tbuckley/cabot-search huggingface dataset:
Utilization and sequencing of targeted therapy and cytoreductive nephrectomy in non–clear cell metastatic kidney cancer.
Authors: Liam Connor Macleod, Scott S. Tykodi, Sarah Holt, John L. Gore
Journal: Journal of Clinical Oncology (2016)

615 Background: Many patients with metastatic kidney cancer (mRCC) are ineligible for trials due to non-clear cell histology. Efficacy of targeted therapy agents in non-clear cell mRCC is still being investigated. We hypothesized that sequencing CN upfront is associated with improved overall survival. We analyze a population-based cohort of non-clear cell mRCC patients in the targeted therapy era. Methods: Patients from the SEER-Medicare files (2005-2011) with non-clear cell mRCC were categorized as having received upfront targeted therapy or upfront CN. Additional exclusions were age &lt; 66 to avoid confounding by uncaptured non-Medicare coverage, and competing stage IV cancer. Targeted therapy was identified through Medicare Part D files. Cox proportional hazards regression determined association between treatment groups, clinical and cancer-related characteristics, and the main outcome, median overall survival (OS). Propensity matching controlled for measurable confounding in treatment selection. Results: Of 1,326 mRCC cases, 528 met inclusion criteria of whom 433 (82%) received targeted agents and 172 (33%) underwent CN. Of those not having CN, 74% were diagnosed by biopsy, 10% by cytology, and 16% radiographically (confirmed at autopsy). Thirteen percent received CN then targeted therapy (OS 14 mos, IQR 9-25), 2.5% received targeted therapy then CN (OS 14 mos, IQR 9-26), 18% received CN only (OS 14 mos, IQR5-40), 67% received targeted therapy only (OS 9 mos, IQR 4-19). On multivariable Cox proportional hazards regression upfront CN (regardless of post-CN therapy) was associated with improved OS (HR 0.54,95% CI 0.41,0.72). Using propensity scores, upfront CN patients (N = 161) were matched to upfront targeted therapy patient (N = 111) and the average treatment effect of CN was 8.3 months survival improvement (95% CI 4.0, 13.2). Conclusions: Although utilization of targeted agents in non-clear cell mRCC exceeds 80%, those with greatest OS received CN either upfront or after targeted therapy, though the latter was rare (2.5%). The variety of sequencing strategies observed is evidence of uncertainty regarding the best care for non-clear cell mRCC patients given limited options.
Treatment of advanced or metastatic hepatocellular cancer (HCC): Interim analysis of a single-arm phase II study of bevacizumab and RAD001.
Authors: G. Treiber
Journal: Journal of Clinical Oncology (2010)

4102 Background: mTOR inhibitors are emerging drugs for treatment (Tx) of advanced hepatocellular cancer (HCC), their therapeutic effects may be potentiated by combination with anti-VEGF partners (Treiber G, Expert Rev Anticancer Ther 2009). Methods: Pts with histologically confirmed advanced HCC are included. Tx consists of RAD001 in a daily start dose of 5 mg orally and bevazicumab 5mg/kg iv every 2 weeks, up to 24 weeks. Primary endpoint is TTP, secondary endpoints are OS, RR, changes in biomarkers, and safety and tolerability besides PK analysis. Pts with either a CPT score > 9, a CLIP score > 3, or a Performance Status of ECOG > 2 are not eligible. Results: As of time of submission, 26/32 pts have been recruited (4 vs. 22 with Child Pugh B vs. A). 9/26 pts went out of the trial prematurely for various reasons (1 consent withdrawl, 3 worsening of performance status, 2 infections, 1 HCC unrelated surgery, 1 thrombocytopenia, 1 with unallowed radiation Tx). 12/17 pts have met their TTP endpoint (median of 76 vs. 146 days on ITT and PP basis). No major responses have been seen so far. Dose adjustements for RAD001 were performed in 38% of pts. There was considerable variation in 16 pts with individual Css min levels of RAD001 at week 1, ranging from 6.9 to 45.1 ng/mL (median 15.3), independently of CPT score. Median levels at week 2, 4, 8, and 12 (including dose modifications) were 11.9, 8.2, 6.6, and 7.25 ng/mL. Over time, 14 vs 47 drug level measurements occured under 2.5 vs. 5 mg/d of RAD 001, resulting in median Css min levels of 5.7 vs. 11.8 ng/mL, p < 0.0001. Conclusions: Combination Tx of RAD001 and bevazicumab is tolerated acceptably. TTP in those patients on active Tx is comparable to sorafenib monotherapy. First data for OS will be available by March 2009. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis
Surgical practice patterns and long-term survival for early-stage rectal cancer.
Authors: Karyn Beth Stitzenberg, Dolly Penn, Hanna Kelly Sanoff, Michael O. Meyers
Journal: Journal of Clinical Oncology (2013)

