tbuckley/cabot-search huggingface dataset:
Impact of the smallest surgical margin on local recurrence in soft tissue sarcoma treated with surgery with or without radiotherapy: First ten year results of a prospective treatment protocol at Helsinki University Central Hospital
Authors: M. Tarkkanen, M. Sampo, R. Huuhtanen, E. Tukiainen, T. Bohling, C. Blomqvist
Journal: Journal of Clinical Oncology (2007)

10064 Background: A single-institution experience using a prospective treatment protocol for soft tissue sarcoma (STS) of the extremity and trunk wall was reviewed. Special interest of smallest surgical margin on local control was taken. Methods: Between 1987 and 1997 361 patients with STS were treated by the STS Group at Helsinki University Central Hospital. Patients with borderline malignancies or metastatic disease were excluded leaving 270 patients to the present study. All patients included underwent surgery. Postoperative radiotherapy was administered if the smallest surgical margin was less than 2.5 cm when there was no natural barrier, irrespective of tumor grade. Results: With a median follow-up of 6.6 years, the 5-year local control for the whole study population was 76 %. On multivariate analysis, the smallest surgical margin in centimeters, adequacy of treatment according to protocol and postirradiation sarcoma were prognostic for local control. A margin of at least 2,5 cm yielded recurrence-free rate of 89 % at five years. Conclusions: Our findings show that size, depth and grade of the tumor, and patient`s age at diagnosis do not have independent prognostic effect on local control, nor has recurrent disease at referral. Instead, surgical margin in centimeters and adequacy of treatment according to protocol had independent prognostic value for local control. This is encouraging since these factors can be affected by aggressive local treatment. Soft tissue sarcomas should be referred to a specialized multimodality treatment group before biopsy or any surgery. A surgical margin of 2–3 cm yield a reasonable local control in STS even without radiotherapy. No significant financial relationships to disclose.
Expression of the CDK inhibitor p27<sup>kip1</sup> and oxidative DNA damage in renal cell carcinoma
Authors: A. Sgambato, A. Camerini, F. De Luca, C. Valsuani, O. Siclari, G. Genovese, A. Boninsegna, M. Cecchi, A. Cittadini, D. Amoroso
Journal: Journal of Clinical Oncology (2009)

e16008 Background: Deregulation of the normal cell cycle is a frequent event in human tumors and plays an important role in malignant transformation. p27 kip1 is a negative regulator of the G1 phase, is frequently lost in tumor cells and, in some cases, its alteration is coupled with oxidative DNA damage. Methods: We evaluated the expression of p27 kip1 and the extent of endogenous oxidative DNA damage (by means of 8-hydroxydeoxyguanosine [8-OHdG] levels) by immunostaining in a series of 125 (median age 64[range23–86]yrs) renal cell carcinomas (RCCs); furthermore, the prognostic significance of their alterations was tested. Median values of expression were used as cut-off. p27 kip1 expression was also evaluated by Western Blot in a second series of 34 fresh-frozen RCCs. Results: to date, median follow-up is 29[range 4 - 104] months. p27 kip1 expression was lost in a significant fraction of tumors (55%) with a median percentage of positive cells of 20% [range 0–60%). Loss of p27 kip1 staining correlated with higher tumor grade (p=0.049). Recurrence (p=0.007) and death (p=0.006) from RCCs were significantly more frequent in patients p27 kip1 -negative compared with positive ones. Kaplan-Meier analysis showed a significant separation between high vs low p27 kip1 expression groups for both disease-free (p=0.011) and overall (p=0.002) survival. At multivariate analysis, loss of p27 kip1 expression was the only independent risk predictor for recurrence (HR=4.326, p=0.014) and death (HR=4.915, p=0.012) from RCCs when tumor size, tumor grade and stage were included. No significant correlation with clinical or pathological parameters and outcome was found for 8- OHdG. p27 kip1 total protein levels showed a variable behaviour at WB analysis with a modest trend toward a global reduction but an elevation in some cases. Conclusions: loss of p27 kip1 is frequent in human RCCs and is a powerful predictor of poor outcome. p27 kip1 alteration are not related to endogenous oxidative DNA damage. The behaviour of p27 kip1 at WB analysis is probably related to the elevation of the cytoplasmatic (and inactive) fraction. No significant financial relationships to disclose.
Adam J. Krakowski, MD. The Fifth President of the International College of Psychosomatic Medicine
Journal: Psychotherapy and Psychosomatics (1982)

