Patterns of Failure Following Preoperative Chemotherapy and Stereotactic Body Radiation Therapy and Resection for Patients with Borderline Resectable or Locally Advanced Pancreatic Cancer.

BACKGROUND: The role of neoadjuvant stereotactic body radiation therapy (SBRT) in the treatment of pancreatic adenocarcinoma (PDAC) is controversial and the optimal target volumes and dose-fractionation are unclear. The aim of this study is to report on treatment outcomes and patterns of failure of patients with borderline resectable (BL) or locally advanced (LA) pancreatic cancer following preoperative chemotherapy and SBRT. METHODS: We conducted a single-institution, retrospective study of patients with BL or LA PDAC. Patients received neoadjuvant chemotherapy and SBRT was prescribed to 30 Gy over 5 fractions to the pancreas planning tumor volume (PTV). A subset of patients received a simultaneous integrated boost to the high risk vascular PTV and/or elective nodal irradiation (ENI). Following neoadjuvant chemoradiation, all patients underwent subsequent resection. Overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMPFS), and locoregional control (LRC) estimates were obtained using Kaplan-Meier analysis. RESULTS: Twenty-two patients with BL (18) or LA (4) PDAC were treated with neoadjuvant chemotherapy and SBRT followed by resection from 2011-2022. Following neoadjuvant treatment, 5 patients (23%) achieved a pathologic complete response (pCR) and 16 patients (73%) had R0 resection. At 24 months, there were no isolated locoregional recurrences (LRRs), 9 isolated distant recurrences (DRs), and 5 combined LRRs and DRs. Two LRRs were in-field, 2 LRRs were marginal, and 1 LRR was both in-field and marginal. 2-year median LRC, LRRFS, DMPFS, PFS, and OS were 77.3%, 45.5%, 31.8%, 31.8%, and 59.1%, respectively. For BL and LA cancers, 2-year LRC, DMPFS, and OS were 83% vs. 75%, (p = 0.423), 39% vs. 0% (p = 0.006), and 61% vs. 50% (p = 0.202), respectively. ENI was associated with improved LRC (p = 0.032) and LRRFS (p = 0.033). Borderline resectability (p = 0.018) and lower tumor grade (p = 0.027) were associated with improved DMPFS. CONCLUSIONS: Following preoperative chemotherapy and SBRT, locoregional failure outside of the target volume occurred in 3 of 5 recurrences; ENI was associated with improved LRC and LRRFS. Further studies are necessary to define the optimal techniques for preoperative radiation therapy.

Phase 1 Study of Hypofractionated Proton Beam Radiation Therapy in Adjuvant Pancreatic Cancer (PROTON-PANC).

PURPOSE: Despite improvement in systemic therapy, patients with pancreatic ductal adenocarcinoma (PDAC) frequently experience local recurrence. We sought to determine the safety of hypofractionated proton beam radiation therapy (PBT) during adjuvant chemotherapy. METHODS AND MATERIALS: Nine patients were enrolled in a single-institution phase 1 trial (NCT03885284) between 2019 and 2022. Patients had PDAC of the pancreatic head and underwent R0 or R1 resection and adjuvant modified FOLFIRINOX (mFFX) chemotherapy. The primary endpoint was to determine the dosing schedule of adjuvant PBT (5 Gy × 5 fractions) using limited treatment volumes given between cycles 6 and 7 of mFFX. Patients received PBT on days 15 to 19 in a 28-day cycle before starting cycle 7 (dose level 1, DL1) or on days 8 to 12 in a 21-day cycle before starting cycle 7 (DL2). RESULTS: The median patient age was 66 years (range, 52-78), and the follow-up time from mFFX initiation was 12.5 months (range, 6.2-37.4 months). No patients received preoperative therapy. Four had R1 resections and 5 had node-positive disease. Three patients were enrolled on DL1 and 6 patients on DL2. One dose-limiting toxicity (DLT) occurred at DL2 (prolonged grade 3 neutropenia resulting in discontinuation of mFFX after cycle 7). No other DLTs were observed. Four patients completed 12 cycles of mFFX (range, 7-12; median, 11). No patients have had local recurrence. Five of 9 patients had recurrence: 3 in the liver, 1 in the peritoneum, and 1 in the bone. Six patients are still alive, 4 of whom are recurrence-free. The median time to recurrence was 12 months (95% CI, 4 to not reached [NR]), and median overall survival was NR (95% CI, 6 to NR; 2-year survival rate, 57%). CONCLUSIONS: PBT integrated within adjuvant mFFX was well tolerated, and no local recurrence was observed. These findings warrant further exploration in a phase 2 trial.

