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Most Cited International Journal of Radiation Oncology • Biology • Physics Articles
The most cited articles published since 2011, extracted from Scopus.
Palliative radiotherapy for bone metastases: An ASTRO evidence-based guidelineStephen Lutz | Lawrence Berk | Eric Chang | Edward Chow | Carol Hahn | Peter Hoskin | David Howell | Andre Konski | Lisa Kachnic | Simon Lo | Arjun Sahgal | Larry Silverman | Charles Von Gunten | Ehud Mendel | Andrew Vassil | Deborah Watkins Bruner | William Hartsell
Volume 79, Issue 4, March 2011, Pages 965-976
Purpose: To present guidance for patients and physicians regarding the use of radiotherapy in the treatment of bone metastases according to current published evidence and complemented by expert opinion. Methods and Materials: A systematic search of the National Library of Medicine's PubMed database between 1998 and 2009 yielded 4,287 candidate original research articles potentially applicable to radiotherapy for bone metastases. A Task Force composed of all authors synthesized the published evidence and reached a consensus regarding the recommendations contained herein. Results: The Task Force concluded that external beam radiotherapy continues to be the mainstay for the treatment of pain and/or prevention of the morbidity caused by bone metastases. Various fractionation schedules can provide significant palliation of symptoms and/or prevent the morbidity of bone metastases. The evidence for the safety and efficacy of repeat treatment to previously irradiated areas of peripheral bone metastases for pain was derived from both prospective studies and retrospective data, and it can be safe and effective. The use of stereotactic body radiotherapy holds theoretical promise in the treatment of new or recurrent spine lesions, although the Task Force recommended that its use be limited to highly selected patients and preferably within a prospective trial. Surgical decompression and postoperative radiotherapy is recommended for spinal cord compression or spinal instability in highly selected patients with sufficient performance status and life expectancy. The use of bisphosphonates, radionuclides, vertebroplasty, and kyphoplasty for the treatment or prevention of cancer-related symptoms does not obviate the need for external beam radiotherapy in appropriate patients. Conclusions: Radiotherapy is a successful and time efficient method by which to palliate pain and/or prevent the morbidity of bone metastases. This Guideline reviews the available data to define its proper use and provide consensus views concerning contemporary controversies or unanswered questions that warrant prospective trial evaluation. Copyright © 2011 Elsevier Inc.
Stereotactic body radiotherapy (SBRT) for operable Stage i non-small-cell lung cancer: Can SBRT be comparable to surgery?Hiroshi Onishi | Hiroki Shirato | Yasushi Nagata | Masahiro Hiraoka | Masaharu Fujino | Kotaro Gomi | Katsuyuki Karasawa | Kazushige Hayakawa | Yuzuru Niibe | Yoshihiro Takai | Tomoki Kimura | Atsuya Takeda | Atsushi Ouchi | Masato Hareyama | Masaki Kokubo | Takuyo Kozuka | Takuro Arimoto | Ryusuke Hara | Jun Itami | Tsutomu Araki
Volume 81, Issue 5, December 2011, Pages 1352-1358
Purpose: To review treatment outcomes for stereotactic body radiotherapy (SBRT) in medically operable patients with Stage I non-small-cell lung cancer (NSCLC), using a Japanese multi-institutional database. Patients and Methods: Between 1995 and 2004, a total of 87 patients with Stage I NSCLC (median age, 74 years; T1N0M0, n = 65; T2N0M0, n = 22) who were medically operable but refused surgery were treated using SBRT alone in 14 institutions. Stereotactic three-dimensional treatment was performed using noncoplanar dynamic arcs or multiple static ports. Total dose was 45-72.5 Gy at the isocenter, administered in 3-10 fractions. Median calculated biological effective dose was 116 Gy (range, 100-141 Gy). Data were collected and analyzed retrospectively. Results: During follow-up (median, 55 months), cumulative local control rates for T1 and T2 tumors at 5 years after SBRT were 92% and 73%, respectively. Pulmonary complications above Grade 2 arose in 1 patient (1.1%). Five-year overall survival rates for Stage IA and IB subgroups were 72% and 62%, respectively. One patient who developed local recurrences safely underwent salvage surgery. Conclusion: Stereotactic body radiotherapy is safe and promising as a radical treatment for operable Stage I NSCLC. The survival rate for SBRT is potentially comparable to that for surgery. © 2011 Elsevier Inc.
How does intensity-modulated radiotherapy versus conventional two-dimensional radiotherapy influence the treatment results in nasopharyngeal carcinoma patients?Shu Zhen Lai | Wen Fei Li | Lei Chen | Wei Luo | Yuan Yuan Chen | Li Zhi Liu | Ying Sun | Ai Hua Lin | Meng Zhong Liu | Jun Ma
Volume 80, Issue 3, July 2011, Pages 661-668
Purpose: To compare the results of intensity-modulated radiotherapy (IMRT) with those of two-dimensional conventional radiotherapy (2D-CRT) in the treatment of patients with nasopharyngeal carcinoma (NPC). Methods and Materials: A retrospective review of data from 1,276 patients with biopsy-proven, nonmetastatic NPC was performed. All patients had undergone magnetic resonance imaging and were staged according to the sixth edition of the American Joint Committee on Cancer staging criteria. Radiotherapy was the primary treatment for all patients. Results: Of the 1,276 patients, 512 were treated with IMRT and 764 with 2D-CRT. The 5-year actuarial local relapse-free survival (LRFS), the nodal relapse-free survival (NRFS), the distant metastasis-free survival (DMFS), and the disease-free survival (DFS) rates were 92.7%, 97.0%, 84.0%, and 75.9%, respectively, for the IMRT group, and 86.8%, 95.5%, 82.6%, and 71.4%, respectively, for the 2D-CRT group. In stage T1 patients, improvement of LRFS in the IMRT group was even significantly higher than in the 2D-CRT group (100% vs. 94.4%; p = 0.016). A trend of improvement of DFS was observed in the IMRT group compared with the 2D-CRT group but without reaching statistical significance. NRFS and DMFS rates were similar in the two groups. Conclusions: A greater improvement of treatment results with IMRT than with 2D-CRT was demonstrated primarily by achieving a higher local tumor control rate in NPC patients, especially in the early T stage patients. The goal of better control of both local failure in advanced, nonmetastatic NPC patients and of distant failure should be addressed in future studies. © 2011 Elsevier Inc.
Randomized double-blind placebo-controlled trial of bevacizumab therapy for radiation necrosis of the central nervous systemVictor A. Levin | Luc Bidaut | Ping Hou | Ashok J. Kumar | Jeffrey S. Wefel | B. Nebiyou Bekele | Sujit Prabhu | Monica Loghin | Mark R. Gilbert | Edward F. Jackson
Volume 79, Issue 5, April 2011, Pages 1487-1495
Purpose: To conduct a controlled trial of bevacizumab for the treatment of symptomatic radiation necrosis of the brain. Methods and Materials: A total of 14 patients were entered into a placebo-controlled randomized double-blind study of bevacizumab for the treatment of central nervous system radiation necrosis. All patients were required to have radiographic or biopsy proof of central nervous system radiation necrosis and progressive neurologic symptoms or signs. Eligible patients had undergone irradiation for head-and-neck carcinoma, meningioma, or low- to mid-grade glioma. Patients were randomized to receive intravenous saline or bevacizumab at 3-week intervals. The magnetic resonance imaging findings 3 weeks after the second treatment and clinical signs and symptoms defined the response or progression. Results: The volumes of necrosis estimated on T2-weighted fluid-attenuated inversion recovery and T1-weighted gadolinium-enhanced magnetic resonance imaging scans demonstrated that although no patient receiving placebo responded (0 of 7), all bevacizumab-treated patients did so (5 of 5 randomized and 7 of 7 crossover) with decreases in T2-weighted fluid-attenuated inversion recovery and T1-weighted gadolinium-enhanced volumes and a decrease in endothelial transfer constant. All bevacizumab-treated patients - and none of the placebo-treated patients - showed improvement in neurologic symptoms or signs. At a median of 10 months after the last dose of bevacizumab in patients receiving all four study doses, only 2 patients had experienced a recurrence of magnetic resonance imaging changes consistent with progressive radiation necrosis; one patient received a single additional dose of bevacizumab and the other patient received two doses. Conclusion: The Class I evidence of bevacizumab efficacy from the present study in the treatment of central nervous system radiation necrosis justifies consideration of this treatment option for people with radiation necrosis secondary to the treatment of head-and-neck cancer and brain cancer. © 2011 Elsevier Inc.
Improved clinical outcomes with high-dose image guided radiotherapy compared with non-IGRT for the treatment of clinically localized prostate cancerMichael J. Zelefsky | Marisa Kollmeier | Brett Cox | Anthony Fidaleo | Dahlia Sperling | Xin Pei | Brett Carver | Jonathan Coleman | Michael Lovelock | Margie Hunt
Volume 84, Issue 1, September 2012, Pages 125-129
Purpose: To compare toxicity profiles and biochemical tumor control outcomes between patients treated with high-dose image-guided radiotherapy (IGRT) and high-dose intensity-modulated radiotherapy (IMRT) for clinically localized prostate cancer. Materials and Methods: Between 2008 and 2009, 186 patients with prostate cancer were treated with IGRT to a dose of 86.4 Gy with daily correction of the target position based on kilovoltage imaging of implanted prostatic fiducial markers. This group of patients was retrospectively compared with a similar cohort of 190 patients who were treated between 2006 and 2007 with IMRT to the same prescription dose without, however, implanted fiducial markers in place (non-IGRT). The median follow-up time was 2.8 years (range, 2-6 years). Results: A significant reduction in late urinary toxicity was observed for IGRT patients compared with the non-IGRT patients. The 3-year likelihood of grade 2 and higher urinary toxicity for the IGRT and non-IGRT cohorts were 10.4% and 20.0%, respectively (p = 0.02). Multivariate analysis identifying predictors for grade 2 or higher late urinary toxicity demonstrated that, in addition to the baseline Internatinoal Prostate Symptom Score, IGRT was associated with significantly less late urinary toxicity compared with non-IGRT. The incidence of grade 2 and higher rectal toxicity was low for both treatment groups (1.0% and 1.6%, respectively; p = 0.81). No differences in prostate-specific antigen relapse-free survival outcomes were observed for low- and intermediate-risk patients when treated with IGRT and non-IGRT. For high-risk patients, a significant improvement was observed at 3 years for patients treated with IGRT compared with non-IGRT. Conclusions: IGRT is associated with an improvement in biochemical tumor control among high-risk patients and a lower rate of late urinary toxicity compared with high-dose IMRT. These data suggest that, for definitive radiotherapy, the placement of fiducial markers and daily tracking of target positioning may represent the preferred mode of external-beam radiotherapy delivery for the treatment of prostate cancer. © 2012 Elsevier Inc. All rights reserved.
