Radiation therapy in the management of desmoid tumors

Purpose: To evaluate the outcome of patients with extra-mesenteric desmoid tumors treated with radiation therapy, with or without surgery.

Methods and Materials: The outcome for 75 patients receiving radiation for desmoid tumor with or without complete gross resection between 1965 and 1994 was retrospectively reviewed utilizing univariate and multivariate statistical methods.

Results: With a median follow-up of 7.5 years, the overall freedom from relapse was 78% and 75% at 5 and 10 years, respectively. Of the total, 23 patients received radiation for gross disease because it was not resectable. Of these 23 patients, 7 sustained local recurrence, yielding a 31% actuarial relapse rate at 5 years. Radiation dose was the only significant determinant of disease control in this group. A dose of 50 Gy was associated with a 60% relapse rate, whereas higher doses yielded a 23% relapse rate (p < 0.05). The other 52 patients received radiation in conjunction with gross total resection of tumor. The 5- and 10-year relapse rates were 18% and 23%, respectively. No factor correlated significantly with disease outcome. There was no evidence that radiation doses exceeding 50 Gy improved outcome. Positive resection margins were not significantly deleterious in this group of irradiated patients. For all 75 patients, there was no evidence that radiation margins exceeding 5 cm beyond the tumor or surgical field improved local-regional control. Ultimately, 72 of the 75 patients were rendered disease-free, but 3 required extensive surgery (amputation, hemipelvectomy) to achieve this status. Significant radiation complications were seen in 13 patients. Radiation dose correlated with the incidence of complications. Doses of 56 Gy or less produced a 5% 15-year complication rate, compared to a 30% incidence with higher doses (p < 0.05).

Conclusions: Radiation is an effective modality for desmoid tumors, either alone or as an adjuvant to resection. For patients with negative resection margins, postoperative radiation is not recommended. Patients with positive margins should almost always receive 50 Gy of postoperative radiation. Unresectable tumors should be irradiated to a dose of approximately 56 Gy, with a 75% expectation of local control.     

Diagnosis and management of desmoid tumors and fibrosarcoma

Fibrous tumors represent a diverse subtype of soft tissue tumors and can represent benign conditions as well as frankly malignant sarcomas. Desmoid tumors and dermatofibrosarcoma protuberans are more difficult to classify and tend to be considered in the intermediate risk category. They are distinct entities, but both are locally aggressive processes which are plagued with attendant morbidity and high recurrence rates. Complete surgical resection is the mainstay of treatment.     

Abdominal desmoid tumors

Desmoid tumors are rare, benign, fibromatous lesions that are the result of abnormal proliferation of myofibroblasts. Desmoid tumors can be classified as extra-abdominal and abdominal. Abdominal desmoid tumors are either superficial or intraabdominal. These tumors are associated with a high recurrence rates, even if their microscopic characters indicate a benign disease; their biologic behavior often indicates rather a "malignant" disease, which can cause even the death. Intraabdominal desmoid tumors can engulf surrounding viscera and vessels, thereby greatly complicating their surgical treatment. Management is multidisciplinary. Simple observation is a reasonable management option for asymptomatic patients; spontaneous regression of these tumors may be observed. Complete excision is the treatment of choice for tumors causing symptoms or complications. Surgery should be minimized as much as feasible, while at the same time achieving free margins. Adjuvant therapy should be considered in selected cases; the role of other management options (including gene transfer therapy) is currently under intensive investigation.     

Update on desmoid tumors

Desmoid tumors (DTs) are histologically benign proliferations of stromal cells but may grow locally aggressive. Overall, DTs are rare (0.03% of all neoplasms). A minority of DTs is associated with Gardner syndrome and mutations of the familial adenomatous polyposis (FAP) gene. Most spontaneous DTs are associated with mutations of the beta-catenin gene. This mutation results in the activation of Wnt/catenin signaling. Due to their variable clinical presentation and behavior, no standard approach for DTs can be recommended. In most cases of DTs of the extremities surgical extirpation is indicated, whereas in many other cases, a multimodal and multidisciplinary concept should be followed. In this review article, we discuss the diagnosis, pathogenesis, and treatment options for DTs, including targeted therapy with tyrosine kinase inhibitors.     

Low-dose chemotherapy of desmoid tumors

Eight patients with desmoid tumors, symptomatic, and none a candidate for conservative surgery, were treated with weekly vinblastine, maximum dose 10 mg/week, and methotrexate, maximum dose 50 mg/week. Symptomatic relief was obtained in all patients. Using Eastern Cooperative Oncology Group (ECOG) criteria, two patients had a complete remission, one of which has lasted for 30 months, four patients have had partial remissions, one patient has had a mixed response, and one patient who has been treated for only 4 weeks, a minimal response. Toxicity has been minor and transient. Chemotherapy appears to be an acceptable alternative to radical surgery in selected patients with desmoid tumors.     

