Matthew T. Ballo

Desmoid Tumor: Prognostic Factors and Outcome After Surgery, Radiation Therapy, or Combined Surgery and Radiation Therapy

PURPOSE To evaluate the therapeutic value of resection and the potential benefits of and indications for adjuvant and definitive radiation therapy for desmoid tumors. MATERIALS AND METHODS We performed a retrospective review of 189 consecutive cases of desmoid tumor treated with surgical resection, resection and radiation therapy, or radiation therapy alone. Treatment was surgery alone in 122 cases, surgery and radiation therapy in 46, and radiation therapy alone in 21. Median follow-up was 9.4 years. RESULTS Overall, 5- and 10-year actuarial relapse rates were 30% and 33%, respectively. Uncorrected survival rates were 96%, 92%, and 87% at 5, 10, and 15 years, respectively. For the patients treated with surgery, the actuarial relapse rates were 34% and 38% at 5 and 10 years, respectively. Among 78 patients with negative margins, the 10-year recurrence rate was 27%, whereas 40 margin-positive patients had a 10-year relapse rate of 54% (P = .003). Tumors located in an extremity also had a poorer prognosis than did those in the trunk. For patients treated with radiation therapy for gross disease, the 10-year actuarial relapse rate was 24%. For patients treated with combined resection and radiation therapy, the 10-year actuarial relapse rate was 25%. The addition of radiation therapy offset the adverse impact of positive margins seen in the surgical group. CONCLUSION Wide local excision with negative pathologic margins is the treatment of choice for most desmoid tumors. Function-sparing resection is appropriate because adjuvant radiation therapy can offset the adverse impact of positive margins. Unresectable disease should be treated with definitive radiation therapy.

Mortality After Cure of Testicular Seminoma

PURPOSE To determine the incidence of potentially treatment-related mortality in long-term survivors of testicular seminoma treated by orchiectomy and radiation therapy (XRT). PATIENTS AND METHODS From all 477 men with stage I or II testicular seminoma treated at The University of Texas M.D. Anderson Cancer Center (Houston, TX) with post-orchiectomy megavoltage XRT between 1951 and 1999, 453 never sustained relapse of their disease. Long-term survival for these 453 men was evaluated with the person-years method to determine the standardized mortality ratio (SMR). SMRs were calculated for all causes of death, cardiac deaths, and cancer deaths using standard US data for males. RESULTS After a median follow-up of 13.3 years, the 10-, 20-, 30-, and 40-year actuarial survival rates were 93%, 79%, 59%, and 26%, respectively. The all-cause SMR over the entire observation interval was 1.59 (99% CI, 1.21 to 2.04). The SMR was not excessive for the first 15 years of follow-up: SMR, 1.30 (95% CI, 0.93 to 1.77); but beyond 15 years the SMR was 1.85 (99% CI, 1.30 to 2.55). The overall cardiac-specific SMR was 1.61 (95% CI, 1.21 to 2.24). The cardiac SMR was significantly elevated only beyond 15 years (P <.01). The overall cancer-specific SMR was 1.91 (99% CI, 1.14 to 2.98). The cancer SMR was also significant only after 15 years of follow-up (P <.01). An increased mortality was evident in patients treated with and without mediastinal XRT. CONCLUSION Long-term survivors of seminoma treated with post-orchiectomy XRT are at significant excess risk of death as a result of cardiac disease or second cancer. Management strategies that minimize these risks but maintain the excellent hitherto observed cure rates need to be actively pursued.

Optimizing Treatment of Desmoid Tumors

PURPOSE This study compared a large series of desmoid patients treated at a single institution to a previously published series from the same institution to determine if patient population characteristics, treatment approaches, and clinical outcomes had undergone change over the two study periods. MATERIALS AND METHODS Data from a prospective soft tissue tumor database was used to analyze clinical courses of 189 desmoid patients treated at The University of Texas M.D. Anderson Cancer Center (UTMDACC) from 1995 to 2005 as compared with 189 UTMDACC desmoid patients treated between 1965 and 1994. RESULTS A nearly three-fold increase in annualized UTMDACC desmoid referral volume with significantly higher percentages and numbers of primary desmoid tumor referrals to UTMDACC was observed in the most recent study period. Significantly increased systemic therapy use and decreased reliance on surgery alone was observed more recently. While the recent series patients had higher rates of macroscopic residual disease and equivalent rates of positive microscopic margins after definitive surgery, the estimated 5-year local recurrence rate of 20% was improved compared with the 30% rate observed in the earlier series. CONCLUSION Increased awareness of the complex multidisciplinary management needed for desmoid tumor control may underlie significantly increased numbers of referrals to UTMDACC, especially primary untreated desmoids. Increased neoadjuvant treatments may be associated with improved desmoid patient outcomes. These trends should be supported, particularly if personalized molecular-based therapies are to be rapidly and effectively deployed for the benefit of those afflicted by this rare and potentially debilitating disease.

