O. Kenneth Macdonald

Malignant phyllodes tumor of the female breast: Association of primary therapy with cause-specific survival from the Surveillance, Epidemiology, and End Results (SEER) Program

Malignant phyllodes tumor is a rare and potentially aggressive breast neoplasm. Little information is available regarding the optimal management of these lesions and rarer still are data regarding survival. The current study used a large population database to determine prognostic factors that predict cause‐specific survival (CSS).

Incidence, mortality, and prognostic factors of small cell carcinoma of the cervix.

OBJECTIVE: To compare the incidence, mortality, and presentation of small cell carcinoma of the cervix with other histologies. METHODS: From 1977 to 2003, 290 women with small cell carcinoma of the cervix uteri were identified from the Surveillance, Epidemiology, and End Results database. Also, 27,527 patients with squamous cell carcinoma of the cervix and 5,231 patients with adenocarcinoma of the cervix were identified for comparison. The annual incidence was calculated and examined for trend. Patient and disease characteristics were compared among histologies. Univariable analyses were conducted using the log-rank test. Multivariable analysis was performed using Cox regression. RESULTS: The mean annual incidence for small cell carcinoma was 0.06 per 100,000 women, compared with 6.6 and 1.2 for squamous cell carcinoma and adenocarcinoma, respectively. There were significant differences at presentation between small cell carcinoma compared with squamous cell carcinoma and adenocarcinoma for race, treatment, International Federation of Gynecology and Obstetrics stage, and lymph node involvement (P<.05). A trend for improved survival was identified for adenocarcinoma (P=.036) and squamous cell carcinoma (P<.001) but not for small cell carcinoma (P=.672). Five-year survival for small cell carcinoma (35.7%) was worse compared with squamous cell carcinoma (60.5%, hazard ratio 0.55; 95% confidence interval (CI) 0.43–0.69) and adenocarcinoma (69.7%, hazard ratio 0.48; 95% CI 0.37–0.61). On multivariable analysis, age, stage, and race were prognostic for survival in women with small cell carcinoma (P<.05). CONCLUSION: Small cell carcinoma is a rare histology of cervical cancer associated with a worse prognosis and a predilection for nodal and distant metastasis. The decrease in survival was marked in early-stage and node-negative patients. Because of the high rates of nodal involvement even with early-stage disease, multimodality treatment with radiotherapy and chemotherapy should be considered. LEVEL OF EVIDENCE: II

Evaluation of the use of prophylactic cranial irradiation in small cell lung cancer

Prophylactic cranial irradiation has been used in patients with small cell lung cancer to reduce the incidence of brain metastasis after primary therapy. The purpose of this study was to evaluate the effects of prophylactic cranial irradiation (PCI) on overall survival and cause‐specific survival.

Increased Bowel Toxicity in Patients Treated With a Vascular Endothelial Growth Factor Inhibitor (VEGFI) After Stereotactic Body Radiation Therapy (SBRT)

PURPOSE Gastrointestinal injury occurs rarely with agents that affect the vascular endothelial growth factor receptor and with abdominal stereotactic body radiation therapy (SBRT). We explored the incidence of serious bowel injury (SBI) in patients treated with SBRT with or without vascular endothelial growth factor inhibitor (VEGFI) therapy. METHODS AND MATERIALS Seventy-six patients with 84 primary or metastatic intra-abdominal lesions underwent SBRT (median dose, 50 Gy in 5 fractions). Of the patients, 20 (26%) received VEGFI within 2 years after SBRT (bevacizumab, n=14; sorafenib, n=4; pazopanib, n=1; sunitinib, n=1). The incidence of SBI (Common Terminology Criteria for Adverse Events, version 4.0, grade 3-5 ulceration or perforation) after SBRT was obtained, and the relationship between SBI and VEGFI was examined. RESULTS In the combined population, 7 patients (9%) had SBI at a median of 4.6 months (range, 3-17 months) from SBRT. All 7 had received VEGFI before SBI and within 13 months of completing SBRT, and 5 received VEGFI within 3 months of SBRT. The 6-month estimate of SBI in the 26 patients receiving VEGFI within 3 months of SBRT was 38%. No SBIs were noted in the 63 patients not receiving VEGFI. The log-rank test showed a significant correlation between SBI and VEGFI within 3 months of SBRT (P=.0006) but not between SBI and radiation therapy bowel dose (P=.20). CONCLUSIONS The combination of SBRT and VEGFI results in a higher risk of SBI than would be expected with either treatment independently. Local therapies other than SBRT may be considered if a patient is likely to receive a VEGFI in the near future.

