Dermatofibrosarcoma protuberans: treatment results of 35 cases.

BACKGROUND AND PURPOSE: This study evaluates the treatment results of patients with dermatofibrosarcoma protuberans. PATIENTS AND METHODS: Between August 1987 and July 1998, 35 consecutive patients with pathologically proved dermatofibrosarcoma protuberans received surgery with or without radiation therapy. Their treatment results were analyzed retrospectively. RESULTS: The patient ages ranged from 5 to 67 years (median 37 years). There were 24 males and 11 females. The anatomic sites of tumor were: trunk in 21, extremity in eight, and head and neck region in six. The maximal dimension of tumor ranged from 1.5 to 25 cm. Surgery techniques included local excision and wide excision with or without graft or flap. Adjuvant radiation therapy was given to 11 patients, with a dose ranging from 46 to 68 Gy (one pre-operative, ten post-operative). At a median follow-up of 50 months (range 11-131 months), there were 11 patients (nine patients without radiation therapy) who developed local failure. Salvage therapy (excision with or without radiation therapy) was given to all of them, and ten achieved disease control. Some patients had treatment-related moderate cosmetic or functional problems. CONCLUSIONS: Dermatofibrosarcoma protuberans is a malignancy of a high cure rate, and adjuvant radiation therapy can reliably decrease the local recurrence rate and prevent mutilation and functional deficit caused by repeated surgery.     

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.     

Significance of dose in postoperative radiotherapy for soft tissue sarcoma

PURPOSE: For soft tissue sarcoma, adjuvant postoperative radiotherapy improves the local control rate over surgery alone. However, the issue of a dose-control relationship is controversial and was addressed in this study. METHODS AND MATERIALS: We retrospectively reviewed the records of 775 consecutive patients who received postoperative external beam radiotherapy and used univariate and multivariate analysis to determine whether a dose-control relationship exists for the whole group and for specific high-risk subgroups. RESULTS: With a median follow-up of 12.3 years, overall local control rates were 82%, 80%, and 79% at 5, 10, and 15 years. Factors adverse for local control were positive resection margins; tumor location in the head and neck and deep trunk; presentation with locally recurrent disease; patient age >64 years; histopathologic subtype of malignant fibrous histiocytoma, neurogenic sarcoma or epithelioid sarcoma; and tumor size >10 cm. In multivariate analysis, radiation dose > or = 64 Gy vs. <64 Gy independently correlated with improved local control. Significant interactions were noted between increased effectiveness of a higher dose and presentation with locally recurrent disease, with head and neck and deep trunk tumor sites, and with positive or uncertain resection margins such that local control was specifically improved under these circumstances with doses on the order of 64-68 Gy compared with doses on the order of 60 Gy. Higher dose, however, did not completely abrogate the adverse effect of positive margins. CONCLUSION: After gross total resection, soft tissue sarcoma with features predictive of a higher than average local recurrence rate benefited from doses of 64-68 Gy compared with 60 Gy.     

Desmoid tumors: a 20-year radiotherapy experience

From 1964 through 1984, 45 patients were referred for radiation therapy for desmoid tumor. Fourteen patients had inoperable lesions, or gross residual disease after incomplete resection. Thirty-one patients received postoperative XRT for positive margins or concern about the adequacy of the margin. The minimum follow-up was 2 years, maximum 22 years, median 7.6 years. No patient was lost to follow-up. The primary site was head and neck in 5, upper extremity in 10, chest wall and back in 8, abdomen 2, pelvis 4, and lower extremity 16. All patients were treated with megavoltage radiation therapy using shrinking field techniques. Large fields received a median dose of 50 Gy in 25 fractions. Boost fields were used in the majority of patients to deliver an additional dose of 7 to 27 Gy. The range of total doses was 50 to 76.2 Gy. Three patients received a boost with neutrons. Analysis of patients with inoperable or gross residual showed tumor control in 10 of 14 with a median follow-up of 9.4 years. Resolution of gross disease occurred at a range of 1/2 to 64.3 months with a median of 9 months. There was no evidence of a higher probability of ultimate control at higher doses. Tumor control was equal for men and women. The ten patients with local control had doses from 50 to 76.2 Gy whereas the four patients with in field failures had tumor doses of 57 to 66.4 Gy. There was no difference in median dose for patients with local control (60.3 Gy) versus those with tumor recurrence (60 Gy). For subclinical disease, 31 patients receiving postoperative or preoperative XRT had a 77 percent probability of local control in spite of the history of multiple tumor recurrences; local control was achieved in 8 of 9 with negative or uncertain margins and 16 of 22 with positive margins. An analysis of local control as a function of the number of operations revealed that patients referred for adjuvant radiotherapy with no more than two operative procedures had an 88 percent probability of local control, versus 66 percent for more than two operative procedures. All grade 3 complications (defined as requiring surgical intervention or prolonged hospitalization) occurred with doses above 60 Gy. Management of recurrences was successful in 8 of the 11 patients and no patient has died of tumor.(ABSTRACT TRUNCATED AT 400 WORDS)     

