Local Control Rates For Patients Research Articles

Clinicopathologic features and long-term outcome of patients with medullary breast carcinoma managed with breast-conserving therapy (BCT)

The purpose of this study is to compare the clinical characteristics and outcome of medullary carcinoma to infiltrating ductal carcinoma of the breast in a large cohort of conservatively managed patients with long-term follow-up. Chart records of patients with invasive breast cancer managed with breast-conserving therapy (BCT) at the therapeutic radiology facilities of Yale University School of Medicine before 2001 were reviewed. Forty-six cases (1971-2001) were identified with medullary histology; 1,444 patients with infiltrating ductal carcinoma served as a control group. The medullary cohort presented at a younger age with a higher percentage of patients in the 35 years or younger age group (26.1% vs. 6.6%, p < 0.00001). Twelve patients with medullary histology underwent genetic screening, and 6 patients were identified with deleterious mutations. This group showed greater association with BRCA1/2 mutations compared with screened patients in the control group (50.0% vs. 15.8%, p = 0.0035). The medullary cohort was also significantly associated with greater T stage and tumor size (37.0% vs. 17.2% T2, mean size 3.2 vs. 2.5 cm, p = 0.00097) as well as negative ER (84.9% vs. 37.6%, p < 0.00001) and PR (87.5% vs. 48.1%, p = 0.00001) status. As of February 2003, median follow-up times for the medullary and control groups were 13.9 and 14.0 years, respectively. Although breast relapse-free rates were not significantly different (76.7% vs. 85.2%), 10-year distant relapse-free survival in the medullary cohort was significantly better than in the control group (94.9% vs. 77.5%, p = 0.028). Despite poor clinicopathologic features, patients with medullary histology demonstrate favorable long-term distant relapse-free survival. Local control rates of patients with medullary and infiltrating ductal carcinoma are comparable. These findings suggest that patients diagnosed with medullary carcinoma are appropriate candidates for BCT and are associated with favorable long-term prognosis.

Influence of site on the therapeutic ratio of adjuvant radiotherapy in soft-tissue sarcoma of the extremity

The ultimate goal of adjuvant radiotherapy (RT) in soft-tissue sarcoma of the extremity is to improve the therapeutic ratio by increasing local control while minimizing morbidity. Most efforts in trying to improve this ratio have focused on the sequencing of RT and surgery, with little attention to the potential influence of the tumor site. The purpose of this study was to determine the influence of tumor site on local control and complications in a group of patients with primary high-grade soft-tissue sarcoma of the extremity treated at a single institution with postoperative RT. Between July 1982 and December 2000, 369 adult patients with primary high-grade soft-tissue sarcoma of the extremity were treated with limb-sparing surgery and postoperative RT. Patients who underwent surgery or RT outside our institution were excluded. The tumor site was the upper extremity (UE) in 103 (28%) and the lower extremity (LE) in 266 (72%). The tumor was < or = 5 cm in 98 patients (27%), and the microscopic margins were positive in 44 (12%). Of the 369 patients, 104 (28%) underwent postoperative external beam RT (EBRT), 233 (63%) postoperative brachytherapy (BRT), and 32 underwent a combination (9%); 325 (88%) received a "conventional" radiation dose, defined as 60-70 Gy for EBRT, 45 Gy for BRT, and 45-50 Gy plus 15-20 Gy for EBRT plus BRT. Complications were assessed in terms of wound complications requiring repeat surgery, fracture, joint stiffness, edema, and Grade 3 or worse peripheral nerve damage. The UE and LE groups were balanced with regard to age, depth, margin status, and type of RT (EBRT vs. BRT +/- EBRT). However, more patients in the UE group had tumors < or = 5 cm and more received a conventional radiation dose (p = 0.01 and P = 0.03, respectively). With a median follow-up of 50 months, the 5-year actuarial rate of local control, distant relapse-free survival, and overall survival for the whole population was 82% (95% confidence interval [CI], 77-86%), 61% (95% CI, 56-66%), and 71% (95% CI, 66-76%), respectively. The 5-year local control rate in patients with UE STS was 70% (95% CI, 60-80%) compared with 86% (95% CI, 81-91%) for LE STS (p = 0.0004). On multivariate analysis, an UE site (p = 0.001; relative risk [RR], 3; 95% CI, 2-5) and positive resection margins (p = 0.02; RR, 2; 95% CI, 1-4) were significant predictors of poor local control. The RT type or radiation dose, age, tumor depth, and size were not significant predictors of local control. The 5-year wound reoperation rate was 1% (95% CI, 0-3) in the UE compared with 11% (95% CI, 7-15) in the LE (p = 0.002). On multivariate analysis, the UE site retained its significance as a predictor of low wound complications (p = 0.001; RR, 0.08; 95% CI, 0.01-0.7). The site did not significantly influence the incidence of fracture (p = 0.7), joint stiffness (p = 0.2), edema (p = 0.5), or Grade 3 or worse peripheral nerve damage (p = 0.3). The UE site is associated with a greater rate of local recurrence compared with the LE. This difference was independent of other variables and could not be accounted for by an imbalance between the two groups. With a lower wound complication rate associated with an UE site, it would be of interest to determine whether preoperative RT and/or intensity-modulated RT can increase the local control in UE sarcomas, thus improving the therapeutic ratio.

