Equivalent uniform dose, D(90), and V(100) correlation with biochemical control after low-dose-rate prostate brachytherapy for clinically low-risk prostate cancer.

PURPOSE: To assess the correlation of postimplant dosimetric quantifiers with biochemical control of prostate cancer after low-dose-rate brachytherapy. MATERIALS AND METHODS: Generalized equivalent uniform dose (EUD), dose in Gy to 90% of the prostate gland (D(90)), and percentage of the prostate receiving 100% of the prescribed dose (V(100)) were calculated from the postimplant dose-volume histogram (DVH) for 140 patients undergoing low-dose-rate prostate brachytherapy (LDRPB) monotherapy from 1997 to 2003 at Duke University and the Durham VA Medical Center. Biochemical recurrence was defined according to the American Society for Therapeutic Radiology and Oncology consensus definition. RESULTS: Median followup after LDRPB was 50 months. There was a 7% biochemical recurrence rate (10/140) at last clinical followup. The median EUD was 167 Gy (range, 41-245). The median D(90) was 139 Gy (range, 45-203). The median V(100) was 88% (range, 44-100). The overall 5-year biochemical recurrence-free survival (bRFS) was 94.2%. The 5-year bRFS was 100% for EUD> or =167 Gy and 89.4% for EUD <167 Gy (p=0.008); 100% for D(90) > or =140 Gy and 90.4% for D(90) <140 Gy (p=0.020); 100% for V(100) > or =88%; and 90.3% for V(100) <88% (p=0.017). There was no statistically significant correlation between any of these factors and overall survival. CONCLUSIONS: In our series of 140 patients with low-risk prostate cancer treated with LDRPB alone, we observed a statistically significant correlation between EUD, D(90), and V(100) and bRFS. The generalized EUD, a calculated value that incorporates the entire prostate DVH, appears to be at least as well correlated with bRFS as D(90) or V(100), and may more completely represent the totality of the dose distribution.

Paclitaxel-based chemoradiotherapy in the treatment of patients with operable esophageal cancer.

PURPOSE: To compare a neoadjuvant regimen of cisplatin/5-fluorouracil (5-FU) and concurrent radiation therapy (RT) with paclitaxel-based regimens and RT in the management of operable esophageal (EC)/gastroesophageal junction (GEJ) cancer. METHODS AND MATERIALS: All patients receiving neoadjuvant chemotherapy (CT) and RT for EC/GEJ cancer at Duke University between January 1995 and December 2004 were included. Clinical end points were compared for patients receiving paclitaxel-based regimens (TAX) vs. alternative regimens (non-TAX). Local control (LC), disease-free survival (DFS), and overall survival (OS) were estimated using the Kaplan-Meier method. Chi-square analysis was performed to test the effect of TAX on pathologic complete response (pCR) rates and toxicity. RESULTS: A total of 109 patients received CT-RT followed by esophagectomy (95 M; 14 F). Median RT dose was 45 Gy (range, 36-66 Gy). The TAX and non-TAX groups comprised 47% and 53% of patients, respectively. Most (83%) TAX patients received three drug regimens including platinum and a fluoropyrimidine. In the non-TAX group, 89% of the patients received cisplatin and 5-FU. The remainder received 5-FU or capecitabine alone. Grade 3-4 toxicity occurred in 41% of patients receiving TAX vs. 24% of those receiving non-TAX (p = 0.19). Overall pCR rate was 39% (39% with TAX vs. 40% with non-TAX, p = 0.9). Overall LC, DFS, and OS at 3 years were 80%, 34%, and 37%, respectively. At 3 years, there were no differences in LC (75% vs. 85%, p = 0.33) or OS (37% vs. 37%, p = 0.32) between TAX and non-TAX groups. CONCLUSIONS: In this large experience, paclitaxel-containing regimens did not improve pCR rates or clinical end points compared to non-paclitaxel-containing regimens.

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.

Predictors of severe gastrointestinal toxicity after external beam radiotherapy and interstitial brachytherapy for advanced or recurrent gynecologic malignancies.

