Allogeneic stem cell transplantation for Philadelphia chromosome-positive acute myeloid leukemia.

Philadelphia chromosome-positive acute myeloid leukemia (Ph(+)-AML) has a poor response to anthracycline- and cytarabine-containing regimens, high relapse rate, and dismal prognosis. Although therapy with imatinib and allogeneic stem cell transplantation (allo-SCT) is promising, relatively short follow-up limits understanding of long-term results of these therapies. This report describes the outcomes of 3 cases of Ph(+)-AML diagnosed and transplanted at the University of Nebraska Medical Center between 2004 and 2011. These patients, young and without major comorbidities, received induction therapy with 7 days of cytarabine and 3 days of idarubicin along with imatinib and consolidation therapy with high-dose cytarabine (with or without imatinib). All patients underwent 10/10 HLA-matched peripheral blood allo-SCT (sibling donor for first and third patients and unrelated donor for the second patient; all had acute graft-versus-host disease (GVHD), and the first and third patients had chronic GVHD. All patients are currently alive and experiencing complete remission at 116, 113, and 28 months after diagnosis, respectively. This report shows that the use of allo-SCT with resultant graft-versus-leukemia effect and the addition of imatinib can result in long-term remission and possible cure in some patients with Ph(+)-AML.

Non-small cell lung cancer.

Most patients with non-small cell lung cancer (NSCLC) are diagnosed with advanced cancer. These guidelines only include information about stage IV NSCLC. Patients with widespread metastatic disease (stage IV) are candidates for systemic therapy, clinical trials, and/or palliative treatment. The goal is to identify patients with metastatic disease before initiating aggressive treatment, thus sparing these patients from unnecessary futile treatment. If metastatic disease is discovered during surgery, then extensive surgery is often aborted. Decisions about treatment should be based on multidisciplinary discussion.

The impact of signet-ring cell carcinoma histology on bladder cancer outcome.

BACKGROUND: Signet-ring cell carcinoma (SRCC) of the urinary bladder is a rare entity. No previous studies have directly compared the cancer-specific survival of patients with SRCC to patients with urothelial carcinoma (UC) of the urinary bladder. MATERIALS AND METHODS: Patients with diagnosis of urinary bladder SRCC and UC were identified in the Surveillance, epidemiology, and end results program (SEER) (2001-2004). Demographic of patients and clinical characteristics at diagnosis were compared. Differences in cancer-specific survival were compared using univariate and multivariate analysis. RESULTS: A total of 103 patients with SRCC and 14,648 patients with UC were indentified. Patients with SRCC were younger (P < 0.001), more commonly presented with higher-grade histology (P < 0.001) and advanced stage disease (P < 0.001), in comparison with patients with UC. The 3-year cancer-specific survival rate was 67.0% for patients with UC and 33.2% for SRCC. On multivariate analysis, there was an increased mortality risk in patients with SRCC versus UC (HR 1.49, 95% CI 1.11-2.00, P < 0.01). CONCLUSIONS: Even after adjusting for demographic, surgical, and pathological factors, cancer-specific survival rate was significantly worse in patients with SRCC compared to UC. Further research into the biology of this rare tumor is required to explain these results.

Current concepts in the diagnosis and management of small-cell lung cancer.

Despite a decreasing incidence in the United States, small-cell lung cancer (SCLC) remains a major clinical problem, with approximately 30,000 new cases each year. The diagnosis of SCLC is usually not difficult. The Veterans Administration Lung Study Group (VALSG) staging system is less accurate than the American Joint Committee of Cancer tumor-node-metastasis (TNM) system (7th edition) at predicting survival in SCLC, especially in lower stage disease. Surgery has not played a major part in the management of SCLC, but emerging data suggest that resection may have a role in earlier stage disease. While the frontline treatment of SCLC has not changed significantly in the past decade, newer agents that are currently being investigated provide hope for better treatment of relapsed/refractory disease for the future.

Clinical features of sarcomatoid carcinoma (carcinosarcoma) of the urinary bladder: analysis of 221 cases.