Radiation therapy for aggressive fibromatosis (desmoid tumors): Results of a national Patterns of Care Study

After a general Patterns of Care Study (PCS) the German Cooperative Group on Radiotherapy for Benign Diseases (GCG-BD) initiated a multicenter cohort study to analyze the radiation therapy practice for aggressive fibromatosis. In 2002 a PCS was conducted in all German radiotherapy (RT) institutions by mailing a standardized structured questionnaire, to assess patients accrual, number, pretreatment, treatment indications, RT, and target volume concepts for irradiation in aggressive fibromatosis. In addition, the treatment outcome of individual patients was evaluated. The PCS was structured and analyzed according to the model for quality assessment by Donabedian in three major components: structure, process, and outcome evaluation. A total of 101 institutions returned the questionnaire: 52.7% reported satisfactory clinical data and experience for inclusion in this analysis. A total accrual rate of 278 patients per year was reported with median number of 2 cases (1-7 cases) per institution. Satisfactory data for a long-term clinical evaluation was reported for 345 patients from 19 different institutions. The applied total doses ranged between 36 and 65 Gy (median, 60 Gy). The local control rate was 81.4% in primary RT for unresectable tumors and 79.6% in postoperative RT. No acute or late radiation toxicities > Grade 2 (RTOG) were observed. No clear dose-response relationship could be established, but there was a tendency toward a lower local control rate in patients with a higher number of operative procedures before RT and patients treated for recurrent aggressive fibromatosis. This study comprises the largest database of cases reported for RT in aggressive fibromatosis. Radiotherapy provides a high local control rate in the postoperative setting and in unresectable tumors. This PCS may serve as a starting point for a national or international prospective multicenter study or registry, or both.

Clinical results of proton beam therapy for cancer of the esophagus

To present the results of proton beam therapy for patients with esophageal cancer. This study reviewed 46 patients with esophageal cancer who were treated between 1985 and 1998 using proton beams with or without X-rays. All patients had locoregionally confined disease; all but one had squamous cell carcinoma. Of the 46 patients, 40 received combinations of X-rays (median, 48 Gy) and protons (median, 31.7 Gy) as a boost. The median total dose of combined X-ray and proton radiation for the 40 patients was 76.0 Gy (range, 69.1-87.4 Gy). The remaining 6 patients received only proton beam therapy (median, 82.0 Gy; range, 75-89.5 Gy). The 5-year actuarial survival rate for the 46 patients, patients with T1 (n = 23), and those with T2-T4 (n = 23) was 34%, 55%, and 13%, respectively. The 5-year disease-specific survival rate for the 46 patients, those with T1, and those with T2-T4 was 67%, 95%, and 33%, respectively. The 5-year local control rate for patients with T1 and T2-T4 lesions was 83% and 29%, respectively. The site of the first relapse was locoregional for 16 patients and distant organs for 2 patients. The results suggest that proton beam therapy is an effective treatment for patients with locally confined esophageal cancer. Additional studies are required to determine the optimal total dose, fractionation schedule, and best combinations of protons and conventional X-rays with or without chemotherapy.

