tbuckley/cabot-search huggingface dataset:
Prospective observational comparison of outcomes in African American and Caucasian patients receiving second-line treatment with pemetrexed for advanced non-small cell lung cancer (NSCLC).
Authors: E. J. Pennella, G. Pohl, A. C. Girvan, K. Winfree, B. Martinez, C. K. Obasaju, M. S. Walker, E. J. Stepanski, L. S. Schwartzberg, A. A. Adjei
Journal: Journal of Clinical Oncology (2011)

e18008 Background: Few prospective studies have evaluated the impact of race and ethnicity on clinical outcomes, during lung cancer treatment. This prospective observational study evaluated the impact of ethnicity on disease control rate (DCR) in patients (pts) with NSCLC treated with second-line pemetrexed (P). Methods: Eligibility criteria included stage IIIB or IV NSCLC pts receiving single-agent P for second-line therapy in routine clinical practice. Sites were selected to ensure high minority representation. Due to persistent challenges in achieving desired enrollment of Hispanic and Asian pts, the focus of the study was narrowed to a comparison of pts self-reporting as Caucasian (C) and African American (AA). This report describes findings regarding the primary endpoint of the study, DCR. Some pts remain under observation—full characterization of survival will be available in early 2011. Non-inferiority was evaluated using logistic regression analysis for DCR controlling for predefined covariates: age, gender, income, marital status, insurance type, smoking status, ECOG performance score, disease stage, histology, comorbidities, time from end of first-line to initiation with P, prior exposure to first-line platinum, first-line paclitaxel, and number of first-line cycles. The DCR of AAs was considered non-inferior to Cs if the upper 95% confidence bound on the adjusted odds ratio (OR) for Cs vs AAs was less than 1.78, corresponding to a difference in proportion of 14% assuming Cs to have a DCR of approximately 50%. The bound was chosen to be one-half of the anticipated difference between treatment and no second-line treatment. Results: The unadjusted DCR was 43.4% (116/267) for C and 45.8% (27/59) for AA (unadjusted OR=0.91). The adjusted OR for the comparison of C to AA in the final logistic regression model was 0.79 (95% CI, 0.41, 1.51). This upper 95% confidence bound was within the pre-specified acceptable bound of 1.78. Conclusions: Based on pre-specified analyses, DCR of AAs was non-inferior to Cs. Hence, ethnicity is not considered a significant predictor of disease control following second-line treatment with P.
Outcomes of perioperative systemic therapy (ST) in patients with R0 resection of metastatic colorectal cancer (mCRC).
Authors: Richard M. Lee-Ying, Daniel John Renouf, Howard John Lim, Caroline Speers, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2016)

496 Background: Adjuvant fluoropyrimidine (FP) +/- oxaliplatin (OX) ST improves overall survival (OS) following curative resection of stage II or III CRC, while other regimens do not. Utility of pseudo-adjuvant ST in mCRC patients who achieved R0 resection of their metastases remains controversial. We aim to describe population-based outcomes based on choice of ST. Methods: Patients diagnosed with mCRC from 2003 to 2010 and referred to any 1 of 5 cancer centers in British Columbia, Canada were reviewed. We categorized patients who underwent a successful R0 resection of their metastases into 3 groups based on receipt of peri-operative ST: 1) FP alone; 2) OX-based; and 3) non-standard or no ST. We compared OS using multivariate Cox regression models that adjusted for potential confounders. Results: We identified and reviewed 1,641 patients with mCRC among whom 225 achieved R0 resection of their metastases. In this cohort, median age was 63 years (Interquartile range (IQR) 55-70), 118 (52%) were men, 196 (87%) reported ECOG 0/1, 149 (66%) had a colonic primary, and 103 (46%) presented with de novo metastatic disease. The site of metastatic resection was hepatic in 144 (64%), pulmonary in 34 (15%), locoregional in 11(5%), and other in 36 (16%). A total of 122 (54%) received standard ST. Regimens included 28 (12%) FP alone, 94 (42%) OX-based, 25 (11%) irinotecan and 38 (17%) including bevacizumab. The median duration of ST was 10 cycles (IQR 7-12), with 56% and 44% delivered pre- and post-operatively, respectively. In multivariate analyses, liver or lung involvement (HR 0.60, 95% CI 0.40-0.88, p=0.01) predicted for improved OS when compared to metastases affecting other organs or sites. Receipt of OX-based ST was the only regimen associated with better OS, while the rest were not (Table). Conclusions: Findings from this population-based cohort of mCRC suggest that use of a defined course of OX-based ST for pseudo-adjuvant intent around the time of R0 resection of liver or lung metastases is correlated with improved OS. [Table: see text]
mTOR inhibitor therapy for metastatic sarcomatoid clear cell renal cell carcinoma (ccRCC).
Authors: Diogo Assed Bastos, Martin Henner Voss, Christoph Karlo, Albulena Ajeti, Sujata Patil, Darren Richard Feldman, Ana M. Molina, Robert John Motzer
Journal: Journal of Clinical Oncology (2013)

