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Biomedical subjects

William G Kraybill

Publications and source records attributed to William G Kraybill.

16 recordsLinked to original sources
PubMed2006

Randomized multicenter trial of hyperthermic isolated limb perfusion with melphalan alone compared with melphalan plus tumor necrosis factor: American College of Surgeons Oncology Group Trial Z0020.

PURPOSE: To determine in a randomized prospective multi-institutional trial whether the addition of tumor necrosis factor alpha (TNF-alpha) to a melphalan-based hyperthermic isolated limb perfusion (HILP) treatment would improve the complete response rate for locally advanced extremity melanoma. PATIENTS AND METHODS: Patients with locally advanced extremity melanoma were randomly assigned to receive melphalan or melphalan plus TNF-alpha during standard HILP. Patient randomization was stratified according to disease/treatment status and regional nodal disease status. RESULTS: The intervention was completed in 124 patients of the 133 enrolled. Grade 4 adverse events were observed in 14 (12%) of 129 patients, with three (4%) of 64 in the melphalan-alone arm and 11 (16%) of 65 in the melphalan-plus-TNF-alpha arm (P = .0436). There were two toxicity-related lower extremity amputations in the melphalan-plus-TNF-alpha arm, and one disease progression-related upper extremity amputation in the melphalan-alone arm. There was no treatment-related mortality in either arm of the study. One hundred sixteen patients were assessable at 3 months postoperatively. Sixty-four percent of patients (36 of 58) in the melphalan-alone arm and 69% of patients (40 of 58) in the melphalan-plus-TNF-alpha arm showed a response to treatment at 3 months, with a complete response rate of 25% (14 of 58 patients) in the melphalan-alone arm and 26% (15 of 58 patients) in the melphalan-plus-TNF-alpha arm (P = .435 and P = .890, respectively). CONCLUSION: In locally advanced extremity melanoma treated with HILP, the addition of TNF-alpha to melphalan did not demonstrate a significant enhancement of short-term response rates over melphalan alone by the 3-month follow-up, and TNF-alpha plus melphalan was associated with a higher complication rate.

Adult↗
PubMed2006

Phase II study of neoadjuvant chemotherapy and radiation therapy in the management of high-risk, high-grade, soft tissue sarcomas of the extremities and body wall: Radiation Therapy Oncology Group Trial 9514.

PURPOSE: On the basis of a positive reported single-institution pilot study, the Radiation Therapy Oncology Group initiated phase II trial 9514 to evaluate its neoadjuvant regimen in a multi-institutional Intergroup setting. PATIENTS AND METHODS: Eligibility included a high-grade soft tissue sarcoma > or = 8 cm in diameter of the extremities and body wall. Patients received three cycles of neoadjuvant chemotherapy (CT; modified mesna, doxorubicin, ifosfamide, and dacarbazine [MAID]), interdigitated preoperative radiation therapy (RT; 44 Gy administered in split courses), and three cycles of postoperative CT (modified MAID). RESULTS: Sixty-six patients were enrolled, of whom 64 were analyzed. Seventy-nine percent of patients completed their preoperative CT and 59% completed all planned CT. Three patients (5%) experienced fatal grade 5 toxicities (myelodysplasias, two patients; infection, one patient). Another 53 patients (83%) experienced grade 4 toxicities; 78% experienced grade 4 hematologic toxicity and 19% experienced grade 4 nonhematologic toxicity. Sixty-one patients underwent surgery. Fifty-eight of these were R0 resections, of which five were amputations. There were three R1 resections. The estimated 3-year rate for local-regional failure is 17.6% if amputation is considered a failure and 10.1% if not. Estimated 3-year rates for disease-free, distant-disease-free, and overall survival are 56.6%, 64.5%, and 75.1%, respectively. CONCLUSION: This combined-modality treatment can be delivered successfully in a multi-institutional setting. Efficacy results are consistent with previous single-institution results.

Adult↗
PubMed2006

American Joint Committee on Cancer clinical stage as a selection criterion for sentinel lymph node biopsy in thin melanoma.