Radiotherapy and prognostic factors for thymoma: A retrospective study of 175 patients

To assess the factors that predict local control and survival in patients with thymoma treated with adjuvant radiotherapy (RT) and suggest strategies for optimizing adjuvant RT. The study population comprised 47 patients with noninvasive thymoma and 128 patients with invasive thymoma. Treatment was surgery in 175 patients and radiotherapy in 169 patients; 25 patients also received adjuvant chemotherapy. The clinical factors (age, histologic features, stage, presence of myasthenia gravis) and therapeutic factors (extent of operation, irradiation dose, and field size) were retrospectively recorded and accessed using multivariate analysis. The overall survival rate at 5 and 10 years was 86.4% and 80.6%, respectively. Only 2 patients had a relapse in the noninvasive group. None died of thymoma during the study period. The patients with invasive disease had a 5- and 10-year disease-free survival rate of 64.4% and 55.6%, respectively, with 24 intrathoracic failures, 14 extrathoracic failures, and 8 combined failures. The univariate and multivariate analyses showed that Mosaoka stage and extent of resection were the important prognostic factors for patient with invasive thymoma. The 5-year survival rate and local control rate was 96% and 96% for Stage II, 77.8% and 56.4% for Stage III, 56.6% and 42.7% for Stage lVa, and 35.6% and 21.6% for Stage IVb (p < 0.0001 among different stage groups), respectively. The 5-year local control rate in patients with the tumor bed irradiated was 68.2%, comparable to the group treated with an extended RT field (66.6%). Age, histopathologic findings, radiation dose, and presence of myasthenia gravis were not statistically significant prognostic factors. Disease stage and extent of resection affected the prognosis of invasive thymoma patients. Extending the radiation field prophylactically was not associated with greater local control and is of questionable value for patients with invasive thymoma.

Intracranial meningeal hemangiopericytoma: the role of radiotherapy: report of 29 cases and review of the literature.

The current retrospective study was undertaken to evaluate the treatment outcomes of patients with meningeal hemangiopericytoma (M-HPC), to define the role of radiotherapy in the management of the disease, and to report on the patterns of failure. The medical records of 29 patients with nonmetastatic M-HPC treated at The University of Texas M. D. Anderson Cancer Center (Houston, TX) between August 1979 and March 1999 were reviewed. Fifteen patients (52%) underwent macroscopic total resection ('gross total resection' [GTR]), 10 (34%) underwent subtotal resection (STR), and 4 (14%) had unknown extent of surgery. Ten of 24 patients received adjuvant radiotherapy. The 5, 10, and 15-year overall survival rates were 85%, 68%, and 43%, respectively. The local control rates at 5 and 10 years were 68% and 22%, respectively. Two patients experienced disease recurrence at another intracranial site. Sixteen patients (55%) developed extraneural metastases. Four patients (14%) developed spinal metastases. The 5-, 10-, and 15-year distant metastasis-free survival rates were 80%, 46%, and 21%, respectively. The 5-year local control rates for patients treated with GTR and STR were 84% and 38%, respectively (P=0.003). Of the 15 patients treated with GTR, 3 received adjuvant radiotherapy as part of their initial treatment. Malignant disease did not recur locally in these three patients. However, the effect of the adjuvant radiotherapy on local control was not statistically significant. M-HPCs can recur locally or distantly in the neural axis or as extraneural distant metastases. Based on literature review and the patterns of failure in the current series, attempting to perform GTR followed by limited-field radiotherapy appeared to represent a reasonable approach for the initial management of M-HPC.

Role of radiotherapy in Ewing tumors

The objective of this review article is to outline the role of radiotherapy in a curative multimodal treatment concept. We have analyzed the data from major multi-institutional prospective trials in Ewing tumors for to evaluate the impact of radiotherapy on local control and survival. Surgery yields in general better local control and survival figures as compared to radiotherapy. The efficacy of radiotherapy as compared to surgery varies among the studies and seems to be dependent on patient selection and sequencing with chemotherapy. Combined local therapy (surgery plus post- or pre-operative radiotherapy) has yielded excellent local control rates in patients with high-risk lesions (e.g., pelvic tumors); although not proven by randomized studies, an impact on survival is likely. Indications for post-operative radiotherapy are unradical or marginal resections and poor histological response. In patients with chest wall primaries, adjuvant hemithorax irradiation has reduced the relapse rate significantly. Pre-operative irradiation offers theoretical advantages. Bilateral lung irradiation (as consolidation after chemotherapy) seems to improve prognosis in patients with metastases at diagnosis. Patients with high-risk lesions probably benefit from combined local treatment (surgery plus radiotherapy). Improving local control after radiotherapy is a major issue for future studies, and sequencing with chemotherapy seems to be critical factor. The possible curative potential of radiotherapy in metastatic disease requires further investigation.