PURPOSE: The aim of this retrospective review of patients with gynecologic malignancies treated with external beam radiotherapy (EBRT) and interstitial brachytherapy was to determine the rate of Grade > or =2 rectovaginal fistula and Grade > or =4 small bowel obstruction as defined by the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0. METHODS AND MATERIALS: Thirty-six patients with primary and recurrent gynecologic cancers were treated with EBRT and interstitial brachytherapy. Median doses to tumor, bladder, and rectum were 75 Gy, 61 Gy, and 61 Gy, respectively. A univariate analysis was performed to identify variables that correlated with toxicity. RESULTS: At median follow-up of 19 months, the 3-year risk of small bowel obstruction was 6%. Those patients with prior abdomino-pelvic surgery who received EBRT with antero-posterior fields had higher rates of obstruction than patients without prior abdomino-pelvic surgery or those who received EBRT with four fields (50% vs. 0%, p < 0.0001). The 3-year risk of rectovaginal fistula was 18% and was significantly higher in patients who received >76 Gy to the rectum compared with those who received < or =76 Gy (100% vs. 7%, p = 0.009). CONCLUSIONS: Patients treated with EBRT and interstitial brachytherapy after abdomino-pelvic surgery should receive EBRT with four fields and the cumulative rectal dose should be < or =76 Gy.

Radiation-induced narrowing of the tracheobronchial tree: an in-depth analysis.

PURPOSE: Symptomatic narrowing of the tracheobronchial tree is not a common clinical problem after conventional-dose external beam radiation therapy but has been described when higher doses are utilized. This in-depth study quantifies changes in the caliber of the trachea and mainstem bronchi after high-dose external beam radiation therapy (EBRT). METHODS AND MATERIALS: As part of an IRB-approved prospective clinical trial to assess for radiation-induced lung injury, patients with thoracic malignancies had pre- and serial post-RT CT scans in the radiation oncology department. This report focuses on 18 enrolled patients who received high-dose (> or = 73.6 Gy) EBRT for NSCLC. The caliber of the trachea, right mainstem bronchus, and left mainstem bronchus were measured utilizing three-dimensional coordinates in axial and coronal planes such that multiple measurements were made of each structure. The decrease in airway caliber was tested for significance using a one-sided Wilcoxon matched-pairs signed-ranks test. The correlation between airway caliber changes, dose, and follow-up interval was tested using the Spearman rank correlation coefficient and the effect of chemotherapy on airway narrowing was evaluated with a one-sided exact Wilcoxon rank sum test. RESULTS: There was no significant narrowing of the trachea for all dose and time points. There were significant decreases in the caliber of both mainstem bronchi on axial measurements (p = 0.07 and 0.005 for right and left mainstem bronchi, respectively). Decrease in airway caliber ranged from 6 to 57% and appeared to be dose dependent (p = 0.08), progressed with increasing time post-RT (p = 0.04), and was worse in patients who also received chemotherapy (p = 0.04). CONCLUSION: High-dose EBRT (> or = 73.6 Gy) appears to cause narrowing of the mainstem bronchi as early as 3 months post radiation therapy. Additional study is needed to assess the impact of such narrowing on RT-induced pulmonary symptoms.

Adjuvant external-beam radiotherapy with concurrent chemotherapy after resection of primary gallbladder carcinoma: a 23-year experience.

PURPOSE: Primary adenocarcinoma of the gallbladder is a rare malignancy. To better define the role of adjuvant radiation therapy and chemotherapy, a retrospective analysis of the outcome of patients undergoing surgery and adjuvant therapy was undertaken. METHODS AND MATERIALS: Twenty-two patients with primary and nonmetastatic gallbladder cancer were treated with radiation therapy after surgical resection. Median radiation dose was 45 Gy. Eighteen patients received concurrent 5-fluorouracil (5-FU) chemotherapy. Median follow-up was 1.7 years in all patients and 3.9 years in survivors. RESULTS: The 5-year actuarial overall survival, disease-free survival, metastases-free survival, and local-regional control of all 22 patients were 37%, 33%, 36%, and 59%, respectively. Median survival for all patients was 1.9 years. CONCLUSION: Our series suggests that an approach of radical resection followed by external-beam radiation therapy with radiosensitizing 5-FU in patients with locally advanced, nonmetastatic carcinoma of the gallbladder may improve survival. This regimen should be considered in patients with resectable gallbladder carcinoma.

