Radiation Therapy for Pancreatic Cancer: Executive Summary of an ASTRO Clinical Practice Guideline.

PURPOSE: This guideline systematically reviews the evidence for treatment of pancreatic cancer with radiation in the adjuvant, neoadjuvant, definitive, and palliative settings and provides recommendations on indications and technical considerations. METHODS AND MATERIALS: The American Society for Radiation Oncology convened a task force to address 7 key questions focused on radiation therapy, including dose fractionation and treatment volumes, simulation and treatment planning, and prevention of radiation-associated toxicities. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS: The guideline conditionally recommends conventionally fractionated or stereotactic body radiation for neoadjuvant and definitive therapy in certain patients and conventionally fractionated regimens for adjuvant therapy. The task force suggests a range of appropriate dose-fractionation schemes and provides recommendations on target volumes and sequencing of radiation and chemotherapy. Motion management, daily image guidance, use of contrast, and treatment with modulated techniques are all recommended. The task force supported prophylactic antiemetic medication, and patients may also benefit from medications to reduce acid secretion. CONCLUSIONS: The role of radiation in the management of pancreatic cancer is evolving, with many ongoing areas of active investigation. Radiation therapy is likely to become even more important as new systemic therapies are developed and there is increased focus on controlling local disease. It is important that the nuances of available data are discussed with patients and families and that care be coordinated in a multidisciplinary fashion.

Accuracy of positron emission tomography in identifying hilar (N1) lymph node involvement in non-small cell lung cancer: Implications for stereotactic body radiation therapy.

PURPOSE: To assess the efficacy of preoperative positron emission tomography (PET) to stage the ipsilateral hilum in resected non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: All patients who underwent surgery for NSCLC between 1995 and 2008 were evaluated. Patients who underwent preoperative PET imaging at our institution and had hilar nodal sampling were included. Those whose primary tumors extended to the hilum or who received preoperative chemotherapy or radiation therapy were excluded. All PET studies were interpreted by an attending nuclear medicine radiologist and were scored as positive or negative in the hilum or peribronchial area based on visual analysis alone. A 2-sided Fisher exact test compared patient subgroups. RESULTS: During the time interval, 1558 patients underwent surgery for NSCLC, of whom 484 were eligible for this analysis. The ipsilateral hilum was positive on preoperative PET in 107 patients. The median number of N1 lymph nodes sampled was 4 (range, 1-31). Positive ipsilateral N1 lymph nodes were identified pathologically in 91 patients (19%). Among the 91 patients with involved N1 lymph nodes, 40 were PET positive resulting in a sensitivity of 44%. Among 393 patients without pathologic involvement of hilar lymph nodes, 326 were PET negative resulting in a specificity of 83%. The positive predictive and negative predictive values were 37% and 86%, respectively. CONCLUSIONS: Positron emission tomography appears to have limitations in staging the ipsilateral hilar lymph nodes. Invasive sampling is appropriate if treatment would differ based on the nodal status.

Preoperative chemoradiotherapy for locally advanced gastric cancer.

BACKGROUND: To examine toxicity and outcomes for patients treated with preoperative chemoradiotherapy (CRT) for gastric cancer. METHODS: Patients with gastroesophageal (GE) junction (Siewert type II and III) or gastric adenocarcinoma who underwent neoadjuvant CRT followed by planned surgical resection at Duke University between 1987 and 2009 were reviewed. Overall survival (OS), local control (LC) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Toxicity was graded according to the Common Toxicity Criteria for Adverse Events version 4.0. RESULTS: Forty-eight patients were included. Most (73%) had proximal (GE junction, cardia and fundus) tumors. Median radiation therapy dose was 45 Gy. All patients received concurrent chemotherapy. Thirty-six patients (75%) underwent surgery. Pathologic complete response and R0 resection rates were 19% and 86%, respectively. Thirty-day surgical mortality was 6%. At 42 months median follow-up, 3-year actuarial OS was 40%. For patients undergoing surgery, 3-year OS, LC and DFS were 50%, 73% and 41%, respectively. CONCLUSIONS: Preoperative CRT for gastric cancer is well tolerated with acceptable rates of perioperative morbidity and mortality. In this patient cohort with primarily advanced disease, OS, LC and DFS rates in resected patients are comparable to similarly staged, adjuvantly treated patients in randomized trials. Further study comparing neoadjuvant CRT to standard treatment approaches for gastric cancer is indicated.

Technical considerations in radiation therapy for gastroesophageal junction cancer.