Background. Urinary bladder sarcomatoid carcinoma (carcinosarcoma) is rare. The objective of this study was to examine the epidemiology, natural history, and prognostic factors of urinary bladder carcinosarcoma using population-based registry. Methods. The Surveillance, Epidemiology, and End Results (SEER) Program database was used to identify cases by tumor site and histology codes. The association between clinical and demographic characteristics and long-term survival was examined. Results. A total of 221 histology confirmed cases were identified between 1973 and 2004, this accounted for approximately 0.11% of all primary bladder tumors during the study period. Median age of the patients was 75 years (range 41-96). Of the patients with a known tumor stage (N = 204), 72.5% had a regional or distant stage; 98.4% of patients with known histology grade (N = 127), had poorly or undifferentiated histology. Multiple primary tumors were indentified in about 40% of study subjects. The majority of patients (95.9%) received cancer directed surgery, 35.8% had radical or partial cystectomy, 15.8% of patients received radiation therapy combination with surgery. The median overall survival was 14 months (95% CI 7-21 months). 1-, 5-, and 10-year cancer specific survival rate were 53.9%, 28.4% and 25.8%. In a multivariate analysis, only tumor stage was found to be a significant prognostic factor for disease-specific survival. Conclusions. Urinary bladder carcinosarcoma commonly presented as high grade, advanced stage and aggressive behavior with a poor prognosis. Emphasis on early detection, including identification of risk factors is needed to improve the outcome for patients with this malignancy.

A phase I study of weekly doxorubicin and oral topotecan for patients with relapsed or refractory small cell lung cancer (SCLC): A Fred and Pamela Buffet Cancer Center Clinical Trials Network study.

BACKGROUND: Relapsed/refractory small cell lung cancer (SCLC) has a poor prognosis, with no good options. We evaluated a novel combination of topotecan and doxorubicin, providing sequential topoisomerase I and II inhibition, in this setting. MATERIALS AND METHODS: Adult patients (>19 years) with relapsed/refractory SCLC, who had received at least one prior chemotherapy regimen were eligible. Patients received escalating doses of oral topotecan on days 1-5 of each three week cycle (maximum - 5 cycles). The dosing cohorts were: 0.85 mg/m2, 1.05 mg/m2, 1.35 mg/m2, 1.65 mg/m2 and 2.30 mg/m2. All patients received weekly doxorubicin 20 mg/m2 intravenously starting day 6 of the first cycle and continued weekly for a maximum of 15 weeks. In the absence of pre-specified dose limiting toxicities (DLT), patients were enrolled serially to escalated dose level cohorts. RESULTS: Twenty-two patients were enrolled, of which 20 were evaluable. Median age was 61 years; 74% were male and 95% were Caucasian. Hematologic side effects were the most common adverse events. There were no therapy-related Grade 5 toxicities. Incidence of DLT based on cohorts were: DL2: 1/6 (Grade 4 thrombocytopenia), DL3: 1/6 (AST elevation) and DL4: 2/4 (Grade 4 thrombocytopenia). Response rate was 20% (4/20) and disease control rate (SD + PR) was 36%. The median progression free and overall survival were 3.6 months and 6 months, respectively. CONCLUSIONS: The combination of topotecan and doxorubicin was safe and effective in relapsed/refractory SCLC. The maximum tolerated dose of oral topotecan was 1.35 mg/m2 when given concurrently with weekly doxorubicin.

Association of positive family history with survival of patients with lung cancer.

BACKGROUND: Risk factors for development of lung cancer include a family history of the disease. The effect of family history on lung cancer outcomes is unknown. A study was conducted to investigate this. METHODS: The medical records of all patients with lung cancer seen in an academic medical oncology lung cancer clinic between 1999 and 2006 were reviewed for outcomes and family history of lung cancer. chi(2)-test and Wilcoxon test were used for univariate comparisons, while Cox Proportional Hazards regression analysis was used to evaluate the adjusted risk of death. Univariate probability of survival was computed using Kaplan-Meier estimate and compared using the log-rank test. RESULTS: Of the 560 patients evaluated, 289 (51%) were male and 519 (93%) had a smoking history. Of the 148 patients (26%) with a family history of lung cancer, 115 had an affected first-degree relative. No association between family history and histology or stage at diagnosis was detected. Median survival in patients with a family history of lung cancer was 53 months compared to 58 months in patients without such a history (p=0.06). Patients with a positive family history had an adjusted relative risk of death of 1.65 (95% CI: 1.07-2.56; p=0.02) compared to those without a family history. This risk was especially increased in those with an affected first-degree relative (RR: 1.72; 95% CI: 1.08-2.75, p=0.02). CONCLUSIONS: Lung cancer patients with a first-degree relative with lung cancer have a poorer outcome than those without such a history.