Early pulmonary toxicity following lung stereotactic body radiation therapy delivered in consecutive daily fractions

BACKGROUND AND PURPOSE Identify the incidence of early pulmonary toxicity in a cohort of patients treated with lung stereotactic body radiation therapy (SBRT) on consecutive treatment days. MATERIAL AND METHODS A total of 88 lesions in 84 patients were treated with SBRT in consecutive daily fractions (Fx) for medically inoperable non-small cell lung cancer or metastasis. The incidence of pneumonitis was evaluated and graded according to the NCI CTCAE v3.0. RESULTS With a median follow-up of 15.8 months (range 2.5-28.6), the median age at SBRT was 71.8 years (range 23.8-87.8). 47 lesions were centrally located and 41 were peripheral. Most central lesions were treated with 48Gy in 4 Fx, and most peripheral lesions with 54Gy in 3 Fx. The incidence of grade ≥ 2 pneumonitis was 12.5% in all patients treated, and 14.3% among the subset of patients treated with 54Gy in 3 Fx. A total of two grade 3 toxicities were seen as one grade 5 toxicity in a patient treated for recurrence after pneumonectomy. CONCLUSIONS Treating both central and peripheral lung lesions with SBRT in consecutive daily fractions in this cohort was well tolerated and did not cause excessive early pulmonary toxicity.

Proton Beam Radiotherapy Versus Three-Dimensional Conformal Stereotactic Body Radiotherapy in Primary Peripheral, Early-Stage Non–Small-Cell Lung Carcinoma: A Comparative Dosimetric Analysis

PURPOSE Proton radiotherapy (PT) and stereotactic body radiotherapy (SBRT) have the capacity to optimize the therapeutic ratio. We analyzed the dosimetric differences between PT and SBRT in treating primary peripheral early-stage non-small-cell lung cancer. METHODS AND MATERIALS Eight patients were simulated, planned, and treated with SBRT according to accepted techniques. SBRT treatments were retrospectively planned using heterogeneity corrections. PT treatment plans were generated using single-, two-, and three-field passively scattered and actively scanned proton beams. Calculated dose characteristics were compared. RESULTS Comparable planning target volume (PTV) median minimum and maximum doses were observed between PT and SBRT plans. Higher median maximum doses 2 cm from the PTV were observed for PT, but higher median PTV doses were observed for SBRT. The total lung mean and V5 doses were significantly lower with actively scanned PT. The lung V13 and V20 were comparable. The dose to normal tissues was lower with PT except to skin and ribs. Although the maximum doses to skin and ribs were similar or higher with PT, the median doses to these structures were higher with SBRT. Passively scattered plans, compared with actively scanned plans, typically demonstrated higher doses to the PTV, lung, and organs at risk. CONCLUSIONS Single-, two-, or three-field passively or actively scanned proton therapy delivered comparable PTV dose with generally less dose to normal tissues in these hypothetic treatments. Actively scanned beam plans typically had more favorable dose characteristics to the target, lung, and other soft tissues compared with the passively scanned plans. The clinical significance of these findings remains to be determined.

Prognostic significance of histology and positive lymph node involvement following radical hysterectomy in carcinoma of the cervix

Objective:Lymph node (LN) metastasis portends a poor outcome in women with carcinoma of the uterine cervix. We queried a large database to analyze the importance of number of positive LN and histology in relation to survival after radical hysterectomy and lymphadenectomy. Methods:Data were collected from the Surveillance, Epidemiology, and End Results Program on women who had primary surgery for the years 1988 to 2003 (n = 4559). Statistical analyses were performed using conventional methods. Results:The median number of LNs examined per patient has significantly declined in recent years (P = 0.003). The 5-year rates of cause specific and overall survival were 94% and 91%, 76% and 69%, 62% and 58%, and 41% and 35%, for 0, 1 to 2, 3 to 9 and ≥10 positive LNs, respectively. Pathologic LN involvement was associated with higher grade, higher stage, larger tumor size, and squamous cell histology. Predictors for both cause specific and overall survival on multivariate analysis included number of involved LN, histology, tumor grade, tumor size, disease stage, and pelvis or paraaortic lymphatic involvement. Conclusions:Adenocarcinoma histology independently predicted for a more aggressive phenotype, particularly in women with LN involvement. The number of LNs examined did not independently predict for survival when adjusted for patient and disease characteristics, providing context for the investigation of sentinel node biopsy or other sampling methods. LN positive disease in carcinoma of the cervix predicts a prognosis that is inversely related to the number of involved nodes. Tumor grade, size, and FIGO stage were associated with increasing risk for lymph node metastases.

Survival outcomes in resected extrahepatic cholangiocarcinoma: effect of adjuvant radiotherapy in a surveillance, epidemiology, and end results analysis.

