Cause-specific Research Articles

Long-term outcomes of radiotherapy for stage II testicular seminoma: The Mayo Clinic experience.

327 Background: To report long-term outcomes of patients (pts) treated with radiotherapy (RT) for stage II testicular seminoma. Methods: Between 1974 and 2007, 52 pts received RT for clinical stage II testicular seminoma after radical inguinal orchiectomy; 3 pts were excluded due to no clinical follow-up. CT staging was used for 46 pts (94%). Estimates of overall (OS), relapse-free (RFS), and cause-specific (CSS) survival were determined using the Kaplan-Meier technique. Major cardiac event (MCE) was defined as myocardial infarction, coronary artery bypass grafting or stenting, or valve replacement. Second malignancy (SM) was defined as biopsy-confirmed malignancy occurring in the RT field. Results: The median pt age was 35 years. AJCC stage was IIA (n=23), IIB (n=7), IIC (n=15), and unknown (n=4). Three pts were treated for paraortic recurrence during surveillance for stage I seminoma. Four pts with IIB (n=1) or IIC (n=3) disease were treated with chemotherapy in addition to RT. The median total RT dose was 30.4 Gy. Prophylactic mediastinal/supraclavicular (MSCV) RT was given to 24 pts (49%). The median follow-up was 18 years (range 0.4-37). Estimates of OS, RFS, and CSS at 10 and 20 years were 94% and 81%, 79% and 70%, and 96% and 96%, respectively. OS, RFS, and CSS were not significantly different between stage groups. Recurrence occurred in 9 pts (18%); sites were MSCV (n=6), para-aortic (n=1), lung (n=1), and peritoneal cavity (n=1). Seven pts were successfully salvaged, while 2 pts died of seminoma. No patient with stage IIA/B that received prophylactic MSCV RT (n=11) experienced MSCV relapse. Among patients that did not receive prophylactic MSCV RT, 2 of 13 (15%) with stage IIA and 3 of 6 (50%) with stage IIB experienced MSCV relapse. MCE occurred in 10 pts (20%) at a median of 18 years (range 7-30) after RT. SM occurred in 5 pts (10%) at a median of 27 years (range 20-34) after RT. Conclusions: Infradiaphragmatic RT alone was associated with a significant risk of MSCV failure, particularly in patients with stage IIB disease, suggesting that chemotherapy may be the optimal treatment in this patient cohort. Most MCE and SM events occurred more than 20 years after RT, highlighting the importance of vigilant long-term follow-up.

Survival differences between preoperative and postoperative radiation in esophageal cancer treated with combined modality therapy: A SEER analysis.

78 Background: The effect of radiation therapy (RT) sequencing with surgery on clinical outcomes for locally advanced esophageal cancer patients is unclear. We hypothesized that RT given prior to surgery has superior survival outcomes compared to RT delivered after surgery. Methods: Patients with the following inclusion criteria were identified within 17 Surveillance, Epidemiology, and End Results (SEER) registries from 1988-2006: adenocarcinoma or squamous cell carcinoma of the esophagus, esophagectomy, and RT. Data on demographics, tumor characteristics, and survival outcomes were extracted and compared between patients receiving preoperative and those receiving postoperative RT. Cox regression univariate and multivariate analyses were performed to identify parameters that were associated with cause-specific (CSS) and overall survival (OS). Results: A total of 2,579 patients met the defined criteria. Of these patients, 1,689 received preop RT and 890 received postop RT. Patients receiving preop RT compared to postop RT had improved 5-yr CSS (41% vs. 31%, p<0.0001) and OS (33% vs. 23%, p<0.0001). On univariate analysis, RT sequence, histology, T stage, nodal status, number lymph nodes examined, age, gender, marital status, race, and county income were significant independent predictors of OS. On multivariate analysis ( table ), preop RT continued to remain statistically significant for OS (HR 0.88; p = 0.034). Conclusions: Preoperative RT is associated with superior overall and cause-specific survival compared to postoperative RT and should be the preferred approach in combination with surgery for locally advanced esophageal cancer. [Table: see text]

Adenoid cystic carcinoma of parotid gland treated with surgery and radiotherapy: Long-term outcomes, QoL assessment and review of the literature