Intraoperative high-dose-rate brachytherapy for paranasal sinus tumors

Purpose Advanced and recurrent tumors of the paranasal sinuses can be difficult to irradiate to high doses with standard external beam radiotherapy (EBRT), conventional brachytherapy, or intraoperative electron beams. We, therefore, explored the role of intraoperative high-dose-rate brachytherapy (IOHDR) as a boost to EBRT in primary tumors or as sole adjuvant treatment in recurrent disease. Methods and materials Between 1992 and 1998, 34 patients with locally advanced tumors arising in the paranasal sinuses were treated with IOHDR after maximal surgical excision. Twenty-seven patients with new primaries underwent gross resection and 10–12.5 Gy IOHDR followed by 45–50 Gy EBRT. Seven previously irradiated (45–63 Gy) patients with recurrent disease were treated with 15–20 Gy of IOHDR alone after gross excision. Local control and overall survival were analyzed using the Kaplan-Meier method and compared using the log–rank test. Results After a mean follow-up of 6 years (range 34–120 months), the 1-, 3-, and 5-year actuarial survival rate was 80%, 62%, and 44%, respectively. The overall local control rate at 1 and 5 years was 75% and 65%, respectively, and distant failure was documented in 44% of patients. Subgroup analysis revealed that the presence of gross disease after surgical resection was the strongest prognosticator, with a 5-year survival and local control rate of 17% and 50%, respectively, compared with 60% and 68%, respectively, for microscopic disease. The local control rates of patients with new primaries were similar to those of patients treated for recurrent disease (63% vs. 71%), probably because gross residual disease occurred only in the group of patients with new primaries. The addition of EBRT to IOHDR increased the 5-year disease-free survival rate from 27% to 44% but had no effect on local control (64% vs. 65%). Conclusion IOHDR can be safely used to deliver a high radiation dose to locally advanced and recurrent tumors in the paranasal sinuses. In an attempt to improve outcome, we are now adding limited-dose EBRT (20–30 Gy) after 17.5 Gy of IOHDR in previously irradiated patients and increasing the EBRT dose for both microscopic (50–54 Gy) and gross residual disease (60–65 Gy) after 15 Gy of IOHDR in previously unirradiated patients. Chemosensitization should also be considered in previously irradiated patients and in those with gross residual disease. Interstitial boosting techniques, which can deliver higher doses at depth, should also be considered in patients with gross residual disease.

Radiotherapy of early-stage glottic cancer: analysis of factors affecting prognosis.

This study is a retrospective analysis of 134 patients treated with radiotherapy at our hospital. The sample included 88 stage T1 and 46 stage T2 patients. Sixty-two patients had anterior commissure involvement, 37 patients had impaired vocal cord mobility, and 24 patients had supraglottic or subglottic extension. Irradiation was given, with the dose ranging from 60 to 72 Gy. Laryngectomy was the main salvage treatment for local recurrence. The 5-year initial and final local control rates were 71% and 83%, and the 10-year initial and final local control rates were 69% and 80%, comparable to the results of other series. The 5-year rate of overall survival with final larynx preservation was 77%. Multivariate analysis revealed that anterior commissure involvement is prognostic of a poor outcome in patients with T1 glottic cancer. Further subgroup analysis revealed that a fraction size of > 200 cGy could overcome the negative impact of anterior commissure involvement and significantly improve the 5-year local control rate in T1 patients (100% at > 200 cGy versus 45% at < or = 200 cGy; p = .04). Subglottic extension of the glottic cancer predicted poor outcome in T2 patients. The 5-year local control rates of patients with and without subglottic extension were 9% and 77%, respectively (p < .001). According to our results, radiotherapy with a fraction size of > 200 cGy is recommended for T1 disease with anterior commissure involvement. For patients with T2 disease and subglottic extension, radiotherapy alone produces poor results. Further improvement of outcomes by other treatment strategies needs to be investigated.

Radiation therapy for aggressive fibromatosis (desmoid tumors) — results of a national patterns of care study

Radiation therapy for aggressive fibromatosis (desmoid tumors) — results of a national patterns of care study

Radiotherapy for patients with early-stage glottic carcinoma: univariate and multivariate analyses in a group of consecutive, unselected patients.

