Original Article
The Role of Adjuvant Radiotherapy in the Local Management of Desmoplastic Melanoma B. Ashleigh Guadagnolo, MD, MPH1; Victor Prieto, MD, PhD2; Randal Weber, MD3; Merrick I. Ross, MD4; and Gunar K. Zagars, MD1
BACKGROUND: In the current study, the authors sought to evaluate outcomes, specifically with respect to adjuvant radiotherapy (RT), for patients with desmoplastic melanoma. METHODS: The records of 130 consecutive patients who presented between 1985 and 2009 with nonmetastatic desmoplastic melanoma and were treated curatively with either surgery alone (59 patients; 45%) or surgery and postoperative RT (71 patients; 55%) were retrospectively reviewed. Ages ranged from 21 years to 97 years (median age, 66 years). The location of the primary tumor was in the head and neck region in 62% of patients. Only 5 patients (4%) had lymph node involvement at the time of presentation. RESULTS: The median follow-up was 6.6 years (range, 11 months-24 years). Overall survival rates at 5 years and 10 years were 69% and 53%, respectively. Disease-specific survival rates were 84% and 80%, respectively, at 5 years and 10 years. The actuarial rate of local recurrence was 17% at 5 years and beyond. Of the patients who underwent surgery without receiving postoperative RT, 14 (24%) experienced local recurrence. Of the 71 patients treated with surgery and postoperative RT, 5 (7%) experienced local recurrence. In a Cox multivariate regression model, improved local control was significantly associated with the receipt of postoperative RT (P 5.009). CONCLUSIONS: Surgery followed by postoperative RT appears to provide superior C 2013 American local control compared with surgery alone for patients with desmoplastic melanoma. Cancer 2014;120:1361–8. V Cancer Society. KEYWORDS: desmoplastic melanoma, adjuvant irradiation, local control, prognostic factors, perineural invasion.
INTRODUCTION Desmoplastic melanoma is relatively rare variant of malignant melanoma that exhibits distinct clinical behavior from nondesmoplastic melanoma. The overall prognosis for patients with desmoplastic melanoma is believed to be favorable compared with patients with conventional melanoma subtypes in that distant metastases and regional lymph node metastases are relatively infrequent compared with nondesmoplastic melanoma.1–3 However, some investigators have suggested that local recurrence (LR) rates for desmoplastic melanoma are higher than for conventional melanoma4–6 and correspondingly emphasized the importance of aggressive local therapy in determining the overall disease-specific outcomes for patients with this malignancy.7,8 The role of radiotherapy (RT) as an adjuvant to wide local excision remains uncertain. Although it has been suggested that wide local excision is adequate to eradicate localized desmoplastic melanoma,9 many reports have suggested that adjuvant RT improves local control for this disease.3,4,10,11 Given the relative rarity of desmoplastic melanoma, all of the published literature for this disease to the best of our knowledge consists of retrospective reviews of clinical outcomes and potential prognostic factors. The data are conflicting with regard to whether neurotropism, a feature that is common although not universal in patients with desmoplastic melanoma, portends an increased risk of local failure. Similarly, a head and neck location of the primary tumor has been shown to be a potential poor prognostic factor, which is of particular relevance because these tumors commonly occur in a head and neck location. Finally, of particular recent interest is the prognostic extent of desmoplasia in the tumor (ie, whether the tumor is pure desmoplastic melanoma or whether the extent of desmoplasia occurs as some component of an otherwise nondesmoplastic melanoma lesion [combined=mixed desmoplastic melanoma]).12,13 Investigators have reported on various implications of the extent of desmoplasia with regard to whether it affects the risks of LR or disease-specific death. We
Corresponding author: B. Ashleigh Guadagnolo, MD, MPH, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 97, Houston, TX 77030; Fax: (713) 563-2331; [email protected] 1 Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas; 2Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas; 3Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas; 4Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
See editorial on pages 1315-8 and related article on pages 1369-78. DOI: 10.1002/cncr.28415, Received: April 2, 2013; Revised: June 20, 2013; Accepted: July 1, 2013, Published online October 18, 2013 in Wiley Online Library (wileyonlinelibrary.com)
Cancer
May 1, 2014
1361
Original Article