Functional Imaging of Liver Cancer (FLIC): Study protocol of a phase 2 trial of 18F-DCFPyL PET/CT imaging for patients with hepatocellular carcinoma.

BACKGROUND: While prostate specific membrane antigen (PSMA) is overexpressed in high-grade prostate cancers, it is also expressed in tumor neovasculature and other malignancies, including hepatocellular carcinoma (HCC). Importantly, no functional imaging for HCC is clinically available, making diagnosis and surveillance following local therapies particularly challenging. 18F-DCFPyL binds with high affinity to PSMA yet clears rapidly from the blood pool. PET imaging with 18F-DCFPyL may represent a new tool for staging, surveillance and assessment of treatment response in HCC. The purpose of this Functional Imaging Liver Cancer (FLIC) trial is to assess the ability of 18F-DCFPyL-PET/CT to detect sites of HCC. METHODS: This is a phase II multi-site prospective imaging trial with a plan to enroll 50 subjects with suspected HCC on standard of care CT or MRI and eligible for standard local treatment. Participants will undergo a baseline 18F-DCFPyL-PET/CT, prior to therapy. Subjects will also be scanned with 18F-FDG-PET/CT within 2 weeks of 18F-DCFPyL-PET/CT. Participants will undergo histopathologic assessment and standard of care local treatment for HCC within a multidisciplinary team context. Participants with histopathologic confirmation of HCC and a positive baseline 18F-DCFPyL-PET/CT will undergo a post-treatment 18F-DCFPyL-PET/CT during the first routine follow-up, typically within 4-8 weeks. Subjects with negative baseline 18F-DCFPyL-PET/CT will not be re-scanned after treatment but will remain in follow-up. Participants will be followed for 5-years to assess for progression-free-survival. The primary endpoint is the positive predictive value of 18F-DCFPyL-PET for HCC as confirmed by histopathology. Secondary endpoints include comparison of 18F-DCFPyL-PET/CT with CT, MRI, and 18F-FDG-PET/CT, and evaluation of the value of 18F-DCFPyL-PET/CT in assessing treatment response following local treatment. Exploratory endpoints include next generation sequencing of tumors, and analysis of extracellular vesicles to identify biomarkers associated with response to therapy. DISCUSSION: This is a prospective imaging trial designed to evaluate whether PSMA-PET/CT imaging with 18F-DCFPyL can detect tumor sites, assess local treatment response in HCC patients, and to eventually determine whether PSMA-PET/CT could improve outcomes of patients with HCC receiving standard of care local therapy. Importantly, this trial may help determine whether PSMA-selective radiopharmaceutical therapies may be beneficial for patients with HCC. CLINICAL TRIAL REGISTRATION: NIH IND#133631. Submission date: 04-07-2021. Safe-to-proceed letter issued by FDA: 05.07.2021. NIH IRB #00080. ClinicalTrials.gov Identifier NCT05009979. Date of Registry: 08-18-2021. Protocol version date: 01-07-2022.

National evaluation of patterns and predictors of underuse of multimodal therapy for high-risk extremity soft tissue sarcoma.