Contemporary randomized trials have demonstrated that radiation therapy combined with chemotherapy and surgery improves survival in both the neoadjuvant and adjuvant treatment of gastroesophageal cancers. Consequently, radiation treatment planning and administration have taken on an added importance to ensure optimal outcomes as well as minimize treatment-related morbidity. This article highlights recent technical advances and considerations for radiation therapy planning for gastroesophageal junction tumors.

How well does the new lung cancer staging system predict for local/regional recurrence after surgery?: A comparison of the TNM 6 and 7 systems.

INTRODUCTION: To evaluate how well the tumor, node, metastasis (TNM) 6 and TNM 7 staging systems predict rates of local/regional recurrence (LRR) after surgery alone for non-small cell lung cancer. METHODS: All patients who underwent surgery for non-small cell lung cancer at Duke between 1995 and 2005 were reviewed. Those undergoing sublobar resections, with positive margins or involvement of the chest wall, or those who received any chemotherapy or radiation therapy (RT) were excluded. Disease recurrence at the surgical margin, or within ipsilateral hilar and/or mediastinal lymph nodes, was considered as a LRR. Stage was assigned based on both TNM 6 and TNM 7. Rates of LRR were estimated using the Kaplan-Meier method. A Cox regression analysis evaluated the hazard ratio of LRR by stage within TNM 6 and TNM 7. RESULTS: A total of 709 patients were eligible for the analysis. Median follow-up was 32 months. For all patients, the 5-year actuarial risk of LRR was 23%. Conversion from TNM 6 to TNM 7 resulted in 21% stage migration (upstaging in 13%; downstaging in 8%). Five-year rates of LRR for stages IA, IB, IIA, IIB, and IIIA disease using TNM 6 were 16%, 26%, 43%, 35%, and 40%, respectively. Using TNM 7, corresponding rates were 16%, 23%, 37%, 39%, and 30%, respectively. The hazard ratios for LRR were statistically different for IA and IB in both TNM 6 and 7 but were also different for IB and IIA in TNM 7. CONCLUSIONS: LRR risk increases monotonically for stages IA to IIB in the new TNM 7 system. This information might be valuable when designing future studies of postoperative RT.

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.

Radiation therapy advances for treatment of anal cancer.

Radiation therapy (RT) is established as the primary treatment of squamous cell carcinoma of the anus. Multiple randomized trials have shown that combined modality therapy with RT, 5-fluorouracil, and mitomycin-C results in high rates of local control, disease-free survival, and sphincter preservation. However, treatment-related toxicity using conventional radiation approaches remains high and may compromise therapeutic efficacy because of prolonged treatment breaks and inability to deliver adequate radiation dose. Recent developments, including the use of PET for staging, radiation planning, and response assessment, and advanced RT planning using intensity-modulated radiation therapy (IMRT), may decrease acute and late treatment-related toxicity, provide high-dose target conformality, and permit safe radiation dose escalation. This article reviews the basic principles of IMRT and highlights current literature on these recent advances and the application of new RT techniques.

Intensity-modulated radiation therapy for anal cancer.

The contemporary treatment of anal cancer is combined-modality therapy with radiation therapy, fluorouracil, and mitomycin. This therapy results in long-term disease-free survival and sphincter preservation in the majority of patients. Tempering these positive results is the high rate of treatment-related morbidity associated with chemoradiation therapy for anal cancer. The use of intensity-modulated radiation therapy (IMRT) has the potential to reduce acute and chronic treatment-related toxicity, minimize treatment breaks, and potentially improve disease-related outcomes by permitting radiation dose escalation in selected cases.

Influence of demographic factors on outcome of collecting duct carcinoma: a Surveillance, Epidemiology, and End Results (SEER) database analysis.

BACKGROUND: Collecting duct carcinoma (CDC) is a rare tumor that is difficult to analyze in a single-institution setting. The Surveillance, Epidemiology, and End Results (SEER) database was used to examine demographics and outcomes of CDC. PATIENTS AND METHODS: The SEER registry was queried for patients diagnosed with CDC from 1973 to 2004 who also had available demographic, stage, and survival information (n = 98). Stage at presentation as a function of gender and as a function of race were compared using the chi2 test. Relative survival (RS) curves were computed and were compared using the log-rank test; stage-specific relative survival rates were compared across subgroups using the chi2 test. Stage at presentation was not influenced by race (P = .5) or by gender (P = .488). RESULTS: Three-year relative survival rates for localized, regional, and distant disease were 93%, 45%, and 6%, respectively (P < .001). Three-year RS were 58% and 33% for White and Black patients, respectively (P = .354), and for males and females, RS was 58% and 45%, respectively (P = .475). Furthermore, there were no significant differences in 3-year stage-specific relative survival rates by race (P = .425) or gender (P = .245). CONCLUSION: this study is the largest analysis of CDC and the first to explore the influence of demographic factors on outcomes. Within stated limitations, there appear to be no significant differences in patterns of disease presentation or relative survival rates based on race or sex. Further work is needed to improve outcomes, particularly for patients with regional or distant disease at presentation.