74例隆突型皮肤纤维肉瘤的治疗与预后分析

Objective： To study treatment and prognostic factor in 74 patients with dermatofibrosarcoma protuberans. Methods： From August 1990 to November 1999, 74 patients with dermatofibrosarcoma protuberans （DFSP） confirmed by pathology were treated in Cancer Hospital of Sun Yat-sen University. 72 cases were given wide excision and 2 cases were given local excision. All of 74 cases, 52 cases had surgical resection alone, and 22 cases had surgical resection combined with radiotherapy. Total dose of radiotherapy was 50-70 Gy. Results： The rate of recurrence was 36.1% for all patients. The 5-year recurrence-free survival （RFS） rate was 66%. The 5-year recurrence-free survival rates for resection alone and combined with radiotherapy were 58% and 90%, respectively （P=-0.0187）. The 5-year recurrence-free survival rates for positive microscopic margins and negative microscopic margins were 57% and 75%, respectively （P=0.0468）. Conclusion： Post-operation radiotherapy is an effective treatment to decrease the recurrence rate for the patients with positive microscope, or the patients without suitable surgical treatment.     

Long-term outcomes for desmoid tumors treated with radiation therapy

PURPOSE: To evaluate long-term outcomes in patients with desmoid fibromatosis treated with radiation therapy (RT), with or without surgery. METHODS AND MATERIALS: Between 1965 and 2005, 115 patients with desmoid tumors were treated with RT at our institution. The median age was 29 years (range, 8-73 years). Of the patients, 41 (36%) received RT alone (median dose, 56 Gy) for gross disease, and 74 (64%) received combined-modality treatment (CMT) consisting of a combination of surgery and RT (median dose, 50.4 Gy). RESULTS: Median follow-up was 10.1 years. Local control (LC) rates at 5 and 10 years were 75% and 74%, respectively. On univariate analysis, LC was significantly influenced by tumor size (< or =5 cm vs. 5-10 cm vs. >10 cm) (p = 0.02) and age (< or = 30 vs. >30 years) (p = 0.02). There was no significant difference in LC for patients treated with RT alone for gross disease vs. CMT. For patients treated with CMT, only tumor size significantly influenced LC (p = 0.02). Patients with positive margins after surgery did not have poorer LC than those with negative margins (p = 0.38). Radiation-related complications occurred in 20 (17%) of patients and were associated with dose >56 Gy (p = 0.001), age < or =30 years (p = 0.009), and receipt of RT alone vs. CMT (p = 0.01). CONCLUSIONS: Desmoid tumors are effectively controlled with RT administered either as an adjuvant to surgery when resection margins are positive or alone for gross disease when surgical resection is not feasible. Doses >56 Gy may not be necessary to control gross disease and are associated with high rates of radiation-related complications.     

Adjuvant external beam radiation therapy with concurrent chemotherapy in the management of gallbladder carcinoma.