459 Background: Local excision (LE) is considered a standard option only for patients with T1N0 rectal cancer and those who are medically unfit for proctectomy. The growing numbers of case series suggest that use of LE may be increasing. The objectives of this study are to characterize practice patterns for surgical management of rectal cancer and determine the comparative effectiveness of LE versus proctectomy for overall survival (OS) for Stage I rectal cancer. Methods: National Cancer Database data were used to identify all patients with rectal cancer diagnosed from 1998-2010. Patient and tumor characteristics associated with procedure type were examined. Kaplan-Meier plots and Cox proportional hazards models, controlling for patient and tumor characteristics and receipt of radiation (XRT), were used to compare OS for Stage I cases from 1998-2005. Results: 147,553 (50%) of 296,068 cases were excluded due to prior malignancy, non-invasive disease, distant metastases, failure to receive definitive surgery, treatment indicated to be palliative, or receipt of neoadjuvant therapy. 76,756 (69%) cases were treated with proctectomy and 34,697 (31%) with LE. Use of LE steadily increased from 23% in 1998 to 41% in 2010, p&lt;0.001. LE was most commonly used for Stage I cases. Women, older patients, patients with less comorbidities, black patients, uninsured patients, and those with T1 tumors were more likely to receive LE than other Stage I patients. Socioeconomic status and rurality were not associated with use of LE. Adjuvant XRT was used for 12% of T1 tumors and 46% of T2 tumors after LE and 5% of T1 tumors and 12% of T2 tumors after proctectomy. For patients with T1N0 tumors, adjusted OS was associated with receipt of proctectomy (HR 0.83; 95%CI 0.77, 0.89) but not XRT. For patients with T2N0 tumors, adjusted OS was associated with both proctectomy and XRT: LE only HR 1.0; proctectomy only HR 0.70; LE+XRT HR 0.70; proctectomy+XRT HR 0.70. Conclusions: Use of LE for rectal cancer is increasing. LE alone is associated with poorer long-term OS than proctectomy. For patients with larger tumors, those that receive adjuvant XRT in addition to LE have significantly better OS than those who receive LE alone.
The PI3Kdelta Inhibitor, CAL-101, Inhibits Migration of Primary Pre-B ALL to SDF1alpha: Treatment Implications for Overcoming Cell-Adhesion-Mediated Drug Resistance
Authors: EunJi Gang, Hye Na Kim, Yann Duchartre, Stephanie Nicole Shishido, Sajad Khazal, Etai Adam, Nour Abdel-Azim, Chintan Parekh, Hisham Abdel-Azim, Deepa Bhojwani, Nora Heisterkamp, Alan S. Wayne, Yong-Mi Kim
Journal: Blood (2015)
Postoperative survivin expression in stage III non-small cell lung cancer (NSCLC) patients treated with neoadjuvant chemoradiation.
Authors: M. J. Fidler, S. Basu, K. A. Kaiser-Walters, E. Hadziahmetovic, M. Batus, D. Steker, J. Coon, P. Bonomi
Journal: Journal of Clinical Oncology (2010)

7034 Background: In a previous report, high pretreatment survivin was associated with poor prognosis and low pretreatment survivin was associated with pathological complete response (pCR) in stage III NSCLC patients treated with neoadjuvant chemoradiation (Fidler et al ASCO 2009). The objective of this study was to compare survivin expression in pretreatment tissue with expression in post-treatment in patients with residual tumor after neoadjuvant chemoradiation. Methods: Stage III patients who underwent neoadjuvant platinum based chemoradiation (40Gy) with sufficient pretreatment tissue available were identified. Patients with less than a pathological CR were selected for analysis. Tumors were stained for nuclear and cytoplasmic expression of suvivin (frequency 0-4 and intensity 0-4) by Immunohistochemistry (IHC) (Novus Biologicals). Data was analyzed using the McNemar's test. Results: 33 patients who underwent neoadjuvant chemoradiation had pretreatment tissue with adequate tumor specimens for analysis. 19 patients had available tumor remaining in pathological specimens after definitive resection. Patient characteristics: 10 females, median age 61.4; 11 adenocarcinoma, 6 squamous. For these 19 patients, median OS: 20.0 months, median time to recurrence: 11.7 months. Residual tumors had increased cytoplasmic survivin intensity compared with the same patients' pretreatment specimens (p=0.013). Conclusions: In this small sample size, residual tumor had increased cytoplasmic survivin expression compared with pretreatment tissue specimens suggesting that survivin may be a mechanism for resistance to chemoradiation. Adding agents that target survivin to chemoradiation is a reasonable strategy to improve outcomes in locally advanced NSCLC. These results require validation in a larger number of patients. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly Lilly
Micro-RNAs in stage II colorectal cancer: Is there any role?
Authors: Salem Eid Mohamed, Nasr Mohamed Ali Allahloubi, Abeer Ahmed Bahnassy, Ola Khorshid, Mohamed Elsayed Gadelmola
Journal: Journal of Clinical Oncology (2016)

