tbuckley/cabot-search huggingface dataset:
Do body mass index (BMI) and body surface area (BSA) influence the outcome of metastatic renal cell carcinoma?
Authors: S. Waalkes, V. Gruenwald, C. Seidel, H. Eggers, G. Wegener, F. Jentzmik, R. Hofmann, M. Schrader, M. Kuczyk, A. J. Schrader
Journal: Journal of Clinical Oncology (2011)

e15162 Background: Obesity increases the risk of developing renal cell carcinoma (RCC); however, it remains unclear whether obesity is associated with RCC aggressiveness and survival. A recently published study even proposed Obesity as a independent (positive) prognostic factor for localized renal cell carcinoma (RCC; Waalkes et al.). Additionally at the ASCO annual meeting 2010 Choueiri et al. presented data indicating that obesity might be associated with a favorable prognosis in patients with metastasized RCC (mRCC). Methods: On basis of two study groups we evaluated if BMI or a BSA above average (>1.98 m2 for male, >1.74 m2 for women in the EU) is of prognostic relevance for patients with mRCC. Results: Group A (n=293): Patients with primary mRCC treated between 1990 and 2005 with palliative nephrectomy in the cytokine era. Group B (n=107): mostly mRCC-patients treated with nephrectomy and 1st line therapy with TKI from 2006 to 2009. Mean Age, BMI and BSA in groups A (respectively B) was 61.9 years (61.0 years), 25.5 kg/m2 (25.7 kg/m2) and 1.93 m2 (1.97 m2). 28.4% (33.6%) were women and 9.7% (15%) were classified as non-clear cell (ncRCC) malignancies. In Kaplan Meier Analysis there was no evidence for group A and B that BMI (p=0,89 / 0,95) or BSA (p=0,86 / 0,7; Mantel-Cox) had any influence on prognosis of patients with mRCC. In multivariate analysis BMI and BSA also failed to prove as independent prognostic factors. Solely the subgoup of ncRCC in group A was related to a significantly worse prognosis. Conclusions: The evaluation of two large study populations treated in the era of cytokines and TKIs was not able to show a prognostic relevance of obesity in mRCC.
Phase I/II study of sorafenib in combination with intermittent hepatic arterial infusion chemotherapy using cisplatin for unresectable advanced hepatocellular carcinoma with portal vein tumor thrombus.
Authors: Morihiko Ishizaki
Journal: Journal of Clinical Oncology (2015)

441 Background: Our purpose in the study was to ascertain the feasibility of a combination therapy with sorafenib and hepatic arterial infusion therapy (HAIC) using cisplatin (CDDP) for unresectable advanced HCC included portal vein tumor thrombus. Methods: Phase I study: Soraenib was administered continuously, whereas CDDP was given on day1, 8, and 15. The dose of sorafenib was escalated in two steps from 400 to 800 mg/body, whereas the dose of CDDP was escalated in three steps from 20 to 25 and 30 mg/m 2 . We estimate the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of this therapy, to determine the recommended dose (RD). Phase II study: Thirty-five patients with unresectable HCC received this therapy under RD, and the efficacy and safety were assessed. Results: Phase I study: 15 patients (11 male/4 female, median age: 73.1 years) with unresectable advanced HCC have been enrolled. None of the patients treated with sorafenib 400mg and cisplatin 20 mg/m 2 experienced DLT. Three of three patients treatd with sorafenib 800mg and cisplatin 20 mg/m 2 experienced DLTs (two serum bilirubin elevation and one hepatic encephalopathy). None of the patients treated with sorafenib 400mg and cisplatin 25 mg/m 2 experienced DLT. One of six patients treated with sorafenib 400mg and cisplatin 30 mg/m 2 experienced dose-limiting thrombocytopenia, and One of them experienced dose-limiting serum aspartate aminotransferase elevation. Phase II study: 35 patients (27 male / 8 female, median age : 69.2 years) with unresectable advanced HCC have been enrolled. The clinical response were rated as 9 partial response (PR), 18 stable disease (SD), and 8 progressive disease (PD). Conclusions: In this study, RD of this therapy was sorafenib 400mg/body and CDDP 30 mg/m 2 . Sorafenib in combination with intermittent HAIC using CDDP for unresectable advanced HCC was expected to be safe and effective treatment. Clinical trial information: 000008571.
FOLFIRI regimen as second-/third-line chemotherapy in patients with advanced pancreatic adenocarcinoma refractory to gemcitabine and platinum salts: A retrospective series of 70 patients.
Authors: C. Neuzillet, O. Hentic, B. Rousseau, V. Rebours, L. Bengrine-Lefèvre, E. Raymond, P. Ruszniewski, C. Louvet, P. Hammel
Journal: Journal of Clinical Oncology (2011)