Heterotopic ossification in high-energy wartime extremity injuries: prevalence and risk factors.

BACKGROUND: Heterotopic ossification in the extremities remains a common complication in the setting of high-energy wartime trauma, particularly in blast-injured amputees and in those in whom the definitive amputation was performed within the zone of injury. The purposes of this cohort study were to report the experience of one major military medical center with high-energy wartime extremity wounds, to define the prevalence of heterotopic ossification in these patients, and to explore the relationship between heterotopic ossification and other potential independent predictors. METHODS: We retrospectively reviewed the records and radiographs of all combat-wounded patients admitted to this institution between March 1, 2003, and December 31, 2006. Patients with a minimum of two months of radiographic follow-up who underwent at least one orthopaedic procedure on an extremity constituted our study group; those who underwent at least one orthopaedic procedure but had not had heterotopic ossification develop constituted the control group. Variables recorded for each study subject included age and sex, location and mechanism of injury, method(s) of fracture fixation, number of débridement procedures, duration of negative pressure therapy, location of heterotopic ossification, presence and severity of traumatic brain injury, and Injury Severity Scores. RESULTS: During the study period, 1213 war-wounded patients were admitted. Of those patients, 243 (157 in the heterotopic ossification group and eighty-six controls) met the inclusion criteria. The observed rate of heterotopic ossification was 64.6%. A significant relationship was detected between heterotopic ossification and the presence (p = 0.006) and severity (p = 0.003) of a traumatic brain injury. Risk factors for the development of heterotopic ossification were found to be an age of less than thirty years (p = 0.007, odds ratio = 3.0), an amputation (p = 0.048, odds ratio = 2.9), multiple extremity injuries (p = 0.002, odds ratio = 3.9), and an Injury Severity Score of >or=16 (p = 0.02, odds ratio = 2.2). CONCLUSIONS: The prevalence of heterotopic ossification in war-wounded patients is higher than that in civilian trauma. Although trends associated with local wound conditions were identified, the risk factors for the development of heterotopic ossification found in this study suggest that systemic causes predominate.

Obesity following kidney transplantation and steroid avoidance immunosuppression.

Obesity is an important co-morbidity within end-stage renal disease (ESRD) and renal transplant populations. Previous studies have suggested that chronic corticosteroids result in increased body weight post-transplant. With the recent adoption of steroid-sparing immunosuppressive strategies, we evaluated the effect of these strategies on body mass index (BMI) after renal transplantation. We examined 95 renal transplant recipients enrolled in National Institutes of Health clinical transplant trials over the past three yr who received either lymphocyte depletion-based steroid sparing or traditional immunosuppressive therapy that included steroids for maintenance immunosuppression. Recipients were overweight prior to transplant and no significant differences existed in pre-transplant BMI among treatment groups. Regardless of therapy, BMI increased post-transplant in all recipients. The BMI increase consisted of an average weight gain of 5.01 +/- 7.12 kg (mean, SD) post-transplant. Additionally, in a number of recipients placed on maintenance steroids, subsequent withdrawal at a mean of 100 d post-transplant had no impact on weight gain. Thus, body weight and BMI increase following kidney transplantation, even in the absence of steroids. Thus, patients gain weight after renal transplantation regardless of the treatment strategy. Steroid avoidance alone does not reduce risk factors associated with obesity in our patient population.

Role of total skin electron beam therapy for leukemia cutis in pediatric patients.

The role of radiation therapy for those with leukemia cutis, particularly pediatric patients, remains unclear. This report describes the first two cases of disseminated leukemia cutis in adolescents treated with total skin electron beam therapy. Both patients had resolution of their skin disease and significant palliation of symptoms. Total skin electron irradiation is an option for adolescents suffering from significant extramedullary leukemia involving the skin. While it is uncertain if this treatment has any improvement in disease-free survival, the benefits of total skin electron therapy for symptom palliation should be considered.