Bronchial stenosis: an underreported complication of high-dose external beam radiotherapy for lung cancer?

PURPOSE: To assess the incidence of clinically significant bronchial stenosis in patients treated with high doses (i.e., >70 Gy) of twice-daily external beam radiation therapy (RT). METHODS AND MATERIALS: The outcomes of 103 patients with unresectable non-small-cell lung cancer, treated twice daily to doses ranging from 7080 to 8640 cGy between 1992 and 2001, were analyzed. Most were treated on prospective clinical trials. For the dose-effect comparison, the patients were divided on the basis of the total dose: 67 received 74 Gy (range, 70.8-74.5 Gy; median, 73.6 Gy), 20 received 80 Gy, and 16 received 86 Gy (range, 85.2-86.4 Gy; median, 86.4 Gy). Sixty-six patients received sequential chemotherapy before RT. RT-induced bronchial stenosis was defined as symptomatic airway narrowing diagnosed by bronchoscopy or computed tomography scan without evidence of recurrent tumor in that region. RESULTS: Eight patients developed RT-induced, clinically significant, bronchial stenosis 2-48 months (median, 6 months) after RT. The 1-year and 4-year actuarial rate of stenosis was 7% and 38%, respectively. The median overall survival was 2.5 years (5 of 8 were alive at the writing of this report). A suggestion was also found of a dose-response effect with external beam radiotherapy-induced stenosis, with a rate of 4% and 25% at a dose of approximately 74 Gy and 86 Gy, respectively. CONCLUSION: Radiation therapy-induced bronchial stenosis is a significant clinical complication of dose escalation for lung cancer. This complication has been previously mentioned in the literature, but ours is the largest report to date, and the findings suggest that the risk rises with increasing dose. It is likely that this process would manifest in more patients if their disease were controlled well enough for more prolonged survival.

Routine use of approximately 60 Gy once-daily thoracic irradiation for patients with limited-stage small-cell lung cancer.

PURPOSE: To review the outcome of patients with limited-stage small-cell lung cancer receiving daily thoracic irradiation (RT) to approximately 60 Gy. METHODS AND MATERIALS: The records of patients treated with RT for limited-stage small-cell lung cancer between 1991 and 1999 at Duke University were retrospectively reviewed. Sixty-five patients were identified who had received continuous course once-daily 1.8-2 Gy fractions to approximately 60 Gy (range 58-66). All patients received chemotherapy (CHT); 32 received concurrent RT/CHT and 33 sequential CHT and then RT. Prophylactic cranial RT was administered to 17 patients. The time from diagnosis to local failure, tumor progression, and death was assessed using actuarial methods. The median follow-up for all patients was 16.7 months and for surviving patients was 29.6 months. The median age was 64 years (range 36-83), and the median Karnofsky performance status was 80 (range 50-100). RESULTS: The 3-year actuarial rate of local failure, progression-free survival, and overall survival was 40%, 25%, and 23%, respectively. One case of acute Grade 3 esophagitis developed. Ten late complications occurred: four pulmonary, two esophageal, two infectious, one leukemia, and one retinal toxicity with prophylactic cranial RT. Six were mild and resolved with treatment. CONCLUSION: CHT plus approximately 60 Gy of once-daily RT for limited-stage small-cell lung cancer was generally well tolerated. The survival rates were less than have been reported using 45 Gy in 1.5-Gy twice-daily fractions (2-year overall survival rate 47% compared with 30% in this study), but may be comparable because fewer than one-half our patients received concurrent CHT/RT and only 26% received prophylactic cranial RT. The relatively low rate of normal tissue morbidity in our patients supports the use of conventional once-daily fractionation to > or = 60 Gy. A randomized trial would be required to compare the outcomes after maximally tolerated dose twice-daily RT vs. maximally tolerated dose daily RT.

Long-term changes in pulmonary function tests after definitive radiotherapy for lung cancer.