272 Background: Gemcitabine-based regimen is a standard of first-line chemotherapy in patients with advanced pancreatic adenocarcinoma (PAC) and 5-FU/oxaliplatin combination is an option for second line (Oettle, 2009). Some data suggest a potential efficacy of 5-FU/irinotecan regimen (FOLFIRI) as first-line treatment (Taïeb, 2007)or in patients with gemcitabine/platinum-refractory advanced PAC (Yoo, 2009; Gebbia, 2010). Methods: All consecutive patients with unresectable advanced PAC (01-2005/05-2010) and OMS≤2 received FOLFIRI-1 (irinotecan 180 mg/m 2 D1, n=60) or FOLFIRI-3 regimen (irinotecan 100 mg/m 2 D1/D3 n=10) after failure of gemcitabine- and platinum-based chemotherapies as a systematic policy in two institutions. Following data were analyzed: tumor response, progression free survival (PFS), overall survival rate (OS), and grade 3-4 toxicities. Results: Seventy patients were studied. Median age was 60 years (range: 24-81); 37 (52.9%) were male; 30 (42.9%) were PS 0, 27 were PS 1 and 13 were PS 2. Cancer was locally advanced in 15.7% and metastatic in 84.3% of patients. Before FOLFIRI regimen, patients received 1 line (n=24, 34.3%), 2 lines (n=40, 57.1%) or ≥ 3 lines (n=6, 8.8%) chemotherapy. PFS with previous line was less than 3 months in most patients. Tumor control was achieved in 31 (44.3%) patients (partial response: 5, stable disease: 26). PFS was 17% at 12 months and 3% at 24 months. Median PFS was 23 weeks (range: 2-147). OS was 24% at 12 months and 9% at 24 months. Median OS was 24 weeks (range: 2-147). From the initial diagnosis, 1-year and 2-year survivals were 79% and 32%. Dose adaptation was required in 21 (30.0%) patients. Eighteen (25.7%) patients had grade 3-4 toxicities, mainly hematologic (n=13) or digestive (n=6). Febrile neutropenia occurred in 3 patients without death. Conclusions: FOLFIRI regimen after failure of gemcitabine- and platinum-based regimens for advanced PAC in our study had an acceptable toxicity and a surprising efficacy in patients OMS 0-2. These results suggest that FOLFIRI regimen should be further tested as first-line chemotherapy in patients with advanced pancreatic cancer. No significant financial relationships to disclose.
A randomized controlled trial of a cardiopulmonary resuscitation (CPR) video decision support tool for seriously ill hospitalized patients with advanced cancer.
Authors: Areej El-Jawahri, Jennifer S. Temel, Kavitha Ramchandran, Vicki A. Jackson, Yuchiao Chang, Elizabeth Walker-Corkery, Eileen Mann, Angelo E. Volandes
Journal: Journal of Clinical Oncology (2015)

7 Background: Discussing CPR preferences with patients with advanced cancer who are hospitalized is a critical component of end-of-life decision making. However, these discussions are challenging and often avoided by clinicians. We examined the impact of a CPR video decision tool on patients’ choices and knowledge about CPR, and their comfort with watching the video. Methods: We conducted a multi-center randomized controlled trial of 116 patients with advanced cancer hospitalized at two academic oncology centers. We randomized patients to either a 3-minute video describing CPR (n = 52) or standard-oncology care (n = 64). The primary outcome was participants’ preferences for CPR (immediately after viewing the video in the intervention arm). Secondary outcomes included patients’ knowledge (using 5-item questionnaire with higher score reflects greater knowledge), and intervention participants’ comfort with watching the video. Results: The mean age was 66 years (SD = 12); 50% were women, 84% were white, and 48% had lung or gastrointestinal cancer. Only 47% of study participants reported having a discussion about their CPR preferences at the time of admission to the hospital. At baseline, there were no differences in patients’ preferences for not wanting CPR between the intervention and control arms (63% vs. 58%, P = 0.79). After the intervention, participants randomized to the video were more likely not to want CPR (81% vs. 58%, P = 0.03) and were more knowledgeable (mean knowledge score 4.3 vs. 3.2, P &lt; 0.0001) versus control participants. In the intervention arm, 81% of participants found the video helpful, and 94% felt comfortable watching it and would recommend it to others. Conclusions: Seriously ill hospitalized patients with advanced cancer who watched a CPR video decision support tool were more likely not to want CPR and were better informed about their options. Participants reported feeling comfortable watching the video and would recommend it to others facing similar decisions. Video decision support tools can facilitate end-of-life decision-making for hospitalized patients with advanced cancer. Clinical trial information: NCT01527331.
Treatment of brain metastases in patients with testicular germ cell tumors.
Authors: J. Martinez-Cedillo
Journal: Journal of Clinical Oncology (2011)