Radiotherapy (RT) has a remarkable success rate in the treatment of patients with glottic carcinoma. The objectives of the current study were to assess the results in a group of consecutive patients with comparable characteristics who were treated with RT (6-megavolt photon linear accelerator) and to determine the prognostic factors that may influence local control in patients with early-stage glottic carcinoma. The impact on local control of tobacco smoking and second primary malignancies also was investigated. Four hundred ten patients with T1-T2 squamous cell carcinoma of the glottis who were treated between 1986 and 2001 were analyzed retrospectively with regard to local control and overall survival. Potential prognostic factors for local control were evaluated with univariate and multivariate models. The impact of technologic advances also was evaluated. The 5-year and 10-year overall survival rates were 83% and 63.5%, respectively. The overall 10-year local control rate for patients with T1-T2 glottic carcinoma was 89%. The median time to recurrence was 7 months. Univariate analysis showed that tumor category, tumor size, macroscopic appearance of the lesion, RT fraction size, persistent edema, year of RT treatment, unchanged dysphonia, and surgical option all had a significant influence on local control; whereas multivariate analysis showed that only persistent dysphonia and year of RT treatment were significantly associated with increased local control. A 22.2% rate of second primary malignancies was reported: second primary tumors were the major cause of death in the patients studied. Only 2 patients died of laryngeal carcinoma; 304 patients were alive with their disease in complete remission, 1 patient was alive with recurrent laryngeal carcinoma after undergoing salvage surgery, and 103 patients died of either intercurrent disease or a second primary tumor. The use of a 6-megavolt photon linear accelerator achieved a high rate of local control in patients with T1-T2 glottic carcinoma. Dysphonia and the year of RT treatment were the most important prognostically significant factors for patient outcome. The occurrence of a second primary tumor was the most frequent cause of death, especially among patients who did not stop smoking after a diagnosis of glottic carcinoma.

Postoperative radiotherapy increases locoregional control of patients with stage IIIA non–small-cell lung cancer treated with induction chemotherapy followed by surgery

Purpose To determine the effectiveness of postoperative radiotherapy (RT) in patients with Stage IIB and Stage IIIA non–small-cell lung cancer (NSCLC) treated with induction chemotherapy followed by surgery. Methods and materials We retrospectively reviewed the treatment records of 98 patients (58 men and 40 women; median age 61 years, range 31–91) with Stage IIB and Stage IIIA NSCLC who were treated with induction chemotherapy followed by surgery at our institution between January 1990 and December 2000. Patients were grouped by treatment (chemotherapy/surgery alone vs. chemotherapy/surgery/RT), by disease stage and nodal classification. The rates of local control (LC), disease-specific survival, disease-free survival, and overall survival (OS) were calculated using the Kaplan-Meier method. Results Of the 98 patients, 40 had Stage IIB and 58 had Stage IIIA. The clinical disease stage and N stage were significantly greater in those patients who underwent RT than in those who did not; however, no statistically significant differences were identified in the additional characteristics between those receiving and not receiving RT within each stage or nodal group. The overall 5-year actuarial LC rate was 81% in the RT group and 54% in the chemotherapy/surgery–alone group ( p = 0.07). Postoperative RT significantly improved the 5-year LC rate in patients with Stage IIIA disease (from 35% to 82%, p = 0.01). Postoperative RT did not significantly improve the 5-year OS rate (30% with RT vs. 49% without) for all patients or for patients with Stage IIIA disease. The disease-specific survival and disease-free survival rates did not differ between the treatment groups. Patients who responded to induction chemotherapy had a significantly greater 5-year OS rate (49%) than did those with stable or progressive disease (22%, p = 0.003). Conclusion Postoperative RT in patients with Stage IIIA NSCLC treated with induction chemotherapy followed by surgery significantly improved LC without improving OS. Significantly improved survival was observed in all patients who responded to induction chemotherapy compared with those with stable or progressive disease.

Results of low- and high-dose-rate interstitial brachytherapy for T3 mobile tongue cancer

Purpose: To evaluate the treatment results of low-dose-rate (LDR) and high-dose-rate (HDR) interstitial brachytherapy (ISBT) for T3 mobile tongue cancer. Material and methods: Between 1974 and 1992, 61 patients with T3 mobile tongue cancer were treated with LDR ISBT using 192Ir hairpins with or without single pins. In addition, between 1991 and 1999, 14 patients were treated with HDR ISBT. For nine patients treated with ISBT alone, the total dose was 59–94 Gy (median 72 Gy) within one week in LDR ISBT and 60 Gy/10 fractions/5 days in HDR ISBT. For 66 patients treated with a combination therapy of external beam radiotherapy (EBRT) and ISBT, the total dose was 12.5–60 Gy (median 30 Gy) of EBRT and 50–112 Gy (median 68 Gy) within 1 week in LDR ISBT or 32–60 Gy (median 48 Gy)/8–10 fractions/5–7 days in HDR ISBT. Results: The 2- and 3-year local control rates of all patients were both 68%. The 2- and 3-year local control rates of patients treated with LDR ISBT were both 67%, and those with HDR ISBT were both 71%. The local control rate of patients treated with HDR ISBT was similar to those with LDR ISBT. Conclusions: ISBT for T3 mobile tongue cancer is effective and acceptable. The treatment result of HDR ISBT is almost similar to that of LDR ISBT for T3 mobile tongue cancer.