undertook a review of our clinical experience at the University of Texas MD Anderson Cancer Center (MDACC) for patients with localized desmoplastic melanoma who were treated definitively with either surgery or surgery followed by postoperative irradiation. The goal of the current study was to report on outcomes, specifically with respect to adjuvant RT, as well as prognostic factors for patients with this disease. MATERIALS AND METHODS Between 1985 and 2009, 130 consecutive patients with nonmetastatic desmoplastic melanoma presented for definitive local management at MDACC. Review of the medical records and RT charts that constitute the data for the current study commenced after approval was obtained from our Institutional Review Board. Patients underwent a full history and physical examination, routine blood tests, and appropriate imaging before receiving treatment. A histologic diagnosis of desmoplastic melanoma was confirmed in each case through a review of the pathology slides by a pathologist at MDACC at the time of presentation. Patient and Tumor Characteristics
Of the patients in this study, 85 (65%) were men and 45 (35%) were women ranging in age from 21 years to 97 years (median, 66 years). The anatomic distribution of the primary lesions were as follows: 29 (22%) on the scalp, 44 (34%) on the face, 7 (5%) on the neck, 19 (15%) on the trunk, 26 (20%) on the upper extremity, and 5 (4%) on the lower extremity. Thus, 62% of the patients presented with a head and neck presentation of desmoplastic melanoma. Twenty of the 130 patients (15%) presented to MDACC with a recurrent presentation of their disease, with 13 patients having undergone 1 prior surgery, 6 patients having had 2 prior surgeries, and 1 patient having had 3 prior surgeries for their disease. None of the patients who developed disease recurrence had received prior RT. Of the 117 patients for whom information regarding Clark level was available, 44 patients (38%) had Clark level IV disease and 73 (62%) had Clark level V disease. American Joint Commission on Cancer14 T classifications were as follows: 1 patient (1%) with T1 disease, 15 patients (13%) with T2 disease, 32 patients (27%) with T3 disease, and 69 patients (59%) with T4 disease. The median tumor thickness of the primary lesion was 5.1 mm (range, 1 mm-30 mm). Patients were designated as having pure desmoplastic melanoma (100 patients; 77%) if their pathology 1362
report indicated that there were no other invasive melanoma histologic subtypes in the specimen. Patients whose pathology report indicated that their melanoma contained only a desmoplastic component or desmoplastic features in the presence of other histologic subtypes were coded as having combined=mixed desmoplastic melanoma (30 patients; 23%). For the current study, the extent of desmoplasia as a percentage of the specimen could not be retrospectively determined in all patients. Information regarding perineural invasion was available for 101 patients and of those, 66 (65%) exhibited perineural invasion. Of these, 5 patients presented with named nerve invasion. Of those 89 patients for whom the presence of ulceration was evaluated, it was found to be present in 9 patients (10%). Treatment
The decision to use adjuvant RT for patients with desmoplastic melanoma was at the discretion of the treating surgeon and radiation oncologist for each patient and practice patterns varied among practitioners over the years encompassed by this study. Management of the primary lesion was accomplished with surgery alone in 59 patients (45%) and surgery followed by postoperative RT in 71 patients (55%). Surgery was as follows: wide local excision in 122 patients (94%), excisional biopsy in 2 patients, total rhinectomy in 2 patients, lower lip excision and segmental mandibulectomy in 2 patients, amputation of a toe in 1 patient, and wide local excision plus orbital exenteration in 1 patient. After definitive surgery, 121 patients (93%) had negative resection margins and 9 patients (7%) had positive or uncertain resection margins. There was no significant correlation noted between the presence of positive or uncertain resection margins and the receipt of postoperative RT (P 5 .413). Specifically, 3 of the 9 patients with positive=uncertain resection margins received postoperative RT and 6 did not. Eighty-three patients (64%) underwent a plastic surgery closure procedure as part of their definitive surgical management. Assessment of regional lymphatics was as follows. A total of 64 patients were found to have no clinical evidence of lymph node involvement, and the lymph node regions were subsequently observed; and 56 patients underwent sentinel lymph node biopsy, none of whom were found to have lymph node involvement. Two patients underwent excisional biopsy of a clinically suspicious lymph node mass, one of which was confirmed to be metastatic disease. Three patients underwent selective lymphadenectomy, one of who had confirmed lymph node disease at the time of presentation. Five patients Cancer
May 1, 2014
Radiotherapy for Desmoplastic Melanoma/Guadagnolo et al
Figure 1. Disease-specific, disease-free, and overall survival rates are shown for the entire cohort.
