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Radiotherapy alone or surgery in spinal cord compression? The choice depends on accurate patient selection
No full textTo the Editor:
We read with great interest the editorial by Kwok, Regine, and Patchell,1 in which they suggest caution in implementing the results in clinical practice of our phase III randomized clinical trial on hypofractionated radiotherapy in metastatic spinal-cord compression (MSCC).2 We feel obliged to reply by answering point by point to the major reported criticisms.
As stated in the paper, only MSCC patients with a short life expectancy entered onto the trial. The majority of patients (229; 83%) had low Karnofsky performance status (KPS) and the remaining 47 (17%) enrolled with a good KPS, and had poor life expectancy and bad prognosis for the presence of unfavorable histologies.
Although 30 Gy in 3-Gy daily fractions represents the most common fractionation schedule used in patients with MSCC in the United States, the optimal radiotherapy (RT) regimen for treating MSCC is still unknown and many schedules are reported in the literature.3 In some published trials, 4 to 5 Gy daily for 3 days followed by 4 days of rest, and then five to 16 daily doses of 2 to 3 Gy have been administered with both good results and tolerance.4-8 Studies concerning RT for patients with painful bone metastases have shown that low fraction regimens and high single doses have a clinical outcome similar to more protracted regimens, also in patients with vertebral metastases.9
Considering that higher RT doses per fraction is one of the possible factors that may be associated with radiation-induced late spinal cord morbidity, in our previous trials we adopted different hypofractionation regimens on the basis of the patient's life expectancy.3,8 A safer fractionation of 3 to 30 Gy in 10 fractions over 2 weeks was administered to patients with a long life expectancy (approximately 15% of observed cases). Split-course RT of three fractions of 5 Gy each, 4 days of rest, and then five fractions of 3 Gy each, to a total dose of 30 Gy in 2 weeks, was adopted for patients with short life expectancy.8 In recent phase II trial, we have proved the feasibility and effectiveness of a short-course RT (two fractions 8 Gy) in the patients with less than 6 months of life.3 With this background, this prospective randomized phase III trial was performed to compare the aforementioned split-course regimen with the short-course RT in patients with MSCC and short life expectancy. Other MSCC patients who did not enter onto the study, underwent to 3 to 30 Gy regimen.
We agree with Kwok, Regine, and Patchell in being worried about radiation-induced myelopathy (RIM) that may result in heavy neurologic deficits. Of 465 MSCC patients submitted to RT at our center between 1988 and 1997, 13 living patients treated with the aforementioned split- or short-course regimens survived for 2 years or more were reviewed to evaluate RIM. This trial, the only one published on RIM in long-term–surviving MSCC patients, showed an excellent spinal cord tolerance to the hypofractionated RT schedules adopted, with only one case of suspected RIM.10
Furthermore, three randomized Medical Research Council trials on non–small-cell lung cancer have shown the effectiveness of two fractions 8.5 Gy RT in the palliation of symptoms caused by thoracic disease. This regimen has given the same outcome and toxicity as three other regimens used for comparison. Only one of 550 patients submitted to this hypofractionation schedule presented a suspected RIM.11-13 Recently Macbeth14 encourage a wider use of 8 Gy × 2 fractionation in palliative RT.
Another important support on the feasibility of the hypofractionated RT can be derived by the radiobiology. The effect of an RT schedule on tumor control and on late toxicity depends on both the total dose and the dose per fraction. Each schedule adopted can be compared with the equivalent dose in 2-Gy fraction (EQD2), which is calculated using the equation Undefined control sequence derived from the linear-quadratic model.15 The tolerance dose (5% late toxicity within 5 years) for RIM is 50 Gy for conventional fractionation (a dose per fraction of 2 Gy).16 For the end point myelopathy, the EQD2 must be calculated with an α/β ratio of 2 Gy, resulting in an EQD2 of 45 Gy and 40 Gy for the split-course (5 Gy × 3; 3 Gy × 5) and short-course (8 Gy × 2) schedules, respectively. Thus, whatever of these two RT regimens are adopted, relevant late toxicity appears to be extremely unlikely.
As reported in our article,2 responders were considered either those patients who retained or regained the ability to walk. This definition of response, shared by the majority of authors, can be acceptable because untreated MSCC patients generally deteriorate and develop neurologic dysfunction.3-7 Also the authors of the editorial have adopted these criteria in defining response in their recent trial.17 So, we do not understand the reason for which they argume against our results and want to limit the percentage of response to only patients who have improved after RT.