e15155 Background: Patients with TGCT who present with brain metastases have poor prognosis. Approximately 3% of patients with metastases disease will present brain metastases. There are few reports reporting the long-term results of these patients. Methods: We retrospectively report the long-term results of 18 patients with brain metastases from TGCT presented at our institute from 2000 - 2010. Results: The median age at diagnoses of brain metastases was 24.7 years. The histology of the primary tumor was: yolk sac tumor 12 patients,mature teratoma 9, coricocarcinoma 8 and embrional carcinoma 8. All patients had mixed histology, none of patients had pure histology. 10 patients had brain metastases at diagnoses and 8 developed them during follow-up after cisplatin-based chemotherapy. The main neurological symptoms were headache, seizures and disorientation. Only 2 patients were asymptomatic. Ten patients presented with one brain lesion, 4 with 2 lesions, 3 with 3 lesions, and one patient with 4 lesions. The treatment of brain metastases was as follow: 13 patients whole-brain irradiation only, 4 patients surgery only, one patient surgery and RT. All patients received cisplatin-based chemotherapy. In patients with brain metastases during the follow-up, median time to recurrence was 9.1 months. The median survival was 60 months for patients with brain metastases at diagnoses and 41 months for those who developed brain metastases during the follow up. 4 of 13 patients who received RT only are alive compared with 3 of patients who were treated with surgery alone. The patient that were treated with RT and surgery are also alive. Conclusions: Long term survival can be achieved in patients with brain metastases from TGCT. Patients who presented with brain metastases at primary diagnoses had better prognosis than those who present them after chemotherapy. Although there were few patients, we can see that patients treated with surgery had a better prognosis than those treated with RT. Patients with metastases at diagnoses should receive intense treatment modalities for curative intent. On the contrary, patients who developed metastases after chemotherapy have poor prognosis and maybe should receive the least toxic treatment, like a palliative radiation therapy.
A study of two ODM-201 formulations with a safety and tolerability extension phase in patients with metastatic chemotherapy-naive castration-resistant prostate cancer (CRPC).
Authors: Christophe Massard, Teuvo L. J. Tammela, Egils Vjaters, Vilnis Lietuvietis, Petri Bono, Heidi Penttinen, Pirjo Nykänen, Amir Snapir, Leena Mattila, Karim Fizazi
Journal: Journal of Clinical Oncology (2014)

115^ Background: This open phase I trial assessed the bioavailability, and the effect of food on the bioavailability of ODM-201 600mg tablets compared to a 600mg capsule formulation. Efficacy, safety, and tolerability of ODM-201 were studied in the extension period. Methods: The study had two parts: a pharmacokinetic (PK), and a safety and tolerability part. Dosing was 600mg bid with or without food. In the PK part, three single doses of ODM-201 were given over 3 weeks. In the extension part patients could continue treatment until disease progression or until an intolerable adverse event or condition that prevented further dosing of ODM-201. Results: Thirty men with metastatic chemotherapy-naïve castration-resistant prostate cancer (CRPC) were enrolled, the median age was 68. The median prostate-specific antigen (PSA) was 18.2 ng/mL and testosterone 23.1 ng/dL at baseline. Food interaction was observed when ODM-201 formulations were administered after a high fat content breakfast compared to administration at fast. AUC and C max values were about 50% lower after fast. Twenty nine patients have completed the 4-week visit. The PSA response rate (50% or more PSA decline) was 86%, with a median PSA decrease of -66% (-96, 5) at week 4 (N=18/21). Most commonly reported adverse events so far are fatigue, abdominal pain, diarrhea, hematuria, and nausea. Conclusions: ODM-201 600mg bid as tablets has comparable PK to capsules used in the phase II ARADES trial. It is well tolerated and has good PSA response in chemotherapy-naïve patients with CRPC . Clinical trial information: NCT01784757.
Uncertainty in the management of thyroid cancer.
Authors: Megan Haymart, Mousumi Banerjee, Di Yang, Andrew Stewart, James Sisson, Ronald J. Koenig, Gerard M. Doherty, Jennifer J. Griggs
Journal: Journal of Clinical Oncology (2012)