Cell-Specific Radiosensitization by gold nanoparticles at megavoltage radiation energiesSuneil Jain | Jonathan A. Coulter | Alan R. Hounsell | Karl T. Butterworth | Stephen J. McMahon | Wendy B. Hyland | Mark F. Muir | Glenn R. Dickson | Kevin M. Prise | Fred J. Currell | Joe M. O'Sullivan | David G. Hirst
Volume 79, Issue 2, February 2011, Pages 531-539
Purpose: Gold nanoparticles (GNPs) have been shown to cause sensitization with kilovoltage (kV) radiation. Differences in the absorption coefficient between gold and soft tissue, as a function of photon energy, predict that maximum enhancement should occur in the kilovoltage (kV) range, with almost no enhancement at megavoltage (MV) energies. Recent studies have shown that GNPs are not biologically inert, causing oxidative stress and even cell death, suggesting a possible biological mechanism for sensitization. The purpose of this study was to assess GNP radiosensitization at clinically relevant MV X-ray energies. Methods and Materials: Cellular uptake, intracellular localization, and cytotoxicity of GNPs were assessed in normal L132, prostate cancer DU145, and breast cancer MDA-MB-231 cells. Radiosensitization was measured by clonogenic survival at kV and MV photon energies and MV electron energies. Intracellular DNA double-strand break (DSB) induction and DNA repair were determined and GNP chemosensitization was assessed using the radiomimetic agent bleomycin. Results: GNP uptake occurred in all cell lines and was greatest in MDA-MB-231 cells with nanoparticles accumulating in cytoplasmic lysosomes. In MDA-MB-231 cells, radiation sensitizer enhancement ratios (SERs) of 1.41, 1.29, and 1.16 were achieved using 160 kVp, 6 MV, and 15 MV X-ray energies, respectively. No significant effect was observed in L132 or DU145 cells at kV or MV energies (SER 0.97-1.08). GNP exposure did not increase radiation-induced DSB formation or inhibit DNA repair; however, GNP chemosensitization was observed in MDA-MB-231 cells treated with bleomycin (SER 1.38). Conclusions: We have demonstrated radiosensitization in MDA-MB-231 cells at MV X-ray energies. The sensitization was cell-specific with comparable effects at kV and MV energies, no increase in DSB formation, and GNP chemopotentiation with bleomycin, suggesting a possible biological mechanism of radiosensitization. Copyright © 2011 Elsevier Inc.
Fractionation for whole breast irradiation: An American society for radiation oncology (ASTRO) evidence-based guidelineBenjamin D. Smith | Soren M. Bentzen | Candace R. Correa | Carol A. Hahn | Patricia H. Hardenbergh | Geoffrey S. Ibbott | Beryl McCormick | Julie R. McQueen | Lori J. Pierce | Simon N. Powell | Abram Recht | Alphonse G. Taghian | Frank A. Vicini | Julia R. White | Bruce G. Haffty
Volume 81, Issue 1, September 2011, Pages 59-68
Purpose: In patients with early-stage breast cancer treated with breast-conserving surgery, randomized trials have found little difference in local control and survival outcomes between patients treated with conventionally fractionated (CF-) whole breast irradiation (WBI) and those receiving hypofractionated (HF)-WBI. However, it remains controversial whether these results apply to all subgroups of patients. We therefore developed an evidence-based guideline to provide direction for clinical practice. Methods and Materials: A task force authorized by the American Society for Radiation Oncology weighed evidence from a systematic literature review and produced the recommendations contained herein. Results: The majority of patients in randomized trials were aged 50 years or older, had disease Stage pT1-2 pN0, did not receive chemotherapy, and were treated with a radiation dose homogeneity within ±7% in the central axis plane. Such patients experienced equivalent outcomes with either HF-WBI or CF-WBI. Patients not meeting these criteria were relatively underrepresented, and few of the trials reported subgroup analyses. For patients not receiving a radiation boost, the task force favored a dose schedule of 42.5 Gy in 16 fractions when HF-WBI is planned. The task force also recommended that the heart should be excluded from the primary treatment fields (when HF-WBI is used) due to lingering uncertainty regarding late effects of HF-WBI on cardiac function. The task force could not agree on the appropriateness of a tumor bed boost in patients treated with HF-WBI. Conclusion: Data were sufficient to support the use of HF-WBI for patients with early-stage breast cancer who met all the aforementioned criteria. For other patients, the task force could not reach agreement either for or against the use of HF-WBI, which nevertheless should not be interpreted as a contraindication to its use. Copyright © 2011 Elsevier Inc.
70 Gy versus 80 Gy in localized prostate cancer: 5-year results of GETUG 06 randomized trialVéronique Beckendorf | Stéphane Guerif | Elisabeth Le Prisé | Jean Marc Cosset | Agnes Bougnoux | Bruno Chauvet | Naji Salem | Olivier Chapet | Sylvain Bourdain | Jean Marc Bachaud | Philippe Maingon | Jean Michel Hannoun-Levi | Luc Malissard | Jean Marc Simon | Pascal Pommier | Men Hay | Bernard Dubray | Jean Léon Lagrange | Elisabeth Luporsi | Pierre Bey
Volume 80, Issue 4, July 2011, Pages 1056-1063
Purpose: To perform a randomized trial comparing 70 and 80 Gy radiotherapy for prostate cancer. Patients and Methods: A total of 306 patients with localized prostate cancer were randomized. No androgen deprivation was allowed. The primary endpoint was biochemical relapse according to the modified 1997-American Society for Therapeutic Radiology and Oncology and Phoenix definitions. Toxicity was graded using the Radiation Therapy Oncology Group 1991 criteria and the late effects on normal tissues-subjective, objective, management, analytic scales (LENT-SOMA) scales. The patients' quality of life was scored using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-item cancer-specific and 25-item prostate-specific modules. Results: The median follow-up was 61 months. According to the 1997-American Society for Therapeutic Radiology and Oncology definition, the 5-year biochemical relapse rate was 39% and 28% in the 70- and 80-Gy arms, respectively (p = .036). Using the Phoenix definition, the 5-year biochemical relapse rate was 32% and 23.5%, respectively (p = .09). The subgroup analysis showed a better biochemical outcome for the higher dose group with an initial prostate-specific antigen level >15 ng/mL. At the last follow-up date, 26 patients had died, 10 of their disease and none of toxicity, with no differences between the two arms. According to the Radiation Therapy Oncology Group scale, the Grade 2 or greater rectal toxicity rate was 14% and 19.5% for the 70- and 80-Gy arms (p = .22), respectively. The Grade 2 or greater urinary toxicity was 10% at 70 Gy and 17.5% at 80 Gy (p = .046). Similar results were observed using the LENT-SOMA scale. Bladder toxicity was more frequent at 80 Gy than at 70 Gy (p = .039). The quality-of-life questionnaire results before and 5 years after treatment were available for 103 patients with no differences found between the 70- and 80-Gy arms. Conclusion: High-dose radiotherapy provided a better 5-year biochemical outcome with slightly greater toxicity. © 2011 Elsevier Inc.
Outcomes of stereotactic ablative radiotherapy in patients with potentially operable stage i non-small cell lung cancerFrank J. Lagerwaard | Naomi E. Verstegen | Cornelis J A Haasbeek | Ben J. Slotman | Marinus A. Paul | Egbert F. Smit | Suresh Senan
Volume 83, Issue 1, May 2012, Pages 348-353
Background: Approximately two-thirds of patients with early-stage non-small-cell lung cancer (NSCLC) in The Netherlands currently undergo surgical resection. As an increasing number of fit patients have elected to undergo stereotactic ablative radiotherapy (SABR) in recent years, we studied outcomes after SABR in patients with potentially operable stage I NSCLC. Methods and Materials: In an institutional prospective database collected since 2003, 25% of lung SABR cases (n = 177 patients) were found to be potentially operable when the following patients were excluded: those with (1) synchronous lung tumors or other malignancy, (2) prior high-dose radiotherapy/pneumonectomy, (3) chronic obstructive pulmonary disease with a severity score of 3-4 according to the Global initiative for Obstructive Lung Disease classification. (4) a performance score of ≥3, and (5) other comorbidity precluding surgery. Study patients included 101 males and 76 females, with a median age of 76 years old, 60% of whom were staged as T1 and 40% of whom were T2. Median Charlson comorbidity score was 2 (range, 0-5). A SABR dose of 60 Gy was delivered using a risk-adapted scheme in 3, 5, or 8 fractions, depending on tumor size and location. Follow-up chest computed tomography scans were obtained at 3, 6, and 12 months and yearly thereafter. Results: Median follow-up was 31.5 months; and median overall survival (OS) was 61.5 months, with 1- and 3-year survival rates of 94.7% and 84.7%, respectively. OS rates at 3 years in patients with (n = 59) and without (n = 118) histological diagnosis did not differ significantly (96% versus 81%, respectively, p = 0.39). Post-SABR 30-day mortality was 0%, while predicted 30-day mortality for a lobectomy, derived using the Thoracoscore predictive model (Falcoz PE et al. J Thorac Cardiovasc Surg 2007;133:325-332), would have been 2.6%. Local control rates at 1 and 3 years were 98% and 93%, respectively. Regional and distant failure rates at 3 years were each 9.7%. Toxicity was mild, with grade ≥3 radiation pneumonitis and rib fractures in 2% and 3%, respectively. Conclusions: Patients with potentially operable disease who underwent primary SABR had a median OS that exceeded 5 years. This finding supports ongoing randomized clinical trials comparing surgery and SABR in cases of operable stage I NSCLC. © 2012 Elsevier Inc. All rights reserved.
