Long-term outcomes of radiotherapy for pituitary adenomas

PURPOSE: To evaluate long-term local control and toxicity for pituitary adenomas treated with fractionated radiotherapy (RT). METHODS AND MATERIALS: The records of 100 patients with pituitary adenomas treated between 1983 and 2003 were retrospectively reviewed. Thirty-one patients had hormone-secreting tumors; 69 patients were treated with surgery and postoperative RT. Median follow-up was 6.7 years (range, 0.6-20.2 years) for all patients and 6.2 years (range, 2-20.2 years) for living patients. The mean dose delivered was 45 Gy (range, 43-50.4 Gy). RESULTS: The 10-year actuarial local control rates for nonsecreting and secreting adenomas were 98% and 73%, respectively (p = 0.0015). Actuarial 10-year cause-specific survival (CSS) rates were 95% and 88%, and overall survival rates were 66% and 79% for nonsecreting and secreting adenomas, respectively. Involvement of the sphenoid sinus was found to be significantly associated with decreased 10-year CSS (p = 0.0453). When compared with the two- or three-field techniques, stereotactic RT was associated with improved CSS (p = 0.0775). CSS was not significantly associated with hormone excretion, extent of surgery, or whether RT was administrated postoperatively or for salvage after a postsurgical recurrence. New cases of hypopituitarism occurred in 35 patients. One patient experienced vision loss, and one patient developed a post-treatment glioma. CONCLUSIONS: This is one of the most mature series in the literature that documents excellent results with fractionated RT for pituitary adenoma. We recommend 45 Gy at 1.8 Gy per fraction using stereotactic noncoplanar fields.     

Intravaginal brachytherapy alone for intermediate-risk endometrial cancer

PURPOSE: Despite the results of the Gynecologic Oncology Group trial No. 99 (GOG#99), some unanswered questions still remain about the role of adjuvant radiotherapy (RT) for intermediate-risk endometrial cancer. First, can intravaginal brachytherapy (IVRT) alone substitute for external beam RT but without added morbidity? Second, is the high-risk (HR) definition from GOG#99 a useful tool to predict pelvic recurrence specifically? The purpose of this study was to try to answer these questions in a group of patients with Stage IB-IIB endometrial carcinoma treated with high-dose-rate (HDR) IVRT alone. METHODS AND MATERIALS: Between November 1987 and December 2002, 382 patients with Stage IB-IIB endometrial carcinoma were treated with simple hysterectomy followed by HDR-IVRT alone at our institution. Comprehensive surgical staging (CSS), defined as pelvic washings and pelvic/paraaortic lymph node sampling, was performed in 20% of patients. The mean age was 60 years (range, 29-92 years). Lymphovascular invasion (LVI) was present in 14% of patients. The median HDR-IVRT dose was 21 Gy (range, 6-21 Gy), given in three fractions. Complications were assessed in terms of late Radiation Therapy Oncology Group (Grade 3 or worse) toxicity of the GI tract, genitourinary GU tract, and vagina. RESULTS: With a median follow-up of 48 months, the 5-year vaginal/pelvic control rate was 95% (95% confidence interval [CI], 93-98%). On multivariate analysis, a poor vaginal/pelvic control rate correlated with age > or =60 years old (relative risk [RR], 3, 95% CI, 1-12; p = 0.01), International Federation of Gynecology and Obstetrics (FIGO) Grade 3 (RR, 9, 95% CI, 2-35; p = 0.03), and LVI (RR, 4, 95% CI, 1-13; p = 0.051). The depth of myometrial invasion and CSS, however, were not significant. With regard to pelvic control specifically, the presence of GOG#99 HR features did not affect the pelvic control rate. The 5-year rate for HR patients was 96% (95% CI, 90-100%) vs. 96% (95% CI, 94-99%) for those without HR disease (p = 0.48). Even when the CSS effect was taken into account, the influence of HR features on pelvic control was still not significant (p = 0.51). In contrast, pelvic control was significantly influenced when patients were grouped according to CSS and stage/grade substages. For those with Stage IB Grade 3-IIB and no CSS, the 5-year pelvic control rate was 86% compared with 97% for those with Stage IB Grade 3-IIB and CSS, 97% for Stage IB, Grade 1-2 without CSS, and 100% for those with Stage IB, Grade 1-2 and CSS (p = 0.027). The 5-year disease-free survival rate was 93% (95% CI, 90-96%). On multivariate analysis, poor disease-free survival correlated with age > or =60 years (RR, 5; 95% CI, 1-18; p = 0.002), FIGO Grade 3 (RR 5, 95% CI 2-17; p = 0.013), and LVI (RR 3, 95% CI 1-8; p = 0.054). Unlike pelvic control, disease-free survival was significantly affected by GOG#99 HR features, with a 5-year rate of 87% (95% CI, 76-99%) vs. 94% (95% CI, 91-97%) for those without HR features (p = 0.027). The 5-year overall and disease-specific survival rate was 93% and 97%, respectively. The overall 5-year actuarial rate of Grade 3 or worse complications was 1% (95% CI, 0-2%). CONCLUSION: Tumor grade, depth of invasion, and the use of CSS were better predictors of pelvic control than the GOG#99 HR factors. IVRT alone seemed to provide adequate tumor control with very low morbidity. Therefore, it seems prudent to consider it for intermediate-risk patients because of its superior therapeutic ratio compared with that for surgery alone or pelvic RT. Additional follow-up, however, with a larger number of patients is needed, especially for those with LVI.     