A phase II study of estramustine, docetaxel, and exisulind in patients with hormone- refractory prostate cancer: results of cancer and leukemia group B trial 90004.

PURPOSE: Docetaxel/estramustine is a known active regimen in hormonerefractory prostate cancer (HRPC). A phase II study was conducted to assess the safety and efficacy of docetaxel/estramustine combined with exisulind, an apoptotic antineoplastic drug. PATIENTS AND METHODS: Eighty men with chemotherapy-naive HRPC were enrolled in a multicenter, cooperative group study. The treatment regimen consisted of oral estramustine (280 mg 3 times daily for 5 days), docetaxel 70 mg/m2, oral exisulind (250 mg twice daily), oral dexamethasone (8 mg twice daily for 3 days), and oral warfarin (2 mg daily). RESULTS: Seventy-five eligible patients were treated with a median of 6 cycles of therapy. Fortyseven patients (62.7%; 95% CI, 50.7%-73.6%) had a > or = 50% decline in prostate-specific antigen levels. Forty-six patients had measurable disease with 6 partial responses (13%; 95% CI, 4.9%-26.3%). The main grade 3/4 toxicities were neutrophils (79%), fatigue (15%), and thrombosis/embolism (10%). The median time to first progression was 5.1 months (95% CI, 4.4-6.3 months) and the median survival time was 17.8 months (95% CI, 14.7-20.1 months). CONCLUSION: The combination of estramustine/docetaxel/exisulind was associated with significant thomboembolic toxicity despite prophylactic warfarin. The contribution of exisulind to toxicity is uncertain. Prostate-specific antigen decline, response rates, and progression-free and overall survival are similar to those reported with docetaxel/estramustine.

Limited-stage small-cell lung cancer: therapeutic options.

Almost 40% of patients with newly diagnosed small-cell lung cancer (SCLC) have disease confined to the ipsilateral hemithorax and within a single radiation port, i.e., limited-stage disease. The median survival for this group of patients after treatment is approximately 15 months, with one in every four patients surviving 2 years. Current optimal treatment consists of chemotherapy with platinum/etoposide, given concurrently with thoracic radiation. Surgery may represent an option for very early-stage disease, but its added value is uncertain. Prophylactic cranial irradiation (PCI) is used for patients with limited-stage SCLC who have achieved a complete response following initial therapy, as it decreases the risk of brain metastases and provides an overall survival benefit. Newer targeted agents are currently being evaluated in this disease and hold the promise of improving current outcomes seen in patients with early-stage disease.

Weekly vinorelbine and paclitaxel in older patients with advanced non-small cell lung cancer: A phase II Fred and Pamela Buffet Cancer Center Clinical Trials Network study.

OBJECTIVE: Platinum-based doublet chemotherapy is the standard for most patients with advanced non-small cell lung cancer (NSCLC). Toxicity concerns limit chemotherapy for patients over 70years. Vinorelbine and paclitaxel are effective as single agents in advanced NSCLC. This phase II study evaluates safety and efficacy of a combination of these two agents in patients >70years with advanced NSCLC. MATERIALS AND METHODS: Patients with treatment naïve metastatic NSCLC received two cycles comprising 6 weekly doses of vinorelbine and paclitaxel, with restaging scans at week 8. Patients with radiographic progression came off study. The estimated sample size was 29. Toxicity analyses were conducted after 10 patients and again after 19 patients were enrolled. Outcomes were safety and efficacy, progression free (PFS) and overall survival (OS) and quality of life (QOL). RESULTS: The study closed at second interim analysis as 6/19 patients had ≥grade 4 non-hematologic toxicity (respiratory failure, sepsis, ischemic encephalopathy, pneumonia, hypoxemia, cardiopulmonary arrest, neutropenic fever, death). Of the 16 evaluable patients, 7 completed the study. Disease control rate (partial response+stable disease) was 47% (n=9); 37% (n=7) progressed. No complete responses were seen. Median PFS was 3.5months (95% CI: 1.4, 5.5) and OS 7.8months (95% CI: 1.9, 13.6). QOL did not change compared to baseline, at week 9, but increased at week 17. CONCLUSIONS: Although the combination met its response end points, increased toxicity makes this combination unsuitable for older patients. While QOL improved over the study, the small sample hinders interpretation.