Oligometastases treated with stereotactic body radiotherapy: Long-term follow-up of prospective studyMichael T. Milano | Alan W. Katz | Hong Zhang | Paul Okunieff
Volume 83, Issue 3, July 2012, Pages 878-886
Purpose: To analyze the long-term survival and tumor control outcomes after stereotactic body radiotherapy (SBRT) for metastases limited in number and extent. Methods and Materials: We prospectively analyzed the long-term overall survival (OS) and cancer control outcomes of 121 patients with five or fewer clinically detectable metastases, from any primary site, metastatic to one to three organ sites, and treated with SBRT. Freedom from widespread distant metastasis (FFDM) was defined as metastatic disease not amenable to local therapy (i.e., resection or SBRT). Prognostic variables were assessed using log-rank and Cox regression analyses. Results: For breast cancer patients, the median follow-up was 4.5 years (7.1 years for 16 of 39 patients alive at the last follow-up visit). The 2-year OS, FFDM, and local control (LC) rate was 74%, 52%, and 87%, respectively. The 6-year OS, FFDM, and LC rate was 47%, 36%, and 87%, respectively. From the multivariate analyses, the variables of bone metastases (p =.057) and one vs. more than one metastasis (p =.055) were associated with a fourfold and threefold reduced hazard of death, respectively. None of the 17 bone lesions from breast cancer recurred after SBRT vs. 10 of 68 lesions from other organs that recurred (p =.095). For patients with nonbreast cancers, the median follow-up was 1.7 years (7.3 years for 7 of 82 patients alive at the last follow-up visit). The 2-year OS, FFDM, and LC rate was 39%, 28%, and 74%, respectively. The 6-year OS, FFDM, and LC rate was 9%, 13%, and 65%, respectively. For nonbreast cancers, a greater SBRT target volume was significantly adverse for OS (p =.012) and lesion LC (p <.0001). Patients whose metastatic lesions, before SBRT, demonstrated radiographic progression after systemic therapy experienced significantly worse OS compared with patients with stable or regressing disease. Conclusions: Select patients with limited metastases treated with SBRT are long-term survivors. Future research should address the therapeutic benefit of SBRT for these patients. © 2012 Elsevier Inc. All rights reserved.
Long-term outcomes from a prospective trial of stereotactic body radiotherapy for low-risk prostate cancerChristopher R. King | James D. Brooks | Harcharan Gill | Joseph C. Presti
Volume 82, Issue 2, February 2012, Pages 877-882
Purpose: Hypofractionated radiotherapy has an intrinsically different normal tissue and tumor radiobiology. The results of a prospective trial of stereotactic body radiotherapy (SBRT) for prostate cancer with long-term patient-reported toxicity and tumor control rates are presented. Methods and Materials: From 2003 through 2009, 67 patients with clinically localized low-risk prostate cancer were enrolled. Treatment consisted of 36.25 Gy in 5 fractions using SBRT with the CyberKnife as the delivery technology. No patient received hormone therapy. Patient self-reported bladder and rectal toxicities were graded on the Radiation Therapy Oncology Group scale (RTOG). Results: Median follow-up was 2.7 years. There were no grade 4 toxicities. Radiation Therapy Oncology Group Grade 3, 2, and 1 bladder toxicities were seen in 3% (2 patients), 5% (3 patients), and 23% (13 patients) respectively. Dysuria exacerbated by urologic instrumentation accounted for both patients with Grade 3 toxicity. Urinary incontinence, complete obstruction, or persistent hematuria was not observed. Rectal Grade 3, 2, and 1 toxicities were seen in 0, 2% (1 patient), and 12.5% (7 patients), respectively. Persistent rectal bleeding was not observed. Low-grade toxicities were substantially less frequent with QOD vs. QD dose regimen (p = 0.001 for gastrointestinal and p = 0.007 for genitourinary). There were two prostate-specific antigen (PSA), biopsy-proven failures with negative metastatic workup. Median PSA at follow-up was 0.5 ± 0.72 ng/mL. The 4-year Kaplan-Meier PSA relapse-free survival was 94% (95% confidence interval, 85%-102%). Conclusion: Significant late bladder and rectal toxicities from SBRT for prostate cancer are infrequent. PSA relapse-free survival compares favorably with other definitive treatments. The current evidence supports consideration of stereotactic body radiotherapy among the therapeutic options for localized prostate cancer. © 2012 Elsevier Inc.
Dose-fractionation sensitivity of prostate cancer deduced from radiotherapy outcomes of 5,969 patients in seven international institutional datasets: α/β = 1.4 (0.9-2.2) GyRaymond Miralbell | Stephen A. Roberts | Eduardo Zubizarreta | Jolyon H. Hendry
Volume 82, Issue 1, January 2012, Page
Purpose: There are reports of a high sensitivity of prostate cancer to radiotherapy dose fractionation, and this has prompted several trials of hypofractionation schedules. It remains unclear whether hypofractionation will provide a significant therapeutic benefit in the treatment of prostate cancer, and whether there are different fractionation sensitivities for different stages of disease. In order to address this, multiple primary datasets have been collected for analysis. Methods and Materials: Seven datasets were assembled from institutions worldwide. A total of 5969 patients were treated using external beams with or without androgen deprivation (AD). Standard fractionation (1.8-2.0 Gy per fraction) was used for 40% of the patients, and hypofractionation (2.5-6.7 Gy per fraction) for the remainder. The overall treatment time ranged from 1 to 8 weeks. Low-risk patients comprised 23% of the total, intermediate-risk 44%, and high-risk 33%. Direct analysis of the primary data for tumor control at 5 years was undertaken, using the Phoenix criterion of biochemical relapse-free survival, in order to calculate values in the linear-quadratic equation of k (natural log of the effective target cell number), α (dose-response slope using very low doses per fraction), and the ratio α/β that characterizes dose-fractionation sensitivity. Results: There was no significant difference between the α/β value for the three risk groups, and the value of α/β for the pooled data was 1.4 (95% CI = 0.9-2.2) Gy. Androgen deprivation improved the bNED outcome index by about 5% for all risk groups, but did not affect the α/β value. Conclusions: The overall α/β value was consistently low, unaffected by AD deprivation, and lower than the appropriate values for late normal-tissue morbidity. Hence the fractionation sensitivity differential (tumor/normal tissue) favors the use of hypofractionated radiotherapy schedules for all risk groups, which is also very beneficial logistically in limited-resource settings. Copyright © 2012 Elsevier Inc. Printed in the USA. All rights reserved.
Anti-PD-1 blockade and stereotactic radiation produce long-term survival in mice with intracranial gliomasJing Zeng | Alfred P. See | Jillian Phallen | Christopher M. Jackson | Zineb Belcaid | Jacob Ruzevick | Nicholas Durham | Christian Meyer | Timothy J. Harris | Emilia Albesiano | Gustavo Pradilla | Eric Ford | John Wong | Hans Joerg Hammers | Dimitris Mathios | Betty Tyler | Henry Brem | Phuoc T. Tran | Drew Pardoll | Charles G. Drake | Michael Lim
Volume 86, Issue 2, June 2013, Pages 343-349
Purpose: Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults, and radiation is one of the main treatment modalities. However, cure rates remain low despite best available therapies. Immunotherapy is a promising modality that could work synergistically with radiation, which has been shown to increase antigen presentation and promote a proinflammatory tumor microenvironment. Programmed-death-1 (PD-1) is a surface receptor expressed on activated and exhausted T cells, which mediate T cell inhibition upon binding with its ligand PD-L1, expressed on many tumor types including human GBMs. We tested the combination of anti-PD-1 immunotherapy with stereotactic radiosurgery in a mouse orthotopic GBM model. Methods and Materials: We performed intracranial implantation of mouse glioma cell line GL261 transfected with luciferase into C57BL/6 mice. Mice were stratified into 4 treatment groups: (1) control; (2) radiation only; (3) anti-PD-1 antibody only; and (4) radiation plus anti-PD-1 antibody. Overall survival was quantified. The mice were killed on day 21 after implantation to assess immunologic parameters in the brain/tumor, cervical lymph nodes, and spleen. Results: Improved survival was demonstrated with combination anti-PD-1 therapy plus radiation compared with either modality alone: median survival was 25 days in the control arm, 27 days in the anti-PD-1 antibody arm, 28 days in the radiation arm, and 53 days in the radiation plus anti-PD-1 therapy arm (P<.05 by log-rank Mantle-Cox). Long-term survival was seen only in the combined treatment arm, with a fraction (15%-40%) of animals alive at day 180+ after treatment. Immunologic data on day 21 after implantation showed increased tumor infiltration by cytotoxic T cells (CD8+/interferon- γ+/tumor necrosis factor-α+) and decreased regulatory T cells (CD4+/FOXP3) in the combined treatment group compared with the single modality arms. Conclusions: The combination of PD-1 blockade and localized radiation therapy results in long-term survival in mice with orthotopic brain tumors. These studies provide strong preclinical evidence to support combination trials in patients with GBM. © 2013 Elsevier Inc. All rights reserved.