underwent full dissection of the regional lymphatics, 3 of whom were confirmed to have lymph node involvement at the time of diagnosis. Only 5 patients (4%) were found to have lymph node involvement at the time of presentation, 4 with cervical lymph node involvement and 1 with involvement of the inguinal lymph node basin. Of those with lymph node involvement, 4 were among the patients with pure desmoplastic melanoma and 1 had mixed desmoplastic melanoma. Of the 71 patients who received RT, 68 patients were treated with 30 Gray (Gy) in 5 fractions delivered twice weekly (on a Monday=Thursday or Tuesday=Friday schedule) over 2.5 weeks. Two patients received 36 Gy in twice-weekly fractions of 6 Gy per fraction. One patient was treated with 60 Gy in 30 fractions of 200 centigray per fraction. The median total RT dose was 30 Gy (range, 30 Gy-60 Gy) and the median fractional dose was 6 Gy per fraction (range, 2 Gy-6 Gy per fraction). Treatment techniques included appositional electron fields in 52 patients (73%), photon fields in 13 patients (18%), matched photon and electron fields in 5 patients (7%), and intensity-modulated RT in 1 patient (1%). A margin of 3 cm to 4 cm around the surgical site was attempted when possible. Occasionally, wider fields were used to treat regional nerves. Of the 71 patients who received RT to the primary tumor site, 18 (25%) also received RT to the draining lymph node region.
Follow-Up and Statistical Analysis
Follow-up was calculated from the date of surgical resection. The median follow-up of those patients who were Cancer
May 1, 2014
still alive at the time of last follow-up was 6.6 years (range, 11 months-24 years). The Kaplan-Meier method15 was used to calculate the actuarial curves for overall survival (OS), diseasespecific survival (DSS), local control, distant metastatic recurrence, disease-free survival (DFS), and complication rates. The log-rank statistic was used to test for the significance of differences between the curves. Multivariate regression analysis was performed using the Cox proportional hazards model.15 Differences between percentages for categorical variables were analyzed using the chisquare statistic or the Fisher exact test as appropriate. Surgical complications were defined as complications from surgery that could arise within 3 months of the date of surgery (regardless of whether the patient received RT) or that were explicitly deemed a surgical complication by a surgeon. Surgical and RT-related complications were scored as mild (self-limiting and requiring no treatment), moderate (requiring conservative medical management), and severe (requiring surgical intervention or hospitalization. RESULTS Survival
At time of last follow-up, 53 patients had died (41%) with a median survival of 11.8 years. A total of 23 patients (18%) died of their desmoplastic melanoma. The actuarial OS rates at 5 years and 10 years were 69% and 53%, respectively. The DSS rates were 84% and 80%, respectively, at 5 years and 10 years and the DFS rates were 72% and 70%, respectively, at 5 years and 10 years. The last recurrence occurred at 8.7 years from the date of surgical resection. Figure 1 shows the curves for OS, DSS, and DFS. Table 1 shows the univariate DSS. Lymph node involvement at the time of diagnosis and positiveuncertain resection margins were found to be adversely prognostic for DSS (Table 1). On the multivariate analysis, lymph node involvement continued to predict a poorer DSS (P < .0001) as did positive=uncertain resection margins (P 5 .03), even when adjusting for receipt of postoperative RT. Patterns of Disease Recurrence and Survival Implications
Of the 130 patients, 35 (27%) developed disease recurrence. Nineteen patients (15%) experienced LR. The actuarial LR rate was 17% at 5 years and beyond. The interval between surgery and LR ranged from 1 month to 60 months (median, 7 months); all instances of LR were evident by 5 years. Of all 19 patients who developed LR, 1363
Original Article TABLE 1. Univariate Analysis for DSS Characteristic Entire cohort Sex Male Female Extent of desmoplastic component Pure desmoplastic Mixed desmoplastic T classification T1 T2 T3 T4 Lymph nodes at diagnosis No Yes Site Head and neck Trunk/extremity Presented with recurrent disease after prior surgery No Yes Primary local management Surgery Surgery plus RT Final resection margins Negative Positive/uncertain
No. (% of Total)
10-Year DSS Rate
P
130
80%
85 (65) 45 (35)
82% 78%
.46
100 (77) 30 (23)
78% 86%
.28
1 (1) 15 (12) 32 (25) 69 (53)
100% 100% 74% 79%
.26a
125 (96) 5 (4)
80%
The Role of Adjuvant Radiotherapy in the Local Management of Desmoplastic Melanoma B. Ashleigh Guadagnolo, MD, MPH1; Victor Prieto, MD, PhD2; Randal Weber, MD3; Merrick I. Ross, MD4; and Gunar K. Zagars, MD1