To assess outcomes, toxicity and quality-of-life (QoL) of patients with parotid gland adenoid cystic carcinoma (PGACC) treated by surgery and postoperative radiotherapy. Between 1995 and 2010, 46 patients with PGACC were treated with parotidectomy±neck dissection followed by radiotherapy. Endpoints were loco-regional control (LRC), distant metastasis-free (DMFS), disease-free (DFS), cause-specific (CSS), and overall survival (OS), late toxicity, and QoL. After a median follow-up of 58 months (range 4-171), the 5-year Kaplan-Meier estimates of LRC, DMFS, DFS, CSS, and OS were 88%, 78%, 75%, 80%, and 67%, respectively and the 8-year rates were 88%, 75%, 72%, 77%, and 64%, respectively. On multivariate analysis, T-stage, N-stage, tumor grade, and perineural invasion correlate significantly with DMFS and DFS. The overall 5-year cumulative incidence of grade ≥2 late toxicity was 9%. QoL-scores deteriorate during and shortly after treatment but returned in all scales to almost baseline levels within 6 months. Excellent LRC rates were achieved in patients with PGACC treated by surgery and postoperative radiotherapy with low rate of late side-effects and preservation of good QoL. Despite the effective local therapy, 9 of 46 patients (20%) failed distantly. Because effective treatment strategies for this problem are lacking, prospective trials are needed to determine the role of adjuvant systemic or targeted therapy in patients at high risk of DM.

Correlation of radiotherapy with cause-specific and overall survival in clinically node-positive prostate cancer.

9 Background: Clinically staged node-positive prostate adenocarcinoma is a rare entity. We evaluated the role of definitive radiotherapy (RT) in clinical N1 prostate cancer patients who did not undergo prostatectomy and compared their cause-specific (CSS) and overall (OS) survival to men who did not undergo any definitive therapy. Methods: Subjects were identified using the NCI's Surveillance, Epidemiology and End Results (SEER) Program diagnosed between the years 1988 and 2006 with adenocarcinoma of the prostate. Subjects included in the analysis were men with clinically staged node-positive disease, who were otherwise non-metastatic. Descriptive statistics were performed, and CSS and OS was estimated using the methods of Kaplan and Meier. Statistical comparisons of treatment modalities were analyzed using univariate and multivariate Cox regression. Results: A total of 1,100 subjects were identified. The median age was 69 yrs (range 41-95) and median f/u time was 90 months (range 1-255 months). The 5, 10 and 15 yr CSS for men who had no definitive therapy was 71.1%, 50.3% and 35.1% respectively. The 5, 10 and 15 yr CSS for men who had external beam RT was 78.1%, 62.9% and 51.4% respectively. This was significantly different favoring RT on univariate cox regression (Hazard Ratio (HR) =0.66, 95% CI=0.54 to 0.82, P = 0.0002). The 5, 10 and 15 yr OS for men who had no definitive therapy was 56.2%, 29.1% and 14.86% respectively. The 5, 10 and 15 yr OS for men who had external beam RT was 67.8%, 44.2% and 20.4% respectively. This difference was also significant favoring RT on univariate cox regression (HR =0.70, 95% CI 0.59 to 0.81, P < 0.0001). On multivariate Cox regression analysis taking into account age at diagnosis, Gleason sum 2-4, 5-7, and 8-10, year of diagnosis, and presence or absence of definitive RT, RT (HR=0.69, 95% CI=0.56 to 0.86, P = 0.0008), earlier year of diagnosis (HR=0.94, 95% CI=0.92 to 0.97, P < 0.0001), and GS 7 or less was correlated with improved CSS. Conclusions: RT for node-positive subjects is correlated with both clinically and statistically improved cause-specific and overall survival. Patients with clinical N1 prostate adenocarcinoma should be strongly considered for RT. No significant financial relationships to disclose.

Prise en charge de 145 cas de carcinomes à cellules de Merkel

PurposeMerkel cell carcinoma (MCC)/primary cutaneous neuroendocrine carcinoma is a rare and aggressive malignant tumor. Optimal therapeutic strategy has not yet been established. Patients and methodsManagement of 145 patients from five centres was analysed. These data included ages, pathological stages, disease sites, histological and treatment details. Cause-specific (CSS) and overall survivals (OS) were analyzed by the Log-rank and Kaplan-Meier methods. ResultsMedian age was 78 years (47-95.2). We experienced 37 local, 37 regional and 15 distant relapses. In case of relapse, salvage therapy has been proposed whenever the general state of health condition of patient permitted it. ConclusionOur results for the treatment of relapse encourage multidisciplinary approach. Multicenter prospective trials are still needed to clarify and validate the optimal strategy.

Epidemiological trends in renal cell carcinoma (RCC) in the cytokine (CYT) and targeted therapy (TT) eras: A registry analysis of 28,252 patients (pts).