Results of radiotherapy for T2N0 glottic carcinoma: does the “2” stand for twice-daily treatment?

Purpose: Radiotherapy (RT) is often the therapy of choice for patients with Stage T2 glottic carcinoma. This retrospective study updated the results of RT for patients treated at our center. The primary focus of this study was whether a policy of using hyperfractionated RT for these patients resulted in a therapeutic gain. Methods and Materials: A search of the database of patients treated in the Department of Radiation Oncology at The University of Texas M. D. Anderson Cancer Center was performed to identify patients with Stage T2 glottic carcinoma treated with RT alone between 1970 and 1998. A total of 230 patients formed the study cohort. Results: The median follow-up for all patients was 82 months. Of the 230 patients, 180 were treated with parallel-opposed fields, and the median field size was 30 cm 2. Eighty-one patients (36%) were treated with twice-daily fractionation to 74–80 Gy. Eighty-nine patients (38%) were treated with 32–75 Gy at 2-Gy per fraction once daily, and 57 patients (25%) were treated with 2.06–2.26 Gy, once daily, to 66–70 Gy. The 2- and 5-year actuarial local control rate was 75% and 72%, respectively. After salvage therapy, the ultimate 5-year local control and disease-specific survival rate was 91% and 92%, respectively. The presence of subglottic extension and treatment with a daily dose of ≤2 Gy were associated with poorer local control ( p <0.01) on both univariate and multivariate analyses. The 5-year local control rate for patients treated with twice-daily and once-daily RT was 79% and 67%, respectively ( p = 0.06). Conclusion: The 5-year local control rates with hyperfractionated RT for Stage T2 glottic carcinoma approach 80%. Patients treated with twice-daily fractionation to a median dose of 77 Gy had an improvement in local control compared with patients treated with 70 Gy in 35 fractions. The Radiation Therapy Oncology Group is testing these two fractionation schedules in a randomized study. High control rates were also seen in selected patients treated with hypofractionated schedules, leaving the question of the optimal schedule for patients with Stage T2 disease unanswered.

Brachytherapy for early oral tongue cancer: low dose rate to high dose rate.

To examine the compatibility of low dose rate (LDR) with high dose rate (HDR) brachytherapy, we reviewed 399 patients with early oral tongue cancer (T1-2N0M0) treated solely by brachytherapy at Osaka University Hospital between 1967 and 1999. For patients in the LDR group (n = 341), the treatment sources consisted of Ir-192 pin for 227 patients (1973-1996; irradiated dose, 61-85 Gy; median, 70 Gy), Ra-226 needle for 113 patients (1967-1986; 55-93 Gy; median, 70 Gy). Ra-226 and Ir-192 were combined for one patient. Ir-192 HDR (microSelectron-HDR) was used for 58 patients in the HDR group (1991-present; 48-60 Gy; median, 60 Gy). LDR implantations were performed via oral and HDR via a submental/submandibular approach. The dose rates at the reference point for the LDR group were 0.30 to 0.8 Gy/h, and for the HDR group 1.0 to 3.4 Gy/min. The patients in the HDR group received a total dose of 48-60 Gy (8-10 fractions) during one week. Two fractions were administered per day (at least a 6-h interval). The 3- and 5-year local control rates for patients in the LDR group were 85% and 80%, respectively, and those in the HDR group were both 84%. HDR brachytherapy showed the same lymph-node control rate as did LDR brachytherapy (67% at 5 years). HDR brachytherapy achieved the same locoregional result as did LDR brachytherapy. A converting factor of 0.86 is applicable for HDR in the treatment of early oral tongue cancer.

Malignant tumors of the nasal cavity and paranasal sinuses.