BACKGROUND: In the current study, the authors sought to evaluate outcomes, specifically with respect to adjuvant radiotherapy (RT), for patients with desmoplastic melanoma. METHODS: The records of 130 consecutive patients who presented between 1985 and 2009 with nonmetastatic desmoplastic melanoma and were treated curatively with either surgery alone (59 patients; 45%) or surgery and postoperative RT (71 patients; 55%) were retrospectively reviewed. Ages ranged from 21 years to 97 years (median age, 66 years). The location of the primary tumor was in the head and neck region in 62% of patients. Only 5 patients (4%) had lymph node involvement at the time of presentation. RESULTS: The median follow-up was 6.6 years (range, 11 months-24 years). Overall survival rates at 5 years and 10 years were 69% and 53%, respectively. Disease-specific survival rates were 84% and 80%, respectively, at 5 years and 10 years. The actuarial rate of local recurrence was 17% at 5 years and beyond. Of the patients who underwent surgery without receiving postoperative RT, 14 (24%) experienced local recurrence. Of the 71 patients treated with surgery and postoperative RT, 5 (7%) experienced local recurrence. In a Cox multivariate regression model, improved local control was significantly associated with the receipt of postoperative RT (P 5.009). CONCLUSIONS: Surgery followed by postoperative RT appears to provide superior C 2013 American local control compared with surgery alone for patients with desmoplastic melanoma. Cancer 2014;120:1361–8. V Cancer Society. KEYWORDS: desmoplastic melanoma, adjuvant irradiation, local control, prognostic factors, perineural invasion.
INTRODUCTION Desmoplastic melanoma is relatively rare variant of malignant melanoma that exhibits distinct clinical behavior from nondesmoplastic melanoma. The overall prognosis for patients with desmoplastic melanoma is believed to be favorable compared with patients with conventional melanoma subtypes in that distant metastases and regional lymph node metastases are relatively infrequent compared with nondesmoplastic melanoma.1–3 However, some investigators have suggested that local recurrence (LR) rates for desmoplastic melanoma are higher than for conventional melanoma4–6 and correspondingly emphasized the importance of aggressive local therapy in determining the overall disease-specific outcomes for patients with this malignancy.7,8 The role of radiotherapy (RT) as an adjuvant to wide local excision remains uncertain. Although it has been suggested that wide local excision is adequate to eradicate localized desmoplastic melanoma,9 many reports have suggested that adjuvant RT improves local control for this disease.3,4,10,11 Given the relative rarity of desmoplastic melanoma, all of the published literature for this disease to the best of our knowledge consists of retrospective reviews of clinical outcomes and potential prognostic factors. The data are conflicting with regard to whether neurotropism, a feature that is common although not universal in patients with desmoplastic melanoma, portends an increased risk of local failure. Similarly, a head and neck location of the primary tumor has been shown to be a potential poor prognostic factor, which is of particular relevance because these tumors commonly occur in a head and neck location. Finally, of particular recent interest is the prognostic extent of desmoplasia in the tumor (ie, whether the tumor is pure desmoplastic melanoma or whether the extent of desmoplasia occurs as some component of an otherwise nondesmoplastic melanoma lesion [combined=mixed desmoplastic melanoma]).12,13 Investigators have reported on various implications of the extent of desmoplasia with regard to whether it affects the risks of LR or disease-specific death. We
Corresponding author: B. Ashleigh Guadagnolo, MD, MPH, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 97, Houston, TX 77030; Fax: (713) 563-2331; [email protected] 1 Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas; 2Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas; 3Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas; 4Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
See editorial on pages 1315-8 and related article on pages 1369-78. DOI: 10.1002/cncr.28415, Received: April 2, 2013; Revised: June 20, 2013; Accepted: July 1, 2013, Published online October 18, 2013 in Wiley Online Library (wileyonlinelibrary.com)
Cancer
May 1, 2014
1361
Original Article