PURPOSE: To evaluate the long-term changes in pulmonary function tests (PFTs) in patients surviving at least 2 years after definitive radiotherapy (RT) for unresectable lung cancer. METHODS AND MATERIALS: Between 1992 and 2000, 277 patients were enrolled in a prospective clinical study to relate RT-induced changes in lung function with dosimetric and functional metrics. Of these, 128 received definitive RT for lung cancer, and 13 of these had follow-up PFTs for approximately >/=2 years without evidence of recurrent or progressive cancer. PFTs were obtained before RT and approximately every 6 months after RT. The results were evaluated on the basis of each study's "percentage of predicted" of normal values (i.e., adjusted for age, gender, height), and a patient's sequential examinations were compared with their initial study and a percentage of the baseline value was calculated. Follow-up PFTs were available for a median of 38 months (range 23-95). The median patient age was 65 years (range 40-74), 6 patients were men, and 10 were white. Most had Stage T2-T4 and N2-N3. The median RT dose was 71.4 Gy (range 60-73), 6 had twice-daily RT. Four patients received chemotherapy, one concurrent and three neoadjuvant. None of the patients continued to smoke after their treatment. The median pre-RT PFT results were (percentage of predicted) forced expiratory volume in 1 s, 67% (range 24-121); forced vital capacity, 72% (range 45-116); and diffusing capacity of lung for carbon monoxide, 70% (range 41-129). RESULTS: At 6 months, all PFT values had declined, with some stabilization by 1 year. However, after 1 year, a gradual reduction occurred in all three parameters. Ten patients (77%) developed RT-induced respiratory symptoms (2 cough only, 8 dyspnea) at 2-21 months (median 5) after treatment. Two patients required inhalers, another required long-term steroids and oxygen. Of the 8 patients with dyspnea, 7 had an increase in symptoms beyond 2 years. No patient died of RT-induced pulmonary insufficiency. CONCLUSION: RT caused a decline in PFTs that was apparent at 6 months and continued well beyond 1 year. The continued decline in PFTs is suggestive of progressive/evolving RT-induced lung injury. "Late" pulmonary symptoms have also occurred in these patients. Because of the high mortality rate of unresectable lung cancer, few patients can be evaluated for long-term analysis. Additional studies and pooling of data from multiple institutions may help to clarify better the long-term impact of RT on pulmonary function in this subset of patients.

Gastrointestinal toxicity of transperineal interstitial prostate brachytherapy.

PURPOSE: To characterize the severity and time course of rectal toxicity following transperineal prostate brachytherapy using prospectively recorded data, and to determine factors associated with toxicity. METHODS AND MATERIALS: One hundred thirty-four patients with prostate cancer treated with transperineal brachytherapy from 1997 to 1999 had rectal toxicity data available for analysis. Patients with Gleason score (GS) > 6, prostate-specific antigen (PSA) > 6, or stage > T2a were treated initially with external beam radiation therapy followed by brachytherapy boost; patients with none of these features were treated with brachytherapy alone. Both iodine-125 and palladium-103 sources were used, and loaded according to a modified Quimby distribution. At each follow-up, toxicity was recorded according to a modified RTOG gastrointestinal scale. RESULTS: Thirty-nine percent of patients experienced gastrointestinal toxicity, mostly Grade 1. Median duration of symptoms was 6 months. Two patients experienced Grade 3 toxicity, both of whom had minimal symptoms until their 12-month follow-up. There was no Grade 4 or 5 toxicity. The addition of external beam radiation therapy (p = 0.003), higher clinical stage (p = 0.006), and Caucasian race (p = 0.01) were associated with increased incidence of toxicity. CONCLUSION: Most patients with rectal toxicity have very mild symptoms. There is a small risk of severe late toxicity. External beam radiation, higher stage, and race are associated with toxicity.

Increased sectioning of pathologic specimens with ductal carcinoma in situ of the breast: are there clinical consequences?