Epithelioid sarcoma: results of conservative surgery and radiotherapy

PURPOSE: To determine the outcome and prognostic factors for patients with localized epithelioid sarcoma treated with conservative surgery and radiotherapy (RT). METHODS AND MATERIALS: The medical records of 24 patients with nonmetastatic epithelioid sarcoma treated with conservative surgery and RT were reviewed. Preoperative RT was given to 3 patients (median 46.4 Gy) and postoperative RT to 21 patients (median 64.5 Gy). A local (limb-sparing) surgical procedure was performed in all patients. RESULTS: At a median follow-up of 131 months, 14 patients had relapsed and 13 patients had died. The actuarial overall and disease-free survival rate at 10 years was 50% and 37%, respectively. Local, nodal, and metastatic failure occurred in 7, 4, and 10 patients, respectively, yielding a 10-year actuarial local, nodal, and metastatic control rate of 63%, 81%, and 56%, respectively. Univariate analysis revealed that size < or =5 cm and extremity location were favorable prognostic factors for overall, disease-free, and metastasis-free survival. The actuarial 5-year overall, disease-free, and metastasis-free survival rate was 79% vs. 25% (p = 0.002), 51% vs. 13% (p = 0.03), and 79% vs. 13% (p <0.001), respectively, for lesion size < or =5 vs. > 5 cm. The actuarial 5-year overall, disease-free, and metastasis-free survival rate was 77% vs. 39% (p = 0.002), 56% vs. 0% (p = 0.01), and 78% vs. 17% (p = 0.01), respectively, for extremity vs. nonextremity location. Multivariate analysis of the factors correlating with the overall, disease-free, and metastasis-free survival confirmed the favorable prognostic significance of small lesion size. The prognostic significance of extremity location on univariate analysis was explained by an imbalance in the mean tumor sizes. CONCLUSIONS: Epithelioid sarcoma is an aggressive soft-tissue sarcoma, with high rates of local and distant relapse. Local control with conservative surgery and RT compares favorably to published surgical series. The poor outcome for tumors > or =5 cm in size emphasizes the need for effective systemic therapy.     

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.     

Factors associated with local recurrence and cause-specific survival in patients with ductal carcinoma in situ of the breast treated with breast-conserving therapy or mastectomy

PURPOSE: We reviewed our institution's experience treating patients with ductal carcinoma in situ (DCIS) of the breast to determine risk factors for ipsilateral breast tumor recurrence (IBTR) and cause-specific survival (CSS) after breast-conserving therapy (BCT) or mastectomy. MATERIALS AND METHODS: Between 1981 and 1999, 410 cases of DCIS (405 patients) were treated at our institution; 367 were managed with breast-conserving surgery (54 with lumpectomy alone and 313 with adjuvant radiation therapy (RT) [median dose, 45 Gy]). Of these 313 patients, 298 received also a supplemental boost of RT to the lumpectomy cavity (median dose, 16 Gy). Forty-three patients underwent mastectomy; 2 (5%) received adjuvant RT to the chest wall. A true recurrence/marginal miss (TR/MM) IBTR was defined as failure within or adjacent to the tumor bed in patients undergoing BCT. Median follow-up for all patients was 7 years (mean: 6.1 years). RESULTS: Thirty patients (8.2%) experienced an IBTR after BCT (25 [8%] after RT, 5 [9.3%] after no RT), and 2 patients (4.7%) developed a chest wall recurrence after mastectomy. Of the 32 local failures, 20 (63%) were invasive (18/30 [60%] after BCT and 2/2 [100%] after mastectomy), and 37% were DCIS alone. Twenty-four (80%) of the IBTRs were classified as TR/MM. The 10-year freedom from local failure, CSS, and overall survival after BCT or mastectomy were 89% vs. 90% (p = 0.4), 98% vs. 100% (p = 0.7), and 89% vs. 100% (p = 0.3), respectively. Factors associated with IBTR on Cox multivariate analysis were younger age (p = 0.02, hazard ratio [HR] 1.06 per year), electron boost energy < or = 9 MeV (p = 0.03, HR 1.41), final margins < or = 2 mm (p = 0.007; HR, 3.65), and no breast radiation (p = 0.002, HR 5.56). On Cox univariate analysis for BCT patients, IBTR, TR/MM failures, and predominant nuclear Grade 3 were associated with an increased risk of distant metastases and a reduced CSS. CONCLUSIONS: After treatment for DCIS, 10-year rates of local control, CSS, and overall survival were similar after mastectomy and BCT. Young age (<45 years), close/positive margins (< or = 2 mm), no breast radiation, and lower electron boost energies (< or = 9 MeV) were associated with IBTR. Local failure and predominant nuclear Grade 3 were found to have a small (4%-12%) but statistically significantly negative impact on the rates of distant metastasis and CSS. These results suggest that optimizing local therapy (surgery and radiation) is crucial to improve local control and CSS in patients treated with DCIS.     