undertook a review of our clinical experience at the University of Texas MD Anderson Cancer Center (MDACC) for patients with localized desmoplastic melanoma who were treated definitively with either surgery or surgery followed by postoperative irradiation. The goal of the current study was to report on outcomes, specifically with respect to adjuvant RT, as well as prognostic factors for patients with this disease. MATERIALS AND METHODS Between 1985 and 2009, 130 consecutive patients with nonmetastatic desmoplastic melanoma presented for definitive local management at MDACC. Review of the medical records and RT charts that constitute the data for the current study commenced after approval was obtained from our Institutional Review Board. Patients underwent a full history and physical examination, routine blood tests, and appropriate imaging before receiving treatment. A histologic diagnosis of desmoplastic melanoma was confirmed in each case through a review of the pathology slides by a pathologist at MDACC at the time of presentation. Patient and Tumor Characteristics
Of the patients in this study, 85 (65%) were men and 45 (35%) were women ranging in age from 21 years to 97 years (median, 66 years). The anatomic distribution of the primary lesions were as follows: 29 (22%) on the scalp, 44 (34%) on the face, 7 (5%) on the neck, 19 (15%) on the trunk, 26 (20%) on the upper extremity, and 5 (4%) on the lower extremity. Thus, 62% of the patients presented with a head and neck presentation of desmoplastic melanoma. Twenty of the 130 patients (15%) presented to MDACC with a recurrent presentation of their disease, with 13 patients having undergone 1 prior surgery, 6 patients having had 2 prior surgeries, and 1 patient having had 3 prior surgeries for their disease. None of the patients who developed disease recurrence had received prior RT. Of the 117 patients for whom information regarding Clark level was available, 44 patients (38%) had Clark level IV disease and 73 (62%) had Clark level V disease. American Joint Commission on Cancer14 T classifications were as follows: 1 patient (1%) with T1 disease, 15 patients (13%) with T2 disease, 32 patients (27%) with T3 disease, and 69 patients (59%) with T4 disease. The median tumor thickness of the primary lesion was 5.1 mm (range, 1 mm-30 mm). Patients were designated as having pure desmoplastic melanoma (100 patients; 77%) if their pathology 1362
report indicated that there were no other invasive melanoma histologic subtypes in the specimen. Patients whose pathology report indicated that their melanoma contained only a desmoplastic component or desmoplastic features in the presence of other histologic subtypes were coded as having combined=mixed desmoplastic melanoma (30 patients; 23%). For the current study, the extent of desmoplasia as a percentage of the specimen could not be retrospectively determined in all patients. Information regarding perineural invasion was available for 101 patients and of those, 66 (65%) exhibited perineural invasion. Of these, 5 patients presented with named nerve invasion. Of those 89 patients for whom the presence of ulceration was evaluated, it was found to be present in 9 patients (10%). Treatment
The decision to use adjuvant RT for patients with desmoplastic melanoma was at the discretion of the treating surgeon and radiation oncologist for each patient and practice patterns varied among practitioners over the years encompassed by this study. Management of the primary lesion was accomplished with surgery alone in 59 patients (45%) and surgery followed by postoperative RT in 71 patients (55%). Surgery was as follows: wide local excision in 122 patients (94%), excisional biopsy in 2 patients, total rhinectomy in 2 patients, lower lip excision and segmental mandibulectomy in 2 patients, amputation of a toe in 1 patient, and wide local excision plus orbital exenteration in 1 patient. After definitive surgery, 121 patients (93%) had negative resection margins and 9 patients (7%) had positive or uncertain resection margins. There was no significant correlation noted between the presence of positive or uncertain resection margins and the receipt of postoperative RT (P 5 .413). Specifically, 3 of the 9 patients with positive=uncertain resection margins received postoperative RT and 6 did not. Eighty-three patients (64%) underwent a plastic surgery closure procedure as part of their definitive surgical management. Assessment of regional lymphatics was as follows. A total of 64 patients were found to have no clinical evidence of lymph node involvement, and the lymph node regions were subsequently observed; and 56 patients underwent sentinel lymph node biopsy, none of whom were found to have lymph node involvement. Two patients underwent excisional biopsy of a clinically suspicious lymph node mass, one of which was confirmed to be metastatic disease. Three patients underwent selective lymphadenectomy, one of who had confirmed lymph node disease at the time of presentation. Five patients Cancer
May 1, 2014
Radiotherapy for Desmoplastic Melanoma/Guadagnolo et al
Figure 1. Disease-specific, disease-free, and overall survival rates are shown for the entire cohort.
