Robert A. Zlotecki

Retroperitoneal soft tissue sarcoma.

The objective of the current study was to define the optimal treatment for patients with retroperitoneal soft tissue sarcomas (RPS). The authors conducted a review of the pertinent literature and found that the majority of patients had locally advanced RPS at the time of diagnosis. Surgery was the mainstay of treatment, and macroscopic total excision was feasible in approximately 50–67% of patients. The 5‐year probability of local control was approximately 50%, and the likelihood of developing distant metastasis was approximately 20–30%. The 5‐year survival rate was approximately 50%, and deaths due to recurrent RPS continued to occur after 5 years. Postoperative radiotherapy (RT) decreased the likelihood of local recurrence, although it demonstrated no impact on survival. Adjuvant chemotherapy had no proven efficacy. The factor that was found to have the greatest impact on the prognosis for patients with RPS was the ability to achieve a macroscopic total resection. The authors concluded that RPS usually is advanced at the time of diagnosis. The optimal treatment was complete resection. Most patients experienced recurrent disease after surgery, and the most common site of failure was local. Adjuvant RT reduced the risk of local recurrence, but its impact on survival was questionable. Cancer 2005.

Transanal excision of locally advanced rectal cancers downstaged using neoadjuvant chemoradiotherapy

BACKGROUND Our institution has previously demonstrated a survival advantage conferred by preoperative neoadjuvant therapy for locally advanced rectal cancers. We now report our results using transanal excision as definitive surgical therapy in a selected group of patients who experienced significant downstaging of T3 rectal cancers after neoadjuvant therapy. STUDY DESIGN Seventy-four patients diagnosed with locally advanced (T3) rectal cancers were treated with neoadjuvant chemoradiotherapy. After neoadjuvant therapy, 11 (14.9%) patients who had significant downstaging of their tumors were selected to undergo transanal excision of their residual rectal cancers. Intraoperative cryostat evaluation was used to confirm negative margin status, and all patients were subsequently followed with routine endoscopy, transrectal ultrasonography, and digital rectal examinations. RESULTS Tumors were located between 1 cm and 7 cm from the anal verge (mean 4.3 +/- 0.6 cm), and were located in lateral, anterior, and posterior positions. Mean followup was 55.2 +/- 8.9 months (median 47.9 months). Imaging studies using CT, MRI, transrectal ultrasonography, or combination demonstrated suspicious lymph nodes in three patients. After neoadjuvant therapy, these lymph nodes were no longer demonstrated in two patients. There were no local recurrences, nodal metastases, or operative mortalities. One patient (9%) developed distant metastases (pulmonary nodules), and remains alive 30 months after transanal excision. One patient (9%) experienced sphincter laxity, which was successfully repaired, and is now asymptomatic. One patient (9%) developed postoperative urgency that resolved spontaneously. CONCLUSIONS In patients who have initial bulky (T3) lesions, and experience significant downstaging after neoadjuvant chemoradiotherapy, transanal excision appears to be a safe and effective treatment, preserving sphincter function and avoiding laparotomy.

Giant cell tumor of bone.

Objective:To discuss the treatment and outcomes for giant cell tumor (GCT) of bone. Materials and Methods:Review of the pertinent literature. Results:GCT is a rare benign bone lesion most often found in the extremities of women in the third and fourth decades of life. Surgery is the mainstay of treatment and usually consists of intralesional curettage; local control rates range from 80% to 90% after this procedure. Patients with extensive, recurrent, and/or biologically more aggressive tumors may require wide excision. A small subset of patients with incompletely resectable GCTs or with lesions that are surgically inaccessible may be treated with moderate-dose radiotherapy (45–50 Gy) and have a 65% to 80% likelihood of being locally controlled. Conclusion:The majority of patients with GCTs are effectively treated with intralesional curettage. Wide excision or radiotherapy is necessary to cure a relatively limited subset of patients with extensive, aggressive, and/or incompletely resectable GCTs.