4598 Background: Randomized trials of TT have shown significant improvement in RCC pt outcomes, leading to the approval of 6 new agents since 2004. It is uncertain whether this improvement is confined to highly selected pt cohorts in clinical trials or if this benefit has already translated to the broader RCC population. To explore this, we analyzed a large RCC pt registry for epidemiologic trends, comparing the CYT (1998-2003) and TT (2004-2007) eras. Methods: Data from the California Cancer Registry (CCR), a population-based cancer surveillance system, were used. We retrospectively analyzed 28,252 RCC pts diagnosed between ’98-’07. Inter-era differences in clinical variables including year of diagnosis, histology, age, sex, race, stage, nephrectomy (Nx) status, overall (OS) and cause-specific (CSS) survival were assessed. Results: RCC frequency increased from 7.55% to 12.46%. SEER stage at diagnosis was localized in 64.42%, regional in 17.25%, and distant in 16.5%. Nx rate for pts with distant stage was 44%. Non-clear cell histologies increased (10.97% to 19.73%, p<0.001). Inter-era comparisons are shown in the Table. Conclusions: In this initial analysis of a large RCC registry, OS and CSS have not appreciably increased in the TT versus CYT era. These preliminary results suggest that the OS benefit from TT has not yet translated into the general RCC pt population. However, longer follow-up for pts in the TT era is necessary for a more robust comparison of long term OS. Multivariate OS analysis of the CCR database is ongoing. Supported by the Egan Family Fund. Variable Cytokine era (1998-2003)N = 14,956 Targeted therapy era (2004-2007)N = 13,296 Age, median in yrs 63 63 Clear cell histology (n, %) 13,316 (89.03) 10,673 (80.27) White race 9,900 (35.4) 8,209 (29.35) Stage (localized) 9,193 (61.47) 9,008 (67.75) Stage (regional) 2,732 (18.27) 2,141 (16.1) Stage (distant) 2,684 (17.95) 1,977 (14.87) Male sex 9,614 (64.28) 8,598 (64.67) Nephrectomy—yes (all pts) 12,647 (84.56) 11,389 (85.66) 3 yr survival, crude (all pts)* 68% 75% 3 yr survival (cause-specific)* 81% 81% 3 yr survival (cause-specific), clear cell histology* 77% 83% 3 yr survival (cause-specific), distant stage* 19.6% 20.5% * Estimated No significant financial relationships to disclose.

Prostate cancer control and survival in Vietnam veterans exposed to Agent Orange

Background In this study, we evaluated the impact of Agent Orange exposure on survival in Vietnam Veterans undergoing prostate brachytherapy. Methods and Material From May 1995 to January 2005, 81 Vietnam veterans (29 with Agent Orange exposure and 52 without) and 433 nonveterans of comparable age (mean age, 58 years) underwent prostate brachytherapy. The mean follow-up was 5.0 years. Biochemical progression-free survival (bPFS) was defined as a prostate-specific antigen (PSA) ≤ 0.40 ng/mL after nadir. Patients with metastatic prostate cancer or hormone refractory disease without obvious metastases who died of any cause were classified as died of prostate cancer. All other deaths were attributed to the immediate cause of death. Multiple parameters were evaluated for impact on survival. Results At 9 years, Agent Orange–exposed men were least likely to remain biochemically controlled (89.5%, 100%, and 97.2% in Agent Orange–exposed, nonexposed veterans, and nonveterans, respectively, p = 0.012). No significant differences in cause-specific (CSS) ( p = 0.832) or overall survival (OS) ( p = 0.363) were discerned. In multivariate analysis, CSS was best predicted by Gleason Score and day 0 D 90, whereas Gleason Score, % positive biopsies, and D 90 predicted for bPFS. None of the evaluated parameters predicted for OS, however, a trend was identified for better OS in younger patients and those with a higher D 90. In addition, Agent Orange exposure did not predict for any of the survival parameters. To date, 22 patients have died (metastatic prostate cancer two, second malignancies nine, cardiovascular disease eight, trauma two, and pulmonary one). Conclusions In this cohort of prostate brachytherapy patients, Agent Orange exposure did not statistically impact survival in multivariate analysis.

Sick Building Syndrome and the Problem of Uncertainty: Environmental Politics, Technoscience, and Women Workers (review)