PURPOSE: This study was performed to evaluate the outcome of patients with gallbladder cancer who received postoperative concurrent chemotherapy and radiation therapy. METHODS AND MATERIALS: Curative resection followed by adjuvant combined modality therapy with external beam radiation therapy (EBRT) and chemotherapy was attempted in 21 consecutive gallbladder carcinoma (GBC) patients at the Mayo Clinic from 1985 through 1997. All patients received concurrent 5-fluorouracil during EBRT. EBRT fields encompassed the tumor bed and regional lymph nodes (median dose of 54 Gy in 1.8-2.0-Gy fractions). One patient received 15 Gy intraoperatively after EBRT. A retrospective analysis was performed for the end points of local control, distant failure, and overall survival. RESULTS: After maximal resection, 12 patients had no residual disease on pathologic evaluation, 5 had microscopic residual disease, and 4 had gross residual disease. One patient had Stage I disease, and 20 had Stage III-IV disease. With median follow-up of 5 years (range: 2.6-11.5 years), 5-year survival for the entire cohort was 33%. The 5-year survival rate of patients with Stage I-III disease was 65% vs. 0% for those with Stage IV disease (p < 0.02). For patients with no residual disease, 5-year survival was 64% vs. 0% for those with residual disease (p = 0.002). The median survival was 0.6, 1.4, and 5.1 years for patients with gross residual, microscopic residual, and no residual disease, respectively (p = 0.02). The 5-year local control rate for the entire cohort was 73%. Two-year local control rates were 0%, 80%, and 88% for patients with gross residual, microscopic residual, or no residual disease, respectively (p < 0.01). Five-year local control rates were 100% for the 6 patients who received total EBRT doses >54 Gy (microscopic residual, 3 patients; gross residual, 1 patient; negative but narrow margins, 2 patients) vs. 65% for the 15 who received a lower dose (3, gross residual; 2, microresidual; 10, negative margins). CONCLUSION: Patients with completely resected (negative margins) GBC followed by adjuvant EBRT plus 5-fluorouracil chemotherapy had a relatively favorable prognosis, with a 5-year survival rate of 64%. These results seem to be superior to historical surgical controls from the Mayo Clinic and other institutions, which report 5-year survival rates of approximately 33% with complete resection alone. Both tumor stage and extent of resection seemed to influence survival and local control. More aggressive measures using current cancer therapies and integration of new cancer treatment modalities will be required to favorably impact on the poor prognosis of patients with Stage IV or subtotally resected GBC. Additional investigation leading to earlier diagnosis is warranted, because most patients with GBC present with advanced disease.     

Role of brachytherapy in malignant melanoma: a preliminary report

From August 1979 to May 1986, various brachytherapy techniques were applied at Memorial Sloan Kettering Cancer Center (MSKCC) in an adjuvant setting with/without surgery and external radiation therapy in the management of advanced malignant melanoma. Thirty-three patients underwent brachytherapy procedures. The patients' ages ranged from 35 to 82 years, with a median age of 56 years. Fourteen patients had disease localized to the implant site, whereas 19 patients also had disseminated disease elsewhere. The indications for implant were residual gross disease (21), microscopically positive margins (3), and histologically negative but clinically close margins of resection (9). Local control at the implant site was noted in 80% of patients at 6 months and 42% of patients at 1 year; two patients had reached 54 months and 72 months with no evidence of disease. Local control was 100% (9/9) in patients with histologically negative but clinically close margins of resection, and 48% (11/23) with microscopically positive margins and/or gross residual disease. Complications were seen as follows: delay in wound healing (1), wound infections (4), radiation enteritis (1), small bowel obstruction (1). The present study suggests that brachytherapy combined with surgery can achieve a good local control in patients with negative but clinically close margins of resection. In patients with gross residual disease who are at a high risk for local recurrence, approximately one-half can be locally controlled with this approach. These preliminary results should be tested in a prospective controlled study.     

Long-term outcome after postmastectomy radiation therapy for breast cancer patients at high risk for local-regional recurrence