The enigma of desmoid tumors

Opinion statement Desmoid tumors (aggressive fibromatosis) are rare neoplastic tumors that may occur sporadically or in association with familial adenomatous polyposis (FAP). The etiology of these tumors is unknown, but hormonal, genetic, and physical factors play a role in their development and growth. A distinction is often made between desmoids in patients with FAP and those in patients without FAP, but clinically these tumors are treated the same; the only difference is the preferential intra-abdominal location of FAP desmoids. The goal of desmoid treatment is local control. Choosing the appropriate method for achieving local control may be complex as the functional and cosmetic outcomes of each method must be considered. In addition, because desmoids spontaneously regress, any claim of successful intervention must be viewed skeptically. Local control is mainly achieved by surgical intervention and may be improved with the addition of radiation therapy (RT). For patients who cannot undergo surgery, the options for local control include RT and systemic therapies such as hormones, nonsteroidal anti-inflammatory drugs (NSAIDs), interferon, and chemotherapy. Patients with symptomatic, progressive disease who can tolerate chemotherapy should be presented with the option of low-dose or standard antisarcoma chemotherapy. Although it is unclear which regimen is better, patients appear to have quicker responses to the standard antisarcoma therapy. Hormone therapy, NSAIDs, and interferon are used often, with varying success, and should be reserved for minimally symptomatic patients or for patients who do not want or are not candidates for chemotherapy. The treatment of desmoid tumors remains an enigma. As more options become available, selecting the correct therapy becomes more nuanced. Further clinical trials are needed to help the clinician navigate his or her way through the morass of desmoid tumor therapies.     

Combination chemotherapy for desmoid tumors

BACKGROUND: Desmoid tumor (aggressive fibromatosis) is an aggressive fibroblastic proliferation of well circumscribed, locally invasive, differentiated fibrous tissue. For patients with desmoid tumors that are not amenable to surgery or radiation therapy, the use of hormonal agents and nonsteroidal antiinflammatory drugs (NSAIDs) have been attempted, with some success. The use of chemotherapy also has been reported to have activity. METHODS: Seven patients (5 males and 2 females) with a median age of 40 years (range, 17-66 years) who received cytotoxic chemotherapy (combinations of cyclophosphamide and doxorubicin; mitomycin, doxorubicin, and cisplatin; and ifosfamide and etoposide) for desmoid tumor were reviewed retrospectively. Five patients were found to have recurrent tumors. Four patients had familial adenomatous polyposis. Four patients had failed tamoxifen and six had failed NSAIDs prior to receiving cytotoxic chemotherapy. In six patients the desmoid tumor was intraabdominal and one tumor had occurred on the buttock. RESULTS: Patients received a median number of six cycles of chemotherapy (range, two to eight cycles). Objective disease regression occurred in 3 patients. There was an apparent clinical benefit in six patients with the duration of benefit ranging from 3 months to 15 years. The chemotherapy was well tolerated and no treatment-related mortality was reported. CONCLUSIONS: The results of the current study indicate that the use of combination chemotherapy for desmoid tumors may provide long-term clinical benefits.     

Contemporary role of modern brachytherapy techniques in the management of malignant thoracic tumors

Sole brachytherapy for carcinoma of the lung is most often performed using high-dose-rate (HDR) remote afterloading equipment, which delivers the treatment within the tracheobronchial tree in an outpatient setting. It provides excellent, rapid palliation in advanced stages, and can also be used selectively for curative intent in early stages. In better-performance patients, fractionated external beam radiation therapy (EBRT) is preferred to brachytherapy as an initial treatment because it appears to provide a modest gain in survival, and more sustained palliation. In patients with centrally located tumors and limited extent of disease, the combination of external and endoluminal irradiation enables curative treatment options. Intraoperative brachytherapy may complement standard adjuvant treatment in incompletely resected, unresectable, or medically inoperable patients, and has the potential to improve local control in selected cases. Due to the rarity of the disease, the role of endoluminal brachytherapy in the treatment regimen of tracheal neoplasms is not yet clearly defined. The risk of fatal bleeding after endoluminal brachytherapy appears to be correlated with tumor localization and fraction size, but in the majority of cases fatal bleeds are caused by progression of local disease. The use of a distanceable applicator provides a central positioning of the source, prevents the delivery of high-contact doses to the mucosa, and may reduce toxicity. The standard technique for interstitial brachytherapy after breast-conserving surgery and adjuvant EBRT is the use of low-dose-rate (LDR) brachytherapy, but it may also be applied by means of pulsed-dose-rate (PDR) or HDR techniques. Prospective trials comparing different boost techniques and indications are needed to define more precisely the subgroup of patients who are most suitable for interstitial brachytherapy. Reirradiation of chest wall local recurrences using brachytherapy molds is effective and provides a high local control rate with acceptable toxicity.     