450 Background: Sarcomatoid variant describes a histomorphologic pattern with presence of spindle-cell features that can be seen across all subtypes of RCC. It is associated with an aggressive phenotype and poor prognosis. Outcome to mTOR inhibitor therapy was accessed in patients (pts) with ccRCC with sarcomatoid features. Methods: Patients with metastatic sarcomatoid ccRCC treated with mTOR inhibitors at our center were retrospectively identified. Demographic characteristics and treatment outcome were assessed. Overall response rate (ORR) was determined by formal response criteria (RECIST 1.1). Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Results: 29 pts were treated with temsirolimus (18) or everolimus (11). Median age was 57 years (53 to 61) and there were 21 male pts (72%). Median number of metastatic sites was 3 (1 to 7) and 18 pts (62%) had ≥ 3 metastatic sites. Distribution between Memorial Sloan-Kettering Cancer Center risk groups was 14% favorable, 72% intermediate, and 14% poor-risk disease. Median number of prior therapies was 1 (0 to 5) and 79% of pts received mTOR inhibitor as ≥ 2 nd -line of therapy. Three patients (10.3%) achieved a partial response (PR), 11 (38%) stable disease (SD), and 15 (51.7%) had progressive disease (PD). Tumor shrinkage was observed in 9 pts (31%) and the mean change in tumor burden was +24% (-45% to +100%). Median PFS and OS were 3.4 months (CI: 1.4-5.3) and 8.3 months (CI: 4.8- 17), respectively. Conclusions: OS was poor in this heterogeneous group of pts. Future studies to characterize this variant at a molecular level are warranted and might identify predictive markers for clinical outcome in patients treated with mTOR inhibitors. [Table: see text]
Retrospective cohort study on the safety and efficacy of bevacizumab for metastatic colorectal cancer patients: The HGCSG0801 study—Analysis of bevacizumab beyond progression (BBP).
Authors: Hiraku Fukushima, Satoshi Yuki, Yoshimitsu Kobayashi, Kazuteru Hatanaka, Takaya Kusumi, Ayumu Hosokawa, Takuto Miyagishima, Satoshi Takeuchi, Mineo Kudo, Yoshito Komatsu
Journal: Journal of Clinical Oncology (2012)

684 Background: Bevacizumab (BV) is widely used in first-line chemotherapy for metastatic colorectal cancer in Japan, but the use of beyond bevacizumab first progression (BBP) has been controversial yet. Methods: Of patients treated with first-line BV in our retrospective cohort study (HGCSG0801), patients treated with BBP (n=22) and those without BBP ( n=19) in second-line setting were analyzed. The National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was used to assess adverse events. The Response Evaluation in Solid Tumors (RECIST) criteria version 1.0 was used to assess tumor response. The Kaplan–Meier method was used to determine PFS and OS. Log-rank test was used to compare each group in terms of PFS and OS. All statistical tests were performed using SPSS. Results: PS (0/1/2) before second line chemotherapy was 18/3/1 in BBP and 10/8/1 in NBBP, respectively. In the safety analysis, five patients in BBP showed a worsening/newer hypertension, which wasn’t a clinical problem. In the efficacy analysis, the response rate was 22.8% in BBP and 0% in NBBP. The median PFS was better in BBP (6.7 months in BBP and 2.7 months in NBBP), but there was no significant difference in median OS from first BV administration between two groups (27.3 months in BBP and 22.2 months in NBBP). Conclusions: We analyzed BBP in daily practice in Japan. Adverse events were well tolerated, but survival advantage of BBP was not suggested. About the efficacy of BBP, we are waiting the results of ongoing Phase III trials.
Role of repeat staging laparoscopy in locoregionally advanced gastric cancer after completion of neoadjuvant therapy.
Authors: Kenneth Cardona, Qin Zhou, Mithat Gönen, Vivian E. Strong, Murray F. Brennan, Daniel G. Coit
Journal: Journal of Clinical Oncology (2012)