To evaluate the role of radiation therapy in patients with nasal cavity and paranasal sinus tumors. Between October 1964 and July 1998, 78 patients with malignant tumors of the nasal cavity (48 patients), ethmoid sinus (24 patients), sphenoid sinus (5 patients), or frontal sinus (1 patient) were treated with curative intent by radiation therapy alone or in the adjuvant setting. There were 25 squamous cell carcinomas, 14 undifferentiated carcinomas, 31 minor salivary gland tumors (adenocarcinoma, adenoid cystic carcinoma, and mucoepidermoid carcinoma), 8 esthesioneuroblastomas, and 1 transitional cell carcinoma. Forty-seven patients were treated with irradiation alone, 25 with surgery and postoperative irradiation, 2 with preoperative irradiation and surgery, and 4 with chemotherapy in combination with irradiation with or without surgery. The 5-year actuarial local control rate for stage I (limited to the site of origin; 22 patients) was 86%; for stage II (extension to adjacent sites (eg, adjacent sinuses, orbit, pterygomaxillary fossa, nasopharynx; 21 patients) was 65%; and for stage III (destruction of skull base or pterygoid plates, or intracranial extension; 35 patients) was 34%. The 5-year actuarial local control rate for patients receiving postoperative irradiation was 79% and for patients receiving irradiation alone was 49% (p =.05). The 5-, 10-, 15-, and 20-year ultimate local control rates for all 78 patients were 60%, 56%, 48%, and 48%, respectively. The 5-, 10-, 15-, and 20-year cause-specific survival rates for all 78 patients were 56%, 45%, 39%, and 39%, respectively. The 5-, 10-, 15-, and 20-year absolute survival rates for all 78 patients were 50%, 31%, 21%, and 16%, respectively. Of the 67 (86%) patients who were initially seen with node-negative disease, 39 (58%) received no elective neck treatment, and 28 (42%) received elective neck irradiation. Of the 39 patients who received no elective neck treatment, 33 (85%) did not experience recurrence in the neck compared with 25 (89%) of 28 patients who received elective neck irradiation. Most patients who received elective neck irradiation (57%) had stage III disease. Twenty-one (27%) of 78 patients had unilateral blindness develop secondary to radiation retinopathy or optic neuropathy; the complication was anticipated in most of these patients, because the ipsilateral eye was irradiated to a high dose. Four patients (5%) unexpectedly had bilateral blindness develop because of optic neuropathy. All four of these patients received irradiation alone. Surgery and postoperative radiation therapy may result in improved local control, absolute survival, and complications when compared with radiation therapy alone. Elective neck irradiation is probably unnecessary for patients with early-stage disease.

Outcome of primary soft tissue sarcoma of the knee and elbow

Purpose: Concern is frequently raised regarding the tolerance of irradiation over a joint space. The purpose of this study was to determine the outcome in terms of relapse and potential complications in patients with knee and elbow soft tissue sarcoma treated with limb-sparing surgery with or without adjuvant radiotherapy (RT). Methods and Materials: A review of our prospective database between June 1982 and December 1999 identified 86 adult patients with primary soft tissue sarcoma arising from the knee ( n = 65; 76%) or elbow ( n = 21; 24%) treated with limb-sparing surgery. Tumors had high-grade histologic features in 72% and were >5 cm in 48% of patients. Adjuvant RT was given to 46 (54%) of 86 patients. The type of RT was postoperative external beam RT in 63% and brachytherapy in 37%. Of the 46 patients who received RT, 85% ( n = 39) had deep, 78% ( n = 36) high-grade, and 54% ( n = 25) >5-cm tumors. Complications were assessed in terms of wound complications requiring repeated surgery, bone fracture, nerve damage, and joint stiffness. Results: With a median follow-up of 48 months (range 4–175), the 5-year actuarial rate of local control, distant control, and overall survival was 75% (95% confidence interval [CI] 64–85%), 82% (95% CI 73–91%), and 81% (95% CI 71–91%), respectively. The 5-year local control rate for patients who received RT was 80% vs. 71% for those who did not ( p = 0.3). The type of RT did not significantly influence the local control rate. Patients treated with external beam RT had a 5-year local control rate of 84% compared with 73% for those treated with brachytherapy ( p = 0.4). On multivariate analysis, tumor size >5 cm retained its significance as an independent predictor of poor local control ( p = 0.04; relative risk 3; 95% CI 1–6). In addition, high-grade histologic features emerged as an independent predictor of local recurrence ( p = 0.02; relative risk 4; 95% CI 1–20). No statistically significant difference was found between the RT and no-RT group in terms of the 5-year actuarial rate of wound reoperation (10% vs. 3%, p = 0.1), bone fracture (3% vs. 5%, p = 0.5), or nerve damage (6% vs. 3%, p = 0.5). Joint stiffness was significantly higher in the RT group (24% vs. 0%, p = 0.001), but this stiffness was severe to moderate in only 2 patients. Conclusion: On the basis of the findings of this retrospective review, adjuvant RT seems to be relatively well tolerated despite the inclusion of part of the joint space in the irradiation portal. Joint stiffness was seen more frequently with adjuvant RT, but it was moderate to severe in only a small number of patients.