BACKGROUND: Treatment of high-risk extremity soft tissue sarcomas remains widely varied. Despite growing support for a multimodal approach for treatment of these rare and aggressive neoplasms, its dissemination remains underused. This national study aimed to evaluate variations in treatment patterns and uncover factors predictive of underuse of multimodal therapy in high-risk extremity soft tissue sarcomas. METHODS: The 2010 to 2015 National Cancer Database was used to evaluate trends in 3 common treatment patterns: surgery alone, surgery + adjuvant therapy, and neoadjuvant therapy + surgery. Demographic-, sarcoma-, hospital-, and treatment-level factors of 6,725 surgically treated patients with stage II or III intermediate- to high-grade extremity soft tissue sarcomas were evaluated by types of treatment modality. Stepwise multivariable logistic regression was performed to identify factors predictive of each treatment modality. RESULTS: When compared to surgery alone (34.6%) and adjuvant therapy (41.2%), use of neoadjuvant therapy + surgery for high-risk extremity soft tissue sarcomas remained low (25.3%). However, time trend analysis demonstrated that neoadjuvant therapy + surgery has significantly increased by 7% per year, whereas surgery alone decreased by 4% every year (P < .05 for both). Factors predictive of surgery alone were older age, nonprivate insurance, increasing travel distance, and multimorbidity (P < .05). Conversely, factors associated with neoadjuvant therapy + surgery were private insurance, higher education, and care at academic or high-volume institutions (for all, P < .05). Tumor-related factors predictive for neoadjuvant therapy + surgery included size <5 cm and higher-grade tumors (P < .05). CONCLUSION: Adoption of multimodality therapy for high-risk extremity soft tissue sarcomas remains low and gradual in the United States. Dissemination of multimodality therapy will require attention to access and hospital factors to maximize these therapies for high-risk extremity soft tissue sarcomas.

Radical excision for retroperitoneal soft tissue sarcoma: A national propensity-matched outcomes analysis.

BACKGROUND: Given the rarity of retroperitoneal soft tissue sarcoma, few studies have assessed if radical excision of retroperitoneal soft tissue sarcoma with adjacent organs improves survival outcomes. This propensity score-matched study aimed to evaluate the impact of radical excision versus resection of tumor alone. METHODS: The National Cancer Database 2004 to 2015 was used to assess short- and long-term outcomes of resection of tumor alone versus radical excision (tumor plus ≥1 adjacent organs) via 1:1 propensity-matched analyses. Subgroup analyses included low-grade, high-grade, liposarcoma, leiomyosarcoma, adjacent organ involvement alone, localized tumors alone, and high-volume hospitals (≥10 resections/y). Multivariable logistic regression models identified factors associated with radical excision. RESULTS: Comparison of propensity-matched groups (N = 1,139/group) revealed no significant differences in 30-day mortality, 90-day mortality, or overall survival (for all, P > .580). For all subgroup analyses comparing resection of tumor alone with radical excision, including localized tumors without organ invasion (N = 208/group), there were no identified differences in short- or long-term survival. Although it yielded lower R2 resection rates (P = .007), radical excision was associated with greater mean length of stay (P < .001). CONCLUSION: Radical excision was not associated with improved retroperitoneal soft tissue sarcoma survival irrespective of grade, histology, hospital volume, or adjacent organ involvement. Resection of ostensibly involved adjacent viscera may increase morbidity without survival benefit. These results inform ongoing discussion regarding histology-tailored, situation-specific extent of retroperitoneal soft tissue sarcoma resections.

Early Experience of the First Single-Room Gantry Mounted Active Scanning Proton Therapy System at an Integrated Cancer Center.

Introduction: Review the early experience with a single-room gantry mounted active scanning proton therapy system. Material and Methods: All patients treated with proton beam radiotherapy (PBT) were enrolled in an institutional review board-approved patient registry. Proton beam radiotherapy was delivered with a 250 MeV gantry mounted synchrocyclotron in a single-room integrated facility within the pre-existing cancer center. Demographic data, cancer diagnoses, treatment technique, and geographic patterns were obtained for all patients. Treatment plans were evaluated for mixed modality therapy. Insurance approval data was collected for all patients treated with PBT. Results: A total of 132 patients were treated with PBT between March 2018 and June 2019. The most common oncologic subsites treated included the central nervous system (22%), gastrointestinal tract (20%), and genitourinary tract (20%). The most common histologies treated included prostate adenocarcinoma (19%), non-small cell lung cancer (10%), primary CNS gliomas (8%), and esophageal cancer (8%). Rationale for PBT treatment included limitation of dose to adjacent critical organs at risk (67%), reirradiation (19%), and patient comorbidities (11%). Patients received at least one x-ray fraction delivered as prescribed (36%) or less commonly due to unplanned machine downtime (34%). Concurrent systemic therapy was administered to 57 patients (43%). Twenty-six patients (20%) were initially denied insurance coverage and required peer-to-peers (65%), written appeals (12%), secondary insurance approval (12%), and comparison x-ray to proton plans (8%) for subsequent approval. Proton beam radiotherapy approval required a median of 17 days from insurance submission. Discussion: Incorporation of PBT into our existing cancer center allowed for multidisciplinary oncologic treatment of a diverse population of patients. Insurance coverage for PBT presents as a significant hurdle and improvements are needed to provide more timely access to necessary oncologic care.