Indomethacin and ascorbate inhibit desmoid tumors

Administration of indomethacin caused complete resolution of a desmoid tumor after a partial response to radiation. In another patient, this drug caused an immediate response, then became ineffective. When large doses of ascorbic acid were given with indomethacin, slow resolution of the tumor began and has continued for 14 months. Treatment of a third case with indomethacin and ascorbic acid from the beginning produced shrinkage of the tumor which has continued to date.     

Endocrine therapy for desmoid tumors.

Two female patients with desmoid tumors (aggressive fibromatosis) showed tumor regression after endocrine therapy. In one patient, tumor response to tamoxifen has been maintained over several years of treatment. In the second patient, who had inoperable mesenteric fibromatosis, the tumor progressed on tamoxifen but regressed after treatment with Zoladex (goserelin acetate, ICI, Melbourne, Australia) and medroxyprogesterone acetate (MPA). To the authors' knowledge this is the first report of the use of Zoladex in the treatment of desmoid tumors. This review of the literature reveals that the biology of this disease is related to the endogenous hormonal environment and that estrogen receptors have been documented in desmoid tumors. Thirty-five cases are identified where endocrine agents have been employed, with a response rate of 51%. Furthermore, tumors may respond to second-line hormonal therapy after failing to respond to initial endocrine treatment. Endocrine treatments have also been used in other disorders of fibroblastic origin. The authors recommend that endocrine treatment be employed in inoperable desmoid tumors or where there has been postsurgical recurrence. In addition, the role for endocrine therapy in other soft tissue neoplasms should be determined.     

Percutaneous cryoablation for the treatment of extra-abdominal desmoid tumors

Background

Desmoid tumors are rare locally invasive, benign neoplasms that develop along aponeurotic structures. Current treatment is complicated by associated morbidity and high recurrence rates.

Methods

A retrospective, single-institution review identified 23 patients (age: 16-77) with extra-abdominal desmoid tumors who received CT-guided percutaneous cryoablation as either a first-line (61%) or salvage (39%) treatment in 30 sessions between 2014 and 2018. Median maximal lesion diameter was 69 mm (range: 11-209). Intent was curative in 52% and palliative in 48%. Contrast-enhanced cross-sectional imaging was obtained before and after treatment in addition to routine clinical follow-up.

Results

Technical success was achieved in all patients. The median follow-up was 15.4 months (3.5-43.4). Symptomatic improvement was demonstrated in 89% of patients. At 12 months, the average change in viable volume was −80% (range −100% to + 10%) and response by modified response evaluation criteria in solid tumors (mRECIST) was CR 36%, PR 36%, and SD 28% No rapid postablation growth or track seeding was observed. Four patients underwent repeat cryoablation for either residual or recurrent disease. Two patients sustained a major procedural complication consisting of significant neuropraxia.

Conclusion

Cryoablation for desmoid tumors demonstrates a high degree of symptom improvement and local tumor control on early follow-up imaging with relatively low morbidity.     

Role of surgery in the management of soft tissue tumors

Pediatric soft tissue sarcomas (STSs), of which rhabdomyosarcoma is the most common, constitute approximately 5-6% of all cancers in children. Biopsy, being incisional or rarely excisional, is an essential primary diagnostic step, while in some cases it may be followed by primary re-excision to establish a correct diagnosis in which molecular analysis can be helpful. Most European STS treatment groups favor preoperative chemotherapy, sometimes combined with preoperative irradiation. Local therapy is essential, in which surgery remains an important adjunct. However, it has to be applied in a multidisciplinary, combined fashion in close cooperation with oncologists, pathologists and radiotherapeutists. Current 5-year survival in rhabdomyosarcoma reaches 60-70% in nonmetastatic cases and remains below 20% in metastatic situations. Outcome in pediatric nonrhabdomyosarcoma STS is similar.     