PURPOSE: Postmastectomy radiation therapy is often recommended for patients at high risk for local-regional recurrence after mastectomy. However, long-term outcomes after radiation therapy are not well described. PATIENTS AND METHODS: Between 1977 and 1992, 221 patients at high risk for local-regional recurrence of breast cancer after mastectomy were treated with radiation therapy, with or without adjuvant systemic therapy. Patients were classified as high risk because of T3 or T4 tumors (14%), positive lymph nodes (29%), close or positive margins of resection (15%), or multiple risk factors (39%); 4% did not meet current criteria for radiation therapy. The median age of patients was 51 years. Radiation therapy consisted of 45 to 50.4 Gy to the chest wall in 1.8 to 2.0 Gy fractions. The regional lymph nodes were treated in 187 patients (85%). There were 151 patients (68%) who received adjuvant chemotherapy. Patients who received chemotherapy were younger (median age, 48 years vs 64 years) and had more positive lymph nodes (median, 5 vs 1) than patients not receiving chemotherapy. Adjuvant hormonal therapy was utilized in 116 patients (53%). The median follow-up was 4.3 years. RESULTS: The actuarial 10-year local-regional failure rate was 11% (95% CI: 6.5% to 16.7%). The site of first failure was distant metastases in 75 patients (34%), local-regional recurrence in 11 patients (5%), and both sites in three patients (1%); 60% had no evidence of disease at last follow-up. Of the patients who presented with local-regional recurrence as first failure, nine patients (82%) subsequently developed metastatic disease. The median time to local-regional first failure was 1.3 years. The median time to distant metastases after local-regional first failure was 0.3 years. DISCUSSION: Postmastectomy radiation therapy is associated with an 89% rate of local-regional control in this high-risk population. Patients who experience a local-regional recurrence after radiation therapy are at a very high risk for metastatic disease. Radiation therapy after mastectomy is recommended to optimize local-regional control for high-risk breast cancer patients.     

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.     

Dermatofibrosarcoma protuberans: Recurrence is related to the adequacy of surgical margins

Introduction

The aim of the study was to investigate the results of surgical treatment in primary and recurrent dermatofibrosarcoma protuberans (DFSP), with respect to local tumor control.

Patients and methods

Thirty-eight patients were treated between 1971 and 2005 at the University Medical Center Groningen (UMCG). Thirty patients presented with primary disease (79%) and 8 patients with locally recurrent disease (21%). The treatment consisted of surgical resection and in case of marginal or positive resection margins (R1 resection) adjuvant radiotherapy.

Results

Adequate surgical margins as a single modality was associated with 100% local control in all primary DFSPs. Two patients whose resection specimens had microscopically positive resection margins had withdrawn from adjuvant radiotherapy and developed local recurrence (LF rate 7%). Two of the 8 patients referred with a local recurrence developed a second recurrence (LF rate 25%); one of these patients developed distant disease and ultimately died of systemic disease. None of the five patients with DFSP-FS developed LF after treatment at the UMCG.After a median follow-up of 89 (12–271) months, the 10-year disease-free survival was 85% and the 10-year disease specific survival was 100%.

Conclusion

After wide surgical resection of a DFSP or DFSP-FS, or an R1 resection combined with adjuvant radiotherapy the risk of local recurrence is extremely low.     

Radiotherapy for local control of osteosarcoma

PURPOSE: Local control of osteosarcoma in patients for whom a resection with satisfactory margins is not achieved can be difficult. This study evaluated the efficacy of radiotherapy (RT) in this setting. METHODS AND MATERIALS: We identified 41 patients in our sarcoma database with osteosarcomas that either were not resected or were excised with close or positive margins and who underwent RT with external beam photons and/or protons at our institution between 1980 and 2002. Patient charts were reviewed to assess local control, progression-free survival, metastasis-free survival, and overall survival. RESULTS: The anatomic sites treated were head/face/skull in 17, extremity in 8, spine in 8, pelvis in 7, and trunk in 1. Of the 41 patients, 27 (65.85%) had undergone gross total tumor resection, 9 (21.95%) subtotal resection, and 5 (12.2%) biopsy only. The radiation dose ranged from 10 to 80 Gy (median 66). Twenty-three patients (56.1%) received a portion of their RT with protons. Chemotherapy was given to 35 patients (85.4%). Of the 41 patients, 27 (65.85%) were treated for localized disease at primary presentation, 10 (24.4%) for local recurrence, and 4 (9.8%) for metastatic disease. The overall local control rate at 5 years was 68% +/- 8.3%. The local control rate according to the extent of resection was 78.4% +/- 8.6% for gross total resection 77.8% +/- 13.9% for subtotal resection, and 40% +/- 21.9% for biopsy only (p < 0.01). The overall survival rate according to the extent of resection was 74.45% +/- 9.1% for gross total resection, 74.1% +/- 16.1% for subtotal resection, and 25% +/- 21.65% for biopsy only (p < 0.001). Patients with either gross or subtotal resection had a greater rate of local control, survival, and disease-free survival compared with those who underwent biopsy only at 5 years (77.7% +/- 7.5% vs. 40% +/- 21% [p <0.001], 73.9% +/- 8.1% vs. 25% +/- 21.6% [p <0.001], and 51.9% +/- 9.1% vs. 25% +/- 21.6% [p <0.01], respectively). Overall survival was better in patients treated at primary presentation (78.8% +/- 8.6% compared with 54% +/- 17.3% for recurrence) p <0.05). No definitive dose-response relationship for local control of tumor was seen, although the local control rate was 71% +/- 9% for 32 patients receiving doses > or =55 Gy vs. 53.6% +/- 20.1% for 9 patients receiving <55 Gy (p = 0.11). Of 15 patients with tumors >5.3 cm, 9 received doses > or =55 Gy and the local control rate was 80% +/- 17.9%, and 6 received doses <55 Gy with a local control rate of only 50% +/- 25% at 5 years (p = 0.16). Among patients who underwent gross total resection, the local control rate was 77.5% +/- 9.95% in 22 patients with negative margins vs 66.7% +/- 27.2% in 3 patients with positive margins (p = 0.54). Two patients had unknown margin status. CONCLUSION: RT can help provide local control of osteosarcoma for patients in whom surgical resection with widely, negative margins is not possible. It appears to be more effective in situations in which microscopic or minimal residual disease is being treated.     