Long-Term Results of Two Prospective Trials of Preoperative External Beam Radiotherapy for Localized Intermediate- or High-Grade Retroperitoneal Soft Tissue Sarcoma

BackgroundThe reported data on surgery plus radiotherapy for retroperitoneal soft tissue sarcomas (RPS) have been mostly from retrospective studies. We evaluated the long-term outcome of patients with operable RPS who were treated with protocol-based preoperative radiotherapy followed by complete surgical resection.MethodsData from two prospective trials that included preoperative radiotherapy and surgery for patients with radiographically resectable RPS were combined to define long-term relapse rates and survival.ResultsSeventy-two patients with intermediate- or high-grade RPS were treated with preoperative radiotherapy (median dose, 45 Gy; range, 18.0–50.4 Gy). Fifty-four patients (75%) had primary RPS, whereas 18 (25%) had recurrent disease. The median tumor size was 15.5 cm. Sixty-four patients completed the planned preoperative radiotherapy; 57 (89%) underwent laparotomy with curative intent, and 54 (95%) had a macroscopically complete (R0 or R1) resection. With a median follow-up of 40.3 months, 28 patients (52%) who received preoperative radiotherapy and underwent a macroscopically complete resection had recurrences. For the 54 patients who underwent R0 or R1 resection after preoperative radiotherapy, the 5-year local recurrence–free, disease-free, and overall survival rates were 60%, 46%, and 61%, respectively. The median overall survival has not been reached (>60 months).ConclusionsPatients with intermediate- or high-grade RPS treated with preoperative radiotherapy plus complete resection had a median survival >60 months. This compares favorably to historical data for similar patients treated with surgery alone.

The Role of Radiation Therapy in the Management of Dermatofibrosarcoma Protuberans

PURPOSE To evaluate the outcome for dermatofibrosarcoma protuberans treated with conservation surgery and radiation therapy. METHODS AND MATERIALS A retrospective review was performed of 19 consecutive patients with pathologically confirmed dermatofibrosarcoma protuberans who received radiation as an adjuvant to surgical resection. RESULTS The patients ages ranged from 19-76 years (median, 40 years); 12 were men. Lesions were located on the trunk in 8, in the head and neck area in 7, and in an extremity in 4. Tumor size ranged from 1.2 to 15 cm (median, 4 cm). Ten patients had at least 1 prior recurrence following earlier resection. Two patients received preoperative radiation to 50 Gy in 5 weeks. Sixteen patients underwent resection followed by radiation (6 of these had positive resection margins). In another patient, the tumor regrew rapidly after resection and definitive radiation was delivered for gross disease. The 6 patients with positive microscopic margins received a median dose of 60 Gy, as did the 10 with negative margins. The 1 patient with gross disease received 65 Gy. At a median follow-up of 6 years, the only patient to develop local recurrence was treated with definitive radiotherapy for gross disease. Actuarial local control was 95% at 10 years. CONCLUSION Dermatofibrosarcoma protuberans is a radioresponsive tumor and radiation to doses of 50-60 Gy should be considered as an adjuvant to resection if margins are positive. Combined conservation resection and postoperative radiation should also be considered for situations where adequate wide excision alone would result in major cosmetic or functional deficits.

Adult rhabdomyosarcoma: outcome following multimodality treatment.

Childhood rhabdomyosarcoma (RMS) has a relatively good prognosis. Outcome for adults with this disease is poorly documented due to its rarity.

Radiotherapy in the management of giant cell tumor of bone

PURPOSE To evaluate the outcomes of patients with giant cell tumor of bone (GCTB) treated with radiotherapy (RT) with or without surgical resection. METHODS AND MATERIALS We performed a retrospective review of the records from 25 consecutive patients with pathologically confirmed GCTB who had undergone RT between 1956 and 2000. RESULTS Patients ranged in age from 11 to 69 years (median 32); 16 were female and 9 were male. The anatomic distribution of lesions was as follows: cervical spine, 3; temporal bone, 1; thoracic or lumbar spine, 9; sacrum, 8; ilium, 1, and humerus, radius, and thumb metacarpal, 1 each. Tumors ranged in size from 2 to 20 cm (median 9.5) at their maximal dimension. Thirteen patients had been referred for RT for primary GCTB and 12 had been referred with locally recurrent disease after having undergone one or more other treatments. Fourteen patients had undergone RT for gross disease, and the remaining 11 had been treated with RT after gross total resection. In 10 of these 11 patients, the treatment margins were positive or uncertain. Radiation doses ranged from 25 to 65 Gy (median 46). At a median follow-up of 8.8 years (range 0.67-34), 7 patients had developed isolated local recurrence, 2 had developed isolated distant recurrence, and 3 had developed both. The actuarial 5-year overall and disease-free survival rate was 91% and 58%, respectively, and the actuarial 5-year local control and distant metastasis-free survival rate was 62% and 81%, respectively. Univariate analysis suggested that treatment for recurrent disease correlated with a lower disease-free survival rate (83% vs. 33%, p = 0.06), distant metastasis-free survival rate (100% vs. 64%, p = 0.08), and local control rate (83% vs. 42%, p = 0.08) at 5 years. Of the 12 cases of recurrence, 7 were ultimately successfully treated with additional salvage therapy. In 4 of these patients, salvage therapy included interferon-alpha 2b. CONCLUSION RT should be considered an adjuvant to surgery or as alternative therapy in cases of GCTB that are unresectable or in which excision would result in substantial functional deficits. When RT is used as primary therapy, the rate of local control seems to be satisfactory. In heavily pretreated patients, however, RT delivered as it was in this series can result in poor local control, and alternative therapies should be considered.