Impact of boost irradiation with surgically placed radiopaque clips on local control in breast-conserving therapy.

The purpose of this study was to determine whether boost irradiation relying on radiopaque clips placed surgically around the resected margin of breast cancer contributes to increasing the local control rate in patients with close or positive margins in breast-conserving therapy (BCT). Among 837 patients with breast cancer who underwent BCT between November 1987 and December 1998, 181 patients with close or positive surgical margins received boost irradiation following conventional tangential whole breast irradiation. Since 1994, four radiopaque clips were surgically placed around the resected margin of the breast cancer in 155 patients treated with wide excision. The four clips were clearly and accurately identified with a CT-simulator (CT-S). The boost irradiation field was automatically determined with a safety margin of 3 cm according to one-to-one correspondence of radiopaque clips to pathologically close or positive surgical margins. In the remaining 26 patients treated before 1994, the boost irradiation field was determined according to the skin tattoo of the primary tumor. The median follow-up period of the 155 patients receiving the radiopaque clips was 42 months (range: 19 to 78), and that of the 26 patients without the clips was 87 months. Local recurrence was observed in two of the 155 patients who underwent boost irradiation using the radiopaque clips 39 and 54 months after the surgery, while 4 of the 26 patients developed local recurrence 14, 23, 51, and 76 months after BCT. In three of the four patients without the clips developing local recurrences, local recurrences were observed at the margin of the boost irradiation field. The 5-year local recurrence-free survival rate of patients who received boost irradiation with the radiopaque clips was 97%, and that of patients without the clips was 88%. The difference of local recurrence-free survival rates between the patients with and without the clips was significant (p<0.05). Surgically placed radiopaque clips appear to be useful for determining adequate boost field in the BCT using the CT-S and help increase the local control rate.

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.

Long term results of radioactive gold grain implantation for the treatment of persistent and recurrent nasopharyngeal carcinoma

Brachytherapy is useful for the reirradiation of nasopharyngeal carcinoma. In the current study, the long term treatment results of permanent radioactive gold(198) grain interstitial implantation in patients with persistent and recurrent nasopharyngeal carcinoma were reviewed. Gold grain implantation was performed under direct vision with a split palate approach to provide 60 grays (Gy) 0.5 cm away from the plane of implantation. Between August 1986 and May 1999, 106 patients were treated with gold grain implantation (45 patients for persistent disease, 53 patients for first recurrence, and 8 patients for second recurrence in the nasopharynx). All patients had histologically proven disease by biopsy before undergoing implantation. Patients with persistent disease and those with first recurrence did well with the gold grain implantation. The 5-year local control rates for patients with persistent disease, first recurrence, and second recurrence in the nasopharynx were 87.2%, 62.7%, and 23.4%, respectively (P = 0.0004). The 5-year metastasis free survival rates were 68.1%, 60.3%, and 40%, respectively, for the 3 groups (P = 0.048). The overall survival rates at 5 years for the 3 groups were 79.1%, 53.6%, and 42.9%, respectively (P = 0.0047). Patients with computed tomography evidence of disease extension outside the nasopharynx had a lower local control rate compared with patients whose disease was confined to the nasopharynx (5-year local control rate of 52% vs. 72.3%; P = 0.031). The size of the lesion was not found to be an independent prognostic factor for local control after implantation. Multivariate analysis showed only an indication for implantation (persistent disease, first recurrence, and second recurrence) to be a significant prognostic factor for local control. Complications attributed to gold grain implantation included headache, palatal fistula, and mucosal radiation necrosis at the site of implantation, and were reported to occur in 28.3%, 18.9%, and 16%, respectively, of patients. For selected patients with disease confined to the nasopharynx, gold grain implantation is an effective salvage treatment for persistent and recurrent nasopharyngeal carcinoma.