调强适形放疗治疗成人脑膜旁横纹肌肉瘤

目的:横纹肌肉瘤(rhabdomyosarcoma,RMS)多见于儿童,在成人很少见,特别是头颈部脑膜旁横纹肌肉瘤,预后较儿童差;探讨调强适形放疗（intensity modulated radiation therapy,IMRT）治疗成人脑膜旁横纹肌肉瘤的临床结果。方法:从2008年12月31日至2015年7月10日我科连续收治11例均经病理证实的无远处转移成人脑膜旁横纹肌肉瘤,女性7例,男性4例,中位年龄36岁（21~55岁）,出现临床症状至确诊中位时间8周（4~12周）,主要症状为头痛、鼻堵、溢泪、眼眶疼痛、治疗眼球突出、颅神经麻痹等非特异性症状;患者均行增强MRI和CT检查,临床分期:Ⅱ期2例,Ⅲ期9例,其中诊断时7例有淋巴结转移,均无远处转移。病理类型:腺泡型横纹肌肉瘤7例,胚胎型横纹肌肉瘤4例;治疗方式:手术+放疗+化疗治疗8例,放疗+化疗治疗2例,手术+放疗1例;化疗方案均为IE方案（异环磷酰胺,表阿霉素）;11例全部行调强适形放疗,10例行辅助放疗（60~66 Gy）,1例给予根治量放疗（69.96 Gy）;Kaplan-Meier法计算3年累积总生存率。结果:全组中位随访16个月（8~88个月）,Kaplan-Meier法计算3年累积总生存率约为47.1%,估计平均生存时间48.7个月,中位生存时间18个月,最长1例无病生存88个月,3年局部控制率为72.7%;失败类型:远处失败共5例,其中远处转移同时伴局部和淋巴结失败1例（未做手术）,远处转移和淋巴结同时失败1例（未做淋巴结区照射）,远处转移和局部复发1例（未做手术）,2例单纯远处转移（1例未做化疗,1例仅作2周期巩固化疗）,1例单纯淋巴结失败（未做淋巴结区照射）。死亡5例,均有远处转移者。结论:成人脑膜旁RMS是侵袭性很强恶性肿瘤,诊断时多侵犯颅底、颅内或眼眶内,很难手术彻底切除,手术联合IMRT放疗可获得较高局部控制率;尽管采用综合治疗其预后仍然较儿童横纹肌肉瘤差,主要失败方式为远处转移。     

Results of Breast-Conserving Therapy for Ductal Carcinomain situ: The Kyoto University Experiences