Giant cell tumor of the pelvis and sacrum: 17 cases and analysis of the literature.

The optimal treatment of giant cell tumors of the pelvis and sacrum is controversial. Our current patient series was combined with cases identified in a review of the literature published in the past 50 years, yielding a combined group of 239 lesions for study. Recurrence rates were 49% for patients who had radiation therapy alone, 47% for patients who had surgery with intralesional margins, 46% for patients who had surgery with intralesional margins and radiation therapy, and 0% for patients who had surgery with wide margins. Six percent of patients had benign lung metastases develop, 2% of patients had secondary malignancies, 2% of patients died in the perioperative period, and less than 1% of patients had multicentricity. Radiation-induced sarcoma developed in 11% of patients who received radiation for primary or recurrent lesions. Larger doses of radiation therapy did not decrease the rate of local recurrence. Recurrence after surgery and radiation was not lower than after either treatment alone. Local recurrence was more likely in the patients with sacral tumors (48%) than in the patients with pelvic tumors (34%). Disease status was worse in the patients with sacral lesions (23% died of disease) than in the patients with pelvic lesions (6% died of disease).

Adjuvant radiation therapy for resectable retroperitoneal soft tissue sarcoma: the University of Florida experience.

Background:In the management of retroperitoneal sarcomas it is necessary to achieve local control to ensure survival. The role of adjuvant radiation therapy (RT), either pre- or postoperative, remains controversial. Methods:Outcomes for 40 patients with retroperitoneal sarcoma treated with surgery and postoperative RT (n = 25) or preoperative RT (n = 15) were analyzed for variables prognostic for local control, survival, and associated complications. Results:Patterns of failure for patients treated by resection and postoperative RT were local (n = 4), local and distant (n = 3), and distant (n = 3). The failure patterns for preoperative RT cases were local (n = 2), local and distant (n = 2); and distant (n = 4). Median time to local recurrence in the postoperative and preoperative RT series were 1 year and 2.5 years respectively. The margin status was predictive for local control (P = 0.0065) and survival (P = 0.0012), regardless of treatment sequence. Absolute 5-year survival was 12% with positive margins versus 69% if negative. Histologic grade was indicative of the risk for distant metastasis (low grade 8% vs high grade 64%; P = 0.1373), and significantly predicted 5-year absolute survival (low grade 77% vs high grade 34%; P = 0.0267). Postoperative RT was associated with significant complications (infection, hemorrhage, and bowel obstruction—2 cases each). Conclusion:Compared with the surgery-alone series, adjuvant RT appears to improve the probability of local control. Preoperative RT may be the preferred sequence potentially to improve tumor resectability and local–regional control with less risk of complications than with postoperative RT.

Radiation therapy for giant cell tumors of bone.

For giant cell tumors of bone, does radiotherapy provide a safe and effective treatment? This retrospective review includes 24 patients with 26 histologically diagnosed tumors treated with megavoltage radiotherapy between March 1972 and July 1996. Of the 10 recurrent tumors, five had an intralesional resection, two had a biopsy, and three had no biopsy before radiotherapy. Of the 16 previously untreated tumors, one was irradiated after a marginal resection, five after an intracapsular resection, and 10 after biopsy alone. The total doses ranged from 35 to 55 Gy (median, 43 Gy) in fractions of 1.67 to 2.33 Gy per day. Twenty of 26 tumors (77%) were controlled locally. All of the local recurrences occurred within the irradiated field. Five of six patients with local recurrence were treated successfully with additional surgery. Salvage surgery after local recurrence required amputation of an extremity in three patients and a total knee replacement in one patient. The ultimate local control rate was 96% with one patient alive with progressive disease. Lung metastases in one patient were treated successfully with surgery, chemotherapy, and radiotherapy. In one patient a radiation-induced sarcoma developed 22 years after treatment. The authors conclude that radiation therapy is a safe and effective treatment option for benign giant cell tumors of bone. A total dose greater than 40 Gy is the only variable found to significantly influence local control.