BACKGROUND: A significant proportion of newly diagnosed melanomas are thin lesions (< or = 1.00 mm). Because tumor thickness correlates with the risk for nodal metastases, sentinel lymph node (SLN) biopsy in this subset is controversial. Incorporating other prognostic factors (Clark level and ulceration), we evaluated the 6th edition American Joint Committee on Cancer (AJCC) clinical stage as a simple and widely applicable guideline for offering SLN biopsy for thin melanoma. METHODS: This study was a review of a prospective melanoma SLN database from 1993 to 2003 with emphasis on SLN positivity rates based on the 6th edition AJCC primary tumor thickness intervals and clinical stage. RESULTS: Three hundred five patients underwent SLN biopsy, with an overall positivity rate of 17.7%. By the 6th edition AJCC, lesions < or = 1.00 mm had an SLN positivity rate of 6.6%. By 6th edition clinical stage, SLN positivity rates were 4.9% for stage IA and 10.4% for stage IB. By using stage IA as the criterion for not offering SLN biopsy, this procedure would have been avoided in 46% (39 of 85) of < or = 1.00-mm melanoma patients with a negative SLN. CONCLUSIONS: Sixth edition AJCC clinical stage IB as a selection criterion for performing SLN biopsy in thin melanoma identifies most patients with a positive SLN while also avoiding a negative SLN biopsy in many patients. Until additional widely accepted and validated selection criteria are available, SLN biopsy for clinical stage IB, but not stage IA, thin melanomas is a reasonable approach.

Adult↗
PubMed2006

Adjuvant therapy for extremity sarcomas.

Extremity soft tissue sarcomas (STS) represent a rare, heterogeneous malignancy. Surgery is the primary treatment for patients with no evidence of metastatic disease, and for small low-grade superficial tumors in which adequate margins can be obtained, it may be the only therapy indicated. For large, deep tumors or tumors that are close to important neurovascular structures or bone, the addition of radiotherapy to resection has improved local control and increased limb salvage without affecting overall survival. Adjuvant chemotherapy has been an issue of considerable debate. Because 50% of patients with high-risk tumors will develop metastatic disease, effective systemic treatment with chemotherapy is needed. Unfortunately, studies have shown minimal improvement in overall survival when chemotherapy is added to the local treatment of high-risk extremity STS. More recently, a few trials of neoadjuvant chemotherapy consisting of mesna, doxorubicin, ifosfamide, and dacarbazine and high-dose doxorubicin and ifosfamide have shown some early promising results, but at the price of increased toxicity. Targeted therapy has shown some of its best results with gastrointestinal stromal tumors, but so far there has been little success in treating extremity STS. At this time, high-dose adjuvant or neoadjuvant chemotherapy should be given in the setting of a clinical trial to patients with high-risk tumors who can tolerate a potentially toxic chemotherapeutic regimen. The goal of these trials should be to assess new combination therapies, possibly including targeted therapies, for the management of large high-grade, high-risk soft tissue sarcomas.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Melanoma.

Explore the source record for details and available documents.

Algorithms↗
PubMed2005

Long-term management of patients after potentially curative treatment of extremity soft tissue sarcoma: practice patterns of members of the Society of Surgical Oncology.

The optimal strategy for follow-up of extremity soft tissue sarcoma patients after primary treatment with curative intent is not known. The 1592 members of the Society of Surgical Oncology (SSO) were sent a survey to determine their practices. Office visits and chest X-rays were the most frequently performed items for all years. Complete blood count and liver function tests were the most commonly ordered blood tests, but many respondents did not order any blood tests routinely. Imaging studies of the extremities were recommended for most patients during the first postoperative year. Postoperative surveillance strategies after sarcoma treatment vary appreciably among surgeons. Surgeon age, tumor size, tumor grade, and geographic location of the surgeon account for only a modest amount of the variation, suggesting that lack of evidence supporting any particular strategy is the factor responsible for most of the variation. Efforts to provide high-quality evidence on this topic are warranted.

Extremities↗
PubMed2005

Developments in the management of extremity soft tissue sarcomas.

Soft tissue sarcomas, a rare and extremely low prevalence tumor, has no uniform treatment recommendation because there have been few randomized prospective trials to guide management. Recently, there have been surgical, medical, biologic, and genetic advances toward improved treatment. A multidisciplinary approach at specialized treatment centers should be sought because the skill set necessary to implement these advances can be provided and outcomes improved. Centralized care will be crucial to improving survival and functional outcome because it will allow for patients to be effectively entered into prospective randomized trials and create regional and national tissue banks to generate meaningful data.

Animals↗
PubMed2004

The effectiveness of complete decongestive physiotherapy for the treatment of lymphedema following groin dissection for melanoma.