Ethnicity and insurance status predict metastatic disease presentation in prostate, breast, and non-small cell lung cancer.

BACKGROUND: Ethnicity and insurance status have been shown to impact odds of presenting with metastatic cancer, however, the interaction of these two predictors is not well understood. We evaluate the difference in odds of presenting with metastatic disease in minorities compared to white patients despite access to the same insurance across three common cancer types. METHODS: Using the National Cancer Database, a multilevel logistic regression model that estimated the odds of metastatic disease was fit, adjusting for covariates including year of diagnosis, ethnicity, insurance, income, and region. We included adults diagnosed with metastatic prostate, non-small cell lung cancer (NSCLC), and breast cancer from 2004 to 2015. RESULTS: The study cohort consisted of 1 191 241 prostate cancer (PCa), 1 310 986 breast cancer (BCa), and 1 183 029 NSCLC patients. Private insurance was the most protective factor against metastatic presentation. Odds of presenting with metastatic disease were 0.190 [95% CI, 0.182-0.198], 0.616 [95% CI, 0.602-0.630], and 0.270 [95% CI, 0.260-0.279] for PCa, NSCLC, and BCa compared to uninsured patients, respectively. Private insurance provided the most significant benefit to non-Hispanic White PCa patients with 81% reduction in odds of metastatic presentation and conferred the least benefit to African-American NSCLC patients at 30.4% reduction in odds of metastatic presentation. CONCLUSIONS: Insurance status provided the single most protective effect against metastatic presentation. This benefit varied for minorities despite similar insurance. Reducing metastatic disease presentation rates requires addressing social barriers to care independent of insurance.

Variations in Retroperitoneal Soft Tissue Sarcoma Outcomes by Hospital Type: A National Cancer Database Analysis.

PURPOSE: Surgical resection remains the cornerstone of retroperitoneal soft tissue sarcoma (RPS) treatment. Patient- and sarcoma-related factors are well known to influence survival outcomes. The effect of hospital-related factors on long-term survival, however, are not well understood. We sought to assess the relative contribution of hospital-level factors to mortality after surgical treatment of RPS. METHODS AND MATERIALS: The 2004-2015 National Cancer Database was used to identify 10,113 patients who underwent surgical treatment of RPS. Patient-, sarcoma-, hospital-, and treatment-level factors were compared by increasing survival times. Stepwise multivariable Cox regression was performed that controlled for covariates to measure the relative contributions of these factors on overall survival (OS). Effect modification analyses ascertained how hospital type modulates the volume relationship with respect to RPS mortality. RESULTS: Factors predictive of worsening OS were older age, nonprivate insurance, low income, presence of comorbidities, tumor histology, high grade or stage, and R2 resection (for all, P < .05). Increasing hospital surgical volume predicted decreasing risk of death across all survival times. However, analysis by hospital type demonstrated that compared with academic centers, the risk of death at community centers increased significantly as surgical volume increased (hazard ratio, 1.26; 95% CI, 1.03 to 1.53). CONCLUSION: Hospital factors affect mortality after surgical treatment of RPS. Specifically, hospital type alters the surgical volume-outcome relationship for RPS mortality such that community centers perform worse with increasing volumes. Recommendations that higher surgical volume improves outcomes cannot be applied universally and must be re-examined in other complex surgical cancers.

Regionalization of Retroperitoneal Sarcoma Surgery to High-Volume Hospitals: Missed Opportunities for Outcome Improvement.