Reviewed by: Sick Building Syndrome and the Problem of Uncertainty: Environmental Politics, Technoscience, and Women Workers Christian Warren Michelle Murphy . Sick Building Syndrome and the Problem of Uncertainty: Environmental Politics, Technoscience, and Women Workers. Durham, N.C.: Duke University Press, 2006. x + 253 pp. Ill. $74.95 (cloth, 0-8223-3659-6), $21.95 (paperbound, 0-8223-3671-5). Let there be no uncertainty: our buildings have a long history of making us sick. Crowded and unsanitary homes always abetted tuberculosis and other infectious diseases; the advent of gaslight and central heat produced both methane and carbon dioxide poisoning, while toxic pigments in paints and wallpaper sickened and killed thousands of children; and poorly designed and badly ventilated buildings [End Page 487] contributed to the shattering rates of occupational mortality and morbidity that once characterized the American workplace. These relatively specific illnesses are of course not the subject of Michelle Murphy's sometimes frustrating but ultimately satisfying study. Neither, however, is sick building syndrome by itself her chief subject. Instead, the heart of this book is the very uncertainty of sick building syndrome. Paradox and irony loom large as well, it would seem, since sick building syndrome "came to be defined formally through its very lack of causal explanation" (p. 6), and unlike Legionnaires' disease or contamination by specific toxicants, "if a cause was found, a building no longer had sick building syndrome" (p. 108). This irony, with its allusion to earnest quests for comprehensible cause, points to Murphy's central thesis about the imperceptibility and uncertainty surrounding sick building syndrome and many other nonspecific illnesses of the late twentieth century: that uncertainties "can be the tangible, and even purposeful, result of human action" and that inaction born of those uncertainties, too, can be "the purposeful product of state and corporate efforts" (p. 180). Sick building syndrome arose in the late twentieth century as a consequence of the particular office spaces that ventilation engineers, office designers, and management created and of the "methods, tools, and actions" employed by the workers in those spaces, to make office health problems into "a phenomenon about which things could be said and done" (p. 79). But no description of the origins of sick building syndrome can explain away its uncertainties, often formulated in "simplistic" debates "formulated in all-or-nothing terms: Is sick building syndrome a real, physically caused, phenomenon or not?" (p. 109). Where one comes down on that simplistic question tends to code along political lines. Simply noting the stark contrast between today's workplace conditions and those of fifty years ago can seem to support an antilabor stance that sees sick-building syndrome as "simply a phantasm of illness" (p. 7). But arguments for the syndrome's reality can seem to dismiss modern biomedicine, which has not been able to reconcile sick building syndrome to its dose–response curves, thresholds, and specificity of cause. Murphy chooses not to resolve the uncertainties that surround the syndrome but rather to examine how "ordinary people created knowledge about and experienced their everyday environment" (p. 4). The central chapters proceed in roughly chronological order. The first two survey the technological and social factors in the creation of the modern office workplace. The next two chapters look at the development of "popular epidemiology" as a way for workers to challenge the industrial toxicologists' dismissal of environmental dangers in these engineered environments. The most fully conceived and sharply focused chapter discusses an episode of sick building syndrome in an unexpected place: the Environmental Protection Agency's bleak and deteriorating modern home office in the 1980s. The next chapter addresses the rise in the 1980s and 1990s of professional building investigators who employed the outlook and models of "systems ecology" in order to make sick building syndrome explainable as something much more multifaceted and dynamic than exposure to a single substance. A somewhat experimentally framed last chapter on multiple [End Page 488] chemical sensitivity (MCS) focuses on the personal experiences of MCS sufferers, dominated by their "abjection," a twilight-zone status characterized by social and biomedical exclusion: MCS was "an invalid bodily state" (p. 152). Murphy's language brims with postmodern social science jargon; nevertheless, her style is...

Response to The J-Point Revisited

We thank Dr Rosendorff1 for his interest in our editorial2 accompanying the article by Thune et al.3 The data presented by Thune et al3 indicated, in their words, an association (but no definite specification of cause and effect) between low blood pressure and adverse cardiovascular outcomes. As you suggest for their data, low pressure may not be an independent variable in the prediction of future adverse cardiovascular outcomes. Instead, low pressure may be the result of previous anterior myocardial infarction, Q-wave myocardial infarction, and/or degree of elevation of creatine kinase, genuine independent variables. We agree and would add …

Obesity Is Not Predictive of Overall Survival Following Permanent Prostate Brachytherapy

To evaluate the impact of obesity on cause-specific (CSS), biochemical progression-free (bPFS), and overall survival (OS) following prostate brachytherapy. From April 1995 through March 2003, 1093 consecutive patients underwent brachytherapy for clinical T1b-T3a (2002 AJCC) prostate cancer. The median follow-up was 5.6 years. Evaluated body mass index (BMI) subgroups were < 25 (n = 258), 25.0 to 29.9 (n = 547), 30.0 to 34.9 (n = 214), and > or = 35 (n = 74) kg/m2, respectively. A total of 430 (39.9%) and 589 (53.9%) of the patients received androgen deprivation therapy or supplemental external beam radiation therapy, respectively. Multiple clinical, treatment, and dosimetric parameters were evaluated as predictors of CSS, bPFS, and OS. The 11-year CSS, bPFS, and OS for the entire cohort were 97.5%, 95.6%, and 77.6%, respectively. BMI did not impact CSS or bPFS for any of the BMI cohorts. However, OS was statistically lower in patients with a BMI < 25 kg/m2 (P = 0.014). A Cox linear regression analysis demonstrated that Gleason score was the best predictor of CSS while percent-positive biopsies, risk group, V100 and hypertension predicted for bPFS. Patient age and tobacco use were the strongest predictors of OS. A total of 128 patients have died with 108 (84.4%) of the deaths the result of cardiovascular/pulmonary disease (73) and second malignancies (35). To date, 12 patients have died of metastatic prostate cancer. Obesity did not impact CSS, bPFS, or OS in patients treated with permanent prostate brachytherapy. Cardiovascular or pulmonary disease and second malignancies substantially outweighed prostate cancer as competing causes of death.

