteristics evaluated were age, race, tumor size, stage, pathologic tumor margins, axillary nodal involvement, estrogen and progesterone receptor status, Black's nuclear grade, type of surgery, and use of adjuvant therapy. RESULTS: Of 1083 patients, 54% presented with stage I disease and 46% with stage II disease. Median age was 50 years, and median follow-up was 9 years. Axillary nodes were positive in 31% of the patients who underwent axillary dissection. LRR developed in 6%, LRR followed by systemic recurrence in 5%, and systemic recurrence alone in 13%; 76% had no evidence of recurrence at last follow-up. Age, tumor size, positive lymph nodes, and not receiving chemotherapy or hormonal therapy were independent predictors of LRR. Disease-specific survival among patients with LRR was similar to that among patients with no recurrence. CONCLUSIONS: Multidisciplinary treatment strategies should be used to accomplish durable locoregional control after BCT.

Adult↗

Long-term complications associated with breast-conservation surgery and radiotherapy.

BACKGROUND: Breast-conservation surgery plus radiotherapy has become the standard of care for early-stage breast cancer; we evaluated its long-term complications. METHODS: We selected patients treated with surgery and radiotherapy between January 1990 and December 1992 (an era in which standard radiation dosages were used) with follow-up for at least 1 year. Patients were prospectively monitored for treatment-related complications. Median follow-up time was 89 months. RESULTS: A total of 294 patients met the selection criteria. Grade 2 or higher late complications were identified in 29 patients and included arm edema in 13 patients, breast skin fibrosis in 12, decreased range of motion in 4, pneumonitis in 2, neuropathy in 2, fat necrosis in 1, and rib fracture in 1. Arm edema was more common after lumpectomy plus axillary node dissection than after lumpectomy alone. Arm edema occurred in 18% of patients who underwent surgery plus irradiation of the lymph nodes and 10% who underwent surgery without nodal irradiation. CONCLUSIONS: Breast-conservation surgery plus radiotherapy was associated with grade 2 or higher complications in only 9.9% of patients. Half of these complications were attributable to axillary dissection, it is hoped that lower complication rates can be achieved with sentinel lymph node biopsy. Breast-conservation surgery and radiotherapy is associated with grade 2 or greater complications in only 9.9% of patients. Nearly half of these complications are attributable to axillary dissection.

Adult↗

Treatment and outcome of patients with intracystic papillary carcinoma of the breast.

BACKGROUND: Intracystic papillary carcinoma (IPC) of the breast is a rare form of noninvasive breast cancer. An appreciation of associated pathology with IPC may be critical in surgical decision-making. METHODS: The medical records of all patients with IPC treated between 1985 and 2001 were retrospectively reviewed. Three patient groups were identified according to the pathologic features of the primary tumor: IPC alone, IPC with associated ductal carcinoma in situ (DCIS), and IPC with associated invasion with or without DCIS. Types of treatment and outcomes were compared between groups. RESULTS: Forty patients were treated for IPC during the study period. Fourteen had pure IPC, 13 had IPC with DCIS, and 13 had IPC with invasion. The incidence of recurrence and the likelihood of dying of IPC did not differ between the three groups regardless of the type of surgery (mastectomy or segmental mastectomy) performed and whether radiation therapy was administered. The disease-specific survival rate was 100%. CONCLUSIONS: When IPC is identified, it is frequently associated with DCIS and or invasion. Standard therapy should be based on associated pathology. The role of radiation therapy in pure IPC remains to be determined.

Adult↗

Steps toward mapping the human vasculature by phage display.

The molecular diversity of receptors in human blood vessels remains largely unexplored. We developed a selection method in which peptides that home to specific vascular beds are identified after administration of a peptide library. Here we report the first in vivo screening of a peptide library in a patient. We surveyed 47,160 motifs that localized to different organs. This large-scale screening indicates that the tissue distribution of circulating peptides is nonrandom. High-throughput analysis of the motifs revealed similarities to ligands for differentially expressed cell-surface proteins, and a candidate ligand-receptor pair was validated. These data represent a step toward the construction of a molecular map of human vasculature and may have broad implications for the development of targeted therapies.