It always seemed rather peculiar that an individual few know is asked to introduce someone everybody knows.When President Reagan visited Chicago recently, he did not ask Governor Thompson or Mayor Byrne to introduce him.No, he asked what's-his-name to do it.There was no match and no contest.Anyway it is my humble pleasure to introduce to you the President of the International College of Psychosomatic Medicine, a man everyone knows through his quarterly messages in our Bulletin and his persistent letters and telephone calls that awaken us either early in the morning or late in the evening.Who could not remember him?Who could forget him?This man has relentlessly pursued the purposes of this organi zation, upholding (while suggesting revisions) our Constitution, governing the psychosomaticists of the free world while encouraging those in lands where freedom has a different designation.In this area, alone, he has cham pioned the academic freedom of the brethren he left behind, once the cer tainty of Western democratic processes were doomed.In migrating to the United States following the tumultuous period preceding, during and fol lowing World War II, as soldier and prisoner, as physician and captive, he served in an area of the United States where there were few trained psychia trists and in an institution for the criminally insane in which almost every prison guard developed peptic ulcer disease.This experience obviously must have extended his interest in psychosomatic medicine.He has never informed us of what effect this experience had on his own health.Since 1953, he has been the mainstay of psychiatric practice in Plattsburgh, N.Y., in the poorest county of that state.At times, single-handedly, he has been the only psychiatrist caring for the psychiatric needs of patients at the Champlain Valley Physicians Hospital Medical Center, the Plattsburgh
Single-agent compared to combination first-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) and a performance status (PS) of 2
Authors: P. Bonomi, V. M. Villaflor, F. B. Oldham, L. Sandilac, J. W. Singer
Journal: Journal of Clinical Oncology (2007)

7637 Background: Impaired performance status in NSCLC is associated with poor prognosis and reduced tolerance for treatment- related toxicities. Current treatment guidelines agree that PS 2 patients with advanced NSCLC benefit from systemic chemotherapy; however, no consensus exists on specific treatment recommendations; i.e., single-agent vs. combination chemotherapy. Methods: Two recent phase III randomized trials in advanced NSCLC (STELLAR 3 and 4) enrolled exclusively PS 2 patients and compared experimental treatment to either standard combination chemotherapy (paclitaxel/carboplatin; P/C), or single agent chemotherapy (vinorelbine or gemcitabine; V or G). An exploratory comparison of the control arms was performed to determine the degree of benefit and amount of added toxicity associated with standard combination vs. single agent chemotherapy. Results: Combination chemotherapy resulted in improved time to progression compared to single agent ( Table ). However, no statistical difference between treatment arms was noted for overall survival and 1-yr survival. Adverse events are listed in the table . Overall, the frequency of serious adverse events was 40% in the combination-arm and 35% in the single agent-arm. When only considering drug-related toxicities, the frequency of serious adverse events was 21% in the combination-arm and 5% in the single agent-arm. Conclusions: PS 2 patients receiving single agent chemotherapy have a similar outcome compared to those receiving combination chemotherapy; serious treatment related toxicities are less frequent with single agent therapy. Based on the currently available evidence, the use of single-agent therapy seems reasonable in PS 2 patients. [Table: see text] [Table: see text]
Risk factors for peritoneal carcinomatosis in gastric cancer patients, and outcomes following resection and hyperthermic intraperitoneal chemotherapy (HIPEC).
Authors: Ki Won Kim, Oliver Chow, Kunal Parikh, Sima Blank, Ghalib Jibara, Daniel M. Labow, Spiros P. Hiotis
Journal: Journal of Clinical Oncology (2012)