To assess if there has been increased sectioning of pathologic specimens with ductal carcinoma in situ (DCIS), identify sources of this change, and consider the clinical consequences, pathologic data from patients who underwent initial excisional biopsies at our institution and were referred to the radiation oncology department with DCIS from 1992-2002 were retrospectively reviewed. One hundred forty-four of 480 patients with DCIS were eligible for review. Specimen size was recorded as length, to the nearest 0.1 cm, in 3 dimensions. Specimen volume was approximated by the product of the 3 dimensions of the specimen. The primary endpoint was the number of microscopic sections taken from gross specimens, corrected for specimen size. Other analysis included margin status, use of a previous stereotactic needle biopsy, and whether a subsequent repeat excision was performed. Over time, there was an increase in size of the excisional biopsy specimens (mean of 49 cm3 from 1992 to 1994 and 90 cm3 from 2001 to 2002; P = 0.045). Mean numbers of slides per centimeter of specimen were 2.5, 2.7, 3.9, and 5.8 for the intervals 1992-1994, 1995-1997, 1998-2000, and 2001-2002, respectively (P < 0.001 for 1992-1997 vs. 1998-2002). Adjusting for volume, the increase over time in the number of slides per specimen was statistically significant (parameter significance, P < 0.001). For a given volume, the number of slides increased approximately 9.1% per year, on average, during the study period. The positive margin rates were 52%, 46%, 23%, and 25% from 1992 to 1994, from 1995 to 1997, from 1998 to 2000, and from 2001 to 2002, respectively. The degree of sectioning, corrected for specimen length and volume, increased over time.

M6P/IGF2R loss of heterozygosity in head and neck cancer associated with poor patient prognosis.

BACKGROUND: The mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) encodes for a multifunctional receptor involved in lysosomal enzyme trafficking, fetal organogenesis, cytotoxic T cell-induced apoptosis and tumor suppression. The purpose of this investigation was to determine if the M6P/IGF2R tumor suppressor gene is mutated in human head and neck cancer, and if allelic loss is associated with poor patient prognosis. METHODS: M6P/IGF2R loss of heterozygosity in locally advanced squamous cell carcinoma of the head and neck was assessed with six different gene-specific nucleotide polymorphisms. The patients studied were enrolled in a phase 3 trial of twice daily radiotherapy with or without concurrent chemotherapy; median follow-up for surviving patients is 76 months. RESULTS: M6P/IGF2R was polymorphic in 64% (56/87) of patients, and 54% (30/56) of the tumors in these informative patients had loss of heterozygosity. M6P/IGF2R loss of heterozygosity was associated with a significantly reduced 5 year relapse-free survival (23% vs. 69%, p = 0.02), locoregional control (34% vs. 75%, p = 0.03) and cause specific survival (29% vs. 75%, p = 0.02) in the patients treated with radiotherapy alone. Concomitant chemotherapy resulted in a better outcome when compared to radiotherapy alone only in those patients whose tumors had M6P/IGF2R loss of heterozygosity. CONCLUSIONS: This study provides the first evidence that M6P/IGF2R loss of heterozygosity predicts for poor therapeutic outcome in patients treated with radiotherapy alone. Our findings also indicate that head and neck cancer patients with M6P/IGF2R allelic loss benefit most from concurrent chemotherapy.

Implementing and integrating a clinically driven electronic medical record for radiation oncology in a large medical enterprise.

PURPOSE/OBJECTIVE: While our department is heavily invested in computer-based treatment planning, we historically relied on paper-based charts for management of Radiation Oncology patients. In early 2009, we initiated the process of conversion to an electronic medical record (EMR) eliminating the need for paper charts. Key goals included the ability to readily access information wherever and whenever needed, without compromising safety, treatment quality, confidentiality, or productivity. METHODOLOGY: In February, 2009, we formed a multi-disciplinary team of Radiation Oncology physicians, nurses, therapists, administrators, physicists/dosimetrists, and information technology (IT) specialists, along with staff from the Duke Health System IT department. The team identified all existing processes and associated information/reports, established the framework for the EMR system and generated, tested and implemented specific EMR processes. RESULTS: Two broad classes of information were identified: information which must be readily accessed by anyone in the health system versus that used solely within the Radiation Oncology department. Examples of the former are consultation reports, weekly treatment check notes, and treatment summaries; the latter includes treatment plans, daily therapy records, and quality assurance reports. To manage the former, we utilized the enterprise-wide system, which required an intensive effort to design and implement procedures to export information from Radiation Oncology into that system. To manage "Radiation Oncology" data, we used our existing system (ARIA, Varian Medical Systems.) The ability to access both systems simultaneously from a single workstation (WS) was essential, requiring new WS and modified software. As of January, 2010, all new treatments were managed solely with an EMR. We find that an EMR makes information more widely accessible and does not compromise patient safety, treatment quality, or confidentiality. However, compared to paper charts, time required by clinicians to access/enter patient information has substantially increased. While productivity is improving with experience, substantial growth will require better integration of the system components, decreased access times, and improved user interfaces. $127K was spent on new hardware and software; elimination of paper yields projected savings of $21K/year. One year after conversion to an EMR, more than 90% of department staff favored the EMR over the previous paper charts. CONCLUSION: Successful implementation of a Radiation Oncology EMR required not only the effort and commitment of all functions of the department, but support from senior health system management, corporate IT, and vendors. Realization of the full benefits of an EMR will require experience, faster/better integrated software, and continual improvement in underlying clinical processes.