Potential clinical efficacy of intensity-modulated conformal therapy

PURPOSE The purpose of this study was to examine the potential benefit of using intensity-modulated conformal therapy for a variety of lesions currently treated with stereotactic radiosurgery or conventional radiotherapy. METHODS AND MATERIALS Intensity-modulated conformal treatment plans were generated for small intracranial lesions, as well as head and neck, lung, breast, and prostate cases, using the Peacock Plan treatment-planning system (Nomos Corporation). For small intracranial lesions, intensity-modulated conformal treatment plans were compared with stereotactic radiosurgery treatment plans generated for patient treatment at the University of Florida Shands Cancer Center. For other sites (head and neck, lung, breast, and prostate), plans generated using the Peacock Plan were compared with conventional treatment plans, as well as beams-eye-view conformal treatment plans. Plan comparisons were accomplished through conventional qualitative review of two-dimensional (2D) dose distributions in conjunction with quantitative techniques, such as dose-volume histograms, dosimetric statistics, normal tissue complication probabilities, tumor control probabilities, and objective numerical scoring. RESULTS For small intracranial lesions, there is little difference between intensity-modulated conformal treatment planning and radiosurgery treatment planning in the conformation of high isodose lines with the target volume. However, stereotactic treatment planning provides a steeper dose gradient outside the target volume and, hence, a lower normal tissue toxicity index. For extracranial sites, objective numerical scores for beams-eye-view and intensity-modulated conformal planning techniques are superior to scores for conventional treatment plans. The beams-eye-view planning technique prevents geographic target misses and better excludes healthy tissues from the treatment portal. Compared with scores for the beams-eye-view planning technique, scores for intensity-modulated conformal plans using the Peacock Plan were significantly better for the lung and head and neck cases studied, equivalent for prostate cases, and inferior for breast cases. CONCLUSION Using the entire 3D data set to construct radiotherapy plans through virtual simulation is always advantageous, whether done for stereotactic radiosurgery, beams-eye-view conformal therapy, or intensity-modulated conformal treatment. Intensity modulation of the photon beam further enhances treatment planning under specific conditions. In general, the intensity-modulated technique is advantageous for large, irregular targets with critical structures in close proximity. Intensity-modulated treatment planning does not appear advantageous for stereotactic radiosurgery or treatment of the intact breast.

Radiotherapy for local control of aggressive fibromatosis

PURPOSE To evaluate local control rates in patients treated with radiotherapy for aggressive fibromatosis. METHODS AND MATERIALS Fifty-three patients with histologically confirmed aggressive fibromatosis were treated with radiotherapy at the University of Florida between march 1975 and June 1992. The minimum length of follow-up was 2 years; 81% of the patients had follow-up for at least 5 years. The lesions arose in an extremity or limb girdle (39 patients), the trunk (10 patients), or the head and neck area (4 patients). Twenty-four patients were treated for gross disease and 29 for presumed microscopic residual disease after one or more operations. Patients were treated with total doses between 35 and 70 Gy; 83% of patients received 50 to 60 Gy. RESULTS Local control was achieved in 23 of 29 patients (79%) treated postoperatively for microscopic residual disease and in 21 of 24 patients (88%) treated for gross disease; gross disease was controlled in all 8 patients with previously untreated lesions and in 13 of 16 patients treated postoperatively for gross residual or recurrent disease. Overall, aggressive fibromatosis was locally controlled in 83% of treated patients. All nine treatment failures occurred in patients with extremity lesions 4 to 68 months after initiation of treatment. Three recurrences were in the irradiated field, two were out of the field, and four were at the field margin. Eight patients were salvaged with surgery alone or combined with postoperative radiotherapy. A functional limb was maintained in 38 of 39 patients with extremity or limb girdle lesions. Pathologic fracture occurred in three patients; two patients required rod fixation for treatment. CONCLUSIONS Radiotherapy is a valuable adjunct to surgery in the management of aggressive fibromatosis and can be used alone in patients with unresectable or inoperable disease.