BACKGROUND: The purpose of this study was to evaluate the results of breast-conserving therapy (BCT), defined as the combination of breast-conserving surgery with axillary dissection and definitive radiation therapy for ductal carcinoma in situ (DCIS). METHODS: Between November 1987 and March 1998, 33 patients with DCIS undergoing BCT at our hospital were examined. The mean age was 48. All patients underwent quadrantectomy or wide excision as well as axillary dissection. Radiation therapy consisted of 50 Gy to the ipsilateral whole breast. Boost irradiation of 10 Gy was given to 15 patients with close or positive margins. Nearly all patients received adjuvant chemotherapy with 5-fluorouracil or its derivatives and adjuvant endocrine therapy with tamoxifen for 2 years. RESULTS: The minimum and median follow-up periods were 32 and 80 months, respectively. All patients but one were followed. Only one patient had a non-invasive local recurrence, 23 months after her operation. This patient was salvaged with simple mastectomy. Her prognostic index score was 8. The five-year local control rate was 97%. No serious acute or late complications were noted. CONCLUSION: The results of this retrospective study substantiate favorable data and appear to confirm the efficacy and reasonable local recurrence rate of BCT for the treatment of DCIS.     

Intraoperative radiation therapy for recurrent head-and-neck cancer: the UCSF experience

PURPOSE: To review a single-institutional experience with the use of intraoperative radiation therapy (IORT) for recurrent head-and-neck cancer. METHODS AND MATERIALS: Between 1991 and 2004, 137 patients were treated with gross total resection and IORT for recurrence or persistence of locoregional cancer of the head and neck. One hundred and thirteen patients (83%) had previously received external beam radiation as a component of definitive therapy. Ninety-four patients (69%) had squamous cell histology. Final surgical margins were microscopically positive in 56 patients (41%). IORT was delivered using either a modified linear accelerator or a mobile electron unit and was administered as a single fraction to a median dose of 15 Gy (range, 10-18 Gy). Median follow-up among surviving patients was 41 months (range, 3-122 months). RESULTS: The 1-year, 2-year, and 3-year estimates of in-field control after salvage surgery and IORT were 70%, 64%, and 61%, respectively. Positive margins at the time of IORT predicted for in-field failure (p = 0.001). The 3-year rates of locoregional control, distant metastasis-free survival, and overall survival were 51%, 46%, and 36%, respectively. There were no perioperative fatalities. Complications included wound infection (4 patients), orocutaneous fistula (2 patients), flap necrosis (1 patient), trismus (1 patient), and neuropathy (1 patient). CONCLUSIONS: Intraoperative RT results in effective disease control with acceptable toxicity and should be considered for selected patients with recurrent or persistent cancers of the head and neck.     

Spinal cord ependymomas in adults: analysis of 15 cases

This retrospective analysis was performed to examine the outcome of patients with spinal cord ependymomas treated with surgery and postoperative radiation therapy between 1982 and 1998. There were 10 male and 5 female patients, ranging from 16 to 74 years of age with a median age of 38 years. Surgery was gross total resection in 2 patients, subtotal resection in 10, biopsy in 3. All patients received radiation therapy with a total dose of 40-56 Gy. The 5 and 10 year overall survival rates were 83.3 and 83.3%, respectively. Twelve patients are still alive at a median follow-up period of 70 months. Of the 15 patients, 6 developed recurrent disease on follow-up. The median time to recurrence was 45 months (range: 24-80 months). Local failure within the initial irradiated volume occurred in 3 out of 6 patients who received less than 45 Gy and 2 out of 8 patients treated with more than 45 Gy. Four out of the six failures were salvaged with additional treatment. Re-irradiation was used as a part of salvage or sole treatment in 3 cases. The patient who was salvaged with radiation therapy only died of disease progression 41 months following recurrence and the other two who received a combination of surgery, radiotherapy or chemotherapy were still alive 57 and 30 months following relapse. The present study shows that surgery and post-operative radiation treatment for spinal ependymoma patients resulted in high survival rates. Patients with residual disease after surgery should be treated with radiation therapy with a dose of more than 45 Gy. Re-irradiation may be the treatment of choice for recurrent patients having less than complete resection or no surgery.     