Small cell carcinoma of the lung. A progress report of 15 years' experience

To assess the results of therapeutic advances in the treatment of small cell carcinoma of the lung (SCCL) achieved during the past 15-year period at a single large institution, 508 patients treated between 1968 and 1982 were divided into two groups: 157 patients (66 in the category of limited-stage disease and 91 in the extensive-stage disease category) treated with low-dose small-volume radiotherapy (RT) (time dose fractionation [TDF] 49-66) and with cyclophosphamide alone or a COPP program during the first period of 7 years (1968-1974); 351 patients (180 in limited and 171 in extensive stage) treated with multidrug chemotherapy (CT) and high-dose large-volume RT (TDF 73-89) during the second period of 8 years (1975-1982). For patients with limited-stage cancer, 5-year actuarial survivals were 3% versus 7% for the periods 1968-1974 versus 1975-1982, respectively, P less than 0.01. For patients with extensive-stage cancer, the median survival time (MST) and 2-year actuarial survivals were 5 months and 2% versus 7 months and 4% for the periods 1968-1974 versus 1975-1982, respectively. To evaluate the outcome of a contemporary approach, i.e., CT alone, with RT reserved for locoregional failure, 180 patients with limited-stage cancer who were treated (1975-1982) were further analyzed for MST, 2- and 5-year actuarial survival figures, and local-tumor control rates according to the therapeutic approaches employed: CT + RT (112); CT alone (36); RT alone (17); and surgery (S) +/- CT +/- RT (15). Although the 36 patients in CT alone seems a small number, 17 of the 36 patients were enrolled in this approach in 1981-1982, reflecting a shift of emphasis from RT to CT. The MST and 2-year actuarial survival figures were 11 months and 0% versus 13 months and 21% for CT alone versus CT + RT respectively, P less than 0.05. CT + RT achieved a 5-year cure rate of 8%. S +/- CT +/- RT or RT alone also achieved 5-year cure rates of 8% and 10.5%, respectively, in selected subsets of patients. Local relapse rates were 80% (29/36) versus 25% (28/112) for CT alone versus CT + RT. These data emphasize the importance of thoracic RT given at the early phase of treatment to improve long-term survival for patients with limited-stage SCCL.     

Carcinoma of the major salivary glands treated by surgery or surgery plus postoperative radiotherapy

From 1975 to 1987, 87 patients with carcinomas of the major salivary glands (70 parotid and 17 submandibular) were treated at our institution by either surgery or surgery followed by postoperative radiotherapy (RT). Surgical procedures included superficial (24%) or total (56%) parotidectomies and submandibular gland resection (20%). Postoperative RT usually began 2 to 4 weeks following surgery. Using 4 MV photons or, infrequently, 60Co, the majority of patients received 6000 cGy in 6 weeks to the parotid region (ranged from 4500 to 7000 cGy). Determinant actuarial survival was 74% at 5 years and 71% at 10 years. For patients with previously untreated disease, 5 of 19 (26%) treated by surgery alone experienced local recurrence, whereas only 2 of 50 (4%) recurred locally following surgery plus postoperative RT (p = 0.01). For patients presenting with recurrent disease, 4/4 (100%) failed locally following surgery as opposed to 3/14 (21%) following surgery plus postoperative RT (p = 0.01). The determinant 5-year actuarial survival for patients receiving postoperative RT was 75% versus 59% for surgery alone. Results were analyzed by multivariate methods using determinant survival or recurrence as endpoints. Five important prognostic factors were identified. (a) Facial nerve paresis was predictive of poor outcome (p less than 0.001) with 3-year relapse free survival of 13%. (b) Undifferentiated histology was associated with decreased survival (p = 0.002). (c) Male sex was associated with poor outcome (p = 0.008). (d) Skin invasion resulted in decreased survival (p = 0.012). (e) Radiotherapy was associated with improved survival (p = 0.014). In addition, postoperative RT was effective in preventing local recurrence (p less than 0.001). The data demonstrate the efficacy of postoperative RT in improving survival and local control for patients with carcinomas of the major salivary glands.     