underwent full dissection of the regional lymphatics, 3 of whom were confirmed to have lymph node involvement at the time of diagnosis. Only 5 patients (4%) were found to have lymph node involvement at the time of presentation, 4 with cervical lymph node involvement and 1 with involvement of the inguinal lymph node basin. Of those with lymph node involvement, 4 were among the patients with pure desmoplastic melanoma and 1 had mixed desmoplastic melanoma. Of the 71 patients who received RT, 68 patients were treated with 30 Gray (Gy) in 5 fractions delivered twice weekly (on a Monday=Thursday or Tuesday=Friday schedule) over 2.5 weeks. Two patients received 36 Gy in twice-weekly fractions of 6 Gy per fraction. One patient was treated with 60 Gy in 30 fractions of 200 centigray per fraction. The median total RT dose was 30 Gy (range, 30 Gy-60 Gy) and the median fractional dose was 6 Gy per fraction (range, 2 Gy-6 Gy per fraction). Treatment techniques included appositional electron fields in 52 patients (73%), photon fields in 13 patients (18%), matched photon and electron fields in 5 patients (7%), and intensity-modulated RT in 1 patient (1%). A margin of 3 cm to 4 cm around the surgical site was attempted when possible. Occasionally, wider fields were used to treat regional nerves. Of the 71 patients who received RT to the primary tumor site, 18 (25%) also received RT to the draining lymph node region.
Follow-Up and Statistical Analysis
Follow-up was calculated from the date of surgical resection. The median follow-up of those patients who were Cancer
May 1, 2014
still alive at the time of last follow-up was 6.6 years (range, 11 months-24 years). The Kaplan-Meier method15 was used to calculate the actuarial curves for overall survival (OS), diseasespecific survival (DSS), local control, distant metastatic recurrence, disease-free survival (DFS), and complication rates. The log-rank statistic was used to test for the significance of differences between the curves. Multivariate regression analysis was performed using the Cox proportional hazards model.15 Differences between percentages for categorical variables were analyzed using the chisquare statistic or the Fisher exact test as appropriate. Surgical complications were defined as complications from surgery that could arise within 3 months of the date of surgery (regardless of whether the patient received RT) or that were explicitly deemed a surgical complication by a surgeon. Surgical and RT-related complications were scored as mild (self-limiting and requiring no treatment), moderate (requiring conservative medical management), and severe (requiring surgical intervention or hospitalization. RESULTS Survival
At time of last follow-up, 53 patients had died (41%) with a median survival of 11.8 years. A total of 23 patients (18%) died of their desmoplastic melanoma. The actuarial OS rates at 5 years and 10 years were 69% and 53%, respectively. The DSS rates were 84% and 80%, respectively, at 5 years and 10 years and the DFS rates were 72% and 70%, respectively, at 5 years and 10 years. The last recurrence occurred at 8.7 years from the date of surgical resection. Figure 1 shows the curves for OS, DSS, and DFS. Table 1 shows the univariate DSS. Lymph node involvement at the time of diagnosis and positiveuncertain resection margins were found to be adversely prognostic for DSS (Table 1). On the multivariate analysis, lymph node involvement continued to predict a poorer DSS (P < .0001) as did positive=uncertain resection margins (P 5 .03), even when adjusting for receipt of postoperative RT. Patterns of Disease Recurrence and Survival Implications
Of the 130 patients, 35 (27%) developed disease recurrence. Nineteen patients (15%) experienced LR. The actuarial LR rate was 17% at 5 years and beyond. The interval between surgery and LR ranged from 1 month to 60 months (median, 7 months); all instances of LR were evident by 5 years. Of all 19 patients who developed LR, 1363
Original Article TABLE 1. Univariate Analysis for DSS Characteristic Entire cohort Sex Male Female Extent of desmoplastic component Pure desmoplastic Mixed desmoplastic T classification T1 T2 T3 T4 Lymph nodes at diagnosis No Yes Site Head and neck Trunk/extremity Presented with recurrent disease after prior surgery No Yes Primary local management Surgery Surgery plus RT Final resection margins Negative Positive/uncertain
No. (% of Total)
10-Year DSS Rate
P
130
80%
85 (65) 45 (35)
82% 78%
.46
100 (77) 30 (23)
78% 86%
.28
1 (1) 15 (12) 32 (25) 69 (53)
100% 100% 74% 79%
.26a
125 (96) 5 (4)
80%