Epidermal Growth Factor Receptor Mutational Status and Brain Metastases in Non-Small-Cell Lung Cancer.

INTRODUCTION: Epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancers (NSCLC) may be more common in patients with brain metastases. Previous studies, however, did not adjust for effects of confounding variables. METHODS: This retrospective study included 1,522 consecutive patients with NSCLC, whose tumors were diagnosed and tested for EGFR mutations at the University of Nebraska Medical Center (Omaha, NE) and Tata Memorial Hospital (Mumbai, India). Multivariate logistic regression was used to identify any association between EGFR status and clinical factors. RESULTS: EGFR mutations were more common in females than males (38.7% v 24.8%), Asians than whites (31.3% v 13.4%), nonsmokers than smokers (40.2% v 14.6%), alcohol nonconsumers than users (32.4% v 15.8%), adenocarcinoma than other histology types (32.7% v 10.3%), and patients with brain metastases than extracranial or no metastases (39.4% v 29.8% v 15.1%; P < .001 for all comparisons). There was a higher likelihood of an EGFR mutation among patients with brain metastases (odds ratio, 1.8; P < .001). The median overall survival (OS) was 19.8 months. Patients with brain metastases had a shorter median OS (15 v 20.6 months; P = .02). However, in the cohort of EGFR mutation-positive patients, there was no difference in median OS between patients with and without brain metastases (20.8 v 25.1 months; P = .11). CONCLUSION: There is a nearly two-fold higher incidence of EGFR mutations in NSCLC among patients with brain metastases at diagnosis. EGFR mutations did not predict for outcomes from brain metastases.

Vincristine-laden platelet transfusion for patients with refractory thrombocytopenia.

BACKGROUND: The aim of the present study was to assess the efficacy of vincristine-laden platelet transfusion for patients with refractory thrombocytopenia. PATIENTS AND METHODS: Twenty evaluable patients who received vincristine-laden platelets for refractory thrombocytopenia were included in this retrospective study. Vincristine (1 mg) was added to the platelets and incubated for one hour prior to transfusion. Serial platelet counts following vincristine-laden platelet transfusion and units of platelets transfused in the week prior to and the week after transfusion of vincristine-laden platelets were evaluated. RESULTS: The underlying diseases of the patients were lung cancer (n =4), breast cancer following autologous hematopoietic stem cell transplantation and acute myeloid leukemia (n=3 each), myelodysplastic syndrome (n=2), acute lymphoid leukemia, chronic lymphoid leukemia, chronic myeloid leukemia, multiple myeloma, ovarian cancer, aspergillosis, cytomegalovirus infection and systemic lupus erythematosus (n = 1 each). The median rate of change of platelet count after transfusion of vincristine-laden platelets was 550/microL/day (range, -1,000 to 12,8001/microL/day; p=0.003). The median change in the number of units of platelets transfused in the week following vincristine-laden platelet transfusion was -1.5 as compared to the week prior to the transfusion (p=0.031). Patients with a primary marrow disorder exhibited no difference in either the rate of change in platelet count or in the difference in the units of platelets transfused compared to those without a primary bone marrow disorder. CONCLUSION: Vincristine-laden platelet transfusion was associated with significantly increased platelet counts and a subsequent decrease in platelet transfusion.

Early Stage Non-Small-Cell Lung Cancer in Octogenarian and Older Patients: A SEER Database Analysis.

BACKGROUND: The median age at diagnosis of lung cancer is 70 years. However, the evidence guiding the management of octogenarians and older patients with non-small-cell lung cancer (NSCLC), is based on data derived from younger patients and may not be appropriate. METHODS: Patients ≥ 80 years diagnosed with clinical stages I and II NSCLC, between 1988 and 2007, were identified from the SEER database. Patients were classified according to treatments received: no treatment, surgery only, radiation only, and surgery + radiation. Factors associated with survival were assessed using the Cox proportional hazards model. RESULTS: There were 1338 cases of early stage NSCLC in octogenarians. Surgery was the most common treatment modality. The median overall survival was 3.8 years for patients who had surgery, compared with 1.6 years, 1.6 years, and 0.9 years for those who received surgery + radiation, radiation alone, and no treatment, respectively (P < .0001). Factors significantly associated with worse overall survival following surgery included increasing age (hazard ratio [HR], 1.08; P = .0005), male gender (HR, 1.33; P = .01), stage II (HR, 2.21; P < .0001), and squamous histology (HR, 1.36; P = .01). CONCLUSION: Surgical resection is associated with long-term survival outcomes in a substantial proportion of octogenarian and older patients with early stage lung cancer and should not be withheld on the basis of age alone.