Primary Gleason pattern does not impact survival after permanent interstitial brachytherapy for Gleason score 7 prostate cancer

The impact of primary Gleason pattern was determined on cause-specific (CSS), biochemical progression-free (bPFS), and overall survival (OS) after brachytherapy for Gleason score 7 prostate cancer. From April 1995 to October 2003, 530 patients underwent brachytherapy for Gleason score 3+4 (n = 300) or Gleason 4+3 (n = 230) prostate cancer. All patients underwent brachytherapy more than 3 years before analysis. The median follow-up was 5.7 years. Of the 530 patients, 412 (77.7%) received supplemental external beam radiation therapy (XRT) and 177 (33.4%) received androgen deprivation therapy. bPFS was defined by a prostate-specific antigen (PSA) </=0.40 ng/mL after nadir. Multiple parameters were evaluated as predictors of CSS, bPFS, and OS. At 10 years, Gleason 3+4 versus 4+3 did not predict for CSS (96.7% vs 93.3%, P = .506), bPFS (97.0% vs 92.9%, P = .085), or OS (77.0% vs 78.0%, P = .933). Cox linear regression analysis demonstrated that clinical stage and radiation dose (D90) predicted for CSS, whereas pretreatment PSA, clinical stage, and prostate size predicted for bPFS. Patient age, diabetes, and tobacco were the strongest predictors for OS. To date, 57 patients have died, with 80.7% due to cardiovascular/pulmonary events or secondary malignancies. Five patients have died of prostate cancer. The primary Gleason pattern did not impact CSS, bPFS, or OS in Gleason score 7 prostate cancer. Deaths from cardiovascular/pulmonary disease and second malignancies were 9.6 times more common than death from prostate cancer.

Effect of obesity on overall survival following permanent prostate brachytherapy

15576 Background: To evaluate the impact of obesity on cause-specific (CSS), biochemical progression-free (bPFS) and overall survival (OS) following prostate brachytherapy. Methods: From April 1995 through March 2003, 1,093 consecutive patients underwent brachytherapy for clinical T1b-T3a (2002 AJCC) prostate cancer. The median follow up was 5.6 years. All patients were implanted at least 3 years prior to analysis. Evaluated body mass index (BMI) subgroups were &lt; 25 (n=258), 25.0 to 29.9 (n=547), 30.0 to 34.9 (n=214) and = 35 (n=74) kg/m2, respectively. Four-hundred and thirty (39.9%) and 589 (53.9%) of the patients received androgen deprivation therapy or supplemental external beam radiation therapy, respectively. Multiple clinical, treatment and dosimetric parameters were evaluated as predictors of CSS, bPFS and OS. Results: The 11 year CSS, bPFS and OS for the entire cohort were 97.5%, 95.6% and 77.6% respectively. BMI did not impact CSS or bPFS for any of the BMI cohorts. However, OS was statistically lower in patients with a BMI &lt; 25 kg/m2 (p = 0.014). A Cox linear regression analysis demonstrated that Gleason score was the best predictor of CSS while percent-positive biopsies, risk group,V100 and hypertension predicted for bPFS. Patient age and tobacco use were the strongest predictors of OS. One-hundred and twenty-eight patients have died with 108 (84.4%) of the deaths the result of cardiovascular/pulmonary disease (73) and second malignancies (35). To date, 12 patients have died of metastatic prostate cancer. Conclusions: Following brachytherapy, obesity did not impact CSS, bPFS or OS. Cardiovascular or pulmonary disease and second malignancies substantially outweighed prostate cancer as competing causes of death. No significant financial relationships to disclose.