e14656 Background: Gastric cancer (GC) contributes significantly to the burden of cancer death in the United States. Unfavorable prognosis in patients with gastric cancer and peritoneal carcinomatosis (GCPC) is well-documented. In this study, a model predictive of GCPC is proposed, and outcomes in patients with GCPC treated with surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) are assessed. Methods: A single-institution analysis of 112 patients treated for GC between the years 2000 and 2011 was performed. Demographic and clinical-pathologic criteria were entered into univariate and multivariate analyses, to identify criteria independently predictive of GCPC. Overall survival in each cohort was determined via Kaplan-Meier analysis. Results: GCPC developed in 28/112 (25%) of GC patients. Several variables were associated with GCPC by univariate analysis (age, p = 0.018; tumor stage, p = 0.004; tumor location, p = 0.046), but only age (≤60) and tumor stage (T3/T4) were independently predictive of GCPC by multivariate analysis (HR = 3.949, p = 0.024; HR = 3.942, p = 0.049, respectively). Intermediate-term survival was not significantly impacted in nine GCPC patients treated with HIPEC (65% 1-year, 39% 3-year without HIPEC; vs. 73% 1-year, 39% 3-year with HIPEC, p = NS). Conclusions: A model to identify gastric cancer patients at highest risk for GCPC is proposed. Although intermediate term survival in a small number of GCPC patients (9) treated with HIPEC is not significantly improved, emerging experience with increased follow-up with HIPEC in larger cohorts is needed. Earlier application of HIPEC targeted at patients at highest risk may be feasible in utilizing a model predictive of GCPC.
The necessity of dynamic contrast enhanced imaging for prostate MRI: A study of pathologic outcomes on prostate biopsy.
Authors: Sasha C. Druskin, Jeffrey J. Tosoian, Allen Young, Kamyar Ghabili, Darian Andreas, Katarzyna Macura, Ashley Ross
Journal: Journal of Clinical Oncology (2017)

52 Background: PIRADS version 2 guidelines for the interpretation of multi-parametric prostate MRI (mpMRI) stipulates that dynamic contrast-enhanced (DCE) imaging be used to classify diffusion weighted imaging (DWI) score 3 peripheral zone lesions into PIRADS-3 (DCE-) or PIRADS-4 (DCE+) lesions. Despite this, it is unknown if DCE based classification separates lesions into clinically meaningful pathologic groups. Because use of contrast adds time, risk (though modest), and cost to mpMRI, we sought to examine whether use of DCE indeed improves detection of clinically-significant cancer. Methods: Using the Johns Hopkins MRI-ultrasound fusion prostate biopsy database and including only patients without a prior diagnosis of prostate cancer (n = 232), we identified patients with peripheral zone DWI-3 or DWI-4 lesions who underwent targeted biopsy of those lesions. Each lesion meeting the MRI criteria was considered separately, and grouped into one of three lesion MRI classifications – DWI-3/DCE-/PIRADS-3, DWI-3/DCE+/PIRADS-4, or DWI-4/PIRADS-4. The rates of benign, grade group (GG) 1, and GG ≥ 2 pathology were compared between the MRI classification groups. Results: One hundred forty-eight peripheral zone DWI-3 or DWI-4 lesions from a total of 106 patients were identified. The rate of benign(%)/GG1(%)/GG ≥ 2(%) biopsy pathology in the groups DWI-3/DCE-/PIRADS-3 (61 lesions), DWI-3/DCE+/PIRADS-4 (37 lesion), and DWI-4/PIRADS-4 (47 lesions) was 68.9/18.0/8.2, 59.5/13.5/18.9, and 44.7/23.4/27.7, respectively (P &gt; 0.05 for the difference in rates of GG ≥ 2 pathology between the two PIRADS-4 groups and the two DWI-3 groups). Conclusions: Given the cost and morbidity of using intravenous contrast agents in prostate MRI, their clinical utility must be determined. In this study, DWI-3 peripheral zone lesions with DCE positivity appear to have a higher rate of clinically-significant (GG ≥ 2) cancer on biopsy. This study supports the use of DCE to better classify DWI-3 peripheral zone lesions however further study with expanded cohorts is indicated.
Morbidity and mortality associated with subsequent meningiomas among childhood cancer survivors exposed to cranial radiotherapy: A report from the Childhood Cancer Survivor Study (CCSS).
Authors: Daniel C. Bowers, Chaya S. Moskowitz, Joanne F. Chou, Claire Marie Mazewski, Joseph Philip Neglia, Gregory T. Armstrong, Wendy M. Leisenring, Leslie L. Robison, Kevin C. Oeffinger
Journal: Journal of Clinical Oncology (2015)