Impact of local management on long-term outcomes in Ewing tumors of the pelvis and sacral bones: the University of Florida experience

PURPOSE: This retrospective analysis describes our 35-year experience with respect to disease control and functional status. PATIENTS AND METHODS: Thirty-five patients with localized Ewing tumors of the pelvis and sacral bones were treated from 1970 to 2005. Twenty-six patients were treated with definitive radiotherapy (RT), and 9 patients were treated with combined local therapy in the form of surgery + RT. The median RT dose was 55.2 Gy. The patients who received RT alone were more likely to be older men with larger tumors exhibiting soft-tissue extension. Patients in the definitive RT group were more likely to receive etoposide and ifosfamide or undergo bone marrow transplant. Median potential follow-up was 19.4 years. RESULTS: The 15-year actuarial cause-specific survival, freedom from relapse rate, and local control rates were 26% vs. 76% (p = 0.016), 28% vs. 78% (p = 0.015), and 64% vs. 100% (p = 0.087), respectively, for patients treated with definitive RT and combined therapy. Overall, tumors <8 cm had significantly better cause-specific survival, but this was unrelated to local control. The median Toronto Extremity Salvage Score for the definitive RT and combined therapy groups were 99 and 94, respectively (p = 0.19). Seven definitive RT patients (27%) had serious complications. CONCLUSION: Combined modality local therapy should be considered if pelvic Ewing tumors are resectable. However, because of the extent of local disease, most patients have unresectable or partially resectable tumors and therefore require RT in some capacity. For this reason, innovative RT strategies are needed to improve long-term disease outcomes and minimize side effects while maintaining an acceptable functional result.     

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.     

Pathologic stage I-II endometrial carcinoma in the elderly: radiotherapy indications and outcome

PURPOSE: To assess the indications for, and the outcome of, adjuvant radiotherapy (RT) in elderly patients with pathologic Stage I-II endometrial carcinoma. METHODS AND MATERIALS: Between 1980 and 2001, 79 elderly (age > or =75 years) patients with pathologic Stage I-II endometrial carcinoma were seen at our institution. All underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy with assessment of peritoneal cytology. Pelvic and paraaortic lymph node sampling was performed in 39 and 29 women, respectively. Patients with Stage IA and IB Grade 1-2 were designated as low risk; those with Stage IB Grade 3 and IC-IIB were designated as high risk. Thirty-four received adjuvant RT consisting of whole pelvic (n = 23) or vaginal brachytherapy (n = 3), or both (n = 8). Actuarial disease-free survival, cause-specific survival, and pelvic recurrence-free survival analyses were performed by the Kaplan-Meier method. RESULTS: Adverse factors were common, including deep (>50%) myometrial invasion (47%), Grade 3 disease (28%), cervical involvement (15%), and unfavorable histologic features (15%). Overall, 46 patients (58%) had high-risk disease. Primarily because of concerns over toxicity, RT was administered in only 73%, 55%, and 67% of patients with deep myometrial invasion, Grade 3 disease, and cervical involvement, respectively. Thirty-one high-risk patients (67%) received adjuvant RT. At a median follow-up of 33.5 months, 19 patients had relapsed, for a 5-year actuarial disease-free survival rate of 67.7%. Ten patients (12%) had recurrence in the pelvis, 9 of whom had been patients treated with surgery alone. The 5-year pelvic recurrence-free survival rate of patients treated with and without RT was 97% and 73.1%, respectively (p = 0.02). The corresponding rates in the high-risk patients were 97% and 47% (p = 0.0001). High-risk patients treated with RT also had better 5-year actuarial disease-free survival (p = 0.0001) and cause-specific survival (p = 0.003) than those treated with surgery alone. RT was well tolerated, with all patients receiving their treatment as planned. Only 1 patient developed significant late toxicity. CONCLUSIONS: Adverse features are common in pathologic Stage I-II elderly endometrial carcinoma patients, and pelvic recurrence is high after surgery alone. Given the improvement in outcome and low incidence of toxicity, our results support the use of adjuvant RT in elderly pathologic Stage I-II patients with high-risk disease.     

Impact of the mode of detection on outcome in breast cancer patients treated with breast-conserving therapy.