Resected pancreatic neuroendocrine tumors: patterns of failure and disease-related outcomes with or without radiotherapy.

PURPOSE: Pancreatic neuroendocrine tumors (NET) are rare and have better disease-related outcomes compared with pancreatic adenocarcinoma. Surgical resection remains the standard of care, although many patients present with locally advanced or metastatic disease. Little is known regarding the use of radiotherapy in the prevention of local recurrence after resection. To better define the role of radiotherapy, we performed an analysis of resected patients at our institution. METHODS: Between 1994 and 2009, 33 patients with NET of the pancreatic head and neck underwent treatment with curative intent at Duke University Medical Center. Sixteen patients were treated with surgical resection alone while an additional 17 underwent resection with adjuvant or neoadjuvant radiation therapy, usually with concurrent fluoropyrimidine-based chemotherapy (CMT). Median radiation dose was 50.4 Gy and median follow-up 28 months. RESULTS: Thirteen patients (39%) experienced treatment failure. Eleven of the initial failures were distant, one was local only and one was local and distant. Two-year overall survival was 77% for all patients. Two-year local control for all patients was 87%: 85% for the CMT group and 90% for the surgery alone group (p = 0.38). Two-year distant metastasis-free survival was 56% for all patients: 46% and 69% for the CMT and surgery patients, respectively (p = 0.10). CONCLUSIONS: The primary mode of failure is distant which often results in mortality, with local failure occurring much less commonly. The role of radiotherapy in the adjuvant management of NET remains unclear.

Radiotherapy in the treatment of patients with unresectable extrahepatic cholangiocarcinoma.

PURPOSE: Extrahepatic cholangiocarcinoma is an uncommon but lethal malignancy. We analyzed the role of definitive chemoradiotherapy for patients with nonmetastatic, locally advanced extrahepatic cholangiocarcinoma treated at a single institution. METHODS AND MATERIALS: This retrospective analysis included 37 patients who underwent external beam radiation therapy (EBRT) with concurrent chemotherapy and/or brachytherapy (BT) for locally advanced extrahepatic cholangiocarcinoma. Local control (LC) and overall survival (OS) were assessed, and univariate regression analysis was used to evaluate the effects of patient- and treatment-related factors on clinical outcomes. RESULTS: Twenty-three patients received EBRT alone, 8 patients received EBRT plus BT, and 6 patients received BT alone (median follow-up of 14 months). Two patients were alive without evidence of recurrence at the time of analysis. Actuarial OS and LC rates at 1 year were 59% and 90%, respectively, and 22% and 71%, respectively, at 2 years. Two patients lived beyond 5 years without evidence of recurrence. On univariate analysis, EBRT with or without BT improved LC compared to BT alone (97% vs. 56% at 1 year; 75% vs. 56% at 2 years; p = 0.096). Patients who received EBRT alone vs. BT alone also had improved LC (96% vs. 56% at 1 year; 80% vs. 56% at 2 years; p = 0.113). Age, gender, tumor location (proximal vs. distal), histologic differentiation, EBRT dose (≤ or >50 Gy), EBRT planning method (two-dimensional vs. three-dimensional), and chemotherapy were not associated with patient outcomes. CONCLUSIONS: Patients with locally advanced extrahepatic cholangiocarcinoma have poor survival. Long-term survival is rare. The majority of patients treated with EBRT had local control at the time of death, suggesting that symptoms due to the local tumor effect might be effectively controlled with radiation therapy, and EBRT is an important element of treatment. Novel treatment approaches are indicated in the therapy for this disease.