238 Background: Little is known about treatment practices in thyroid cancer, a cancer that is increasing in incidence. We sought to identify aspects of thyroid cancer management that have the greatest variation and thereby uncertainty in management. Methods: We surveyed 944 physicians involved in thyroid cancer care from 251 hospitals affiliated with the U.S. National Cancer Database. Using vignettes and additional survey items, physicians were asked questions in the following four domains: thyroid surgery, radioactive iodine use, thyroid hormone replacement post-surgery, and long-term thyroid cancer management. To identify aspects of thyroid cancer management with the greatest uncertainty, we calculated the ratio of observed variation to hypothetical maximum variation under the assumed distribution of the response. Ratios closer to 1 indicate greater uncertainty. Results: There is large uncertainty in multiple aspects of thyroid cancer management, including the role of central lymph node dissections, the role of pretreatment scans before radioactive iodine treatment, and all aspects of long-term thyroid cancer management, including applications of ultrasound and radioactive iodine scans. For the management of small thyroid cancers, uncertainty exist in all domains, including optimal extent of surgery and the role of both radioactive iodine treatment and suppressive doses of thyroid hormone replacement. Conclusions: We identified areas of uncertainty in thyroid cancer management. Since both a lack of data and a lack of acceptance of the existing data may be contributing to the variation demonstrated, to improve the management of thyroid cancer there is a need for more research and more research dissemination.
The effect of incision in the surgical treatment of endometrial cancer and long-term follow-up of a randomized trial of lymphadenectomy: Results of the MRC ASTEC trial.
Authors: H. C. Kitchener
Journal: Journal of Clinical Oncology (2011)

e15583 Background: Total abdominal hysterectomy and bilateral salpingo-oophorectomy is standard treatment for early stage endometrial cancer (EC). Pelvic lymphadenectomy had never been fully evaluated in early endometrial cancer until the ASTEC trial. The primary objective was to determine the benefit or otherwise of lymphadenectomy on overall survival (OS). Primary analyses showed no evidence of an OS benefit with a hazard ratio (HR) of 1.16 (95%CI 0.87-1.54; p=0.31) in favour of standard surgery. A secondary objective was to investigate whether type of incision affects outcome. Methods: Patients with histologically proven EC were randomised to receive no lymphadenectomy (No LN) or lymphadenectomy (LN). The protocol recommended a vertical incision but transverse incisions could be used if appropriate. The updated analysis was planned when 110 deaths were observed in each incision group to detect a 10% difference in 5-year OS with 5% significance level and 90% power. Results: Between 07/1998 and 04/2005, 1408 patients (704 No LN, 704 LN) were randomised. 1286 patients had open (vs laparoscopic) surgery, of these 672 (52%), 522 (40%) and 92 (7%) had vertical, Pfannenstiel and other transverse incisions respectively. More patients in the LN arm had a vertical incision (386) compared to the no LN arm (287). With a median follow-up of 60 months, 251 (18%) patients (115 No LN, 136 LN) had died with a HR of 1.22 (95%CI 0.95-1.56), p=0.12 in favour of standard surgery. 128 (19%) and 102 (17%) deaths were reported in vertical and Pfannenstiel/other transverse groups. There was no evidence of an interaction between type of incision and surgical randomisation for OS (p=0.74). Conclusions: Long term follow-up supports previous findings, with no evidence of a benefit from lymphadenectomy and no evidence that type of surgical incision influences OS.
Variables effecting acute rectal toxicity in 1132 prostate cancer patients treated with conformal irradiation in AIROPROS 0102 trial
Authors: R. Valdagni, V. Vavassori, C. Fiorino, G. Fellin, T. Rancati, F. A. Mauro, F. Munoz, E. Cagna, C. Greco, A. Magli
Journal: Journal of Clinical Oncology (2005)

