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Parameters that predict local control after definitive radiotherapy for squamous cell carcinoma of the head and neck.

PURPOSE: To analyze parameters that may influence the likelihood of local control after definitive radiotherapy for head and neck cancer. METHODS: Between April 1980 and January 2000, 404 patients were treated with definitive RT alone (358 patients) or combined with adjuvant chemotherapy (46 patients) at our institution and were followed up for 0.25 to 20.25 years (median, 3.5 years.) All living patients were followed up for at least 2 years. All patients had the primary tumor volume calculated on pretreatment CT. End points were local control after RT and local control after RT without a severe late complication. Parameters evaluated in multivariate analyses of these end points included primary site, T stage, primary tumor volume, N stage, histologic differentiation, fractionation schedule, adjuvant chemotherapy, and gender. RESULTS: The rates of local control and local control without a severe late complication after RT were significantly influenced by primary tumor volume for patients with cancer of the supraglottic larynx and true vocal cord. In contrast, the rates of local control and local control without severe complications for patients with tumors of the oropharynx and hypopharynx were less influenced by tumor volume. Multivariate analysis of the overall population revealed that the only parameter that was significantly related to the probability of local control after RT was T stage. Multivariate analyses stratified by primary site revealed that tumor volume significantly influenced local control for patients with cancers of the supraglottis (p =.0220) and glottis (p =.0042) but not for those with lesions of the tonsillar fossa/posterior tonsillar pillar (p =.0892), base of tongue (p =.9493), anterior tonsillar pillar/soft palate (p =.5909), and hypopharynx (p =.2282). CONCLUSIONS: The most important parameter that has an impact on local control after RT is T stage. Primary tumor volume also significantly influences the probability of local control in cancers of the supraglottis and glottis.

Adolescent↗

Radiotherapy, local control and survival in lung cancer.

Better local control in locally advanced IIIA-B non small cell lung cancer, not considered for surgery, can be achieved through therapy intensification with non conventional fractionation of radiation dose, concomitant boost to the tumor volume, conformal therapy and combined modality therapy. All these procedures tend to produce an improved response, which, if stable in time, may also improve local control and survival. The reported experiences define a positive and encouraging trend on which new guidelines for a more suitable definition of standard therapies for the disease can be modulated.

Carcinoma, Non-Small-Cell Lung↗

Controlled local delivery of tetracycline HCl in the treatment of periimplant mucosal hyperplasia and mucositis. A controlled case series.

The purpose of this controlled case series was to assess the adjunctive efficacy of controlled topical tetracycline HCl application in the treatment of infection associated periimplant mucositis or mucosal hyperplasia. Eight patients with at least 2 endosseous implants showing clinical signs of periimplant mucosal hyperplasia or mucositis were enrolled. All implants received supra- and subgingival scaling, with half of the implants receiving adjunctive controlled local delivery of tetracycline HCl (test). Control implants did not receive any other therapy aside from scaling. Clinical parameters were assessed at baseline, 4, and 12 weeks. Scaling plus controlled local delivery of tetracycline HCl markedly reduced periimplant mucosal hyperplasia in 4 of 5 test implants and demonstrated a trend towards a reduction of bleeding on probing scores. Scaling alone had no effect on mucosal hyperplasia in the 2 control implants presenting with this condition nor bleeding on probing scores. In both groups, plaque index scores were slightly reduced at 4 weeks but returned to baseline values at 12 weeks, whereas pocket probing depths, clinical attachment levels, and probing bone levels remained unchanged during the course of the trial. The observed trends suggest that scaling plus controlled local delivery of tetracycline HCl may have beneficial effects. Randomized controlled trials employing a sample size high enough to reach sufficient statistical power are needed to definitively assess the efficacy of controlled local tetracycline HCl delivery on periimplant diseases.

Administration, Topical↗

Radiation and Local Control in Early Invasive Breast Cancer.