10000 Background: Survivors of childhood cancer who were exposed to cranial radiotherapy (CRT) are at increased risk of subsequent meningiomas. However, incidence rates, neurological sequelae and impact on mortality are not well defined. Methods: Among 4,221 survivors exposed to CRT, subsequent meningiomas were self-reported and confirmed by pathology, medical records or death certificate. Age of onset of specific neurologic conditions was self-reported and proxy-reported. Standardized incidence ratios (SIRs) and absolute excess risk (AER) were estimated using expected age-, gender-, and calendar-year specific rates from SEER. Hazard ratios (HRs) for neurological sequelae and mortality were estimated using Cox proportional regression. Results: 199 meningiomas were identified among 169 survivors. The median age at meningioma diagnosis was 28 years (range, 7 – 50 years); median age at last follow-up was 32 years of age (range, 9 – 56 years). Median interval from primary cancer to first meningioma diagnosis was 22 years (range, 5 – 37 years). The cumulative incidence of a subsequent meningioma by age 40 years was 5.6% (95% CI: 4.7% – 6.7%). The SIR for a subsequent meningioma was 619.4 (95% CI: 532.7 – 720.2) and the AER was 21.8 per 10,000 person-years (95% CI: 18.5 – 25.1). Within 12 months of diagnosis of a subsequent meningioma, 13.6% of participants reported new-onset seizures, 10.7% auditory-vestibular-visual deficits, 11.8% focal neurological dysfunction and 6.5% severe headaches. With a median follow-up of 72 months following subsequent meningioma diagnosis, 22 (13%) participants died (6 deaths attributed to meningioma). Adjusting for cranial radiotherapy dose, a diagnosis of subsequent meningioma was independently associated with increased all-cause mortality (HR = 2.3; 95% CI: 1.5 – 3.5; p < 0.01). Conclusions: CRT-exposed childhood cancer survivors with subsequent meningiomas experience considerable new-onset neurological morbidity and increased all-cause mortality. Effective screening methods for subsequent meningiomas may reduce neurological morbidity.
Quantitative evaluation of heterogeneities in survival and surgical complication among hospitals: From data of two phase III trials of JCOG9204 and JCOG9907 (JCOG1312-A).
Authors: Kozo Kataoka, Kenichi Nakamura, Junki Mizusawa, Haruhiko Fukuda, Hiroyasu Igaki, Soji Ozawa, Tetsuya Abe, Kazuhiko Hayashi, Takeshi Iwaya, Ken Kato, Yuko Kitagawa, Nobutoshi Ando
Journal: Journal of Clinical Oncology (2014)

e15013 Background: Some studies of heterogeneity in the outcome after esophageal cancer surgery have been reported, but most of them are retrospective studies with domestic cancer registries. We investigated institutional heterogeneities of safety and efficacy of transthoracic esophagectomy with radical lymphadenectomy using two phase III trials conducted in different periods in Japan. Additionally, we investigated the influence of neoadjuvant chemotherapy (NAC) on heterogeneities. Methods: Two phase III trials for cStage II or III esophageal cancer, JCOG9204 (accrual period: 1992-1997, Ando N, JCO 2003) and JCOG9907 (2000-2006, Ando N, Ann Surg Oncol 2011), were analysed. JCOG9204 conducted in 17 hospitals demonstrated that postoperative chemotherapy (92POST; n=114) improved OS compared with surgery alone (92OP; n=114). JCOG9907 conducted in 24 hospitals demonstrated that NAC followed by surgery (99PRE; n=164) improved OS compared with postoperative chemotherapy (99POST; n=166). The influences of period on institutional heterogeneities were evaluated between 92OP+92POST and 99POST for surgical complication and between 92POST and 99POST for 5yOS. The influence of NAC on heterogeneities was evaluated using the surgical complication and 5yOS between 99POST and 99PRE. Heterogeneities were estimated by mixed effect model after adjustment with 5 clinical factors. Results: There were large heterogeneities of surgical complication in 92OP+92POST, but no heterogeneity in 99POST and some in 99PRE. Similar tendency was observed in heterogeneities of 5y OS (See Table). Conclusions: Transthoracic esophagectomy with intensive nodal dissection is a radical surgery, but institutional heterogeneities of safety and efficacy seemed to decrease over time. Newly introduced treatment may cause larger heterogeneities than already established treatment. 92OP+92POST (n=228) 99POST (n=166) 99PRE (n=164) Proportion of surgical complication (Median %[range]) 31.3 [15.0-68.2] 27.7 [27.7-27.7] 35.2 [22.6-46.6] 92POST (n=114) 99POST (n=166) 99PRE (n=164) 5yOS (Median %[range]) 66.4 [64.1-68.9] 44.4 [44.4-44.4] 55.9 [54.0-59.7]
Aspirin and risks of non-colorectal second primary cancer in patients with prior colorectal cancer.
Authors: Yu-Ting Lee, Chung-Jen Teng, Jin-Hwang Liu, Tzeon-Jye Chiou, Po-Min Chen, Cheng-Hwai Tzeng, Chia-Jen Liu
Journal: Journal of Clinical Oncology (2015)