Stereotactic body radiotherapy for primary hepatocellular carcinomaDavid L. Andolino | Cynthia S. Johnson | Mary Maluccio | Paul Kwo | A. Joseph Tector | Jennifer Zook | Peter A S Johnstone | Higinia R. Cardenes
Volume 81, Issue 4, November 2011, Page
Purpose: To evaluate the safety and efficacy of stereotactic body radiotherapy (SBRT) for the treatment of primary hepatocellular carcinoma (HCC). Methods and Materials: From 2005 to 2009, 60 patients with liver-confined HCC were treated with SBRT at the Indiana University Simon Cancer Center: 36 Child-Turcotte-Pugh (CTP) Class A and 24 CTP Class B. The median number of fractions, dose per fraction, and total dose, was 3, 14 Gy, and 44 Gy, respectively, for those with CTP Class A cirrhosis and 5, 8 Gy, and 40 Gy, respectively, for those with CTP Class B. Treatment was delivered via 6 to 12 beams and in nearly all cases was prescribed to the 80% isodose line. The records of all patients were reviewed, and treatment response was scored according to Response Evaluation Criteria in Solid Tumors v1.1. Toxicity was graded according to the Common Terminology Criteria for Adverse Events v4.0. Local control (LC), time to progression (TTP), progression-free survival (PFS), and overall survival (OS) were calculated according to the method of Kaplan and Meier. Results: The median follow-up time was 27 months, and the median tumor diameter was 3.2 cm. The 2-year LC, PFS, and OS were 90%, 48%, and 67%, respectively, with median TTP of 47.8 months. Subsequently, 23 patients underwent transplant, with a median time to transplant of 7 months. There were no ≥Grade 3 nonhematologic toxicities. Thirteen percent of patients experienced an increase in hematologic/hepatic dysfunction greater than 1 grade, and 20% experienced progression in CTP class within 3 months of treatment. Conclusions: SBRT is a safe, effective, noninvasive option for patients with HCC ≤6 cm. As such, SBRT should be considered when bridging to transplant or as definitive therapy for those ineligible for transplant. © 2011 Elsevier Inc.
Consensus guidelines for delineation of clinical target volume for intensity-modulated pelvic radiotherapy for the definitive treatment of cervix cancerKaren Lim | William Small | Lorraine Portelance | Carien Creutzberg | Ina M. Jürgenliemk-Schulz | Arno Mundt | Loren K. Mell | Nina Mayr | Akila Viswanathan | Anuja Jhingran | Beth Erickson | Jennifer De Los Santos | David Gaffney | Catheryn Yashar | Sushil Beriwal | Aaron Wolfson | Alexandra Taylor | Walter Bosch | Issam El Naqa | Anthony Fyles
Volume 79, Issue 2, February 2011, Pages 348-355
Purpose: Accurate target definition is vitally important for definitive treatment of cervix cancer with intensity-modulated radiotherapy (IMRT), yet a definition of clinical target volume (CTV) remains variable within the literature. The aim of this study was to develop a consensus CTV definition in preparation for a Phase 2 clinical trial being planned by the Radiation Therapy Oncology Group. Methods and Materials: A guidelines consensus working group meeting was convened in June 2008 for the purposes of developing target definition guidelines for IMRT for the intact cervix. A draft document of recommendations for CTV definition was created and used to aid in contouring a clinical case. The clinical case was then analyzed for consistency and clarity of target delineation using an expectation maximization algorithm for simultaneous truth and performance level estimation (STAPLE), with kappa statistics as a measure of agreement between participants. Results: Nineteen experts in gynecological radiation oncology generated contours on axial magnetic resonance images of the pelvis. Substantial STAPLE agreement sensitivity and specificity values were seen for gross tumor volume (GTV) delineation (0.84 and 0.96, respectively) with a kappa statistic of 0.68 (p < 0.0001). Agreement for delineation of cervix, uterus, vagina, and parametria was moderate. Conclusions: This report provides guidelines for CTV definition in the definitive cervix cancer setting for the purposes of IMRT, building on previously published guidelines for IMRT in the postoperative setting. Copyright © 2011 Elsevier Inc.
Clinical outcomes and patterns of failure after intensity-modulated radiotherapy for nasopharyngeal carcinomaWai Tong Ng | Michael C H Lee | Wai Man Hung | Cheuk Wai Choi | Kin Chung Lee | Oscar S H Chan | Anne W M Lee
Volume 79, Issue 2, February 2011, Pages 420-428
Purpose: To study and report the clinical outcomes and patterns of failure after intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). Methods and Materials: The treatment outcomes of NPC patients treated with IMRT at Pamela Youde Nethersole Eastern Hospital between 2005 and 2007 were reviewed. The location and extent of locoregional failures were transferred to the pretreatment planning computed tomography for dosimetry analysis. Statistical analyses were performed on dose coverage and locoregional failures. Results: A total of 193 NPC patients were analyzed; 93% had Stage III/IV disease. Median follow-up was 30 months. Overall disease failure (at any site) developed in 35 patients. Among these, there were 23 distant metastases, 16 local failures, and 9 regional failures. Four of the locoregional failures were marginal. Dose conformity with IMRT was excellent. Patients with at least 66.5 Gy to their target volumes had significantly less locoregional failure. The 2-year local progression-free, regional progression-free, distant metastasis-free, and overall survival rates were 95%, 96%, 90%, and 92%, respectively. Conclusions: Intensity-modulated radiotherapy provides excellent locoregional control for NPC. Distant metastasis remains the most difficult challenge, and more effective systemic agents should be explored for patients presenting with advanced locoregional diseases. Copyright © 2011 Elsevier Inc.
Long-term failure patterns and survival in a randomized dose-escalation trial for prostate cancer. Who dies of disease?Deborah A. Kuban | Lawrence B. Levy | M. Rex Cheung | Andrew K. Lee | Seungtaek Choi | Steven Frank | Alan Pollack
Volume 79, Issue 5, April 2011, Pages 1310-1317
Purpose: To report long-term failure patterns and survival in a randomized radiotherapy dose escalation trial for prostate cancer. Materials and Methods: A total of 301 patients with Stage T1b-T3 prostate cancer treated to 70 Gy versus 78 Gy now have a median follow-up of 9 years. Failure patterns and survival were compared between dose levels. The cumulative incidence of death from prostate cancer versus other causes was examined and regression analysis was used to establish predictive factors. Results: Patients with pretreatment prostate-specific antigen (PSA) >10 ng/mL or high-risk disease had higher biochemical and clinical failures rates when treated to 70 Gy. These patients also had a significantly higher risk of dying of prostate cancer. Patients <70 years old at treatment died of prostate cancer nearly three times more frequently than of other causes when they were radiated to 70 Gy, whereas those treated to 78 Gy died of other causes more frequently. Patients age 70 or older treated to 70 Gy died of prostate cancer as often as other causes, and those receiving 78 Gy never died of prostate cancer within 10 years of follow-up. In regression analysis, factors predicting for death from prostate cancer were pretreatment PSA >10.5 ng/mL, Gleason score 9 and 10, recurrence within 2.6 years of radiation, and doubling time of <3.6 months at the time of recurrence. Conclusions: Moderate dose escalation (78 Gy) decreases biochemical and clinical failure as well as prostate cancer death in patients with pretreatment PSA >10 ng/mL or high-risk disease. © 2011 Elsevier Inc.
Predicting radiation pneumonitis after chemoradiation therapy for lung cancer: An international individual patient data meta-analysisDavid A. Palma | Suresh Senan | Kayoko Tsujino | Robert B. Barriger | Ramesh Rengan | Marta Moreno | Jeffrey D. Bradley | Tae Hyun Kim | Sara Ramella | Lawrence B. Marks | Luigi De Petris | Larry Stitt | George Rodrigues
Volume 85, Issue 2, February 2013, Pages 444-450
Background: Radiation pneumonitis is a dose-limiting toxicity for patients undergoing concurrent chemoradiation therapy (CCRT) for non-small cell lung cancer (NSCLC). We performed an individual patient data meta-analysis to determine factors predictive of clinically significant pneumonitis. Methods and Materials: After a systematic review of the literature, data were obtained on 836 patients who underwent CCRT in Europe, North America, and Asia. Patients were randomly divided into training and validation sets (two-thirds vs one-third of patients). Factors predictive of symptomatic pneumonitis (grade ≥2 by 1 of several scoring systems) or fatal pneumonitis were evaluated using logistic regression. Recursive partitioning analysis (RPA) was used to define risk groups. Results: The median radiation therapy dose was 60 Gy, and the median follow-up time was 2.3 years. Most patients received concurrent cisplatin/etoposide (38%) or carboplatin/paclitaxel (26%). The overall rate of symptomatic pneumonitis was 29.8% (n=249), with fatal pneumonitis in 1.9% (n=16). In the training set, factors predictive of symptomatic pneumonitis were lung volume receiving ≥20 Gy (V20) (odds ratio [OR] 1.03 per 1% increase, P=.008), and carboplatin/paclitaxel chemotherapy (OR 3.33, P<.001), with a trend for age (OR 1.24 per decade, P=.09); the model remained predictive in the validation set with good discrimination in both datasets (c-statistic >0.65). On RPA, the highest risk of pneumonitis (>50%) was in patients >65 years of age receiving carboplatin/paclitaxel. Predictors of fatal pneumonitis were daily dose >2 Gy, V20, and lower-lobe tumor location. Conclusions: Several treatment-related risk factors predict the development of symptomatic pneumonitis, and elderly patients who undergo CCRT with carboplatin-paclitaxel chemotherapy are at highest risk. Fatal pneumonitis, although uncommon, is related to dosimetric factors and tumor location. © 2013 Elsevier Inc. All rights reserved.