Local control in the breast after breast-conserving surgery and radiation for the treatment of early invasive breast carcinoma has long been viewed as important to the patient to avoid later need for mastectomy. Now several studies support the hypothesis that local control is related to and impacts upon a patient's survival as well. The factors that predict for local control with this treatment are reviewed. The recent studies that support the link between local breast failure and distant disease are also discussed.

Journal Article↗

Can pretreatment computed tomography predict local control in T3 squamous cell carcinoma of the glottic larynx treated with definitive radiotherapy?

PURPOSE: To determine if pretreatment computed tomography (CT) can predict local control in T3 squamous cell carcinoma of the glottic larynx treated with definitive radiotherapy (RT). METHODS AND MATERIALS: Forty-two patients with previously untreated T3 squamous cell carcinoma of the glottic larynx were treated for cure with RT alone; all had a minimum 2-year follow-up. Tumor volumes and extent were determined by consensus of two head and neck radiologists on pretreatment CT studies. A tumor score was calculated and assigned to each primary lesion depending on the extent of laryngeal spread. Sclerosis of any laryngeal cartilage was recorded. The specific CT parameters assessed were correlated with local control. RESULTS: Tumor volume was a significant predictor of local control. For tumors measuring < 3.5 cm3, local control was achieved in 22 of 26 patients (85%), whereas for tumors > or = 3.5 cm3, local control was achieved in 4 of 16 patients (25%) (p = 0.0002). Sensitivity and specificity using this cutpoint were 85% and 75%, respectively. Tumor score as a measure of anatomic extent was also found to be a significant predictor of local control. The local control rate for tumors assigned a low tumor score (< or = 5) was 78% (21 of 27) compared to 33% (5 of 15) for tumors assigned a high tumor score (6, 7, or 8) (p = 0.008). A significant decrease in the local control rate was observed for cancers involving the paraglottic space at the false vocal cord level (14 of 16 [88%] vs. 12/26 [46%]) (p = 0.010), cancers involving the face of the arytenoid (15 of 18 [83%] vs. 11 of 24 [46%]) (p = 0.024), and tumors involving the interarytenoid region (25 of 36 [69%] vs. 1 of 6 [17%]; p = 0.020). There were 12 patients with sclerosis of both the ipsilateral arytenoid and the adjacent cricoid cartilage. These patients showed a significant decrease in local control (4 of 12 [33%]). CONCLUSION: Pretreatment CT can stratify patients with T3 glottic carcinoma into groups more or less likely to be locally controlled with definitive RT. The local control rate for these tumors can be improved using a CT-based tumor profile; the ideal CT profile for a radiocurable T3 glottic larynx carcinoma is volume < 3.5 cm3 and no or single laryngeal cartilage sclerosis.

Carcinoma, Squamous Cell↗

[Relation between overall treatment time and local control of early glottic laryngeal cancer: comparison of six versus five times per week].

PURPOSE: Local control probabilities of early glottic cancer were evaluated in relation to overall treatment time. MATERIALS AND METHODS: From 1971 to 1996, 162 patients with T1 or T2 glottic cancer were treated with radiation therapy. Fifty-nine patients received irradiation six times per week from 1971 to 1987, and 103 patients received irradiation five times per week from 1987 to 1996. Local control rates were calculated by the Kaplan-Meier method, and the log-rank test was used for statistical analysis. The Cox proportional hazards model was used to evaluate the significance of prognostic variables on local control. RESULTS: The 5-year local control rates were 91.8% for T1 tumors and 78.1% for T2 tumors. There was a statistically significant difference in local control rates between the two groups (p = 0.009). The overall local control rate was 86.4% for both groups, showing no statistically significant difference. Multivariate analysis showed that T stage and overall treatment time were important parameters in relation to local control. CONCLUSIONS: In early glottic cancer, there is no significant difference in local control probabilities between irradiation six times per week and five times per week.

Carcinoma, Squamous Cell↗

Dose response and local control using radiotherapy in non-metastatic Ewing sarcoma.