Effect of Surgical Intervention on Survival of Patients With Clinical N2 Non-Small Cell Lung Cancer: A Veterans' Affairs Central Cancer Registry (VACCR) Database Analysis.

BACKGROUND: Optimal management of locally advanced non-small cell lung cancer (NSCLC) lacks consensus. A retrospective analysis of patient data entered in the Veterans Affairs Central Cancer Registry was conducted to evaluate these issues. PATIENTS AND METHODS: Data of patients with cT1-4, cN2, and cM0 NSCLC diagnosed in the VA Health System between 1995 and 2003 were evaluated. Age, sex, race, smoking history, TNM stage, treatment, and overall survival were abstracted. Survival was compared using multivariate Cox proportional hazards regression analysis. RESULTS: Of the 7328 patients analyzed, 7218 (98.5%) were male, 6061 (82.7%) were white, and 321 (4.4%) were never smokers. The treatment received included: none, 23.8%; chemotherapy alone, 14.3%; radiation alone, 23%; and chemoradiation (sequential or concurrent), 31.4%. Only 7.5% of patients had a surgical resection, with or without multimodality therapy. The median survival (months) of these patient groups were: surgery, 19.3; chemoradiation, 13; chemotherapy alone, 9.2; radiation alone, 7.3; and no treatment, 4 (P<0.0001). African Americans had a significantly decreased risk of mortality compared with whites (hazard ratio 0.92; 95% confidence interval, 0.87-0.98). CONCLUSIONS: Inclusion of surgical resection as a treatment modality was associated with a better overall survival. Also, African Americans appeared to do better than whites. These hypothesis-generating findings should be useful in the ongoing pursuit of better treatment strategies for locally advanced NSCLC.

Autologous transplantation for aggressive non-Hodgkin's lymphoma: results of a randomized trial evaluating graft source and minimal residual disease.

PURPOSE: To determine whether the source of autologous hematopoietic stem cells altered the clinical outcomes of patients undergoing high-dose chemotherapy and hematopoietic stem-cell transplantation (HSCT) for aggressive non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Of 105 high-risk, persistent, or relapsed NHL patients slated for an autologous HSCT entered onto this trial, 93 eligible patients were randomized to receive cytokine-naive autologous bone marrow transplantation (ABMT) (n = 46) or mobilized peripheral-blood stem-cell transplantation (PBSCT) (n = 47). All patients received carmustine, etoposide, cytarabine, and cyclophosphamide as the conditioning regimen. PBSCT patients also received identical mobilization with granulocyte colony-stimulating factor (G-CSF) 10 microg/kg/d, and both groups received G-CSF 5 microg/kg/d after the infusion of the stem-cell product until neutrophil engraftment. RESULTS: PBSCT patients had significantly faster engraftment of all cell lineages: median time to absolute neutrophil count > or = 500/microL, 10 days versus 13 days on the ABMT arm; median time to platelet count greater than 20,000/microL untransfused, 11 days versus 15 days on the ABMT arm; and median time to RBC transfusion independence, 8 days versus 16 days on the ABMT arm. The complete response rate was 72% for PBSCT and 54% for ABMT. The death rate before posttransplant day 100 was 2% on the ABMT arm and 6% on PBSCT arm. Event-free survival was 37% for PBSCT and 37% for ABMT. However, overall survival for PBSCT was 61% compared with 43% for ABMT. CONCLUSION: Patients with aggressive NHL receiving HSCT randomized to PBSCT demonstrated improved neutrophil engraftment and platelet and RBC transfusion independence. The complete response rate and EFS were not statistically different by randomization arm. Patients whose harvests were positive for minimal residual disease by molecular analysis had poorer EFS.

A murine model of bone marrow micrometastasis in breast cancer.