Blood Vessels↗

Preoperative predictors of survival after resection of small hepatocellular carcinomas.

OBJECTIVE: To determine preoperative predictors of survival that can guide the choice of treatment for patients with small hepatocellular cancers (HCCs). SUMMARY BACKGROUND DATA: The treatment of patients with small (</=5 cm in diameter) HCCs is controversial. METHODS: A cohort of 249 patients (69 women, 180 men; median age 62 years) who underwent resection with curative intent for small HCC was identified from a multiinstitutional database. For each patient, the clinical data and pathology slides were reviewed. Six clinical factors (age, gender, preoperative alpha-fetoprotein level, hepatitis serology, number of tumors [single vs. multiple], and Child-Pugh score) and three pathologic factors (hepatitis activity score, fibrosis score, and Edmondson-Steiner tumor grade) that can be determined before surgery were correlated with survival. Log-rank tests and Cox proportional hazards modeling were used to determine factors influencing survival. RESULTS: The median overall survival for the entire cohort was 4.2 years. The estimated overall 5- and 8-year survival rates were 41.1% and 19.8%, respectively. Multivariate Cox analysis indicated that fibrosis score, Edmondson-Steiner grade, and Child-Pugh score were simultaneously significant predictors of survival after resection. A prognostic scoring system based on these covariates was derived and applied to the entire cohort. Patients lacking all three risk factors were assigned a score of 1, patients with one risk factor were assigned a score of 2, and patients with two or three risk factors were assigned a score of 3. Pairwise log-rank tests indicated significant differences in survival between scores 1 and 2, scores 2 and 3, and scores 1 and 3. This scoring system retained its prognostic significance when a subset of 98 patients with positive hepatitis C serology was analyzed separately. CONCLUSIONS: Patients with small HCCs who will derive the least benefit from resection can be identified before surgery using a score based on tumor grade and the severity of underlying liver disease. In these patients, transplantation and/or ablation should be considered as possible alternative therapies.

Carcinoma, Hepatocellular↗

Soft tissue sarcomas.

Sarcomas are a heterogeneous group of rare tumors that arise predominantly from the embryonic mesoderm. They present most commonly as an asymptomatic mass originating in an extremity but can occur anywhere in the body, particularly the trunk, retroperitoneum, or the head and neck. Pretreatment radiologic imaging is critical for defining the local extent of a tumor, staging the disease, guiding biopsies, and aiding in diagnosis. Core-needle biopsy is the preferred biopsy technique for diagnosing soft tissue sarcomas. The American Joint Committee on Cancer (AJCC) staging system for soft tissue sarcomas is based on histologic grade, the tumor size and depth, and the presence of distant or nodal metastases. Despite improvements in local control rates with wide local resections and radiation therapy, metastasis and death remain a significant problem in 50% of patients who present with high-risk soft tissue sarcomas. The most common site of metastasis is the lungs, and metastasis generally occurs within two to three years after the completion of therapy. Progress in the molecular characteristics of these tumors should in the near future translate into molecularly based therapies that can be incorporated into standard treatment strategies.

Gastrointestinal Neoplasms↗

Staging soft tissue sarcoma: evolution and change.

Soft tissue sarcoma (STS) is an extremely heterogeneous group of rare tumors that share a putative mesenchymal cell origin. STS can occur in any soft tissue in the body, yet all share a common feature of primarily disseminating hematogenously, particularly to the lungs. Staging for STS is particularly useful in prognosis, design of effective multimodality treatment programs, and comparing treatment outcomes from different centers and different eras. The current iteration of AJCC STS staging includes Tumor, Grade, Node, and Metastasis with "a" indicating superficial and "b" indicating deep designations. Further opportunities to improve this process exist, particularly as molecular considerations become more apparent, and future evolution into an even more useful STS staging system can be anticipated.

Biomarkers, Tumor↗