The impact of the mode of detection on outcome in patients with early stage breast cancer treated with breast-conserving therapy (BCT) was reviewed. Between January 1980 and December 1987, 400 cases of stage I and II breast cancer were treated with BCT. All patients underwent an excisional biopsy, external beam irradiation (RT) to the whole breast (45-50 Gy), and a boost to 60 Gy to the tumor bed. One hundred twenty-four cases (31%) were mammographically detected, whereas 276 (69%) were clinically detected. Median follow-up was 9.2 years. Patients whose cancers were detected by mammography more frequently had smaller tumors (90% T1 vs. 62%, p < 0.0001), lower overall disease stage (78% stage I vs. 47%, p < 0.0001), were older at diagnosis (78% >50 years vs. 54%, p < 0.001), less frequently received chemotherapy (8% vs. 21%, p = 0.001), and had an improved disease-free survival (DFS) (80% vs. 70%, p = 0.014), overall survival (OS) (82% vs. 70%, p = 0.005), and cause-specific survival (CSS) (88% vs. 77%, p = 0.003) at 10 years. However, controlling for tumor size, nodal status, and age, no statistically significant differences in the 5- and 10-year actuarial rates of local recurrence (LR), DFS, CSS, or OS were seen based on the mode of detection. Initial mode of detection was the strongest predictor of outcome after a LR. The 3-year DFS rate after LR was significantly better in initially mammographically detected versus clinically detected cases (100% vs. 61%, p = 0.011). Patients with mammographically detected breast cancer generally have smaller tumors and lower overall disease stage at presentation. However, the mode of detection does not independently appear to affect the success of BCT in these patients.     

Ewing's sarcoma: surgical resection as a prognostic factor

A retrospective review of 46 cases of Ewing's (43) and extraosseous Ewing's (3) sarcoma was performed to examine for prognostic factors. Follow-up ranged from 27 to 135 months with a mean of 77.6 months, 86% greater than 36 months. Nine (20%) patients presented with distant metastases, 98% received multiagent chemotherapy, and 98% received radiation therapy. Overall actuarial survival and local control at 5 years were .52 +/- .08 and .78 +/- .07, respectively. The freedom from relapse or treatment related mortality at 5 years was .46 +/- .08. In 12 (26%) patients, surgical resection of the involved bone or soft tissue was part of the initial treatment plan. Ninety-two percent (11/12) of these patients also received radiation therapy. In addition to surgical resection, tumor size (less than 500 cc vs. greater than or equal to 500 cc), primary site (central vs. other), and stage were also analyzed for prognostic significance, and where appropriate, were included in Cox multivariate analyses. Considering all patients, the 5-year actuarial survival was .92 +/- .08 vs. .37 +/- .09 for patients receiving and not receiving surgical resection, respectively (p = .001 by logrank, p = .02 by Cox). To make the groups more comparable, 8 patients with local failure and 5 patients with non-evaluable primary sites were excluded. After these exclusions, the presence or absence of surgical resection had decreased significance: .92 +/- .08 vs. .59 +/- .11, respectively; p = .01 by logrank, p = .07 by Cox. Only primary site remained statistically significant: .86 +/- .08 for noncentral sites vs. .38 +/- .16 for central sites, p less than .0002 by logrank, p = .0004 by Cox. Surgical resection when added to local irradiation has prognostic significance in this retrospective review. The reason for this is not clear, but may be related to a decrease in local failure after resection.     

Adjuvant radiotherapy and survival for patients with node-positive head and neck cancer: an analysis by primary site and nodal stage

PURPOSE: Adjuvant radiotherapy (RT) is frequently recommended for node-positive head and neck squamous cell carcinoma (HNSCC) treated with primary surgery. The impact of RT on survival for various subgroups of node-positive HNSCC has not been clearly demonstrated. METHODS AND MATERIALS: Within the Surveillance, Epidemiology, and End Results (SEER) Database, we identified 5297 patients with node-positive (N1 to N3) HNSCC treated with definitive surgery with or without adjuvant RT between 1988 and 2001. The median follow-up was 4.4 years. RESULTS: Adjuvant RT significantly improved 5-year overall survival (46.3%: 95% confidence interval [CI], 44.7-48.0% for surgery + RT, vs. 35.2%: 95% CI, 32.0-38.5% for surgery alone, p < 0.001) and cancer-specific survival (54.8%: 95% CI, 53.2-56.4% for surgery + RT, vs. 46.2% for surgery alone 95% CI, 42.4-50.0%, p < 0.05). Use of adjuvant RT remained a significant predictor of survival on multivariable analysis (hazard ratio [HR], 0.75; 95% CI, 0.68-0.83; p < 0.001). Subset analyses demonstrated that adjuvant RT was associated with significantly improved survival for N1 (HR, 0.78; 95% CI; 0.67-0.90; p = 0.001), N2a (HR, 0.82; 95% CI, 0.67-0.99, p = 0.048) and N2b to N3 nodal disease (HR, 0.62; 95% CI, 0.51-0.75; p < 0.001). Adjuvant RT increased overall survival for node-positive patients with oropharynx (HR, 0.72; 95% CI, 0.57-0.90; p = 0.004), hypopharynx (HR, 0.66; 95% CI, 0.49 to 0.88; p = 0.004), larynx (HR, 0.66; 95% CI, 0.52-0.84; p = 0.001), and oral cavity (HR, 0.84; 95% CI, 0.73-0.98; p = 0.025) primary tumors. CONCLUSIONS: In a large population-based analysis, adjuvant RT significantly improves overall survival for patients with node-positive HNSCC. All nodal stages, including N1, appear to benefit from the addition of RT to definitive surgery.     