Intensity-modulated radiation therapy for anal malignancies: a preliminary toxicity and disease outcomes analysis.

PURPOSE: Intensity-modulated radiation therapy (IMRT) has the potential to reduce toxicities associated with chemoradiotherapy in the treatment of anal cancer. This study reports the results of using IMRT in the treatment of anal cancer. METHODS AND MATERIALS: Records of patients with anal malignancies treated with IMRT at Duke University were reviewed. Acute toxicity was graded using the NCI CTCAEv3.0 scale. Overall survival (OS), metastasis-free survival (MFS), local-regional control (LRC) and colostomy-free survival (CFS) were calculated using the Kaplan-Meier method. RESULTS: Forty-seven patients with anal malignancy (89% canal, 11% perianal skin) were treated with IMRT between August 2006 and September 2008. Median follow-up was 14 months (19 months for SCC patients). Median radiation dose was 54 Gy. Eight patients (18%) required treatment breaks lasting a median of 5 days (range, 2-7 days). Toxicity rates were as follows: Grade 4: leukopenia (7%), thrombocytopenia (2%); Grade 3: leukopenia (18%), diarrhea (9%), and anemia (4%); Grade 2: skin (93%), diarrhea (24%), and leukopenia (24%). The 2-year actuarial overall OS, MFS, LRC, and CFS rates were 85%, 78%, 90% and 82%, respectively. For SCC patients, the 2-year OS, MFS, LRC, and CFS rates were 100%, 100%, 95%, and 91%, respectively. CONCLUSIONS: IMRT-based chemoradiotherapy for anal cancer results in significant reductions in normal tissue dose and acute toxicities versus historic controls treated without IMRT, leading to reduced rates of toxicity-related treatment interruption. Early disease-related outcomes seem encouraging. IMRT is emerging as a standard therapy for anal cancer.

Durable palliation of breast cancer chest wall recurrence with radiation therapy, hyperthermia, and chemotherapy.

BACKGROUND AND PURPOSE: Chest wall recurrences of breast cancer are a therapeutic challenge and durable local control is difficult to achieve. Our objective was to determine the local progression free survival (LPFS) and toxicity of thermochemoradiotherapy (ThChRT) for chest wall recurrence. METHODS: Twenty-seven patients received ThChRT for chest wall failure from 2/1995 to 6/2007 and make up this retrospective series. All received concurrent superficial hyperthermia twice weekly (median 8 sessions), chemotherapy (capecitabine in 21, vinorelbine in 2, and paclitaxel in 4), and radiation (median 45 Gy). Patients were followed up every 1.5-3 months and responses were graded with RECIST criteria and toxicities with the NCI CTC v4.0. RESULTS: Twenty-three (85%) patients were previously irradiated (median 60.4 Gy) and 22 (81%) patients received prior chemotherapy. Median follow-up was 11 months. Complete response (CR) was achieved in 16/20 (80%) of patients with follow-up data, and 1 year LPFS was 76%. Overall survival was 23 months for patients with CR, and 5.4 months in patients achieving a partial response (PR) (p=0.01). Twenty-two patients experienced acute grade 1/2 treatment related toxicities, primarily moist desquamation. Two patients experienced 3rd degree burns; all resolved with conservative measures. CONCLUSIONS: ThChRT offers durable palliation and prolonged LPFS with tolerable acute toxicity, especially if CR is achieved.

Biologically effective dose (BED) correlation with biochemical control after low-dose rate prostate brachytherapy for clinically low-risk prostate cancer.