Development and validation of a heart atlas to study cardiac exposure to radiation following treatment for breast cancerMary Feng | Jean M. Moran | Todd Koelling | Aamer Chughtai | June L. Chan | Laura Freedman | James A. Hayman | Reshma Jagsi | Shruti Jolly | Janice Larouere | Julie Soriano | Robin Marsh | Lori J. Pierce
Volume 79, Issue 1, January 2011, Pages 10-18
Purpose: Cardiac toxicity is an important sequela of breast radiotherapy. However, the relationship between dose to cardiac structures and subsequent toxicity has not been well defined, partially due to variations in substructure delineation, which can lead to inconsistent dose reporting and the failure to detect potential correlations. Here we have developed a heart atlas and evaluated its effect on contour accuracy and concordance. Methods and Materials: A detailed cardiac computed tomography scan atlas was developed jointly by cardiology, cardiac radiology, and radiation oncology. Seven radiation oncologists were recruited to delineate the whole heart, left main and left anterior descending interventricular branches, and right coronary arteries on four cases before and after studying the atlas. Contour accuracy was assessed by percent overlap with gold standard atlas volumes. The concordance index was also calculated. Standard radiation fields were applied. Doses to observer-contoured cardiac structures were calculated and compared with gold standard contour doses. Pre- and post-atlas values were analyzed using a paired t test. Results: The cardiac atlas significantly improved contour accuracy and concordance. Percent overlap and concordance index of observer-contoured cardiac and gold standard volumes were 2.3-fold improved for all structures (p < 0.002). After application of the atlas, reported mean doses to the whole heart, left main artery, left anterior descending interventricular branch, and right coronary artery were within 0.1, 0.9, 2.6, and 0.6 Gy, respectively, of gold standard doses. Conclusions: This validated University of Michigan cardiac atlas may serve as a useful tool in future studies assessing cardiac toxicity and in clinical trials which include dose volume constraints to the heart. © 2011 Elsevier Inc. Printed in the USA. All rights reserved.
Hypofractionated versus conventionally fractionated radiotherapy for prostate carcinoma: Final results of phase III randomized trialEric E. Yeoh | Rochelle J. Botten | Julie Butters | Addolorata C. Di Matteo | Richard H. Holloway | Jack Fowler
Volume 81, Issue 5, December 2011, Pages 1271-1278
Purpose: To evaluate the long-term efficacy and toxicity of a hypofractionated (55 Gy in 20 fractions within 4 weeks) vs. a conventionally fractionated (64 Gy in 32 fractions within 6.5 weeks) dose schedule for radiotherapy (RT) for localized carcinoma of the prostate. Methods and Materials: A total of 217 patients were randomized to either the hypofractionated (n = 108) or the conventional (n = 109) dose schedule. Most patients (n = 156) underwent RT planning and RT using a two-dimensional computed tomography method. Efficacy using the clinical, radiologic, and prostate-specific antigen data in each patient was evaluated before RT and at predetermined intervals after RT until death. Gastrointestinal and genitourinary toxicity using the modified Late Effect in Normal Tissue - Subjective Objective Management Analytic (LENT-SOMA) scales was also evaluated before and at intervals after RT to 60 months. Results: The whole group has now been followed for a median of 90 months (range, 3-138). Of the 217 patients, 85 developed biochemical relapse (nadir prostate-specific antigen level + 2 μg/L), 36 in the hypofractionated and 49 in the conventional group. The biochemical relapse-free, but not overall, survival at 90 months was significantly better with the hypofractionated (53%) than with the conventional (34%) schedule. Gastrointestinal and genitourinary toxicity persisted 60 months after RT and did not differ between the two dose schedules. Multivariate analyses revealed that the conventional schedule was of independent prognostic significance, not only for biochemical failure, but also for an increased risk of worse genitourinary symptoms at 4 years. Conclusions: A therapeutic advantage of the hypofractionated compared with the conventional dose schedule for RT of prostate cancer was evident at 90 months in the present study. © 2011 Elsevier Inc.
Five-Year analysis of treatment efficacy and cosmesis by the American society of breast surgeons mammosite breast brachytherapy registry trial in patients treated with accelerated partial breast irradiationFrank Vicini | Peter Beitsch | Coral Quiet | Mark Gittleman | Vic Zannis | Ricky Fine | Pat Whitworth | Henry Kuerer | Bruce Haffty | Martin Keisch | Maureen Lyden
Volume 79, Issue 3, March 2011, Pages 808-817
Purpose: To present 5-year data on treatment efficacy, cosmetic results, and toxicities for patients enrolled on the American Society of Breast Surgeons MammoSite breast brachytherapy registry trial. Methods and Materials: A total of 1440 patients (1449 cases) with early-stage breast cancer receiving breast-conserving therapy were treated with the MammoSite device to deliver accelerated partial-breast irradiation (APBI) (34 Gy in 3.4-Gy fractions). Of 1449 cases, 1255 (87%) had invasive breast cancer (IBC) (median size, 10 mm) and 194 (13%) had ductal carcinoma in situ (DCIS) (median size, 8 mm). Median follow-up was 54 months. Results: Thirty-seven cases (2.6%) developed an ipsilateral breast tumor recurrence (IBTR), for a 5-year actuarial rate of 3.80% (3.86% for IBC and 3.39% for DCIS). Negative estrogen receptor status (p = 0.0011) was the only clinical, pathologic, or treatment-related variable associated with IBTR for patients with IBC and young age (<50 years; p = 0.0096) and positive margin status (p = 0.0126) in those with DCIS. The percentage of breasts with good/excellent cosmetic results at 60 months (n = 371) was 90.6%. Symptomatic breast seromas were reported in 13.0% of cases, and 2.3% developed fat necrosis. A subset analysis of the first 400 consecutive cases enrolled was performed (352 with IBC, 48 DCIS). With a median follow-up of 60.5 months, the 5-year actuarial rate of IBTR was 3.04%. Conclusion: Treatment efficacy, cosmesis, and toxicity 5 years after treatment with APBI using the MammoSite device are good and similar to those reported with other forms of APBI with similar follow-up. Copyright © 2011 Elsevier Inc.
The abscopal effect associated with a systemic anti-melanoma immune responseEmily F. Stamell | Jedd D. Wolchok | Sacha Gnjatic | Nancy Y. Lee | Isaac Brownell
Volume 85, Issue 2, February 2013, Pages 293-295
The clearance of nonirradiated tumors after localized radiation therapy is known as the abscopal effect. Activation of an antitumor immune response has been proposed as a mechanism for the abscopal effect. Here we report a patient with metastatic melanoma who received palliative radiation to his primary tumor with subsequent clearance of all his nonirradiated in-transit metastases. Anti-MAGEA3 antibodies were found upon serological testing, demonstrating an association between the abscopal effect and a systemic antitumor immune response. A brain recurrence was then treated with a combination of stereotactic radiosurgery and immunotherapy with ipilimumab. The patient experienced a complete remission that included resolution of nodal metastases, with a concomitant increase in MAGEA3 titers and a new response to the cancer antigen PASD1. This case supports the immune hypothesis for the abscopal effect, and illustrates the potential of combining radiotherapy and immunotherapy in the treatment of melanoma. © 2013 Elsevier Inc. All rights reserved.
Local recurrence after complete clinical response and watch and wait in rectal cancer after neoadjuvant chemoradiation: Impact of salvage therapy on local disease controlAngelita Habr-Gama | Joaquim Gama-Rodrigues | Guilherme P. São Julião | Igor Proscurshim | Charles Sabbagh | Patricio B. Lynn | Rodrigo O. Perez
Volume 88, Issue 4, March 2014, Pages 822-828
Purpose To review the risk of local recurrence and impact of salvage therapy after Watch and Wait for rectal cancer with complete clinical response (cCR) after chemoradiation therapy (CRT). Methods and Materials Patients with cT2-4N0-2M0 distal rectal cancer treated with CRT (50.4-54 Gy + 5-fluorouracil-based chemotherapy) and cCR at 8 weeks were included. Patients with cCR were enrolled in a strict follow-up program with no immediate surgery (Watch and Wait). Local recurrence-free survival was compared while taking into account Watch and Wait strategy alone and Watch and Wait plus salvage. Results 90 of 183 patients experienced cCR at initial assessment after CRT (49%). When early tumor regrowths (up to and including the initial 12 months of follow-up) and late recurrences were considered together, 28 patients (31%) experienced local recurrence (median follow-up time, 60 months). Of those, 26 patients underwent salvage therapy, and 2 patients were not amenable to salvage. In 4 patients, local re-recurrence developed after Watch and Wait plus salvage. The overall salvage rate for local recurrence was 93%. Local recurrence-free survival at 5 years was 69% (all local recurrences) and 94% (after salvage procedures). Thirteen patients (14%) experienced systemic recurrence. The 5-year cancer-specific overall survival and disease-free survival for all patients (including all recurrences) were 91% and 68%, respectively. Conclusions Local recurrence may develop in 31% of patients with initial cCR when early regrowths (≤12 months) and late recurrences are grouped together. More than half of these recurrences develop within 12 months of follow-up. Salvage therapy is possible in ≥90% of recurrences, leading to 94% local disease control, with 78% organ preservation. © 2014 Elsevier Inc. All rights reserved.