BACKGROUND: To determine prognostic factors for local control in the radiotherapeutic management of non-metastatic Ewing sarcoma. PROCEDURE: Forty patients with localized Ewing sarcoma (ES) were treated with primary site RT at one institution. Median RT dose was 55.8 Gy (range, 25.5-76 Gy). Chemotherapy was given to 34 patients (85%) with the most common regimen being vincristine, dactinomycin, cyclophosphamide, doxorubicin alternating with ifosfamide and etoposide (VACA + IE) in 10. Median follow-up for surviving patients was 12.3 years (range, 1.7-26.4 years). RESULTS: The 5- and 10-year local control rate was 78.2%. On multivariate analysis, RT dose was the only prognostic factor to impact on local control. The 5- and 10-year local control rate was 88.7% for RT dose >or=49 Gy and was 37.5% for <49 Gy (P = 0.0002, log-rank test). For tumors or=49 Gy and 50.0% for RT dose <49 Gy (P = 0.01, log-rank test). For tumors >8 cm, the 5- and 10-year local control rate was 85.7% for RT dose >or=54 Gy and 26.7% for RT dose <54 Gy (P = 0.006, log-rank test). CONCLUSIONS: Radiotherapy dose was found to influence local control in ES. In particular, patients who received RT doses >or=49 Gy for tumor size or=54 Gy for tumor size >8 cm had improved local control.

Adolescent↗

Prognostic factors for local control and survival in T1 squamous cell carcinoma of the glottis.

PURPOSE: To evaluate the effect of host, tumor, and treatment-related variables on local control and survival in patients with T1N0M0 squamous cell carcinoma of the glottis. MATERIALS AND METHODS: Ninety-one patients with T1N0M0 squamous cell carcinoma of the glottic larynx were analyzed. Median follow-up was 9 years (range 2-25). Patients were treated with daily fractions of 180 cGy to 220 cGy to doses of 5925-7000 cGy (median 6400). The following factors were analyzed: age, sex, histologic grade, disease extent, beam energy, field size, total dose, dose per fraction, and elapsed treatment days. RESULTS: The 5-year actuarial local control was 80%. On univariate analysis, only elapsed treatment days and dose per fraction were significant factors for local control. Local control was 100% if treatment was completed within 42 days, 91% for 43-46 days, 74% for 47-50 days, 65% for 51-54 days, and 50% for 55-66 days (p = 0.0001). In patients treated at < 200 cGy per fraction, local control was 62% as compared to 87% for > or = 200 cGy per fraction (p = 0.006). On multivariate analysis, only elapsed treatment days was a significant factor for local control (p = 0.0001). The 5-year actuarial survival for the whole group was 92%. Elapsed treatment days was the only variable affecting survival. Survival was 100% if treatment was delivered within 42 days, 96% for 43-46 days, 94% for 47-50 days, 91% for 51-54 days, and 67% for 55-66 days (p = 0.02). The 5-year actuarial disease-specific survival was 95%, with treatment duration again being the only significant prognostic factor. Disease-specific survival was 97% for treatment completed within 39-54 days versus 80% for 55-66 days (p = 0.02). Only three (3.3%) patients experienced moderate or severe complications. None of the evaluated parameters impacted significantly on complications. CONCLUSION: We conclude that elapsed days is the most prognostically significant factor for local control and survival in patients treated with radiotherapy for T1 squamous cell carcinoma of the glottis. We recommend that these patients be treated with 210 cGy daily fractions to 6300 cGy.

Carcinoma, Squamous Cell↗

Local control of piriform sinus cancer treated by radiation therapy alone.

Local control rate by radical radiation therapy was analyzed in 33 patients with a piriform sinus cancer. Twenty-five patients (76%) were in stage T3 + T4. Local recurrence-free survival at 3 years was 49% in T1 + T2 and 25% in T3 + T4 (p = 0.01). In T1 + T2 lesions, a biologically effective dose for an acute reaction over 80 Gy and total treatment time less than 70 days appeared to improve local control. In T3 + T4 lesions, good radiation response assessed by the regaining of laryngeal mobility affected local control favorably. An esophageal involvement and destruction of the laryngeal cartilage as well as soft tissue extension precluded the possibility of local control by radiation therapy alone. In addition to the T-stage, other tumor factors should also be considered for predicting local control with radiation therapy.