PURPOSE: Surgery continues to be the dominant therapy for the management of retroperitoneal soft-tissue sarcoma (RPS). Many groups advocate performing these resections at high-volume hospitals (HVHs), given their complexity. We therefore sought to explore whether RPS surgery has indeed begun to regionalize to HVHs in the same manner as pancreatic cancer (PC) surgery during the last decade. METHODS: We identified 70,763 patients who underwent surgical resection for RPS or PC using the National Cancer Database (2004 to 2015). Patients were stratified by hospital surgical volume. We performed an adjusted time trend analysis to compare trends in performance of surgery at HVHs for RPS versus PC. Multivariable logistic analyses were then performed, controlling for covariables, to elucidate relationships between patient-, hospital-, and treatment-related variables that may contribute to these observed trends. RESULTS: Only 9.6% of patients underwent RPS surgery at HVHs. During this time period, the odds ratio of undergoing RPS compared with pancreatectomy at HVHs was 0.65 ( P < .05). Time trend analysis estimated that whereas both procedures are regionalizing, the rate of RPS regionalization grew at 30.5% of the rate of PC (1.017 v 1.056; P < .001) and remained consistent after using several hospital volume thresholds and hospital volume as a continuous variable. CONCLUSION: Results from this retrospective multi-institutional analysis uncovered a lag in the regionalization of surgery for RPS compared with PC surgery. These findings reinforce the call to regionalize surgery for RPS to HVHs in a manner that is similar to that of other procedures in complex cancer surgery.

Social determinants of stage IV anal cancer and the impact of pelvic radiotherapy in the metastatic setting.

Anal cancer is a relatively rare malignancy, and a minority of patients present with metastatic disease in the United States. The National Cancer Database (NCDB) was used to identify factors associated with metastatic disease at presentation and evaluate the role of pelvic radiotherapy in these patients. The NCDB was queried for patients with squamous cell cancer of the anus diagnosed between 2004 and 2013. Patients were stratified by clinical stage at diagnosis, and a binary logistic regression model was created to identify factors associated with metastatic disease at diagnosis. A secondary metastatic cohort was generated and a multivariable Cox proportional hazards model was created to identify factors associated with improved survival. To validate findings, propensity-score matching was performed to generate a 1:1 paired dataset stratified by receipt of pelvic radiotherapy. The primary analysis cohort consisted of 28,500 patients. Facility location, male gender, and lack of insurance were confirmed as independent risk factors for metastatic disease. The metastatic cohort consisted of 1264 patients. Multivariable analysis confirmed female sex, possession of a private or Medicare insurance plan, pelvic radiotherapy, and chemotherapy as independent predictors of improved survival. A propensity-score matched cohort of 730 patients was generated. The median survival was 17.6 months in patients who received radiotherapy versus 14.5 months in those who did not (P < 0.01). In this cohort, male gender and lack of insurance were associated with metastatic disease at presentation. Furthermore, a significant benefit was associated with the use of pelvic radiotherapy. Future prospective research is warranted to confirm these findings.

Gastric Adenocarcinoma: A Multimodal Approach.

Despite its declining incidence, gastric cancer (GC) remains a leading cause of cancer-related deaths worldwide. A multimodal approach to GC is critical to ensure optimal patient outcomes. Pretherapy fine resolution contrast-enhanced cross-sectional imaging, endoscopic ultrasound and staging laparoscopy play an important role in patients with newly diagnosed ostensibly operable GC to avoid unnecessary non-therapeutic laparotomies. Currently, margin negative gastrectomy and adequate lymphadenectomy performed at high volume hospitals remain the backbone of GC treatment. Importantly, adequate GC surgery should be integrated in the setting of a multimodal treatment approach. Treatment for advanced GC continues to expand with the emergence of additional lines of systemic and targeted therapies.

Safety and efficacy of hypofractionated stereotactic body reirradiation in head and neck cancer: Long-term follow-up of a large series.

BACKGROUND: The purpose of this study was to report long-term outcomes for a large cohort of patients with head and neck squamous cell carcinoma (HNSCC) who underwent stereotactic body radiotherapy (SBRT) reirradiation. METHODS: From 2002 to 2011, 85 patients with previously irradiated HNSCC were treated with SBRT to 94 lesions. Some underwent surgery (29%), and many were treated with induction, concurrent, and/or adjuvant chemotherapy or biologic therapy (70%). RESULTS: Reirradiation occurred at a median interval from initial radiotherapy (RT) of 32 months. Median follow-up for survivors was 17.3 months. Two-year Kaplan-Meier estimates of overall survival (OS) and locoregional control for patients and lesions treated with curative intent were 24% and 28%, respectively. Interval from initial RT to SBRT of 2 years or more was associated with improved OS (p = .019). Five patients had grade 3 or higher late toxicity (5.9%). CONCLUSION: SBRT reirradiation results in limited toxicity. Further research is needed to refine optimal roles for SBRT and intensity-modulated radiotherapy (IMRT) reirradiation.