11 Background: Staging laparoscopy (SL) can identify occult, subradiographic metastatic disease, either visible or cytologic, defining patients with stage IV gastric cancer who are unlikely to benefit from gastrectomy. The purpose of this study was to characterize the yield of repeat SL performed immediately prior to gastrectomy following administration of neoadjuvant therapy for locoregionally advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. Methods: Retrospective review of a prospective database identified patients with locoregionally advanced G/GEJ adenocarcinoma (T3−4Nany or TanyN+) that underwent pretreatment SL with negative peritoneal cytology followed by neoadjuvant chemotherapy or chemoradiation. After neoadjuvant therapy, patients underwent repeat SL. The yield of repeat SL to identify metastatic disease (M1) was determined and outcome data were analyzed. Results: From 1994−2010, 164 patients with locoregionally advanced G/GEJ adenocarcinoma were identified who underwent repeat SL immediately prior to gastrectomy. Occult M1 disease was identified in 12 patients (7.3%). Of these 12 patients, M1 disease was identified at laparoscopy in 9 patients (5.5%)—8 patients had visible disease and 1 patient had peritoneal cytology−only M1 disease. M1 disease not identified by SL was discovered at laparotomy in the other 3 patients (1.8%). There were no complications associated with patients who only underwent SL. Median follow-up was 30 months with a median survival of 18 months for patients with M1 disease and 47 months for patients resected with curative intent without M1 disease (p&lt;0.001). Conclusions: Repeat staging laparoscopy following neoadjuvant therapy for locoregionally advanced G/GEJ adenocarcinoma identifies 5−6% of patients with clinically occult, subradiographic M1 disease. The majority of M1 disease is identified at repeat SL rather than at laparotomy and the majority is visible as opposed to cytology−only M1. These patients with occult M1 disease have a poor prognosis, are unlikely to benefit from gastrectomy, and repeat SL can avert the morbidity of a non−therapeutic laparotomy in this patient population.
Achievement of Low or Intermediate-1 Risk Score after Combination Chemotherapy before Stem Cell Transplantation (SCT) May Be Associated with Prolonged Disease-Free Survival (DFS) in Patients with Advanced Myelodysplastic Syndrome (MDS).
Authors: Jaroslav Cermak, Antonin Vitek, Marcela Lukasova, Kyra Michalova, Petr Cetkovsky
Journal: Blood (2004)
Potential predictive markers of chemotherapy for advanced gastric cancer: Biomarker study in GC0301/TOP-002, randomized phase III study of irinotecan plus S-1 versus S-1.
Authors: Naotoshi Sugimoto, Akira Tsuburaya, Ryohei Kawabata, Kazuhiro Nishikawa, Haruhiko Imamoto, Toshimasa Tsujinaka, Taito Esaki, Yosuke Horita, Yutaka Kimura, Tsuneaki Fujiya, Osamu Takayama, Ryo Oono, Hiroshi Yabusaki, Masataka Taguri, Satoshi Morita, Wasaburo Koizumi, Patrick Tan, Motoki Ninomiya, Hiroshi Furukawa, Mitsuru Sasako
Journal: Journal of Clinical Oncology (2014)

55 Background: Irinotecan plus S-1(IRI-S) achieved longer median survival than S-1 monotherapy and was well tolerated for patients with advanced gastric cancer (AGC) in GC0301/TOP-002, but it did not show significant superiority (Gastric Cancer 2011). According to subset analyses, IRI-S may have extra survival benefit in some group of patients, prompting to explore prognostic or predictive markers.We correlated expression of 5 genes related to DNA and anticancer drug metabolism (TS, DPD, Topo-I, ERCC1, TP) with outcome of patients in each arm. Methods: Paraffin-embedded primary tumor specimens before chemotherapy were available from 126 of 326 patients. mRNA expression in microdissected tumors was measured by real-time RT-PCR, and categorized into low and high using the median as a cut-off. Multivariate analysis for overall survival (OS) adjusting baseline factors, gene expression and treatment (S-1/IRI-S) was performed with a Cox regression model. Interaction tests were also carried out between gene expression and treatment. Results: Although baseline factors of the subjects were similar to the entire GC0301/TOP-002 trial, median survival seemed opposite; 13.1M for S-1 and 11.4M for IRI-S arm, p=0.192. 92 samples, 47 of S-1 and 50 of IRI-S arm, were assessable for 5 genes. Multivariate analyses showed that liver metastasis correlated with poor prognosis (HR, 2.73; 95% CI, 1.50-5.01; P=0.011), but no gene was significantly correlated with OS. There were interactions between the treatment effect for DPD and TP. HRs between high and low DPD were 3.02 in S-1 and 0.96 in IRI-S arm, p=0.012 for interaction; while those for TP were 2.98 in S-1 and 0.38 for IRI-S arm, p=0.002. In patients with low TS and high Topo-I (n=18), OS was 11.2M for S-1 and 18.6M for IRI-S arm, p=0.531. Conclusions: The correlative analyses suggest DPD and TP are predictive factor for the first-line treatment of AGC including S-1 and irinotecan. Combined biomarker analyses with the previous randomized phase III study including S-1 or irinotecan is warranted to verify these findings.
Updated interim analysis (IA) of COU-AA-302, a randomized phase III study of abiraterone acetate (AA) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) without prior chemotherapy.
Authors: Dana E. Rathkopf, Matthew Raymond Smith, Johann Sebastian De Bono, Christopher Logothetis, Neal D. Shore, Paul L. De Souza, Karim Fizazi, Peter Mulders, Paul N. Mainwaring, John D. Hainsworth, Tomasz M. Beer, Scott A. North, Yves Fradet, Thomas W. Griffin, Youn Choi Park, Thian San Kheoh, Eric Jay Small, Howard I. Scher, Arturo Molina, Charles J. Ryan
Journal: Journal of Clinical Oncology (2013)