External beam radiotherapy for primary and adjuvant management of aggressive fibromatosis

PURPOSE To review a large single-institution experience in the management of aggressive fibromatosis to determine the effectiveness of external beam radiotherapy (EBRT) and identify the presentation and treatment variables predictive of locoregional control. METHODS AND MATERIALS Between 1975 and 2000, 72 patients were treated with EBRT for a pathologically confirmed diagnosis of aggressive fibromatosis. Thirty patients were treated at the primary presentation and 42 at the time of a locoregional recurrence. Minimal 2-year follow-up data were available for 65 patients (median 6 years). Megavoltage irradiation with 60Co to 20 MV photons or electron therapy was used for all patients. Most patients were treated after attempted complete surgical resection; 16 patients underwent pretreatment biopsy alone. The prescribed treatment was standard (1.8 Gy) daily fractions in 42 cases and 1.2 Gy fractions b.i.d. in 23 cases. The median prescribed dose was 54 Gy. The prognostic variables and treatment results were evaluated by Kaplan-Meier actuarial analysis. RESULTS Locoregional control was achieved in 52 of 65 patients. The 5-year actuarial locoregional control was 83%. Locoregional failure occurred in 13 patients (11 in patients with recurrent tumors). Only two failures occurred within the irradiation fields; nine failures occurred at the field margins. Eleven patients were salvaged by surgery: wide excision in nine and amputation in two. The only prognostic factor significant for locoregional control was primary vs. recurrent presentation (p = 0.0193). The 5-year locoregional control rates for irradiation at initial presentation and at recurrence were 96% and 75%, respectively. The variables without significance for locoregional control included primary tumor location, surgical procedures performed, resection margins, and gross vs. microscopic residual tumor at irradiation. Lymphedema was the most common late effect, occurring in 7 patients, 5 with prior treatment. Bone fracture occurred in 3 patients; all 3 had fibromatosis involving the bone at presentation but without recurrence at the time of fracture. CONCLUSION EBRT is effective treatment for aggressive fibromatosis. The probability of locoregional control decreases with multiple prior recurrences.

Megavoltage radiotherapy for aneurysmal bone cysts

PURPOSE An aneurysmal bone cyst (ABC) is a rapidly expansile and destructive benign tumor of bone that is usually treated by curettage and bone graft, with or without adjuvant treatment. For recurrent tumors, or tumors for which surgery would result in significant functional morbidity, does radiotherapy (RT) provide a safe and effective alternative for local control? PATIENTS AND METHODS Nine patients with histologically diagnosed aneurysmal bone cysts without other associated benign or malignant tumors were treated at the University of Florida with megavoltage RT between February 1964 and June 1992. The patients received local radiotherapy doses between 20 and 60 Gy, with 6 patients receiving 26--30 Gy. In 6 patients the diagnosis was made by biopsy alone; 3 underwent intralesional curettage before RT. Minimum follow-up was 20 months; 7 of 9 patients (77%) had follow-up greater than 11 years. RESULTS No patient experienced a local recurrence (median follow-up, 17 years). One patient required stabilization of the cervical spine 10 months after RT because of dorsal kyphosis from vertebral body collapse. No other significant side effects were experienced, and no patients developed secondary malignancies. Four patients were lost to follow-up: at 20 months, 11.5 years, 17 years, and 20 years after the initiation of treatment, none with any evidence of local recurrence. All of the patients who had significant pain before RT had relief of their symptoms within 2 weeks of completion of therapy. CONCLUSIONS Using modern-day RT, patients with recurrent or inoperable aneurysmal bone cysts can be treated effectively (with minimal toxicity) using a prescribed tumor dose of 26--30 Gy.