1564 Background: Aspirin has been identified as reducing cancer incidence, especially colorectal cancer (CRC), distant metastasis and mortality. Secondary cancer prevention has not been investigated. To examine the potential effects of aspirin on non-colorectal SPMs prevention among patients with previous CRC Methods: We enrolled 92,392 patients with newly diagnosed CRC between January 1, 1997 and December 31, 2011 from the Taiwan’s National Health Insurance database. Participants with more than 90 cumulative defined daily doses (cDDD) of aspirin exposure are defined as aspirin users (n = 7,488) compared with non-users (n = 84,904). Development of non-colorectal SPMs was obtained from the Taiwan’s National Health Insurance database. The Cox proportional hazards model, and the Fine and Gray's proportional hazards model were used to estimate the cause-specific hazard ratios (HRs) and subdistribution HRs, respectively. Data analysis was conducted in April, 2014. Results: During the 15-year study period, 3,880 patients developed non-colorectal SPM among 92,392 recruited CRC participants. We compared 7,488 aspirin users with 84,904 non-users. Overall, the difference for risk of SPM was not significant. The cause-specific hazard ratios (HRs) and subdistribution HRs were 0.99 (95% CI 0.88–1.12) and 1.00 (95% CI 0.88–1.12), respectively. Propensity score analyses were done and matched 6,728 aspirin users with 26,912 non-users. The cumulative incidence of SPM showed no difference (p = 0.824). Conclusions: Among patients with prior CRC, aspirin use did not provide chemoprevention in non-colorectal SPMs.
Impact of nab-paclitaxel-based second-line chemotherapy on the outcomes of pancreatic cancer.
Authors: Neelakanta Dadi, Safi Shahda, Bert H. O'Neil, Amikar Sehdev
Journal: Journal of Clinical Oncology (2017)

483 Background: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with no standard second line chemotherapies. We conducted a retrospective study with the primary aim to examine the effect of second line chemotherapy with nab-paclitaxel-based regimen on the overall survival (OS) and progression-free survival (PFS) of locally advanced and metastatic PDAC patients. Methods: Indiana University Simon Cancer Center (IUSCC) Cancer Registry was used to identify patients with locally advanced or metastatic PDAC between 2009 and 2015. Only patients who received second line chemotherapies were included in the study. These patients were divided in to two groups: a) nab-paclitaxel-based treatment and, b) non-nab-paclitaxel-based treatment. Demographic (age, race, gender, year of diagnosis, family history, comorbidity), clinical (histology, CA 19-9, bilirubin, tumor location, performance status, metastatic sites, chemotherapy, surgery or radiation) and outcome (OS, PFS) characteristics were obtained. OS and PFS were estimate by using Kaplan-Meier method and 95% CI. Cox proportional-hazard model was used for multivariate analysis. Results: Forty-seven (39%) and seventy-three (61%) patients received nab-paclitaxel-based and non-nab-paclitaxel-based second line chemotherapy, respectively. In the univariate analyses, nab-paclitaxel-based treatment was only associated with younger age (60.4 vs. 64 years; P = 0.02). The median PFS was 2.8 and 2.1 months (HR 0.62; 95% CI 0.38-1.02; P = 0.06), and the median OS was 7.5 and 4.7 months (HR 0.67; 95% CI 0.45-1.00; P = 0.05) in patients who received nab-paclitaxel based second line treatment versus not, respectively. Multivariate analyses adjusted for age showed a significantly improved PFS (adjusted HR 0.60, 95% CI 0.36-0.98; P = 0.04) and a suggestion of improved OS (adjusted HR 0.67; 95% CI 0.44-1.01, P = 0.05) in the nab-paclitaxel based second line treatment group versus not, respectively. Conclusions: In a single institution retrospective study, we report significant improvement in the PFS and a suggestion of improvement in the OS with nab-paclitaxel based treatment as compared with non-nab-paclitaxel based treatment in the second line setting.