PURPOSE: To assess the correlation of postimplant dosimetric quantifiers with biochemical control of prostate cancer after low-dose rate brachytherapy. METHODS AND MATERIALS: The biologically effective dose (BED), dose in Gray (Gy) to 90% of prostate (D(90)), and percent volume of the prostate receiving 100% of the prescription dose (V(100)) were calculated from the postimplant dose-volume histogram for 140 patients undergoing low-dose rate prostate brachytherapy from 1997 to 2003 at Durham Regional Hospital and the Durham VA Medical Center (Durham, NC). RESULTS: The median follow-up was 50 months. There was a 7% biochemical failure rate (10 of 140), and 91% of patients (127 of 140) were alive at last clinical follow-up. The median BED was 148 Gy (range, 46-218 Gy). The median D(90) was 139 Gy (range, 45-203 Gy). The median V(100) was 85% (range, 44-100%). The overall 5-year biochemical relapse-free survival (bRFS) rate was 90.1%. On univariate Cox proportional hazards modeling, no pretreatment characteristic (Gleason score sum, age, baseline prostate-specific antigen, or clinical stage) was predictive of bRFS. The BED, D(90), and V(100) were all highly correlated (Pearson coefficients >92%), and all were strongly correlated with bRFS. Using the Youden method, we identified the following cut points for predicting freedom from biochemical failure: D(90) >or= 110 Gy, V(100) >or= 74%, and BED >or= 115 Gy. None of the covariates significantly predicted overall survival. CONCLUSIONS: We observed significant correlation between BED, D(90), and V(100) with bRFS. The BED is at least as predictive of bRFS as D(90) or V(100). Dosimetric quantifiers that account for heterogeneity in tumor location and dose distribution, tumor repopulation, and survival probability of tumor clonogens should be investigated.

Preoperative chemotherapy versus preoperative chemoradiotherapy for stage III (N2) non-small-cell lung cancer.

PURPOSE: To compare preoperative chemotherapy (ChT) and preoperative chemoradiotherapy (ChT-RT) in operable Stage III non-small-cell lung cancer. METHODS AND MATERIALS: This retrospective study analyzed all patients with pathologically confirmed Stage III (N2) non-small-cell lung cancer who initiated preoperative ChT or ChT-RT at Duke University between 1995 and 2006. Mediastinal pathologic complete response (pCR) rates were compared using a chi-square test. The actuarial overall survival, disease-free survival, and local control were estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate Cox regression analysis was also performed. RESULTS: A total of 101 patients who initiated preoperative therapy with planned resection were identified. The median follow-up was 20 months for all patients and 38 months for survivors. The mediastinal lymph nodes were reassessed after preoperative therapy in 88 patients (87%). Within this group, a mediastinal pCR was achieved in 35% after preoperative ChT vs. 65% after preoperative ChT-RT (p = 0.01). Resection was performed in 69% after ChT and 84% after ChT-RT (p = 0.1). For all patients, the overall survival, disease-free survival, and local control rate at 3 years was 40%, 27%, and 66%, respectively. No statistically significant differences were found in the clinical endpoints between the ChT and ChT-RT subgroups. On multivariate analysis, a mediastinal pCR was associated with improved disease-free survival (p = 0.03) and local control (p = 0.03), but not overall survival (p = 0.86). CONCLUSION: Preoperative ChT-RT was associated with higher mediastinal pCR rates but not improved survival.

Concurrent chemoradiotherapy in resected extrahepatic cholangiocarcinoma.

PURPOSE: Extrahepatic cholangiocarcinoma is a rare malignancy. Despite radical resection, survival remains poor, with high rates of local and distant failure. To clarify the role of radiotherapy with chemotherapy, we performed a retrospective analysis of resected patients who had undergone chemoradiotherapy. METHODS AND MATERIALS: A total of 45 patients (13 with proximal and 32 with distal disease) underwent resection plus radiotherapy (median dose, 50.4 Gy). All but 1 patient received concurrent fluoropyrimidine-based chemotherapy. The median follow-up was 30 months for all patients and 40 months for survivors. RESULTS: Of the 45 patients, 33 underwent adjuvant radiotherapy, and 12 were treated neoadjuvantly. The 5-year actuarial overall survival, disease-free survival, metastasis-free survival, and locoregional control rates were 33%, 37%, 42%, and 78%, respectively. The median survival was 34 months. No patient died perioperatively. Patient age