Aged↗

Carcinoma of the tongue in Norway and Wisconsin. II. Influence of site and clinical stage on local control of the tumor.

The local control rates in patients with squamous cell carcinoma of the tongue, treated between 1958 and 1972, were determined by retrospective analysis of the records of 339 patients at the Norwegian Radium Hospital and of 164 patients at the University of Wisconsin Hospitals. The correlation between the clinical stage and the local control rate was good in Norway, less striking in Wisconsin. As the tumor grew in size it generally became increasingly difficult to control. Irradiation and surgery appeared relatively satisfactory in patients with tumors in early stages, but were often inadequate in the advanced tumors. The differences observed between Norway and Wisconsin were statistically significant only for the tumors of the base of the tongue and T2N0, T3N0 and TxN1 tumors of the anterior two-thirds of the tongue.

Carcinoma, Squamous Cell↗

Prognostic factors for local control in hypopharyngeal cancer treated with radical irradiation.

PURPOSE: We retrospectively analyzed prognostic factors for local control in hypopharyngeal cancer. PATIENTS AND METHODS: Twenty-five patients with hypopharyngeal cancer treated with radical irradiation were entered into analyses. Local control according to clinical T stage and subsites of hypopharynx were analyzed. For 8 clinical T2 patients, local control according to findings assessed by pretreatment CT was also evaluated. RESULTS: The 2-year local control rates were 40% for all, 1/2 for T1, 8/11 (73%) for T2, 1/8 (12%) for T3, and 0/4 for T4. Two-year local control rates were 28% for pyriform sinus cancer and 66% for pharyngeal wall cancer. Local control analysis according to CT findings for patients with T2 hypopharyngeal cancer showed that patients without specified involvement beyond the hypopharynx or in the apex had good local control. CONCLUSION: Our preliminary analysis suggested that clinical T2 hypopharyngeal cancer patients without invasion beyond the hypopharynx or in the apex demonstrated on CT had favorable local prognosis when treated with radical irradiation.

Aged↗

T1-T2 squamous cell carcinoma of the glottic larynx treated with radiotherapy: a multivariate analysis of variables potentially influencing local control.

PURPOSE: To examine various parameters that might influence the probability of local control of T1-T2 glottic carcinoma treated with radiotherapy. METHODS AND MATERIALS: Two hundred forty-seven patients with invasive, previously untreated T1-T2 squamous cell carcinoma of the glottic larynx were treated with radiotherapy between May 1977 and December 1989. All patients had a minimum 2-year follow-up. To minimize treatment-related variables, only patients with T1 lesions treated once daily at 225 cGy per fraction and patients with T2 lesions treated once daily at 225 cGy per fraction or twice daily at 120 cGy per fraction were included. Surgical alternative, thickness of the neck at the posterior edge of the lateral fields, vocal cord mobility, anterior commissure involvement, gender, and T stage were evaluated in a multivariate analysis. RESULTS: The 5-year local control rates, calculated by the product-limit method, were T1a, 95%; T1b, 96%; T2a, 87%; and T2b, 76%. The 5-year local control rate for patients with T2 lesions treated with once-daily fractionation was 81% compared with 91% for those who received twice-a-day radiotherapy. For the endpoint of local control with irradiation, the surgical alternative (p = .020) and cord mobility (p = .001) were of independent prognostic significance. CONCLUSION: Of the variables analyzed, only vocal cord mobility and surgical alternative significantly influenced local control. Specifically, anterior commissure involvement and neck thickness did not affect local control.

Carcinoma, Squamous Cell↗

A multiple regression analysis for predicting local control of esophageal carcinoma treated by intracavitary irradiation.