Carcinoma of the extrahepatic biliary system--results of primary and adjuvant radiotherapy

From 1975-1983, 20 patients with primary carcinomas of the gallbladder (GB) or extrahepatic bile ducts (EHBD) were irradiated with curative intent at the Washington University Medical Center and affiliated hospitals. Of the 17 patients with EHBD cancer, one received adjuvant irradiation after gross resection with positive microscopic margins. All others received primary irradiation for unresectable tumors, or for gross residual tumor after incomplete resection. The 8 patients receiving Ir192 implant in addition to external radiation showed improved (p = 0.06) survival compared to the 9 receiving external only: median 15 months (range 1.5-34 + months) versus 7 months (range 2.5-21 months). Failures were predominantly local-regional, with only one patient showing metastatic spread without known local-regional tumor. Adjuvant radiation therapy was given after cholecystectomy to 3 patients with GB cancers showing tumor extension beyond the serosa or to regional lymphatics. Of these, two survived at 22+ and 27+ months; the third died of local recurrence at 5 1/2 months. Although numbers are small, these results appear to support the use of adjuvant radiotherapy in patients with microscopic residual GB cancer. Aggressive local and regional radiotherapy can add to the quality and length of survival in both patient groups, that is, those with resectable lesions with high likelihood of microscopic residual, and also those with unresectable or gross residual disease after surgery.     

Long-term follow-up of axillary node-positive breast cancer patients receiving adjuvant tamoxifen alone: patterns of recurrence

Purpose: To determine the patterns, incidence and risk factors for local-regional recurrence in patients with Stage II and III breast cancer treated with adjuvant tamoxifen alone, without adjuvant radiation.Material and Methods: The records of patients referred to the London Regional Cancer Centre with a diagnosis of breast cancer between 1980–1989 were reviewed. During this time period, it was the policy of the institution to omit local-regional radiation to patients receiving adjuvant systemic therapy. One hundred and fifty axillary node-positive Stage II and III breast cancer patients received adjuvant tamoxifen alone without postoperative local-regional radiation; these patients form the basis of this report.Results: Median follow-up was 67 months for the entire patient group and 85 months for the living patients. During this time, 42% of patients developed a recurrence, 22% first recurred in local-regional sites. The total incidence of local-regional recurrence (including those patients who first relapsed with systemic metastases) was 30%. Of the segmental mastectomy patients, 13% had recurrences in the intact breast. Of the modified radical mastectomy patients, 10% developed chest wall recurrences. Five percent of recurrences were first in the axilla and 6% in the supraclavicular nodes. Five-year actuarial survival for the entire patient group was 79% and disease-free survival was 60%, with a median disease-free survival time of 87 months. Five-year local-regional relapse-free survival was 76%. Five-year local-regional relapse-free survival was < 76% for those patients with 4 or more positive axillary nodes, regardless of tumor size. On univariable analysis, positive resection margins, number of positive axillary nodes, menopausal status, and negative estrogen and progesterone receptors were significant for isolated local-regional recurrence. On multivariable analysis, only positive resection margins and negative receptors remained significant. In terms of regional recurrence specifically, negative estrogen and progesterone-receptor status and positive resection margins were, again, prognostically significant.Conclusions: Postmenopausal women receiving adjuvant tamoxifen who have positive resection margins, ≥ 4 positive axillary nodes and/or negative estrogen and progesterone receptors, are at higher risk of local and regional recurrence and should, therefore, receive local-regional radiation.     

Radical surgical resection and high-dose intraoperative radiation therapy (HDR-IORT) in patients with recurrent gynecologic cancers

OBJECTIVE: To determine the outcome for patients with recurrent gynecologic tumors treated with radical resection and combined high-dose intraoperative radiation therapy (HDR-IORT). METHODS AND MATERIALS: Between November 1993 and June 1998, 17 patients with recurrent gynecologic malignancies underwent radical surgical resection and high-dose-rate brachytherapy. The mean age of the study group was 49 years (range 28-72 years). The site of the primary tumor was the cervix in 9 (53%) patients, the uterus in 7 (41%) patients, and the vagina in 1 (6%) patient. The treatment for the primary disease was surgery with or without adjuvant radiation in 14 (82%) patients and definitive radiation in 3 (18%) patients. The current surgery consisted of exenterative surgery in 10 (59%) patients and tumor resection in 7 (41%) patients. Complete gross resection was achieved in 13 (76%) patients. The mean HDR-IORT dose was 14 Gy (range 12-15). Additional radiation in the form of permanent Iodine-125 implant was given to 3 of 4 patients with gross residual disease. The median peripheral dose was 140 Gy. RESULTS: With a median follow-up of 20 months (range 3-65 months), the 3-year actuarial local control (LC) rate was 67%. In patients with complete gross resection, the 3-year LC rate was 83%, compared to 25% in patients with gross residual disease, p < 0.01. The 3-year distant metastasis disease-free and overall survival rates were 54% and 54%, respectively. The complications were as follows: gastrointestinal obstruction, 4 (24%); wound complications, 4 (24%); abscesses, 3 (18%); peripheral neuropathy, 3 (18%); rectovaginal fistula, 2 (12%); and ureteral obstruction, 2 (12%). CONCLUSION: Radical surgical resection and combined IORT for patients with recurrent gynecologic tumors seems to provide a reasonable local-control rate in patients who have failed prior surgery and/or definitive radiation. Patient selection is very important, however, as only those patients with complete gross resection at completion of surgery appear to benefit most from this radical approach in the salvage setting.     