PURPOSE The benefit of adjuvant radiotherapy (RT) after surgical resection for extrahepatic cholangiocarcinoma has not been clearly established. We analyzed survival outcomes of patients with resected extrahepatic cholangiocarcinoma and examined the effect of adjuvant RT. METHODS AND MATERIALS Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) program between 1973 and 2003. The primary endpoint was the overall survival time. Cox regression analysis was used to perform univariate and multivariate analyses of the following clinical variables: age, year of diagnosis, histologic grade, localized (Stage T1-T2) vs. regional (Stage T3 or greater and/or node positive) stage, gender, race, and the use of adjuvant RT after surgical resection. RESULTS The records for 2,332 patients were obtained. Patients with previous malignancy, distant disease, incomplete or conflicting records, atypical histologic features, and those treated with preoperative/intraoperative RT were excluded. Of the remaining 1,491 patients eligible for analysis, 473 (32%) had undergone adjuvant RT. After a median follow-up of 27 months (among surviving patients), the median overall survival time for the entire cohort was 20 months. Patients with localized and regional disease had a median survival time of 33 and 18 months, respectively (p<.001). The addition of adjuvant RT was not associated with an improvement in overall or cause-specific survival for patients with local or regional disease. CONCLUSION Patients with localized disease had significantly better overall survival than those with regional disease. Adjuvant RT was not associated with an improvement in long-term overall survival in patients with resected extrahepatic bile duct cancer. Key data, including margin status and the use of combined chemotherapy, was not available through the SEER database.

Stereotactic body radiotherapy in the treatment of adrenal metastases.

Objectives:To evaluate the dosimetry, clinical outcomes, and toxicity of patients treated with stereotactic body radiotherapy (SBRT) for adrenal metastases. Materials and Methods:From February 2009 to February 2011, a total of 13 patients were treated with SBRT for metastases to the adrenal glands. Median age was 71 years (range, 60.8 to 83.2). Primary sites included lung (n=6), kidney (n=2), skin (n=2), bladder (n=1), colon (n=1), and liver (n=1). Nine patients had metastases to the left adrenal gland and 4 to the right. The median prescribed total dose was 45 Gy (range, 33.75 to 60 Gy), all in 5 fractions. Results:Median follow-up for living patients was 12.3 months (range, 3.1 to 18 mo). Twelve of the 13 patients (92.3%) were evaluable for local control (LC). The crude LC rate was 100%, with no cases of local or marginal failure. Two patients had a complete response to treatment, 9 patients had a partial response, and 1 patient displayed stable disease. One-year overall survival and distant control were 62.9% and 55%, respectively. Median OS was 7.2 months (range, 2 to 18 mo). Grade 2 nausea was noted in 2 patients. Conclusions:SBRT seems to be a safe and effective measure to achieve LC for adrenal metastases.

Clinical outcomes and dosimetric considerations using stereotactic body radiotherapy for abdominopelvic tumors.

Purpose/ObjectivesTo present clinical outcomes, early toxicity, and dosimetric constraints for patients undergoing stereotactic body radiation therapy (SBRT) for abdominal or pelvic tumors. Materials and MethodsFrom May 2008 to February 2010, 47 patients with 50 lesions in proximity to hollow viscous organs at risk, including stomach, duodenum, small bowel, and colon, underwent SBRT at Mayo Clinic. Treated sites included liver (21), lymph node (14), adrenal gland (6), intramuscular (4), pancreas (3), and spleen (2). Treatment planning was performed with full body immobilization and 4-dimensional computed tomography (CT)-based planning with daily cone-beam CT or stereoscopic kV imaging for pretreatment image guidance. SBRT was delivered in 1 to 5 consecutive daily fractions in a single week. The most commonly prescribed dose was 50 Gy in 5 fractions (median 45 Gy, range: 20 to 60 Gy). Toxicities were scored by CTCAE v.3. Local failure was defined as per the Response Evaluation Criteria in Solid Tumors. ResultsMedian follow-up was 12 months (range: 2 to 28 mo). Tumor responses of the 48 target lesions evaluable by Response Evaluation Criteria in Solid Tumor were complete response in 18 lesions (36%), partial response in 12 lesions (24%), stable disease in 12 lesions (24%), and progressive disease in 6 lesions (12%). Kaplan-Meier estimates of local control, overall survival, and freedom from metastasis at 6 and 12 months were 98%, 90%, and 63%, and 87%, 62%, 37%, respectively. Treatment was well-tolerated acutely without reported grade ≥3 toxicity. Five grade 3 late toxicities were reported, and 1 patient died of complications from duodenal perforation 11 months after SBRT. No dose correlation with toxicity could be established. ConclusionsSBRT is a practical treatment option for patients with abdominopelvic tumors. Relapse typically occurs outside treatment fields, and most patients achieve a favorable response. The dose constraints used in this cohort of patients was associated with acceptable early treatment-related toxicity.