A multiple regression analysis for predicting local control of esophageal carcinoma treated by intracavitary irradiation is reported. In phase I, the value of predicting local control (VPLC) was determined by five parameters: VPLC = 1.38950 - 0.01571 X (age) + 0.04517 X (tumor length) + 0.62167 X (stenosis) + 0.94811 X (deep ulcer) - 0.02969 X (Total dose of intracavitary irradiation). From correlations between VPLC and the local control observed in 19 phase I patients, it was determined that a VPLC value of 0.5 or more predicted local failure and a VPLC of less than 0.5 signified successful local control. In phase II, prediction of local failure or local control was made for another 24 patients by calculating VPLC, and 22 of the 24 cases (91.7%) were correctly predicted. These results indicate that VPLC is a useful index for predicting of local control after intracavitary irradiation in cases with esophageal carcinoma.

Brachytherapy↗

Postoperative radiotherapy for squamous cell carcinoma of the maxillary sinus: analysis of local control and late complications.

This retrospective study was conducted to analyze the local control and late complications in patients with squamous cell carcinoma of the maxillary sinus treated with postoperative radiation therapy following surgery. Between 1979 and 1998, 41 patients with squamous cell carcinoma of the maxillary sinus were treated with postoperative irradiation following partial or total maxillectomy. Tumor classification according to the TNM classification of the International Union Against Cancer (1997) was T2 in 6 patients, T3 in 21 patients, and T4 in 14 patients. Fourteen patients had negative surgical margins, 23 had microscopically positive margins, and 4 had grossly positive margins. Sixteen patients received preoperative intraarterial chemotherapy. The total dose to the primary tumor bed was 40-70 Gy (median: 54 Gy) with a fraction size of 2 Gy. The median follow-up time of the surviving patients was 93 months (range: 25-179 months). Local recurrence was observed in 17 patients (41%), and the 5-year actuarial overall survival and local control rates were 48% and 55%, respectively. In the univariate analysis, surgical margin status and total dose each had a statistically significant impact on local recurrence. For the patients with negative surgical margins, 8 of 9 (89%) patients achieved local control with a dose of 50-54 Gy, while 7 of 10 (70%) patients with microscopically positive margins achieved local control with a dose of 60-64 Gy. There were 11 late complications found in 9 patients; bone necrosis in 2, soft tissue necrosis in 2, trisumus: 2, cellulitis in 1, retinopathy in 1, and vision impairment in 3 patients. A total dose of 60 Gy or more was administered in all patients who suffered late complications except for 2 patients with vision impairment. These results indicated that an optimal dose of postoperative irradiation according to the surgical margin status was necessary to achieve local control for squamous cell carcinoma of the maxillary sinus following surgery. For patients with negative surgical margins, a total dose of 50-54 Gy in conventional fractionation was appropriate to achieve local control as well as to reduce late complications. On the other hand, a dose of 60 Gy or more was required for the patients with microscopic positive margins.

Adult↗

Does pathologic node status affect local control in patients with carcinoma of the head and neck treated with radical surgery and postoperative radiotherapy?

PURPOSE: To evaluate the effect of pathologic lymph node status and nodal stage on local control at the primary site in patients with advanced squamous cell carcinomas of the head and neck, treated with radical surgery and postoperative irradiation. METHODS AND MATERIALS: Fifty-seven patients with advanced squamous cell carcinomas of the oral cavity, oropharynx, hypopharynx, larynx, and supraglottic larynx were analyzed. All patients underwent resection of the primary lesion, neck dissection, and postoperative radiotherapy. Minimum follow-up was 2 years. The median dose to the primary tumor bed was 60.4 Gray (range 39.7-72.0). Besides pathologic nodal status (pN0 vs. pN+) and nodal stage, the following factors were analyzed for their impact on local control: age, gender, T stage, tumor grade, resection margins, interval from surgery to irradiation, dose to the primary site, and overall treatment time. RESULTS: The 3-year actuarial local control rate was 78%. When all patients were analyzed, nodal status (pN0 vs. pN+) did not affect control at the primary site (71% vs. 82%, p = 0.42). Nodal stage (pN0-N2a va. pN2b-N2c) was also not a significant factor for local control (74% vs. 82%, p = 0.57). When only patients with negative margins were analyzed, nodal status again did not impact on local control (79% vs. 90% for pN0 vs. pN+, p = 0.39). On univariate analysis, only tumor grade, margin status, and elapsed days were significant factors for local control. Local control was 85% for patients with negative margins vs. 60% for those with positive margins (p = 0.016). For patients with moderately and poorly differentiated tumors, local control was 86% as compared to 50% for patients with well-differentiated tumors (p = 0.007). When radiotherapy was completed within 50 days, local control was 93% as opposed to 63% for > 50 days (p = 0.016). On multivariate analysis, only margin status (p = 0.002) and tumor grade (p = 0.007) remained significant. CONCLUSION: We conclude that neither the presence of pathologically positive nodes nor nodal stage is a prognostically significant factor for local control in patients who have undergone radical surgery and postoperative radiotherapy for advanced squamous cell carcinomas of the head and neck. We do not recommend a change in treatment philosophy, such as an increase in dose to the primary site, based on the pathologic status of the neck.