Bone marrow (BM) is one of the most common sites and often the first clinical indication of metastatic progression of breast cancer. Multivariate analyses have shown that the presence of cytokeratin positive tumor cells in the marrow of women with newly diagnosed stage I, II or III breast cancer is an independent predictor of survival. The objective of this study was to develop an orthotopic model of spontaneous BM metastasis to facilitate studies of this process. A murine mammary adenocarcinoma cell line, Clone 66, was transduced with the neomycin resistance gene (Cl66neo) and injected orthotopically into female Balb/c mice. Polymerase chain reaction (PCR) for the neo gene performed on BM cells harvested from tumor bearing mice demonstrated as few as 10(2) injected tumor cells produced BM micrometastases at 4 weeks postinjection. Small foci of tumor cells were identified in the mammary fatpad (mfp) without gross evidence of primary tumors. Higher doses of tumor cells produced BM micrometastases, detectable by PCR, at one week post-injection. Constructs containing green fluorescent protein (GFP) and the neomycin resistance gene (neo) were also transduced into Clone 66 cells (Cl66-GFPneo) and injected into the mfp. GFP transduced tumor cells were identified in multiple tissues in addition to BM by flow cytometric analysis (FACS) but less 13% of the animals developed gross metastases. This model is a clinically relevant tool for the analysis of organ specificity of metastasis.

Association between race and survival of patients with non--small-cell lung cancer in the United States veterans affairs population.

BACKGROUND: Racial disparities in outcomes of non-small-cell lung cancer (NSCLC) patients in the United States are well documented. A retrospective analysis of patients in the Veterans Affairs Central Cancer Registry was conducted to determine whether similar disparities exist in a population with a single-payer, accessible health care system. PATIENTS AND METHODS: Demographic data of patients diagnosed with NSCLC between January 1995 and February 2009 were analyzed using Kruskal-Wallis test or the χ(2) test. Multivariate Cox proportional hazards regression analysis was used to compare survival among races. RESULTS: Of the 82,414 patients, 98% were male, 82% had a smoking history, and 81% were Caucasian. Caucasian individuals had better prognostic features compared with African-American individuals (stage I/II [24% vs. 21%]; Grade I/II [21% vs. 17%]). A larger proportion of Caucasian compared with African-American individuals received stage-appropriate treatment (surgery for stage I [48% vs. 41%; P < .001]; chemotherapy for stage IV [18% vs. 16%; P = .003]). African-American individuals had a lower risk of mortality compared with Caucasian individuals (hazard ratio, 0.94; 95% confidence interval, 0.92-0.96). CONCLUSION: Although African-American patients had a higher stage and grade of NSCLC, they had a better overall survival than Caucasian patients. In a single-payer system with accessible health care, previously described racial differences in lung cancer outcomes were not observed.

Outcomes following surgical treatment compared to radiation for stage I NSCLC: a SEER database analysis.

INTRODUCTION: Outcomes following surgery are better than following radiation therapy (RT), for stage I NSCLC. Whether this is due to selection of healthier patients for surgery is unclear. This study was undertaken to compare outcomes between surgical patients and patients who were surgical candidates but did not receive surgery. METHODS: Data of patients with stage I NSCLC between 1988 and 2007, included in the SEER database were analyzed. Overall survival (OS) was examined by treatment type (surgery only, radiation only, surgery and radiation, and no treatment). OS was compared between RT patients who refused surgery and those not fit for surgery. Cox proportional hazards model was used to compare outcomes by treatment type. RESULTS: Data from 8579 patients with stage I NSCLC during 1988-2007 were analyzed. Use of RT alone increased during the study period. An increasing proportion of patients with stage I lung cancer chose to have no treatment. On multivariate analysis, OS was better among patients who had surgery. There was a 56% improvement in survival among patients who had surgery compared to fit patients who refused surgery (HR 0.437, 95% CI 0.301-0.632). Patients who refused surgery had a better OS than those who were not fit for surgery (log-rank p = 0.01). Patients who received RT alone or no treatment had a significant improvement in five-year OS during the latter part of the study period (1998-2002 vs. 1988-1992). CONCLUSIONS: In medically fit patients, outcomes following surgery are better than those following conventional radiation. Hence surgery should be chosen over conventional radiation, whenever possible. Outcomes following RT show an improvement over time reflecting improvement in radiation techniques.