Androgen deprivation therapy does not impact cause-specific or overall survival in high-risk prostate cancer treated with brachytherapy and supplemental external beam

15578 Background: To determine cause-specific (CSS), biochemical progression-free (bPFS) and overall survival (OS) in high risk prostate cancer patients undergoing brachytherapy with or without supplemental therapies. Methods: From April 1995 through July 2002, 204 patients with high risk prostate cancer (Gleason score = 8 and/or PSA &gt; 20 ng/mL and/or clinical stage = T2c) underwent brachytherapy with or without supplemental therapies. Of the 204 patients, 193 (94.6%) received supplemental XRT and 119 (58.3%) received ADT (ADT = 6 months n=40 and ADT &gt; 6 months n = 79). Median follow-up was 7.0 years. All patients were implanted at least 4 years prior to analysis. BPFS was defined by a PSA = 0.40 ng/mL after nadir. Multiple clinical, treatment and dosimetric parameters were evaluated for the impact on survival. Results: The ten-year CSS, bPFS and OS were 88.9%, 86.6% and 68.6%, respectively. A statistically significant difference in bPFS was discerned between hormone naïve, ADT = 6 months and ADT &gt; 6 month cohorts (79.7% vs. 95.0% vs. 89.9%, p= 0.032). ADT did not impact CSS (94.0% vs. 87.1%, p=0.983 ) or OS (65.2% vs. 70.3%, p = 0.713). For bPFS patients, the median post-treatment PSA was &lt; 0.04 ng/mL. A Cox linear regression analysis demonstrated that Gleason score was the best predictor of CSS while percent positive biopsies and duration of ADT best predicted for bPFS. OS was best predicted by Gleason score and diabetes. Thirty-eight patients have died with 26 of the deaths due to cardiovascular/pulmonary disease or second malignancy. Eleven patients have died of metastatic prostate cancer. Conclusions: Androgen deprivation therapy improved 10-year bPFS without statistical impact on CSS or OS. Death as a result of cardiovascular/pulmonary disease and second malignancies were more than twice as common as prostate cancer deaths. Strategies to improve cardiovascular health should positively impact overall survival. No significant financial relationships to disclose.

Prognostic significance of positive lymph nodes in carcinoma of the cervix following radical hysterectomy

5538 Background: Lymph node (LN) metastases portend a poor outcome in women with carcinoma of the uterine cervix, but little data quantitatively evaluate nodal metastasis in relation to prognosis. We queried a large population database to analyze the number of positive LN in relation to survival following radical hysterectomy and lymphadenectomy. Methods: Data were collected from the Surveillance, Epidemiology, and End Results (SEER) Program on women who had primary surgery for the years 1988–2003 (n = 4,559). Analyses using the chi-square test and Cox proportional hazards regression were performed. Exploratory analysis revealed equivalent statistical outcomes in each group for 0 (n = 3,715), 1–2 (n = 552), 3–9 (n = 261), and ≥10 (n = 31) positive LNs, respectively. Results: The median number of LNs removed per patient has significantly declined in recent years (median = 21 for 1988–1998, median = 18 1998–2003, p=.003). The 5-year rates of cause specific (CSS) and overall survival (OS) were 94% and 91%, 76% and 69%, 62% and 58%, and 41% and 35% for 0, 1–2, 3–9 and ≥10 positive LNs, respectively. Favorable stage and grade predicted for survival on multivariate analysis. Adenocarcinoma histology predicted significantly inferior CSS (p=.007) and OS (p=.01) compared to squamous histology in women with positive LNs, but predicted improved OS (p=.004) in women with LN negative disease. An increasing number of LNs removed significantly benefited OS (p=.001). The strongest predictors for both CSS and OS were ≥10 positive LN (HR 1.8 CI 1.2–2.7, p&lt;.0001) a positive LN ratio &gt;25% (HR 1.8 CI 1.5–2.2, p&lt;.0001) and paraaortic LN metastasis (HR 2.1 CI 1.6–2.8, p&lt;.0001). Conclusions: The extent of lympadenectomy has declined since 1988 within the SEER. LN positive disease in carcinoma of the cervix portends a prognosis that is inversely proportional to the number of involved nodes. Adenocarcinoma histology predicted for a more aggressive or benign phenotype depending on LN status. A positive LN ratio &gt;25% demonstrated diminished survival suggesting that the quantitative LN burden is predictive of prognosis. Nodal involvement of the paraaortic region remains a strong indicator of mortality. No significant financial relationships to disclose.

Pre-operative radiotherapy and curative surgery for the management of localized rectal carcinoma