Yttrium-90 Radioembolization in Patients with Hepatocellular Carcinoma Who have Previously Received Sorafenib.

PURPOSE: Yttrium-90 radioembolization (RE) is a locoregional therapy option for hepatocellular carcinoma (HCC). Sorafenib is a multikinase inhibitor used in HCC that can potentially affect the efficacy of RE by altering tumor vascularity or suppressing post-irradiation angiogenesis. The safety and efficacy of sorafenib followed by RE has not been previously reported. MATERIALS AND METHODS: Patients with HCC who received RE after sorafenib were included in this retrospective review. Overall survival, toxicity, and maximal radiographic response and necrosis criteria were examined. RESULTS: Ten patients (15 RE administrations) fit the inclusion criteria. All were Barcelona Clinic Liver Cancer (BCLC) stage C. Median follow-up was 16.5 weeks. Median overall survival and radiographic progression-free survival were 30 and 28 weeks, respectively. Significant differences in overall survival were seen based on Child-Pugh class (p = 0.002) and radiographic response (p = 0.009). Three patients had partial response, six had stable disease, and one had progressive disease. Grade 1 or 2 acute fatigue, anorexia, and abdominal pain were common. Three patients had Grade 3 ascites in the setting of disease progression. Two patients had Grade 3 biochemical toxicity. One patient was sufficiently downstaged following RE and sorafenib to receive a partial hepatectomy. CONCLUSION: Yttrium-90 RE in patients with HCC who have received sorafenib demonstrate acceptable toxicity and rates of radiographic response. However, the overall survival is lower than that reported in the literature on RE alone or sorafenib alone. This may be due in part to more patients in this study having advanced disease compared to these other study populations. Larger prospective studies are needed to determine whether the combination of RE and sorafenib is superior to either therapy alone.

Physician self-reported treatment of brain metastases according to patients' clinical and demographic factors and physician practice setting.

BACKGROUND: Limited data guide radiotherapy choices for patients with brain metastases. This survey aimed to identify patient, physician, and practice setting variables associated with reported preferences for different treatment techniques. METHOD: 277 members of the American Society for Radiation Oncology (6% of surveyed physicians) completed a survey regarding treatment preferences for 21 hypothetical patients with brain metastases. Treatment choices included combinations of whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS), and surgery. Vignettes varied histology, extracranial disease status, Karnofsky Performance Status (KPS), presence of neurologic deficits, lesion size and number. Multivariate generalized estimating equation regression models were used to estimate odds ratios. RESULTS: For a hypothetical patient with 3 lesions or 8 lesions, 21% and 91% of physicians, respectively, chose WBRT alone, compared with 1% selecting WBRT alone for a patient with 1 lesion. 51% chose WBRT alone for a patient with active extracranial disease or KPS=50%. 40% chose SRS alone for an 80 year-old patient with 1 lesion, compared to 29% for a 55 year-old patient. Multivariate modeling detailed factors associated with SRS use, including availability of SRS within one's practice (OR 2.22, 95% CI 1.46-3.37). CONCLUSIONS: Poor prognostic factors, such as advanced age, poor performance status, or active extracranial disease, correspond with an increase in physicians' reported preference for using WBRT. When controlling for clinical factors, equipment access was independently associated with choice of SRS. The large variability in preferences suggests that more information about the relative harms and benefits of these options is needed to guide decision-making.

Risk factors for posttreatment edema in patients treated with stereotactic radiosurgery for meningiomas.