Outcome and pattern of failure in pathologic stage I-II papillary serous carcinoma of the endometrium: implications for adjuvant radiation therapy

PURPOSE: To evaluate the outcome and patterns of failure in women with pathologic Stage I-II papillary serous carcinoma of the uterus and to discuss the implications for adjuvant radiation therapy (RT). METHODS: Twenty-three pathologic Stage I-II uterine papillary serous carcinoma patients were treated at our institution between 1980 and 2001. All underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy and assessment of peritoneal cytology. Pelvic and para-aortic lymph node sampling was performed in 12 and 8 patients, respectively. FIGO stages were as follows: IA = 3, IB = 8, IC = 6, IIA = 5, and IIB = 1. Adjuvant therapies included the following: 9 none, 10 RT (6 pelvic, 1 vaginal brachytherapy, 3 both), 4 chemotherapy, and 1 hormonal therapy. No patient received whole abdominal radiation therapy or para-aortic RT. Disease-free survival, pelvic recurrence-free survival, and cause-specific survival were estimated using the method of Kaplan-Meier, and prognostic factors were analyzed by the log-rank test. Median follow-up was 38.7 months (range: 3-109 months). RESULTS: The 5-year actuarial disease-free survival and cause-specific survival for the entire group was 41% and 73.6%, respectively. Nine patients developed recurrent disease. Five failed in the pelvis, of which 4 relapsed in the vagina. No pelvic failures occurred in women treated with adjuvant RT. Patients treated with adjuvant RT had a better 5-year actuarial pelvic recurrence-free survival (100% vs. 57.5%, p = 0.06) than patients treated with surgery alone. Two patients failed in the abdomen. However, neither developed an isolated abdominal recurrence. Six patients failed in distant sites, primarily the lungs and bone. CONCLUSION: Although patients with pathologic Stage I-II uterine papillary serous carcinomas have organ-confined disease, recurrence is common, particularly in the pelvis and distant sites. Our results suggest that adjuvant RT reduces the risk of pelvic failure. Contrary to traditional assumptions, however, abdominal recurrence was uncommon in our patients, despite the lack of whole abdominal radiation therapy. Our results support the use of pelvic RT in these patients. Future studies should investigate the role of adjuvant chemotherapy.     

A study of postoperative radiotherapy in patients with non-small-cell lung cancer: a randomized trial

PURPOSE: To study the value of postoperative radiotherapy for non-small-cell lung cancer (NSCLC) with positive regional lymph metastases (NI or N2) after radical surgery. MATERIALS AND METHODS: From February 1982 to October 1995, 366 patients with NSCLC and N1 or N2 disease were randomized into postoperative radiotherapy (S + R) (183 patients) and no further treatment (S alone) (182 patients). Postoperative radiotherapy (RT) was administrated 3-4 weeks after radical operation. Irradiated fields covered the bronchial stump, ipsilateral hilum, and most of the mediastinum. The midplane dose was 6000 cGy/30 fractions/6 weeks, with the spinal cord limited to 4000 cGy/20 fractions/4 weeks or less. One hundred thirty-four patients in S + R group and 162 patients in S alone group were evaluated. Clinical data were comparable in both arms, except for the numbers of N2 patients. RESULTS: The 3-year and 5-year overall survival rates were 51.9% and 42.9% in the S + R group and 50.2% and 40.5% in the S alone Group (p = 0.56). The 3-year and 5-year disease-free survival rates were 50.7% +/- 4.7% and 42.9% +/- 5.2% in the S + R group vs. 44.4% +/- 4.3% and 38.2% +/- 4.5% in the S alone group (p = 0.28), respectively. In the patients with NI or T3-4 tumors, there was a trend toward improved survival in the S + R group, especially in the patients with T3-4N1M0. These patients demonstrated 20% improvement in overall survival (p = 0.092) and greater than 20% better disease-free survival (p = 0.057). Postoperative RT reduced local recurrence but had no impact on distant metastases. CONCLUSION: Postoperative RT significantly reduced local relapses, but did not improve overall survival, due to a high frequency of distant metastases in this patient group.     