Preoperative radiotherapy (PRT) has become part of standard practice offered to improve treatment outcomes in patients with rectal cancer. To determine if PRT improves outcome for patients with localized resectable rectal cancer and how it compared with other adjuvant or neoadjuvant strategies. A computerized search was performed December 2006 on MEDLINE (from 1966 to December 2006) and the Cochrane Central Register of Controlled Trials (CENTRAL), conference proceedings, using MeSH and textwords where appropriate to identify randomized trials in PRT and rectal cancer. In addition, MetaRegister of Clinical Trials was searched for ongoing trials. Randomized trials with a PRT arm versus surgery alone, or other neoadjuvant or adjuvant (NA/A) strategies, targeted patients with localized rectal cancer planned for radical surgery were included. Trials were selected, data extracted and quality assessed by 2 authors. Quality was assessed using a 14 point checklist. Summary statistics included Hazard ratios and variances (for the outcomes: overall (OA) mortality, cause specific (CS) mortality, any recurrence and local recurrences (LR)) and Odds Ratio (OR) for other outcomes. Potential sources of heterogeneity hypothesized a priori included study quality, biological effective dose (BED), radiotherapy RT technique, and total mesorectal excision (TME) surgery. Nineteen trials compared PRT versus surgery alone. Overall (OA) mortality was marginally improved HR 0.93 [95% CI -0.87-1](absolute difference is 2% if the expected survival rate is 60%). Local recurrence (LR) was improved but the magnitude of benefit was heterogeneous across trials. Sensitivity analyses suggested greater benefits in patients treated with BED>30Gy(10) and multiple field RT techniques. There was significantly more pelvic or perineal wound infection, late rectal and sexual dysfunction. Nine trials compared PRT vs. other NA/A. Available evidence did not support an OA mortality or sphincter preserving benefit with the use of combined chemoradiotherapy (CRT) or selective postoperative RT. CRT provides incremental benefit for local control compared with PRT, which was independent of the timing of the CT. There was no significant difference in outcome for different intervals between RT and surgery (2 vs. 8 wk). Dose escalation with endocavitary boost showed significant effect on sphincter preservation. Optimal PRT improves LR, OA mortality, but no increase in sphincter sparing procedure. CRT further increases local control. If the objective is to increase the incidence of sphincter sparing surgery, endocavitary boost showed the most promise. Strategies with the potential to improve outcomes, especially OAS and sphincter sparing while reducing acute and late toxicities (rectal and sexual function) are needed to guide future strategy designs.

Obesity is not predictive of overall survival following permanent prostate brachytherapy

Purpose:To evaluate the impact of obesity on cause-specific (CSS), biochemical progression-free (bPFS), and overall survival (OS) following prostate brachytherapy.Materials and Methods:From April 1995 through March 2003, 1093 consecutive patients underwent brachytherapy for clinical T1b-T3a (2002 AJ

Recurrence Patterns of Non-Mycosis Fungoides Cutaneous Lymphoma Following Various Treatment Modalities.

INTRODUCTION: Non-mycosis fungoides (MF) primary cutaneous lymphoma (PCL) is rare, and the more indolent forms seldom progress to fatal, systemic lymphoma. Nevertheless, frequent relapses are common. Although several therapies exist, no standard of care has been established for initial treatment.OBJECTIVES: To compare the role of radiotherapy to other initial treatment options and to evaluate clinicopathologic factors affecting overall, cause-specific, and relapse-free survivalMETHODS: Thirty-eight patients from 1985 to 2006 were retrospectively identified and reviewed with non-MF PCLs including: primary cutaneous anaplastic large cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, primary cutaneous marginal zone B-cell lymphoma, primary cutaneous follicle-center lymphoma, primary cutaneous diffuse large B-cell lymphoma, leg type, or primary cutaneous intravascular large B-cell lymphoma. Regression-free, cause-specific, and overall survival was estimated using the methods of Kaplan and Meier. Outcomes were compared with the log-rank test and Cox regression analysis.RESULTS: 38 patients were included in the analysis with a median follow-up time of 34.6 months (range 2 – 138 months). The distribution of initial treatment was: surgery - 29%, topical therapy - 16%, systemic therapy - 18%, and radiation - 63%. Three patients never received radiation.For the entire cohort, the 5-year overall (OS), cause-specific (CSS), and relapse free survival (RFS) was 86.2%, 88.9%, and 29.5% respectively. Subjects who received radiation therapy (n=24) as part of their initial treatment course had a significantly longer median time to first relapse of 57 months compared to 3.2 months for the 14 subjects who did not receive radiotherapy (log-rank p < 0.0001). Overall survival was significantly improved for subjects whose International Prognostic Index (IPI) score was 0–1 (n=25) versus those whose score was 2 or greater (n=13, p=0.05).Multivariate analysis for RFS revealed that the absence of radiation as part of initial treatment (Hazard Ratio (HR) = 22.2, 95% CI 2.1 – 238.5, p=0.01) and aggregate size less than 10cm (HR 0.04, 95% CI 0.0 – 0.3, p<0.01) significantly altered the risk of relapse.No relapses were observed within the radiation therapy treatment field in 31/35 (89%) subjects following their first course of radiation therapy. Of the 15/35 (43%) of patients that relapsed anywhere following radiation, only 2/15 (13%) relapsed in-field exclusively, 2/15 (13%) relapsed both in and out-of-field, and the remaining 11/15 (73%) relapsed exclusively outside the area treated. No patient relapsed within the treatment field of after 24 months.CONCLUSION: An initial course of radiation therapy significantly delays relapse compared to other therapies for non-MF PCL and provides excellent local control of plaques. Our findings also extend the IPI as prognostic for overall survival for this rare disease. Bulky lesions greater than 10cm in any one dimension are more strongly correlated with relapse.