The good response rate found in our trial is probably due to the early diagnosis and prompt treatment (in 67% of cases, MSCC was diagnosed and treated when patients were ambulant, and 90% of patients maintained this function).2 Considering that the pretreatment ambulatory function is the main determinant for post-treatment gait function, an important message we would like reinforce is the importance of the early diagnosis that can be obtained prescribing MRI or CT for all cancer patients with back pain, osteolysis and/or positive bone scan, even in the absence of clinical neurologic signs of MSCC.2,18
The best or most effective treatment for MSCC patients is still not defined, and the choice between surgery plus RT or RT alone is debatable. In fact, the two published randomized studies comparing surgery plus RT versus RT alone do not conclusively clarify what is the treatment of choice.5,17 Young's trial5 has shown no difference between laminectomy plus RT and RT alone; however, too few patients were enrolled and simple laminectomy is generally considered an inappropriate surgical approach. The other trial was closed at an interim analysis that showed a significant better response rate in the surgical group.17 In our opinion, these data give not a sufficient evidence in favor of surgery plus RT for two important reasons. First, this last randomized study cannot be considered good evidence to recommend surgery plus RT in all MSCC patients because it was available only as an abstract and was closed before reaching the established sample size. Second, in the clinical practice, only a minority of MSCC patients are eligible for surgery: Low KPS, old age, systemic progressive disease, and so on are characteristics that can prevent a surgical approach. Also, the authors of this editorial reported in their abstract that only patients with a single site of cord compression and an expected survival of at least 3 months were enrolled in their phase III trial.17
In conclusion, early diagnosis and a prompt treatment are very important for patients with MSCC. In the clinical practice, the best therapeutic approach might be discussed for each patient between surgeon and radiation oncologist. There are situations in which surgery is surely indicated before RT, but there is not convincing evidence that surgery must be performed for all MSCC patients
Use of 18F-choline positron emission tomography/CT in high-risk prostate cancer: A case of solitary adrenal metastasis
No full textComputed tomography and magnetic resonance imaging detected an isolated adrenal lesion in an elderly man with high-risk prostate cancer who was undergoing radiotherapy (RT) and hormonal therapy (HT). When prostatespecific antigen (PSA) was 31.66 ng/mL, the lesion was not identified as a metastasis by 18F-choline positron emission tomography/computed tomography (18F-choline-PET/CT). When PSA was over 100 ng/mL, 18F-choline-PET/ CT diagnosed the malignancy. After adrenalectomy, PSA returned to normal, and stable disease remission was obtained. This case suggests that atypical metastasis may be underdiagnosed
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Radiotherapy for early-stage prostate cancer in men under 70 years of age
No full textAims: To demonstrate that radiotherapy (RT) is a valid alternative to surgery in men ≤70 years old with localized prostate cancer. Methods: From 1988 to 2009, 214 patients with T1-2 N0 M0 prostate cancer were treated with RT. The effects of patient- and treatment-related risk factors on toxicity were investigated. Results: Median follow-up was 105 months (range 14.2-180). The 5-, 10-, and 15-year biochemical relapse-free survival for all 214 patients was 80%, 61.9%, and 57.5%, respectively. In bivariate analysis, age (≤65 vs 65-70 years) was not a significant factor for biochemical relapse, while radiation dose was (p = 0.05) in multivariate analysis. Cancer-specific survival rates at 5, 10, and 15 years were 98.4%, 93.2%, and 69.7%, respectively. Median overall survival (OS) was 167 months (95% confidence interval 147.3-186.7). The OS rates at 5, 10, and 15 years were 91.8%, 75.8%, and 42.5%, respectively. Acute genitourinary (GU) and gastrointestinal (GI) toxicities occurred in 105 (49%) and 98 patients (45.8%), respectively, with only 2 cases of grade III GI toxicity. Late GU and GI toxicities occurred in 17 (7.9%) and 20 (9.3%) patients, respectively, with 1 grade III GI toxicity and 2 grade III GU toxicities. Risk factors for late toxicity were age and RT dose and technique, which were unrelated to acute toxicity. Conclusions: Age ≤70 years does not consistently confer a negative prognosis for localized prostate cancer. Radiotherapy appears to be a viable alternative to surgery, offering excellent long-term cancer control
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Acute Toxicity Profiles of Hypofractionated Adjuvant and Salvage Radiation Therapy After Radical Prostatectomy: Results of a Prospective Study
No full textPurpose: Hypofractionated radiation therapy (RT) is controversial after radical prostatectomy (RP). In this interim analysis, our prospective observational study assessed acute genitourinary (GU) and gastrointestinal (GI) toxicity after hypofractionated adjuvant and salvage RT, as delivered by helical tomotherapy (HT), in patients with prostate cancer. Methods and Materials: After undergoing RP with or without pelvic lymph node dissection, 112 patients were enrolled. Hypofractionated adjuvant RT (2.25 Gy daily for 29 fractions; total 65.25 Gy) was administered to 40 patients with high-risk features. Hypofractionated salvage RT (2.25 Gy daily for 32 or 33 fractions; total 72-74.25 Gy) was prescribed for 72 patients (24 with biochemical relapse, 48 with local relapse). Toxicity was graded according to the Common Terminology Criteria for Adverse Events version 4.02. The impact of RT on urinary flow was assessed by uroflowmetry. Results: Acute GU toxicity occurred in 41 of 112 patients (36%) (G1 31, G2 10). Acute GI toxicity was observed in 55 (49%) patients (G1 44, G2 11). Uroflowmetry showed that only salvage RT reduced maximum flow significantly (maximum, 68 vs 50 mL/s; P =.003), perhaps because a higher RT dose had been administered. Conclusions: After RP, moderate hypofractionated adjuvant and salvage RT were associated with acceptable incidences of slight-to-moderate acute GU and GI toxicity and had little impact on urinary flow. Prospective trials are warranted with longer follow-up in larger cohorts to confirm these findings
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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