5 Background: AA, a specific inhibitor of CYP17, blocks androgen biosynthesis and improves overall survival (OS) in mCRPC post-docetaxel (Lancet Oncol 2012;13:983-92). This pre-specified updated IA (55% total OS events) extends previous IA for COU-AA-302 evaluating clinical benefit of AA vs prednisone (P) in mildly symptomatic or asymptomatic pts with progressive mCRPC without prior chemotherapy. Methods: 1088 pts were stratified by Eastern Cooperative Oncology Group performance status (ECOG-PS, 0 vs 1) and randomized 1:1 to AA 1000 mg + P 5 mg po BID vs Placebo + P. Co-primary endpoints: radiographic progression-free survival (rPFS) and OS. Median time with 95% CI was estimated using the Kaplan-Meier method. The O’Brien-Fleming Lan-DeMets α-spending function was used for OS. Results: At 55% IA, OS, rPFS and secondary endpoints all favored the AA arm (Table). Median follow-up = 27.1 mos. A post hoc sensitivity multivariate analysis for OS using known prognostic factors supported primary results (HR 0.74, P = 0.0017). Grade 3/4 AEs (AA, P) (%): hypertension 4.2 vs 3.1; hypokalemia 2.6 vs 1.9; ALT↑ 5.5 vs 0.7; AST↑ 3.1 vs 0.9. Conclusions: In updated IA of COU-AA-302, improvement in rPFS (risk reduction 47%) remained statistically significant. Risk of death decreased by 21% but did not reach pre-specified efficacy boundary. Median OS for AA (35.3 mos) is the longest reported for this mCRPC population. Secondary endpoints were clinically and statistically significant; safety profile despite longer exposure remains favorable. Targeting extragonadal androgen synthesis reduces morbidity associated with disease progression in mCRPC pts without prior chemotherapy. Clinical trial information: NCT00887198. [Table: see text]
"3 Steps 4 Health" in survivorship.
Authors: Ann Fonfa, Helayne Waldman
Journal: Journal of Clinical Oncology (2016)

e273 Background: As patient advocates we have spent years gathering and sharing information about simple, natural strategies to reduce risk of treatment-related toxicities and strengthen the immune system in survivorship. Sadly it is well known that many suffer long-term toxicities and are at higher risk for secondary cancers. Survivorship plans are created to help people move forward with their lives; we suggest the “3 Steps 4 Health” program as an addition. Methods: We created a simple 3-step program that absolutely anyone with cancer can incorporate into their own healthful protocol as they move into complete recovery. Since it involves no tools and can be used at the level that an individual is at the time they start, we consider it appropriate for all. Further, we cannot see any objection from the oncologist or staff members. Step 1: Eat one more fruit and one more vegetable every day. This is helpful since studies show few Americans are getting enough fruits or vegetables. The National Cancer Institute considers “Five a Day” a minimum. We want to get people started on the correct path simply and easily. Step 2: Take a walk around the room or neighborhood depending on ability and health status. This has been shown by many studies to help anyone with cancer, undergoing treatment, or in recovery. We are not asking people to become athletes; we are involving them in a plan to improve their health. Step 3:Seven deep breaths in a stressful situation or at bedtime. This step is important to reduce stress and encourage relaxation. Results: As patient advocates, we conduct no research; we scour journals for studies supporting our evidence-based concept. There are now many studies showing the value of one or more of the three steps. Rarely does research examine the concept as a whole. We believe this will occur soon. Conclusions: Every step moves people forward into better health. We believe taking these first steps will lead to more healthful behaviors, better ability to handle conventional cancer treatments, and an easier recovery. In this era of interest in immune response, it makes perfect sense for each individual to strive to be their personal best. Clearly, the “3 Steps 4 Health” program is a beginning at an important time for those who have survived cancer. We will share some of the studies that led us to this position.
Presence of intraductal carcinoma of the prostate on needle biopsy as a prognostic factor for prostate cancer in radical prostatectomy patients.
Authors: Masashi Kato
Journal: Journal of Clinical Oncology (2014)