Adjuvant radiotherapy for cutaneous melanoma: Comparing hypofractionation to conventional fractionation

To examine locoregional control after adjuvant radiotherapy (RT) for cutaneous melanoma and compare outcomes between conventional fractionation and hypofractionation. Between January 1980 and June 2004, 56 patients with high-risk disease were treated with adjuvant RT. Indications for RT included: recurrent disease, cervical lymph node involvement, lymph nodes >3 cm, more than three lymph nodes involved, extracapsular extension, gross residual disease, close or positive margins, or satellitosis. Hypofractionation was used in 41 patients (73%) and conventional fractionation was used in 15 patients (27%). The median age was 61 years (21->90). The median follow-up among living patients was 4.4 years (range, 0.6-14.4 years). The primary site was located in the head and neck in 49 patients (87%) and below the clavicles in 7 patients (13%). There were 7 in-field locoregional failures (12%), 3 out-of-field regional failures (5%), and 24 (43%) distant failures. The 5-year in-field locoregional control (ifLRC) and freedom from distant metastases (FFDM) rates were 87% and 43%, respectively. The 5-year cause-specific (CSS) and overall survival (OS) was 57% and 46%, respectively. The only factor associated with ifLRC was satellitosis (p = 0.0002). Nodal involvement was the only factor associated with FFDM (p = 0.0007), CSS (p = 0.0065), and OS (p = 0.016). Two patients (4%) who experienced severe late complications, osteoradionecrosis of the temporal bone and radiation plexopathy, and both received hypofractionation (5%). Although surgery and adjuvant RT provides excellent locoregional control, distant metastases remain the major cause of mortality. Hypofractionation and conventional fractionation are equally efficacious.

Suicide in the Greek Penal System and the Problem of Various Limitations in Relevant Studies

Suicides in prison are not merely self-destructive acts or a "cry for help." They reflect the inherent need for freedom and the repercussions of imprisonment. SPACE statistics on suicides in prison reveal a rate above 10 per 10,000 in 10 European countries, 4 of which have a rate above 20. Greek data do not appear in all SPACE statistics. This fact has stimulated the present paper. Unpublished data obtained from the Greek Ministry of Justice reveal that Greece belongs to the group of countries with a rate below 10 in 1995 (the year of SPACE statistics). However, the suicide rates fluctuated widely in Greece from a low rate of 3.2 per 10,000 prisoners (convicted, on remand, or hospitalized) in 1982 to the incredibly high rate of nearly 40 in the year 1979 (11 suicides, 10 of which occurred in prison hospitals). A review of the literature indicates that various limitations mentioned in relevant studies lie in the unreliability of data (doubts about the validity of official statistics, missing data in archives, missing files on the victims, suicide in juvenile institutions not always recorded separately, etc.). The research emphasizes the importance of improving suicide statistics (recording, clearing up the incidents of deaths that are recorded without specification of cause, etc.) in order to plan and enforce suicide prevention and intervention strategies that seem to "work" in a particular milieu and are not debatable (e.g., the use of "suicide proof" cells).

Short course continuous, hyperfractionated, accelerated radiation therapy (CHART) as preoperative treatment for rectal cancer

Determine feasibility and toxicity of preoperative short course pelvic CHART (25 Gy in 15 fractions over 5 days) for treatment of clinically resectable primary rectal tumours. Between 1998 and 2004, 20 patients with clinically staged T3 resectable rectal carcinoma were treated in this prospective pilot study with preoperative short course CHART to their pelvis. The aim was for total mesorectal excision within 7 days. Radiation toxicity, surgical morbidity, locoregional control (LRC), overall (OS), cause specific (CSS) and disease free survival (DFS) outcomes were documented. Nineteen of the 20 patients completed planned radiotherapy. One discontinued radiotherapy due to toxicity. All patients underwent potentially curative radical surgery. One patient developed grade 3, and three patients grade 2 gastrointestinal toxicity. With a median follow-up of 31 months (range 0.9–88), there is no grade 3, 4 or 5 late toxicity. Two patients experienced grade 2, and three patients grade 1 late bowel toxicity. Two patients died from postoperative complications, and two developed grade 2 abdominal wound infections. At 3 years LRC is 95% (95% CI 83–100), OS 72% (95% CI 51–94), CSS 86% (95% CI 68–100) and DFS 80% (95% CI 60–100). Two patients died from metastatic disease, one patient from a second primary and one patient is alive after successful resection of hepatic metastases. This small study suggests preoperative short course CHART for clinically resectable rectal carcinoma is feasible with acceptable compliance and tolerable side effects.