Comparative effectiveness of 5 treatment strategies for early-stage non-small cell lung cancer in the elderlyShervin M. Shirvani | Jing Jiang | Joe Y. Chang | James W. Welsh | Daniel R. Gomez | Stephen Swisher | Thomas A. Buchholz | Benjamin D. Smith
Volume 84, Issue 5, December 2012, Pages 1060-1070
Purpose: The incidence of early-stage non-small cell lung cancer (NSCLC) among older adults is expected to increase because of demographic trends and computed tomography-based screening; yet, optimal treatment in the elderly remains controversial. Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare cohort spanning 2001-2007, we compared survival outcomes associated with 5 strategies used in contemporary practice: lobectomy, sublobar resection, conventional radiation therapy, stereotactic ablative radiation therapy (SABR), and observation. Methods and Materials: Treatment strategy and covariates were determined in 10,923 patients aged ≥66 years with stage IA-IB NSCLC. Cox regression, adjusted for patient and tumor factors, compared overall and disease-specific survival for the 5 strategies. In a second exploratory analysis, propensity-score matching was used for comparison of SABR with other options. Results: The median age was 75 years, and 29% had moderate to severe comorbidities. Treatment distribution was lobectomy (59%), sublobar resection (11.7%), conventional radiation (14.8%), observation (12.6%), and SABR (1.1%). In Cox regression analysis with a median follow-up time of 3.2 years, SABR was associated with the lowest risk of death within 6 months of diagnosis (hazard ratio [HR] 0.48; 95% confidence interval [CI] 0.38-0.63; referent is lobectomy). After 6 months, lobectomy was associated with the best overall and disease-specific survival. In the propensity-score matched analysis, survival after SABR was similar to that after lobectomy (HR 0.71; 95% CI 0.45-1.12; referent is SABR). Conventional radiation and observation were associated with poor outcomes in all analyses. Conclusions: In this population-based experience, lobectomy was associated with the best long-term outcomes in fit elderly patients with early-stage NSCLC. Exploratory analysis of SABR early adopters suggests efficacy comparable with that of surgery in select populations. Evaluation of these therapies in randomized trials is urgently needed. © 2012 Elsevier Inc. All rights reserved.
Modern radiation therapy for Hodgkin lymphoma: Field and dose guidelines from the international lymphoma radiation oncology group (ILROG)Lena Specht | Joachim Yahalom | Tim Illidge | Anne Kiil Berthelsen | Louis S. Constine | Hans Theodor Eich | Theodore Girinsky | Richard T. Hoppe | Peter Mauch | N. George Mikhaeel | Andrea Ng
Volume 89, Issue 4, July 2014, Pages 854-862
Radiation therapy (RT) is the most effective single modality for local control of Hodgkin lymphoma (HL) and an important component of therapy for many patients. These guidelines have been developed to address the use of RT in HL in the modern era of combined modality treatment. The role of reduced volumes and doses is addressed, integrating modern imaging with 3-dimensional (3D) planning and advanced techniques of treatment delivery. The previously applied extended field (EF) and original involved field (IF) techniques, which treated larger volumes based on nodal stations, have now been replaced by the use of limited volumes, based solely on detectable nodal (and extranodal extension) involvement at presentation, using contrast-enhanced computed tomography, positron emission tomography/computed tomography, magnetic resonance imaging, or a combination of these techniques. The International Commission on Radiation Units and Measurements concepts of gross tumor volume, clinical target volume, internal target volume, and planning target volume are used for defining the targeted volumes. Newer treatment techniques, including intensity modulated radiation therapy, breath-hold, image guided radiation therapy, and 4-dimensional imaging, should be implemented when their use is expected to decrease significantly the risk for normal tissue damage while still achieving the primary goal of local tumor control. The highly conformal involved node radiation therapy (INRT), recently introduced for patients for whom optimal imaging is available, is explained. A new concept, involved site radiation therapy (ISRT), is introduced as the standard conformal therapy for the scenario, commonly encountered, wherein optimal imaging is not available. There is increasing evidence that RT doses used in the past are higher than necessary for disease control in this era of combined modality therapy. The use of INRT and of lower doses in early-stage HL is supported by available data. Although the use of ISRT has not yet been validated in a formal study, it is more conservative than INRT, accounting for suboptimal information and appropriately designed for safe local disease control. The goal of modern smaller field radiation therapy is to reduce both treatment volume and treatment dose while maintaining efficacy and minimizing acute and late sequelae. This review is a consensus of the International Lymphoma Radiation Oncology Group (ILROG) Steering Committee regarding the modern approach to RT in the treatment of HL, outlining a new concept of ISRT in which reduced treatment volumes are planned for the effective control of involved sites of HL. Nodal and extranodal non-Hodgkin lymphomas (NHL) are covered separately by ILROG guidelines. © 2014 Elsevier Inc.


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Expert Witness Resources
SEAK, Inc. is The Expert Witness Training Company.
We have been serving the needs of expert witnesses of all specialties and levels of experience since 1990. SEAK has trained many thousands of expert witnesses through our Annual National Expert Witness Conference, small group interactive expert witness training seminars, one-on-one expert witness training, expert witness report quality control services, one on one expert witness marketing consulting, and customized on-site expert witness training.
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Call for Nominations to the AHA Board of Directors
In accordance with the AHA bylaws, the AHA Board of Directors approved the appointment of five AHA members, none of whom are current members of the Board or can be nominated for the current election, to serve on the Nominations Committee for the 2016 AHA Board of Directors election. They are Mel Lipman (chair), Kimberly Ellington, Kevin Jagoe, Mandisa Thomas, and Mike Werner. The Nominations Committee was approved at the AHA board meeting on September 26, 2015 in Chicago, Illinois.
The Nominations Committee has issued a call to the AHA membership to nominate candidates to serve on the AHA Board of Directors. Six seats of our twelve member board are up for election in 2016. Nominees must have been members in good standing of the AHA for one or more years immediately prior to nomination. The deadline for submitting candidates is April 15, 2016.
AHA members in good standing will be eligible to vote online for the board. More details on the voting process will be announced in the Spring 2015 issues of Free Mind.
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Dragon Age: Origins - Awakening
Just hope whatever they plan to do i expect a good bang for a buck.
The DLC for Shale was released a long time ago (and there will be no more regarding her), but yes the "Witch Hunt" DLC is coming September 7th alongside the "Lair of the Shadow Broker" DLC for Mass Effect 2.
And yes I do hope it'll be decent, and this topic should be in Origins' board, not Awakening's.
Dragon Age to be rocked by 'Golems of Amgarrak' DLC on Aug. 10
by Randy Nelson (Jul 28th 2010 3:30PM)
You know that Dragon Age: Origins DLC, "Golems of Amgarrak," we just played at Comic-Con? You'll be playing it soon yourself -- on Tuesday, August 10, to be exact, for PS3, 360 and PC. (Unless, that is, you don't like Dragon Age, in which case we can't be friends anymore. Kidding!) BioWare's, ...
Continue Reading
This is the info regards to a new DLC - i rest my case
• Mana
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Skilcraft 4-Part Classification FolderItem#: FPD-102111663 | Model#: NSN4632330
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Four-part classification folder is made of heavy-duty material with 25 point pressboard cover and 17 point Kraft divider page. Double top tabs are tear-resistant and durable. Cover offers a right of center tab. Divider page has a 1/3-cut tab. The reinforced gusset expands up to 2". Metal fasteners are located on the inside of divider. Classification folder is made using 30 percent recycled material.
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These are all the Teen Talk Blog posted on Friday, 3 April, 2009.
New Titles: March
Looking for something new to read, watch, or listen to? Take a look at our list of new teen materials purchased in the month of March. We have two lists:
We post a list of new items at the beginning of each month, so check back for more reading suggestions.
Posted By Logan Library - Teen Talk at 5:31 PM in Category:Books & Reading
The Latest Talk!
May 13, 2016
» Get Your Game On @ Comic Con Mar 23, 2016
» Teens' Top Ten Reads Announced Feb 29, 2016
» Teen Tuesdays...
Every Tuesday Kicked Up a Notch


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------ It is common sense to take a method and try it. If it fails, admit it frankly and try another. But above all, try something. ~ Franklin D Roosevelt 1843
Janome 19606 ,Janome My Excel 4023, Brother 1034D, White 1750C, Kenmore 158.1803, White 764, Brother 780D.
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Cool stuff!!
Forum Rules
Fake news site.
She didn't do an above-average job with the advanced time then. Pretty-boring helium.
I noticed she was reading a lot. It wasn't helping so I didn't dwell on it.
OK, now that was funny. :rotfl:
Something doesn't smell right about The Baltimore Gazette. Odd for an "Baltimore's Oldest News outlet" not to have any wiki page. And their street address, is a shopping mall.
Lester (no last name, he doesn't deserve one) was clearly working at the behest of his bosses. This is an old article but no one is making this connection.


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The Invidiata Collection Real Estate Magazine
Published by Preferred Publishing | 5036 Fairview Street Burlington, Ontario | firstname.lastname@example.com | 289.337.0765
The Summer 2016 issue of The Invidiata Collection is all about historical landmarks. The Greater Toronto Area is full of estates that are rich in history that served a specific purpose when they were built and still have a place in their modern communities. We had the opportunity to get an inside look at Canada's Legendary Lakefront Estate, Chelster Hall. This magnificent home rests on over 10 acres of land right on Oakville's lakeshore. more...
120,000 Copies Per Year
The Invidiata Collection is a glossy 124 page magazine published quarterly and delivered by The Globe & Mail, and by special hand delivery to the most affluent homes in Toronto, Mississauga, Oakville and Burlington.
More Than A Magazine
By partnering with the Invidiata Collection, you will also experience the added benefit of quarterly networking events, referrals and special VIP event invitations.