Carcinoma, Squamous Cell↗

Preoperative radiation, surgical margins, and local control of extremity sarcomas of soft tissues.

The relationship between status of the surgical margin and local control of soft tissue sarcoma of the extremities by preoperative radiation therapy has been assessed in 132 consecutive patients from 1974 to 1988. The 5-year actuarial local control rate was 94% for all patients; the rates were 97% and 82% for the 104 tumors with negative margins and the 28 tumors with positive margins, respectively. The local control rate was independent of the extent of the negative margin. For primary sarcomas, the local control rates were 96%, 97%, and 100%, respectively, for margins that were negative at < or = 1 mm or > 1 mm, or the specimens were negative for tumor; for positive margins the result was 83%. The overall local control rate was lower (not significant) for recurrent than for primary sarcomas: 88% vs. 94%. On the other hand, when stratifying by margin status, no difference was observed in local control results, i.e.: (1) 97% and 91% for primary and recurrent tumors with negative margins, respectively, and (2) 83% and 80% for primary and recurrent tumors with positive margins, respectively. Local control was not significantly higher in those patients who were treated by surgical resection (S), radiation (RT), and re-excision of the previous tumor bed than in those whose radiation therapy was started after the biopsy and followed by one surgical resection. For primary sarcomas that were resected with negative margins the results were: 100% of 15 patients treated by S-RT-S and 96% of 75 patients treated by RT-S.

Actuarial Analysis↗

Cancer of the anal canal and local control.

Concomitant radiochemotherapy is the standard treatment of squamous cell carcinoma of the anal canal. It can afford a high local control rate though the same impact has not been observed on survival. A few reports have concerned the impact of local control on distant metastases and survival. From 1988 to 1998 at the "Divisione di Radioterapia" of the "Università Cattolica del S. Cuore" of Rome 30 patients with squamous cell carcinoma of the anal canal were treated for cure. Treatment consisted of two cycles of radiotherapy (23.4 Gy) with a 4-5 week split in each cycle. 5FU (100 mg/sqm/24 h) was administered in continuous infusion for the first 4 days of therapy; mitomycin C (10 mg/sqm bolus) was administered on day 1, 4-6 weeks after the end of cycle 2 of concomitant radiochemotherapy, patients received a boost of interstitial brachytherapy. Local control on T of all patients was 84% at 5 years. Six patients showed locoregional recurrence: 3 recurrences on T and 4 disease progressions in locoregional lymph nodes. 3 of 6 patients underwent salvage surgery. The initial extent of the disease, the patient's age and brachytherapy boost did not have a statistically significant influence on local control. Two of the 30 patients showed liver metastases, and at their appearance, one patient was free of local disease while the other showed locoregional progression after Miles' operation for salvage. The metastasis-free interval was not significantly influenced by local control, although at 5 years, 96% of patients with local control of T were free of metastases vs 75% of those with recurrence on T (p = 0.22). Overall actuarial survival at 5 years was 75%. The behavior of survival in our experience seemed to be significantly influenced by local control: in the group with local control, 5-year survival was 85% vs 40% of patients with local recurrence (p = 0.01).

Adult↗

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.

Adolescent↗