268 Background: Intraductal carcinoma of the prostate (IDCP) is seen with widely invasive, biologically aggressive prostate cancer. A recent study has shown this morphologic pattern is useful for prognostication of biochemical recurrence after radical prostatectomy, whereas there is no paper to report biopsy finding of IDCP to be a positive predictor of progression-free survival (PFS) and cancer-specific survival (CSS). Methods: This retrospective study included men with high-risk prostate cancer treated with radical prostatectomy between 1991 and 2005, and we reviewed slides of biopsy samples. Presence of IDCP was defined using previously published diagnostic criteria by a single genitourinary pathologist. Analyzed factors included age, prostate-specific antigen (PSA), clinical T stage, higher biopsy Gleason score (bGS), presence of Gleason pattern five, and IDCP on biopsy samples. Finally, a total of 205 patients with high-risk prostate cancer were entered in our retrospective clinicopathological analysis. Results: Patient mean age was 68. Baseline characteristics included a PSA greater than 20 ng/ml at diagnosis in 122 cases (60%), clinical stage greater than T2 (cT) in 86 (42%), and bGS ³a8 in 150 (73%) in all patients. Follow-up period was 86 months on average. The presence of IDCP on needle biopsy was in 75 (37%). Forty-four patients showed clinical failure, and 20 patients died of the disease. Patients with IDCP showed a higher increased PSA level, higher increased bGS, and more advanced cT than those without IDCP (p &lt; 0.0001). In univariate analysis, IDCP (p &lt; 0.0001), cT (p &lt; 0.0001), bGS (p = 0.0002), and presence of Gleason pattern five (p=0.004) were significantly associated with PFS; IDCP (p &lt; 0.001) and cT (p = 0.02) were significantly associated with CSS. In multivariate analysis, IDCP (p&lt; 0.0001; hazard ratio (HR), 3.574) and cT (p= 0.004; HR, 3.087) were significantly associated with PFS; IDCP (p = 0.001; HR, 8.405) and PSA level (p = 0.0044; HR, 2.920) were significantly associated with CSS. Conclusions: Presence of IDCP on needle biopsy can be a significant predictor of PFS and CSS when analyzing factors of biopsy samples in high risk prostate cancer.
Inverse correlation between expression and methylation of RPRM, a TP53 dependent G2 arrest mediator candidate, along the gastric precancerous cascade.
Authors: Alejandro Hernan Corvalan, Maria Jose Maturana, Wilda Olivares, Nicole Roldan, Jacqueline Fry
Journal: Journal of Clinical Oncology (2016)

73 Background: Gastric cancer (GC) is one of first cause of cancer death worldwide. Lesions associated with the gastric precancerous cascade include atrophic gastritis (AG), intestinal metaplasia (IM), dysplasia (DY), and early (EGC)/advanced gastric cancer (AGC). Loss of expression due to aberrant methylation of Reprimo (RPRM), TP53 dependent G2 arrest mediator candidate, has been detected in patients with GC. Here we evaluated the methylation of the promoter region of RPRM in the precursor lesions. Methods: Fresh tissue biopsies from AG (N = 8), IM (N = 6), DY (N = 4), EGC (N = 5) and AGC (N = 8) were included. Expression and methylation levels of RPRM were detected by qPCR and MethyLight, respectively. Sequencing of 30 CpG sites of the promoter of RPRM was performed by Bisulfite sequencing. Results: Relative expression levels of the mRNA of RPRM decrease as gastric precancerous cascade progress, being significant in the transitions IM/DY and EGC/ACG. Methylation of the promoter of RPRM was detected in 4/8 AG, 3/6 IM, 4/4 DY, 5/5 EGC and 8/8 AGC. Spearman correlation analysis showed a significant inverse association between methylation and expression (r = -0.99, P &lt; 0.0001). We observed increase of methylation of the CpG site 24 in the transition EGC to AGC. Conclusions: Our results show an inverse correlation between expression and methylation of RPRM along the gastric precancerous cascade. This inverse correlation is determinant in transitions from IM to DY and EGC to AGC. The identification of specific methylation of CpG site 24 associated EGC to AGC may be critical for the regulation of the RPRM expression. Grant Support: CONICYT-Fondap#15130011 and Fondecyt#1151411 from the Government of Chile