For all general advertising or media kit inquiries, please contact;
Lauren Lowe
Advertising Director
905.510.2344 - email@example.com


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Traditional Yoruba Adire with Indigo | July 30 & 31, 2016
Originally from Nigeria, Gasali Onireke Adeyemo resides in Santa Fe, New Mexico, where shares the arts and culture of the Yoruba people through his fabric art. Since mastering the art of batik painting on fabric and rice paper, indigo dyeing, quilt making, embroidery, appliqué at Nike Center for Arts and Culture, Gasali has traveled the world teaching workshops, showing his work, and sharing the traditionas of the Yoruba culture. His recent workshops include the World Batik Conference, Cross Culture Collaborative Inc., SnowFarm, and Fiber Arts Center.
Bookmaking for Beginners: The Long (Stitch) and Short of It | August 12-13, 2016
Studio artist and gallerist Alicia Bailey, Denver, Colorado, has a particular passion for book works that include elements beyond surface printed images and text; that move beyond traditional book forms and embrace presentation flexibility, innovative page folding tactics, rigid page construction and use of alternative materials.
High Flow: Paper Marbling | June 21, 2016
Derek Chan (b.1981) is a Santa Fe based artist working primarily in painting. He received his BA from UCLA, in 2004, and later his MFA from the University of Illinois, Chicago, in 2007. In 2012, he was selected to participate in the Roswell-Artist-In-Residence program. It was during his time in residence that paper marbling became an integral part of his art practice. He has exhibited in solo, group and collaborative exhibitions in Santa Fe, NM, Chicago, IL, and New York, NY. He has previously taught paper marbling workshops at the Roswell Museum and Art Center, Artisan (Santa Fe) and Center for Contemporary Art (Santa Fe).
Artist Website
Capturing Summer En Plein Air | July 20 – 23, 2016
Tim Deibler has had a life-long passion for art. From his earliest childhood he tried to visually depict the world around him with crayons and paint. After graduating from the Art Institute of Colorado, he worked in the commercial art and video production fields until going full time as a fine artist in 1992. A Signature member of OPA, he has won five Awards of Excellence at the Oil Painters of America's National Juried Show from such distinguished artists as Daniel Gerhartz, Quang Ho, Ramon Kelly and Scott Christensen. Best known for his stunning portrayal of nature in oil, he loves painting the rugged mountain peaks, desert canyons and the pounding surf. With the success of his teaching videos and his book Capturing the Seasons in Oils, he has become a popular teacher and workshop instructor. His work has appeared in many books and publications and can be found in many private and corporate collections.
Artist Website
Peerless Pastel Painting | July 8 – 10, 2016
Self-taught, Denver-based artist Bruce Gomez has worked solely with pastels for nearly 40 years, and has taught workshops for more than 20 years. His award-winning work hangs in major corporate collections, including Qwest, Time-Warner, Excel, Transamerica and the Federal Reserve Bank. His subject matter reflects extensive travels ranging from Paris and Cortona to Telluride and Sedona. Bruce exhibits locally at the Telluride Gallery of Fine Art, which has represented his work since 1985.
Artist Website
Adventures in Photography: Capturing the Commotion of a Well-Traveled Life | July 12 & 13, 2016
Kerry M. Halasz is a photographer based in Santa Fe, New Mexico. Kerry has worked professionally as a portrait and wedding photographer in the Atlanta for 16 years area and has also been fortunate enough to travel the world with her camera, capturing images as she goes and selling them locally in Santa Fe and on the internet. Kerry's travel and lifestyle images have been published in the Denver Post, The Boston Globe, National Geographic Traveller India, The Chicago Sun-Times, The Atlanta Jewish Times and in Jezebel and Cosmopolitan Magazines. Kerry has taught travel and child photography classes at the Showcase School in Atlanta.
Artist Website
Wax and Screen: Combining Techniques for Unique Outcomes | July 29 – 31, 2016
Jeff Hirst is a Chicago based artist who has been exhibiting his work since 1987 and has shown extensively across the United States and Europe. Hirst's work has been shown at The Minneapolis Institute of Arts, the McKinney Contemporary in Dallas, Butters Gallery in Portland, and Arte Internazionale in Matera, Italy. He has been a recipient of a Minnesota State Artist Intuitive grant. Hirst is the owner of Hirst Printmaking, a print shop and teaching facility in Chicago where research and exploration in experimental print ideas meld encaustic and printmaking. In 2016, he will teach numerous venues including Arrowmont School of Arts & Crafts in Tennessee, Cullowhee Mountain Arts in North Carolina, and San Francisco Center for the Book.
Artist Website
Going Out, Going In: A Four-Day Art & Writing Retreat | July 25 – 28, 2016
Brucie Holler, a South Carolina native, received a BFA in painting from Florida State University and did graduate work at the Maryland Institute, College of Art in Baltimore. She then moved to Telluride, Colorado and worked for seven years teaching and serving as Director of Exhibitions for the Ah Haa School for the Arts, a non-profit art school. She has studied with a variety of internationally known painters including Richard Smith, Mario Martinez, and Truman Lowe among others and has shown her work in galleries in Florida, South Carolina and Colorado. She moved back to South Carolina in 1997 where she maintains a studio.
Artist Website
Professional Acting for Adults | August 5 – 7, 2016
Youth Acting for Ages 7-12 | August 8 – 10, 2016
Professional Acting for Teens | August 8 – 10, 2016
With a BFA in musical theatre and an MFA in acting, Keith Jefferson has an extensive performance background in film, TV and live theatre. He has worked alongside such acting greats as Jamie Foxx, Angela Lansbury, and Danny Glover, and under award-winning directors Quentin Tarantino, Hebert Ross and Charles Haid, among others. Drawing from his extensive experience teaching similar workshops around the country, Keith will lead his students on a road of artistic discovery.
Though he is a native Texan, Sam Levy received his BFA from the University of Maryland at College Park and his MFA in Painting from The New York Studio School of Drawing, Painting, and Sculpture. Sam paints and draws the figure and landscape from direct perception. He prefers working with the same motif over an extended period of time. In this way he searches for and discovers pathways, forms, and relationships that he couldn't have known at its outset. His work is an experience in time: a realization of a conversational journey made tangible in paint. The paintings are a sensual experience, both seen and felt.
Sam studied with Bruce Gagnier, John Lees, Stanley Lewis, Graham Nickson and Foon Sham. He moved to New York City in 2003 and worked for the artist Ursula Von Rydingsvard as a sculptor's assistant. He has traveled and worked in Europe and across the United States. He currently lives and works in Brooklyn, NY.
Telluride Painting School | October 3 – 15, 2016
Born in Beijing, China, Ying Li graduated from Anhui Teachers University (1974-77) where she taught 1977-83. She immigrated to the United States in 1983 and received an MFA from Parsons School of Design, NY in 1987. Ying Li is a painter and Professor of Fine Arts at Haverford College. She is known for her highly energetic, on-site landscapes that verge on pure abstraction, yet simultaneously are totally convincing as direct visual experience. Her uncompromising sense of personal vision combined with complete abandon in the possibilities of paint make her work style the epitome of painterliness.
Ying Li lives and works in New York City and Haverford, PA
Artist Website
Wax and Screen: Combining Techniques for Unique Outcomes | July 29 – 31, 2016
Shawna Moore is an established, professional painter and encaustic artist living in Whitefish, Montana. She exhibits her work nationally in galleries and regional museums. Anchored by the use of color and the immediacy of art making, Moore has spent the past 20 years developing and refining her artistic process and intention. Her art integrates elements of painting and drawing, and reflects both her education in architecture and fine art, and her inventive and experimental nature. In recent years, the ancient method of encaustic painting is Moore's medium of choice. This unique and dynamic technique incorporates pigmented bee's wax, which is heated, re-worked, etched and scuffed to achieve dimensional depth. As each layer cools, another can be applied, resulting in a radiant and complex terrain of light, color and texture. Her work is represented locally by Telluride Fine Arts.
Artist Website
Bold Expressive Floral Painting | August 16-18, 2016
Prior to becoming a full-time professional artist 8 years ago, Annie had a successful career in academics at several universities including the University of Colorado. After many years as a part-time artist, Annie studied painting and art history and realized her dream of becoming a full-time professional painter. Annie is represented by several galleries across the country and recently was honored with a museum acquisition of her work for their permanent collection. Annie has used her academic experience to design and teach painting workshops in her studio, at the Georgia O'Keeffe Museum, Ghost Ranch and other venues across the country. Annie has also had a book on painting published by Northlight Books in January, 2015.
Artist Website
Explorations in Pastel Painting | September 6-8, 2016
I have always been an artist and am proud and fond of this innate desire to create, explore, study, delve into and express myself…artistically. My work is my own and I am inspired by many people, places and things. To name a few of each: O'Keeffe, Rembrandt, Bourke-White, the great plains & prairies, the arctic, waterways, innocence, relationships and emotions. As a fourth generation North Dakotan, I have deep family roots and connections to the prairies and plains, which, along with all wide open spaces, have been a source of inspiration to me. As a young teen, my family moved to Minnesota where I fostered a love for the northwoods lake country and, through friends, was introduced to camping and backcountry adventures.
For 23 years I lived in Ely, MN, on the edge of the Boundary Waters Canoe Area Wilderness, where I owned and operated a photography studio and gallery. In late 2012, my husband and I fulfilled a life long dream to live in the mountains and relocated from the Land of 10,000 Lakes to the stunning and arid Four Corners region. As an active outdoor enthusiast, wilderness traveler, educator, athlete, and arts advocate, I am delighted to call Durango, CO my new home.