BACKGROUND: Peritumoral edema is a recognized complication following stereotactic radiosurgery (SRS). OBJECTIVE: To evaluate the risk of posttreatment peritumoral edema following SRS for intracranial meningiomas and determine predictive factors. METHODS: Between 2002 and 2008, 173 evaluable patients underwent CyberKnife or Gamma Knife SRS for meningiomas. Eighty-four patients (49%) had prior surgical resections, 13 patients had World Health Organization grade II (atypical) meningiomas, and 117 patients had a neurological deficit before SRS. Sixty-two tumors were in parasagittal, parafalcine, and convexity locations. The median tumor volume was 4.7 mL (range, 0.1-231.8 mL). The median prescribed dose and median prescribed biologically equivalent dose were 15 Gy (range, 9-40 Gy) and 67 Gy (range, 14-116 Gy), respectively. Ninety-seven patients were treated with single-fraction SRS, 74 received 2 to 5 fractions, and 2 received >5 fractions. RESULTS: The median follow-up was 21.0 months. Thirteen patients (8%) developed symptomatic peritumoral edema, with a median onset time of 4.5 months (range, 0.2-9.5 months). The 3-, 6-, 12-, and 24-month actuarial symptomatic edema rates were 2.9%, 4.9%, 7.7%, and 8.5%, respectively. The crude tumor control rate was 94%. On univariate analysis, large tumor volume (P = .01) and single-fraction SRS (P = .04) were predictive for development of posttreatment edema. CONCLUSION: SRS meningioma treatment demonstrated a low incidence of toxicity; however, large tumor volumes and single-fraction SRS treatment had an increased risk for posttreatment edema. Risk factors for edema should be considered in meningiomas treatment.

Preoperative chemoradiation for rectal cancer using capecitabine and celecoxib correlated with posttreatment assessment of thymidylate synthase and thymidine phosphorylase expression.

PURPOSE: Thymidylate synthase (TS) and thymidine phosphorylase (TP) expression have been shown to be predictors of response to therapy. The toxicity, efficacy, surgical morbidity, and immunohistochemical TS and TP expression were assessed in surgical resection specimens after preoperative chemoradiation. METHODS AND MATERIALS: Twenty patients with clinical stage I to III rectal adenocarcinoma received preoperative chemoradiation and underwent surgical resection 6 weeks later. RESULTS: Posttreatment tumor stages were T1 to T2 and N0 in 30% of patients; T3 to T4 and N0 in 30% of patients; and T1 to T3 and N1 to N2 in 15% of patients. Pathologic complete response (pCR) was evident in 25% and tumor regression occurred in a total of 80% of patients. Anal sphincter-sparing surgery was performed in 80% of cases. Acute and perioperative complications were minimal, with no grade 3/4 toxicity or treatment breaks. Pelvic control was obtained in 90% of patients. With a median follow-up of 65.5 months (range, 8-80 months), the 6-year actuarial survival rate was 75%. Local failure was significantly associated with nonresponse to therapy and with high TS and low TP expression (p = 0.008 and p = 0.04, respectively). CONCLUSIONS: The combination of capecitabine, celecoxib, and x-radiation therapy yields excellent response: a 25% pathologic pCR, no acute grade 3/4 toxicity, and minimal surgical morbidity. Nonresponders expressed significantly increased TS levels and decreased TP levels in posttreatment resection specimens compared to responders.

Fractionated stereotactic radiosurgery for reirradiation of head-and-neck cancer.

PURPOSE: Stereotactic radiosurgery (SRS) is an appealing treatment option after previous radiotherapy because of its precision, conformality, and reduced treatment duration. We report our experience with reirradiation using fractionated SRS for head-and-neck cancer. METHODS AND MATERIALS: From 2002 to 2008, 65 patients received SRS to the oropharynx (n = 13), hypopharynx (n = 8), nasopharynx (n = 7), paranasal sinus (n = 7), neck (n = 7), and other sites (n = 23). Thirty-eight patients were treated definitively and 27 patients with metastatic disease and/or untreated local disease were treated palliatively. Nine patients underwent complete macroscopic resection before SRS. Thirty-three patients received concurrent chemoradiation. The median initial radiation dose was 67 Gy, and the median reirradiation SRS dose was 30 Gy (21-35 Gy) in 2-5 fractions. RESULTS: Median follow-up for surviving patients was 16 months. Fifty-six patients were evaluable for response: 30 (54%) had complete, 15 (27%) had partial, and 11 (20%) had no response. Median overall survival (OS) for all patients was 12 months. For definitively treated patients, the 2-year OS and locoregional control (LRC) rates were 41% and 30%, respectively. Multivariate analysis demonstrated that higher total dose, surgical resection, and nasopharynx site were significantly associated with improved LRC; surgical resection and nonsquamous histology were associated with improved OS. Seven patients (11%) experienced severe reirradiation-related toxicity, including one treatment-attributed death. CONCLUSION: SRS reirradiation for head-and-neck cancer is feasible. This study demonstrates encouraging response rates with acceptable toxicity. Fractionated SRS reirradiation with concurrent chemotherapy in select patients warrants further study.