OBJECTIVE: Groin dissection is performed for the treatment of melanoma and other malignancies. Lymphedema rates as high as 47% have been reported. In 1996, we began using complete decongestive physiotherapy (CDP) in selected patients with lymphedema following groin dissection. Here, we review our results in a small cohort of patients. METHODS: A retrospective review of the medical records of 14 patients, treated with CDP for lymphedema secondary to groin dissection for melanoma was conducted. All patients were treated with CDP at Roswell Park Cancer Institute (RPCI), between 1996 and 2002. Of the 14 patients, 12 underwent groin dissection at RPCI. Response to therapy was measured by limb volume determinations. Patient gender, age, body mass index (BMI), type of operation, type of adjuvant therapy, time to treatment, patient compliance, lymphedema stage, and initial edema were analyzed for association with response to treatment. Incidence was estimated by a review of the operative logs. RESULTS: Fourteen patients were treated with CDP for lymphedema secondary to groin dissection for melanoma, with a median decrease in lymphedema of 60% (range: 35-145%; P = 0.0003). Increased BMI was associated with a decreased response to treatment (P = 0.02). Response to CDP was not effected by time to treatment, patient compliance, lymphedema stage, and initial edema. During this time, 39 groin dissections were done at RPCI. The incidence of lymphedema treated with CDP at RPCI was 31% (12/39; standard error 7.4%). CONCLUSIONS: With a decrease in lymphedema of 60%, CDP may provide relief for patients with lymphedema following groin dissection. Elevated BMI was associated with a decreased response to CDP.

Adult↗
PubMed2004

The prognostic significance of margin width for extremity and trunk sarcoma.

BACKGROUND AND OBJECTIVES: To evaluate the significance of resection margin for soft tissue sarcoma (STS), we determined local recurrence-free interval (LRFI), distant metastases-free interval (DMFI), and overall survival (OS) for primary extremity and truncal STS with clear margins (> or =10 mm), close margins (1-9 mm), and positive margins (0 mm). METHODS: Patients were evaluated via review of charts and tumor specimens. RESULTS: Among 111 patients, tumors were predominantly high grade (86%), > or =5 cm (76%), and deep (81%). A minority of patients received adjuvant radiation (38%) and/or adjuvant chemotherapy (34%). Margin width was > or =10 mm (48%), 1-9 mm (40%), or 0 mm (12%). Margins > or =10 mm were less common for large (P = 0.009) or deep (P = 0.02) tumors. By multivariate analysis, independent factors for LRFI were tumor size (P = 0.04) and margin width (P = 0.03). Independent factors related to DMFI were tumor grade (P = 0.002), size (P = 0.007), and patient age (P = 0.02). Independent factors relating to OS were tumor grade (P = 0.001), size (P = 0.004), and depth (P = 0.03). CONCLUSIONS: Margins > or =10 mm independently predicted longer LRFI and are optimal for extremity STS resection. Adjuvant radiotherapy should be considered for all STS resected with margins <10 mm, and margin width should be considered when reporting and interpreting LR outcomes for these patients.

Chemotherapy, Adjuvant↗
PubMed2004

Palliative surgery of soft tissue sarcoma.

Despite an increasing trend towards early diagnosis of breast cancer,patients still present with locally advanced disease. Also, in some patients chemotherapy will fail, and local and regional recurrence will occur. This article outlines options for palliative care for such patients.

Amputation, Surgical↗
PubMed2004

Costs of follow-up after potentially curative treatment for extremity soft-tissue sarcoma.

Soft-tissue sarcoma is an uncommon cancer with the potential for high rates of recurrence after initial therapy. Multiple surveillance strategies have been developed to follow patients after primary treatment. The purpose of this study was to quantify the costs associated with various published post-treatment surveillance strategies. A literature review covering the years 1982-2003 was performed to find all modern published surveillance methods for extremity soft-tissue sarcoma. Only articles describing an explicit 5-year follow-up strategy were included. Total costs of 5-year follow-up were calculated for each strategy using Medicare-allowed charges as a proxy. Thirty-four articles depicting 54 strategies were identified. Total Medicare-allowed charges in year 2003 dollars ranged from 485 dollars for follow-up of low-grade sarcoma to 21,235 dollars for follow-up of high-grade sarcoma, a 42.8-fold cost differential. The average charge for these 54 strategies was 6,401 dollars. Physical examination and chest x-ray were the most commonly used screening modalities. Several guidelines have been proposed for extremity soft-tissue sarcoma patient follow-up, most prominently those of the National Comprehensive Cancer Network. The literature has yet to reflect the consensus these guidelines suggest. This study shows wide disparity in the costs of 54 specific methods of following soft-tissue sarcoma patients. Clinical trials are needed to identify an optimal surveillance strategy, one balancing gains in survival, quality of life, costs, and societal willingness to expend resources. Such trials have not been conducted due to the rarity of extremity soft-tissue sarcomas and the costs associated with conducting long-term trials. Alternatively, prospective evaluation of imaging modalities used in follow-up should be assessed as part of other trials. Computer simulation analysis also holds great promise as an assessment tool for surveillance strategies because patient participation is not required.