Patients with early stage invasive cancer with close or positive margins treated with conservative surgery and radiation have an increased risk of breast recurrence that is delayed by adjuvant systemic therapy

Purpose: The association between a positive resection margin and the risk of ipsilateral breast tumor recurrence (IBTR) after conservative surgery and radiation is controversial. The width of the resection margin that minimizes the risk of IBTR is unknown. While adjuvant systemic therapy may decrease the risk of an IBTR in all patients, its impact on patients with positive or close margins is largely unknown. This study examines the interaction between margin status, margin width, and adjuvant systemic therapy on the 5- and 10-year risk of IBTR after conservative surgery and radiation.

Methods and Materials: A series of 1,262 patients with clinical Stage I or II breast cancer were treated by breast-conserving surgery, axillary node dissection, and radiation between March 1979 and December 1992. The median follow-up was 6.3 years (range 0.1–15.6). The median age was 55 years (range 24–89). Clinical size was T1 in 66% and T2 in 34%. Seventy-three percent of patients were node-negative. Only 5% of patients had tumors that were EIC-positive. Forty-one percent had a single excision, and 59% had a reexcision. The final margins were negative in 77%, positive in 12%, and close (≤ 2 mm) in 11%. The median total dose to the tumor bed was 60 Gy with negative margins, 64 Gy with close margins, and 66 Gy with positive margins. Chemotherapy ± tamoxifen was used in 28%, tamoxifen alone in 20%, and no adjuvant systemic therapy in 52%.

Results: The 5-year cumulative incidence (CI) of IBTR was not significantly different between patients with negative (4%), positive (5%), or close (7%) margins. However, by 10 years, a significant difference in IBTR became apparent (negative 7%, positive 12%, close 14%, p = 0.04). There was no significant difference in IBTR when a close or positive margin was involved by invasive tumor or DCIS. Reexcision diminished the IBTR rate to 7% at 10 years if the final margin was negative; however, the highest risk was observed in patients with persistently positive (13%) or close (21%) (p = 0.02) margins. The median interval to failure was 3.7 years after no adjuvant systemic therapy, 5.0 years after chemotherapy ± tamoxifen, and 6.7 years after tamoxifen alone. This delay to IBTR was observed in patients with close or positive margins, with little impact on the time to failure in patients with negative margins. The 5-year CI of IBTR in patients with close or positive margins was 1% with adjuvant systemic therapy and 13% with no adjuvant therapy. However, by 10 years, the CI of IBTR was similar (18% vs. 14%) due to more late failures in the patients who received adjuvant systemic therapy.

Conclusion: A negative margin (> 2 mm) identifies patients with a very low risk of IBTR (7% at 10 years) after conservative surgery and radiation. Patients with a close margin (≤ 2 mm) are at an equal or greater risk of IBTR as with a positive margin, especially following a reexcision. A margin involved by DCIS or invasive tumor has the same increased risk of IBTR. A reexcision of an initially close or positive margin that results in a negative final margin reduces the risk of IBTR to that of an initially negative margin. A close or positive margin is associated with an increased risk of IBTR even in patients who are EIC-negative or receiving higher boost doses of radiation. The median time to IBTR is delayed; however, the CI is not significantly decreased by adjuvant systemic therapy in patients with close or positive margins—the 5 year results in these patients underestimate their ultimate risk of recurrence.