Exploring Abstract Painting | July 25-27, 2017
Painting is a very physical and sensual process for me, beginning days or weeks before I ever make a mark. Stretching canvases, mixing new colors and mediums, searching for new tools and methods of working. Each step is as integral as the application of paint and mark. I try to keep myself o -balance and my mind at bay for as long as possible. The work needs to be born from a deeper place–somewhere pure and personal…the place where head, heart and hand come together to create a new narrative. I embark on every painting as if it were a journey – a new destination with new languages to be translated, new waters to be crossed…where each mark becomes a direction, each passage of paint like a new vista I'm seeing for the first time. Once the work is underway I try to keep the painting open to all possibilities, deviations and directions – where it's outcome is not yet known and anything can happen. Getting things wrong is often more exciting than getting things right. Getting lost has surprising outcomes. Working back and forth between organic and architectural elements, patterns and textures, colors that become saturated or atmospheric, tangles of marks that whisper or shout are laid down, discarded, rediscovered and reconsidered. The mystery keeps the work alive for me, and becomes a map of uncharted terrain.
Read more about the Visiting Artist program at Telluride Inside… and Out.


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God is all around us. The question is have we learned to catch His signals? Read More »
Obama's a Commie?
President Obama stood with the rights of the homosexual American. Read More »
Conservative Jesus, Liberal Satan, and Middle of the Road Amway
Do you ghost write for God or Satan? Read More »
Living Water
An emptiness that could only be filled with the true Source of life. Read More »
Book Review: Demonic and Other Tales by Garon Cockrell
Guilt, passion, revenge, dismembered bodies, omnipresent pools of blood, grotesque characters, and vast panoramas of heavenly battle across our world. Read More »
Book Review: Dream Language: The Prophetic Power of Dreams, Revelations, and the Spirit of Wisdom by James W. and Michal Ann Goll
The Golls team together to write an insightful book of studying and interpreting God's secret language of dreams with mankind. Read More »
Book Review: Speaking of Jesus: The Art of Not-Evangelism by Carl Medearis
Did you hear about a man who loved those who hated him, forgave those who were murdering him? Read More »
The Vow: Not exactly what Hollywood says
You might be surprised to know that the true story this film is based on the principle that God alone can hold a marriage together. Read More »
Book Review: Sex God by Rob Bell
...Think about your moment, and think about how it made you feel. You were full, you were alive, you were connected. That is what Sex God is all about. Read More »
Book Review: I Want To Know My Future by Linda Dipman
What do you do when your family, friends and church turn against you? Read More »


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Throw Pillow
The Day We Never Metby Ana Lillith Bar
10% Off + Free Shipping on Everything - Ends Tonight at Midnight PT!
Throw Pillow made from 100% spun polyester poplin fabric, a stylish statement that will liven up any room. Individually cut and sewn by hand, each pillow features a double-sided print and is finished with a concealed zipper for ease of care. Sold with or without faux down pillow insert.
Original: Background - Acrylic paint. People - Prismacolor and Derwent colored pencils on cut-out Canson MI-Teintes, 98 lbs. egg shell, 8.5 x 11 paper.
Model inspiration:
Male: http://fav.me/d7tylh2
Female: http://fav.me/d5eyzky
"...perhaps in the next life we'll get it right."
yellow, blue, green, black, purple, flesh, woman, female, man, male, breasts


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(CHATSWORTH, CA) -- Saturday, June 3rd is almost here and if you haven't called in your RSVP, your time is running out. Shane's World Studio's 10-year anniversary party is the hot "Golden Ticket" to have. In the last 2 weeks Shane's World has sent several oompa loompa's to give out golden tickets to the industries top companies.
"This has gotten way more out of hand then we expected! People are calling non-stop asking for invites and some of the tickets have even been stolen from offices in an effort to go. Luckily we have an exact list of the invitees!" said Jennie Grant, Shane's World Owner. "We are very flattered so many people want to go but we didn't want this to be just like every other party. This is to celebrate our 10 years of success with a special thank you to our friends, colleagues and supporters."
The extravagant anniversary party is being held at a top-secret location and party guests will be please with the phenomenal goodie bags and gift table. The party will feature a live performance by a well-known band, live DJ, gambling tables with prizes, Cigar girls, specialized entertainment, world-class catering and bar service. Shane's World has stated the theme of the party is indulgence.
The party is being held from 7:30 p.m. to midnight. Red carpet is from 7:00 p.m. until 8:45 p.m. Early arrival is suggested. You Must RSVP to be on the list. If you are not on the list you will be turned away. Invitees are to park in the parking lot of the Beverly Hilton located at 9876 Wilshire Boulevard Beverly Hills, CA 90210. You will be given a Shane's World Parking Pass for the Hilton. Upon arrival guests will be quickly shuttled to the secret location.
Shane's World is also announcing their new Contract Star at the event. The name of the contract star has been kept under wraps for a few months now and has been fodder for gossip.
Hotmovies.com and PPPcard.net are the official sponsors of the large event. "We are thrilled that Hotmovies and PPPCard came on board to do this with us. We knew they were good companies to do an event with since we already had solid relationships with them," Said Jennie Grant. Xbiz has been tapped as the official media sponsor for this event, as well.
Invitees need to RSVP as soon as possible as the list is filling up quickly. If you still have not given your RSVP, please call 818-717-8851 or email email@example.com. Media please contact Megan as well to get a media badge.
Megan Stokes
Vice President of Sales, Foreign and Domestic
Tel: 818-717-8851 ext 103
Alt: 888-SW-RULES
Fax: 818-717-9005
AIM: MeganStokes
Darcy Tyler Jailed
Diesel Hits Anna Bell Peaks
Marica Hase Birthday Party
Are You an iDriver?
Sheri's Ranch Joint Venture
Allison Kilgore Returns
Exxxotica Dirty 30
Tera Patrick Available
Young Girl Auditions
Angela White US Resident
PSK Celebrates 13
Jayden Lee at Crazy Horse
Centerfold Features
Alison Tyler at HQNYC
ED Awards Winners
Clubs & Appearances Section Index
Sabrina Deep Bukkake Tour Update
Layton Benton to Exxxotica
Vivid Hosts Texxxas Parties
Dani Daniels in Houston
GFE at Sheri's Ranch
Jenevieve Hexxx at Trixie's
Carnal Comedy at Sapphires
ED Expo Returns to NO
Kendra Sunderland at Sapphire NYC
Gentlemen's Club Live Feed
Leya Falcon at AFFLV
Morgan, Lindemulder Headline Exxxotica
Cindy Starfall Appearances
Priya in NYC
Tony Batman to Big Easy
Elizabeth Bentley Hits Circuit
Allie Haze in Columbus
Vivid NYC Nommed
Raven Bay at Exxxotica
Little Sassee Cassee in OK
Dee, Michaels in Alabama
Nikki Benz Headlines Ohio
Galaxy Stars to Exxxotica
Caribbean Playground Party
Throwback Expo Registration Rates!
Tanya Tate at Comic Con
Bridget the Midget at Vivid Houston
Ideal Image Supperclub Party
Angela Sommers in Houston
Starfall to Exxxotica
Prinzzess at Treasure Chest
Danica Dillon in Bath
Library Girl at Exxxotica
ED Awards Host Thea Vidale
National Porn Star Day
Strippers Ready for Baseball
Karaoke XXX Needs New Location
ED Expo to Big Easy
Layla Price at Foxxx Booth
Nikki Phoenix Party


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I have tested the first Liquid for OS X Yosemite today and it's quite wonderful. First of all, the keyboard shortcut to launch Liquid now works wether you have text selected or not and it uses the OS X accounts
Updates, Future of my writing
Blogging Since I've decided to write a book on Deep Literacy and I find it difficult to press on with writing since the subject area is so potentially large and I have to find some shape to present it in,
Photography Update
The RX-1 is always, always used with VSCO filters. I often use the TRI-X processing and often Fuji Superia or Kodak Portra for people shots (plus about 75% grain for the film). Interestingly though, I find, I use a x2


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Elegant yet sophisticated, The Sperry Winsor is a penny loafer that won't kill your ankles. Genuine hand-sewn construction yields a very wearable, comfortable shoe. A full great leather sock lining allows for sockless wear and a memory foam cushioned bed will have you looking forward to putting them on in the morning. A flexible rubber outsole will move with you instead of staying stiff, with non marking, slip resistant rubber. Get your shiny penny's ready, the Sperry Winsor is here to stay.
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"I think I've ordered four pairs of shoes from PlanetShoes this year. They've all been beautiful, comfortable shoes, delivered on time. What a great site! A real treasure trove for shoe lovers!"
"My experience has been great with Planet Shoes! The shoes were exactly as described and photographed, fit well and were very comfortable! I will recommend Planet Shoes to everyone!"


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People of the Middle East, Untie!
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The Woolrich Company got its start in 1830 when John Rich and Daniel McCormick built a woolen mill in Plum Run, Pennsylvania. As the oldest woolen mill in the United States, Woolrich handles outdoor clothing and home décor "from sheep to store." John Rich bought out his partner in 1845, when the company expanded beyond woolen yarns and fabrics and moved to the town that would become known as Woolrich, Pennsylvania. Offering Woolrich blankets to the army during the American Civil War helped Woolrich establish itself in households across the United States, and their bedding line, including quilts and coverlets, Woolrich comforters and duvets, and full bedding sets remain an important part of the business today.
Woolrich's move into outdoor apparel, such as Woolrich coats, in the 1920s led to outfitting Admiral Byrd's expedition to Antarctica in 1939. Throughout the decades, the company produced exclusively wool-based products, until down-filled jackets and apparel were added in 1971. The company did not add synthetic fabrics until around 1989, but wool remains an important component in most of Woolrich's products, and their return to home furnishings as a main product line in 2001 saw a resurgence of popularity in the soft, natural feel of wool. Today, Woolrich draperies and curtains, throws, and shower curtains and liners often combine the high quality inherent in wool with the durability of a partially synthetic blend, while the look and feel of outdoor life is brought into your home with rustic furnishings and soft-washed prints.
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