The importance of brachytherapy technique in the management of primary carcinoma of the vagina.

This retrospective analysis of 49 cases of primary carcinoma of the vagina treated with radiation therapy alone from 1970-1988 examines the results of treatment with an emphasis on the importance of brachytherapy technique. Thirty-six patients were treated with combined external beam radiation and brachytherapy, 11 patients were treated with external beam alone, and two patients were treated with brachytherapy alone. Brachytherapy techniques used included intracavitary implants, temporary Ir-192 interstitial implants, and permanent I-125 interstitial implants. Intracavitary therapy included the use of a fractionated high dose rate intravaginal cylinder, tandem and ovoids, and a low dose rate intravaginal cylinder. The 5-year actuarial survival was 44% for Stage I (six patients), 48% for Stage II (27 patients), 40% for Stage III (10 patients), and 0% for Stage IVa and IVb (six patients). There was a significant increase in the 5-year actuarial survival for those patients who had brachytherapy as part of their treatment compared to those patients treated with external beam alone (50% vs. 9%) (p < .001). For Stages II and III, there was a trend toward improved actuarial and crude disease free survival with the use of a temporary Ir-192 interstitial implant as part of the treatment compared to the use of intracavitary brachytherapy as part of the treatment (80% vs. 45%) (p = 0.25) and (75% vs. 44%) (p = 0.08), respectively. Brachytherapy plays an important role in the management of primary vaginal cancer. A temporary interstitial implant should be used over an intracavitary form of therapy for more invasive disease.     

Surgery with or without radiation therapy in the management of craniopharyngiomas in children and young adults

PURPOSE: The optimal management of craniopharyngiomas remains controversial, especially in children and young adults. This study reports a single institution's experience with such patients. METHODS AND MATERIALS: Between 1974 and 2001, 76 patients were treated for craniopharyngioma at the Children's Hospital of Philadelphia and the Hospital of University of Pennsylvania (HUP). Of these, 75 patients (97%) were evaluable with long-term follow-up. Although all patients underwent attempted gross total resection, 27 had documentation of less than total resection with 18 of these patients receiving immediate postoperative radiotherapy (RT). An additional 22 patients received RT at HUP after failing surgery alone. RESULTS: Median follow-up for all patients was 7.6 years. The 10-year actuarial overall survival, relapse-free survival, and local control (LC) rates for all patients were 85%, 48%, and 53%, respectively. When comparing the 57 patients treated with surgery alone to the 18 treated with subtotal resection (STR) followed by RT, a significant difference in LC rates at 10 years (42% vs. 84%, respectively; p = 0.004) was noted. However, no statistically significant difference in overall survival was found between the two groups, because RT was highly effective as salvage therapy. Twenty-two patients at HUP treated with RT after relapse had a 10-year ultimate LC rate comparable to that of patients who received RT immediately after STR. CONCLUSION: RT given either immediately after STR or at relapse is effective in controlling craniopharyngiomas.     

Duodenal adenocarcinoma: patterns of failure after resection and the role of chemoradiotherapy

PURPOSE: To report patterns of disease recurrence after resection of adenocarcinoma of the duodenum and compare outcomes between patients undergoing surgery only vs. surgery with concurrent chemotherapy and radiation therapy (CT-RT). METHODS AND MATERIALS: This was a retrospective analysis of all patients undergoing potentially curative therapy for adenocarcinoma of the duodenum at Duke University Medical Center and affiliated hospitals between 1975 and 2005. Overall survival (OS), disease-free survival (DFS), and local control (LC) were estimated using the Kaplan-Meier method. Univariate regression analysis evaluated the effect of CT-RT on clinical endpoints. RESULTS: Thirty-two patients were identified (23 M, 9 F). Median age was 60 years (range, 32-77 years). Surgery alone was performed in 16 patients. An additional 16 patients received either preoperative (n = 11) or postoperative (n = 5) CT-RT. Median RT dose was 50.4 Gy (range, 12.6-54 Gy). All patients treated with RT also received concurrent 5-fluorouracil-based CT. Two patients treated preoperatively had a pathologic complete response (18%), and none had involved lymph nodes at resection. Five-year OS, DFS, and LC for the entire group were 48%, 47%, and 55%, respectively. Five-year survival did not differ between patients receiving CT-RT vs. surgery alone (57% vs. 44%, p = 0.42). However, in patients undergoing R0 resection, CT-RT appeared to improve OS (5-year 83% vs. 53%, p = 0.07). CONCLUSIONS: Local failure after surgery alone is high. Given the patterns of relapse with surgery alone and favorable outcomes in patients undergoing complete resection with CT-RT, the use of CT-RT in selected patients should be considered.     