4610 Background: Acute rectal toxicity (TOX) as a function of pre-treatment and treatment variables has been prospectively analyzed in patients (pts) with prostate cancer treated with conformal radiotherapy (CRT) in AIROPROS 0102 multicenter trial. Methods: Between July 2002/Dec 2003, 1132 pts were accrued in a cooperative study on CRT in prostate cancer. CRT was delivered at doses of 70–80 Gy at 1.8/2.0 Gy/fr. The inter-Institute variability in rectum contouring and in calculating dose volume histograms (DVH) was previously found to be acceptable. Pts filled a questionnaire before and the end of treatment to monitor rectal TOX and to record drug prescription. Correlation among pre-Tx morbidities, androgen deprivation (AD), drug prescription, presence/absence of diabetes or hypertension and acute rectal TOX were assessed by uni- /multivariate (MVA) analyses as well as mean and max rectal dose, rectal volume, ICRU dose and pelvic irradiation. Results: All pts were available. 279/1132 pts exhibited grade 1–2 and 293/1132 grade 3 acute events. When grade 2–3 acute TOX was considered, mean dose was the most predictive negative variable in MVA (p = 0.0004, OR = 1.03) followed by the presence of haemorrhoids (p = 0.057, OR = 1.33) and pelvic CRT (p = 0.06, OR = 1.67); anti-coagulants were found to be protective (p = 0.002, OR = 0.62). When considering together grade 1–3 acute TOX, mean dose was confirmed to be the most predictive variable (p = < 0.0001, OR = 1.03) as well as pelvic XRT (p = 0.06, OR = 1.68). AD resulted to be protective for many end-points in univariate analyses; however, this was not fully confirmed in MVA. This probably suggests the protective effect of AD is mainly due to the reduction of the irradiated rectum as a consequence of the well known AD induced prostate downsizing. Conclusions: These results show that mean rectal dose is the strongest predictor for acute rectal TOX in prostate 3D-CRT and confirm that haemorrhoids and pelvic radiation negatively impact on acute treatment tolerance. Our findings also confirm the efficacy of AD in reducing TOX as a possible consequence of prostate volume reduction. The AIRO Group on Prostate cancer wishes to thank Fondazione L. Monzino for the support No significant financial relationships to disclose.
Disease control rate at 8 weeks as a predictive marker for long-term clinical outcomes in patients with advanced gastric cancer.
Authors: Junho Yi, Gun Min Kim, Hyo Song Kim, Sun Young Rha, Hyun Cheol Chung
Journal: Journal of Clinical Oncology (2012)

22 Background: Survival is the ultimate end-point in field of medical oncology. Although tumor response has been used as surrogate end-point in early phase clinical trial in patients with gastric cancer, clear correlation between tumor response and long-term survival has not been established yet. The objective of the current study is to determine whether early assessment could predict survival in patients with AGC. Methods: A total of 337 patients with AGC who had participated one of the three first-line, prospective, investigator-initiated, randomized trials carried out in Yonsei Cancer Center were included in the analysis. 238 had received fluoropyrimidine (F) + platinum (P), 61 had received F + taxane (T), 38 had received T + P. Response was assessed according to RECIST 1.1 at 8, 14 and 20 weeks after initiation of treatment. The correlation between response at each time point and the OS was evaluated using logistic regression test. Results: The median OS was 13.7 months. (95% CI 11.8 – 15.6) In terms of confirmed tumor response, 1 CR, 84 PRs, 104 SDs and 148 PDs were observed. At every landmark period, disease control rate (DCR, CR + PR + SD) was superior in predicting OS comparing with response rate. (RR, CR + PR) (Table). Among them, 8-week DCR was the most powerful predictor for OS. (HR 0.18, p&lt; .001) There was no significant OS difference between patients with (13.7 months) vs. without (13.9 months) measurable lesions (p = .705) and between patients with 8-week response of PR (18.1 months) vs. SD (15.3 months) (p = .522). Conclusions: Disease control was a better predictor for OS in patients with AGC who had received first-line chemotherapy than response, with disease control at 8 week being the most powerful predictor. This could be used as a surrogate marker for long-term survival in early phase clinical trials. [Table: see text]