Surgical excision versus observation as initial management of desmoid tumors: A population based study

SynopsisDesmoid tumors can be safely managed with watchful waiting, including either observation alone or tamoxifen/NSAIDs. Surgery at first presentation can be associated with significant treatment burden.BackgroundImmediate surgery was historically recommended for desmoid tumors. Recently, watchful waiting, (tamoxifen/NSAIDs or observation alone), has been advocated.MethodsAll diagnoses of desmoid tumor within the Alberta Cancer Registry from August 2004 to September 2015 were identified. Patients with FAP were excluded. Demographics, tumor characteristics and treatment and outcome data were collected. Outcomes were compared between immediate surgery and watchful waiting. The effect of abdominal wall site on progression and recurrence and the effect of microscopic margin on recurrence were assessed with Fisher's exact test.ResultsWe identified 111 non-FAP patients. Median follow-up was 35 months from diagnosis. 74% were female. Mean age was 42. Fifty (45%) underwent watchful waiting, of whom 21(42%) progressed, with median PFS of 10 months. Fifty-three (48%) underwent resection at presentation, of whom 8 (15%) recurred, with median disease-free survival of 22 months.Abdominal wall lesions were equally represented in both groups, and equally likely to progress on watchful waiting (50% vs 39%, p = 0.53), but there was a trend toward decreased recurrence after surgery. (5% vs 23%, p = 0.08).Microscopic margin had no effect on recurrence (14% of margin negative vs 20% of margin positive, p = 1.0).ConclusionsWatchful waiting was successful in 58% of patients, and a further 28% only required one aggressive treatment thereafter, for a total of 86%. Surgery had a favorable recurrence rate (15%), but some recurrences were associated with significant treatment burden. Treatment should be tailored to individual patients in a multidisciplinary setting. A trial of observation appears warranted in most patients.Recurrence rate was not affected by positive margins.     

Margins in extra-abdominal desmoid tumors: a comparative analysis

BACKGROUND AND OBJECTIVES: The main treatment of extra-abdominal desmoid tumors remains surgery, but recurrence rates up to 80% are reported. The impact of microscopic surgical margin status according to the Enneking classification system is discussed controversially. METHODS: Therefore, the authors screened the published literature for reliable data on the importance of a wide or radical excision of extra-abdominal desmoid tumors. All studies with more than ten patients, a surgical treatment only, and margin status stated were included. RESULTS: Only 12 out of 49 identified studies fulfilled the inclusion criteria. One hundred fifty-two primary tumors were excised with wide or radical microscopic surgical margins, while in 260 cases a marginal or intralesional excision was performed. In the first group 41 patients (27%) and in the second one 187 patients (72%) developed a recurrence. Therefore, microscopic surgical margin status according to the Enneking classification system is a significant prognostic factor (P < 0.001). CONCLUSIONS: The data of this review underline the strategy of a wide or radical local excision as the treatment of choice. Furthermore, as a large number of studies had to be excluded from this analysis, exact microscopic surgical margin status should be provided in future studies in order to allow comparability. .     

Therapy of desmoid tumors and fibromatosis using vinorelbine

In patients with either desmoids or fibromatosis who do not tolerate vinblastine and methotrexate because of neurotoxicity, the combination of vinorelbine and methotrexate can be substituted in most. Patients with the same condition who had not been previously treated with a combination of vinblastine and methotrexate responded well to the combination of vinorelbine and methotrexate, with significantly less neurotoxicity and a similar objective and subjective response rate. Sixty percent of patients had either a substantial partial remission or a complete remission. In no patients did the disease progress while they were receiving this therapy. Symptomatic relief, primarily of pain, occurred in 80% of patients. While minimal neurotoxicity was seen in 16% of these patients, it did not interfere with the completion of therapy. The combination of vinorelbine and methotrexate appears to be active in the treatment of both desmoid tumors and fibromatosis and is associated with significantly less neurotoxicity then that seen with the combination of vinblastine and methotrexate. No long-term toxicity was seen in any patient in this series.     

Radiation therapy in the treatment of aggressive fibromatoses (desmoid tumors)

Twenty-five patients with aggressive fibromatoses (desmoid tumors) have been treated or followed in the Department of Radiation Medicine at the Massachusetts General Hospital between 1972 and 1982. Seventeen patients were treated by radiation, 4 for primary and 13 for recurrent disease. Seven patients were treated in conjunction with surgery. Partial or complete regression was achieved in 76%, and 59% are without evidence of disease (NED) at 9 to 94 months follow-up. Eight of ten patients treated primarily with radiation have achieved complete response without an attempt at resection (five) or have achieved stabilization (three) of their disease after some regression. Consistent complete control was seen with doses above 60 Gy. Periods to 27 months were required to observe complete responses. Only three failures within the radiation field were observed, two after low doses (22 and 24 Gy, respectively). Eight patients were seen after resection but with uncertain or histologically minimum positive margins, and were followed regularly and not treated. One patient has failed to date and is NED after resection. Radiation therapy is recommended in those situations where wide-field resection without significant morbidity is not possible for gross local disease. If minimally positive margins exist after resection in a patient who may be followed carefully, frequent follow-up and prompt treatment at recurrence may be an effective alternative to immediate radiation therapy.