Squamous cell carcinoma of the oropharynx: surgery,radiation therapy,or both

BACKGROUND: The treatment of patients with squamous cell carcinoma (SCC) of the oropharynx remains controversial. No randomized trial has addressed adequately the question of whether surgery (S), radiation therapy (RT), or combined treatment is most effective. METHODS: Treatment results from North American academic institutions that used S with or without adjuvant RT (S +/- RT) or used RT alone or followed by neck dissection (RT +/- ND) for patients with SCC of the tonsillar region or the base of tongue were compiled through a MEDLINE search (from 1970 to August, 2000) and from the references cited in each report. Studies were eligible for inclusion if they contained direct, actuarial (life-table), or Kaplan-Meier calculations for the following end points: local control, local-regional control, 5-year absolute survival, 5-year cause specific survival, or severe or fatal treatment complications. Weighted average results, which took into account series size, were calculated for each end point for the purposes of treatment comparison. Results and conclusions were based on data from 51 reported series, representing the treatment of approximately 6400 patients from the United States and Canada. RESULTS: The results for patients with SCC of the base of tongue who underwent S +/- RT versus RT +/- ND, respectively, were as follows: local control, 79% versus 76% (P = 0.087); local-regional control, 60% versus 69% (P = 0.009); 5-year survival, 49% versus 52% (P = 0.2); 5-year cause specific survival, 62% versus 63% (P = 0.4); severe complications, 32% versus 3.8% (P < 0.001); and fatal complications, 3.5% versus 0.4% (P < 0.001). The results for patients with SCC in the tonsillar region who underwent S +/- RT versus RT +/- ND, respectively, were as follows: local control, 70% versus 68% (P = 0.2); local-regional control, 65% versus 69% (P = 0.1); 5-year survival, 47% versus 43% (P = 0.2); 5-year cause specific survival, 57% versus 59% (P = 0.3); severe complications, 23% versus 6% (P < 0.001); and fatal complications, 3.2% versus 0.8% (P < 0.001). CONCLUSIONS: The information in this article provides a useful benchmark for evidence-based counseling of patients with SCC of the oropharynx. The rates of local control, local-regional control, 5-year survival, and 5-year cause specific survival were similar for patients who underwent S +/- RT or RT +/- ND, whereas the rates of severe or fatal complications were significantly greater for the S +/- RT group. Furthermore, available data on the functional consequences of treatment suggest the superiority of RT +/- ND. The authors conclude that RT +/- ND is preferable for the majority of patients with SCC of the oropharynx.     

Outcome and prognostic factors in cerebellar glioblastoma multiforme in adults: a retrospective study from the Rare Cancer Network

PURPOSE: The aim of this study was to assess the outcome in patients with cerebellar glioblastoma (GBM) treated in 15 institutions of the Rare Cancer Network. METHODS AND MATERIALS: Data from a series of 45 adult patients with cerebellar GBM were collected in a retrospective multicenter study. Median age was 50.3 years. Brainstem invasion was observed in 9 (20%) patients. Radiotherapy (RT) was administered to 36 patients (with concomitant chemotherapy, 7 patients). Adjuvant chemotherapy after RT was administered in 8 patients. Median RT dose was 59.4 Gy. Median follow-up was 7.2 months (range, 3.4-39.0). RESULTS: The 1-year and 2-year actuarial overall survival rate was 37.8% and 14.7%, respectively, and was significantly influenced by salvage treatment (p = 0.048), tumor volume (p = 0.044), extent of neurosurgical resection (p = 0.019), brainstem invasion (p = 0.0013), additional treatment after surgery (p < 0.001), and completion of the initial treatment (p < 0.001) on univariate analysis. All patients experienced local progression: 8 and 22 had progression with and without a distant failure, respectively. The 1- and 2-year actuarial progression free survival was 25% and 10.7%, respectively, and was significantly influenced by brainstem invasion (p = 0.002), additional treatment after surgery (p = 0.0016), and completion of the initial treatment (p < 0.001). On multivariate analysis, survival was negatively influenced by the extent of surgery (p = 0.03) and brainstem invasion (p = 0.02). CONCLUSIONS: In this multicenter retrospective study, the observed pattern of failure was local in all cases, but approximately 1 patient of 4 presented with an extracerebellar component. Brainstem invasion was observed in a substantial number of patients and was an adverse prognostic factor.