Extremities↗
PubMed2003

Clinical trials and soft tissue sarcomas.

Soft tissue sarcomas are a challenging disease entity with a variety of histologic subtypes that can arise anywhere on the body. Much effort has been put forward to advance the care of patients with soft tissue sarcomas. Radical amputations have largely given way to limb-sparing procedures. With multimodality treatment, there has been progress in local control rates as well. As knowledge of the basic biology of this disease grows, there likely will be new strategies to treat soft tissue sarcomas. The development of STI-571, and its demonstrated effectiveness in GIST, represents an important advance in the treatment of these tumors and potentially a new paradigm for the development of therapeutic intervention in other sarcomas. Developing collaboration among ACOSOG other cooperative groups in the United States, Canada, and Europe may provide physicians with new venues for asking important clinical questions about these low-incidence tumors. The importance of collaboration in enrolling patients in clinical trials to evaluate these future therapies cannot be overstated.

Clinical Trials as Topic↗
PubMed2003

Extremity soft tissue sarcoma patient follow-up: tumor grade and size affect surveillance strategies after potentially curative surgery.

A large recent survey disclosed considerable variation in the intensity of follow-up after potentially curative surgery for extremity soft tissue sarcoma among highly credentialed clinicians. The source of the variation is not known. The survey was reanalyzed to investigate whether tumor grade and size account for the variation. The 1,592 members of the Society of Surgical Oncology were surveyed to measure their follow-up practices for 10 years after initial therapy for extremity sarcoma. Repeated-measures analysis of variance was used to measure the relationship among follow-up practice patterns and tumor grade, tumor size, and years after surgery. The 318 respondents who performed surgery and also carried out long-term follow-up for their patients with extremity soft tissue sarcoma were considered evaluable; 94% were general surgeons and 5% were orthopedic surgeons. Office visit, complete blood count, liver function tests, chest X-ray, chest computed tomography, extremity computed tomography, and extremity magnetic resonance imaging were ordered significantly more frequently with increasing tumor grade and size. Tumor grade and size significantly impacted physician practice patterns in post-treatment follow-up, although the degree of variation attributable to these variables was modest. These data permit rational design of a randomized clinical trial of two alternative follow-up plans.

Delivery of Health Care↗
PubMed2002

How surgeon age affects surveillance strategies for extremity soft tissue sarcoma patients after potentially curative treatment.

BACKGROUND: The optimal strategy for follow-up of extremity soft tissue sarcoma patients after potentially curative treatment remains unknown. We investigated whether the date of completion of formal surgical training affects choice of surveillance strategy. MATERIALS AND METHODS: The 1,592 members of the Society of Surgical Oncology were asked how often they use 12 separate surveillance modalities during years 1-5 and 10 postsurgery. The motivation underlying follow-up was assessed separately. Repeated-measures analysis of variance was used to compare practice patterns by the year in which the surgeon's formal surgery training was completed, controlling for tumor grade, tumor size, and year postsurgery. RESULTS: Of the 716 respondents, 318 performed surgery and also provided long-term postoperative surveillance for their patients. These respondents were considered evaluable. Erythrocyte sedimentation rate, extremity X ray, and bone scan were the follow-up tests which differed significantly among physician age groups. Surgeons who completed training more than 30 years ago ordered erythrocyte sedimentation rate more frequently (P < 0.001). Surgeons in the 21-30 year category ordered extremity X ray and bone scan more frequently (P < 0.05), but the absolute differences among age groups were quite small. Older surgeons were also significantly more likely to believe that follow-up is clinically worthwhile. CONCLUSIONS: The posttreatment surveillance practice patterns of the members of the Society of Surgical Oncology caring for extremity soft tissue sarcoma patients vary only marginally with the length of time since completion of training. Postgraduate education may be one factor homogenizing surgeon behavior in this important aspect of cancer patient care.

Aging↗