Phase I Trial of Preoperative Concurrent Doxorubicin and Radiation Therapy, Surgical Resection, and Intraoperative Electron-Beam Radiation Therapy for Patients With Localized Retroperitoneal Sarcoma

PURPOSE The primary objective of this phase I trial was to define the maximum-tolerated dose of external-beam radiation with concurrent fixed-dose continuous-infusion doxorubicin followed by surgical resection and electron-beam intraoperative radiation therapy (EB-IORT) for patients with localized, potentially resectable retroperitoneal sarcomas (RPS). PATIENTS AND METHODS Thirty-five patients with radiographically resectable primary or recurrent intermediate- or high-grade RPS were treated. Doxorubicin was administered each week for 4 or 5 weeks as an initial bolus (4 mg/m2) followed by a 4-day continuous infusion (4 mg/m2/d). Concurrent radiation therapy was administered in escalating doses of 18.0, 30.6, 36.0, 41.4, 46.8, or 50.4 Gy in 1.8-Gy fractions. Radiographic restaging was performed 4 to 8 weeks after chemoradiation, and patients with localized disease underwent surgical resection with EB-IORT (15 Gy). RESULTS Chemoradiation was completed as outpatient therapy in 31 patients (89%); four patients required hospital admission during chemoradiation or in the postchemoradiation preoperative period. At the highest radiation dose of 50.4 Gy, two (18%) of 11 patients had grade 3 or 4 nausea. Twenty-nine patients (83%) underwent laparotomy; six patients had interval disease progression and did not undergo surgery. Grossly complete resection (R0 or R1) was performed in 26 (90%) of 29 patients who had surgery. EB-IORT was feasible and successfully administered to 22 patients who had R0 or R1 resections. CONCLUSION Preoperative chemoradiation, surgical resection, and EB-IORT are feasible for patients with RPS. Preoperative external-beam radiation can be administered to a total dose of 50.4 Gy with continuous-infusion doxorubicin.

Complications of combined modality treatment of primary lower extremity soft-tissue sarcomas

Correlations between various patient, tumor, and treatment characteristics and complications in patients undergoing combined modality treatment for primary lower extremity soft‐tissue sarcomas were investigated.

Long-term results of prospective trial of surgery alone with selective use of radiation for patients with T1 extremity and trunk soft tissue sarcomas

Objective:We conducted a prospective trial to define the local recurrence rates for selected patients with T1 soft tissue sarcomas (STS) treated by surgery alone. Summary Background Data:Retrospective data suggest that some patients with small STS can be safely treated by surgery alone. There are no defined criteria to select patients for such treatment. Methods:Patients with T1 primary STS were treated with function-preserving surgery and microscopic assessment of surgical margins. Postoperative external-beam radiation was employed selectively for patients with microscopically positive (R1) final surgical margins. Patients who underwent resection with microscopically negative (R0) final margins did not receive radiotherapy. Results:Eighty-eight eligible and evaluable patients were entered on this protocol between March 1996 and April 2002. Tumor sites included the extremities (n = 60), and trunk (n = 26). Fifty-one patients (58%) had high-grade STS; 60 (68%) had superficial (T1a) disease. Fourteen patients (16%) underwent R1 resection and were treated with postoperative radiation; 74 (84%) underwent R0 resection and were treated by surgery alone. The median follow-up was 75 months. Isolated local recurrences were observed in 11 patients (13%; 6 in R1 arm, 5 in R0 arm). In the R0 surgery-alone arm, the cumulative incidence rates of local recurrence at 5 and 10 years were 7.9% and 10.6%, respectively; and the 5- and 10-year sarcoma-specific death rates were 3.2% and 3.2%. Conclusion:Selected patients with primary T1 STS of the extremity and trunk can be treated by R0 surgery alone with acceptable local control and excellent long-term survival.