566 Background: Patients with stage II CRC have a varying survival outcome. Therefore, it is critical to identify new prognostic biomarkers that can help to identify more aggressive forms of the disease. The aim of this study was to identify the potential prognostic value of miRNAs in patients with stage II CRC. Methods: The study included 124 patients with stage II CRC who attended the NCI - Medical Oncology clinics, received treatment and followed-up during the period from January 2004 to December 2014. The expression levels of the five studied miRNAs were examined by qRT-PCR analysis. Additionally, blood samples were drawn from 41 patients recruited in the study in the last 3 years of recruitment to assess the level of miRNAs in blood. Results: In tumor tissues of 124 patients, miR-137, miR-145 and miR-320 were significantly under-expressed in 39.5%, 38.4% and 52.4% of cases, respectively while miR-21 and miR-498 were significantly over-expressed in 48.4% and 40.3%, respectively. On the other hand, assessment of these miRNAs in the blood of 41 cases revealed that miR-137, miR-145 and miR-320 were significantly under-expressed in 46.3%, 46.3% and 51.2% of cases, respectively while miR-21 and miR-498 were significantly over-expressed in 46.3% and 43.9%, respectively. The concordance between tissue and blood was weak with miR-320 and miR-145 (kappa 40-65%), intermediate with miR-498 and miR-137 (kappa 65-75%) while strong concordance has been achieved with miR-21 (kappa 75-85%). Performance status, over-expression of miR-21 and miR-498 and under-expression of miR-137, miR-145, and miR-320 were associated with significantly inferior DFS and OS in univariate analysis. In a multivariate analysis, deregulated miR-498 and miR-320 were independent prognostic factors for worse DFS, while over-expressed miR-498 and miR-21 were found to be independent prognostic factors for inferior OS. Conclusions: MiRNAs play an important role as prognostic markers in stage II CRC patients. Large-scale collaborative efforts are still absolutely essential to aid in determining the clinical potential of miRNAs as diagnostic, prognostic, and predictive biomarkers in CRC in order to achieve better survival outcomes.
Predictive and prognostic value of tumor-infiltrating lymphocytes in breast cancer treated with neoadjuvant chemotherapy.
Authors: Akiko Matsumoto, Hiromitsu Jinno, Kunihiko Hiraiwa, Tetsuya Nakamura, Junichi Saito
Journal: Journal of Clinical Oncology (2015)

128 Background: The prognostic importance of tumor-infiltrating lymphocytes (TILs) in triple-negative (TN) and HER2-positive breast cancer has been suggested in recent trials. The aim of this study is to evaluate a relationship between TILs and response to neoadjuvant chemotherapy (NAC) as well as long-term outcome in breast cancer including luminal, TN and HER2 subtypes. Methods: Twenty-seven patients receiving NAC from January 2010 to March 2015 at Inagi Municipal Hospital were analyzed. Intratumoral lymphocytes (ItuLy) and stromal lymphocytes (StrLy) were evaluated in hematoxylin and eosin-stained sections from pretherapeutic core needle biopsies. Lymphocyte-predominant breast cancer (LPBC) was defined as tumors with &gt; 50% of ItuLy or StrLy. Results: A total of 27 patients were divided into 13 luminal (48.1%), 3 TN (11.1%) and 11 HER2 (40.7%) subtypes. The median age was 58 years and the median tumor size was 3.0 cm. A significant correlation between ItuLy (the median percentage: 5%) and StrLy (25%) was observed (Pearson correlation coefficient = 0.628, P&lt; 0.01). LPBC comprised 29.6% (8/27) of total population, with higher frequencies of 33.3% and 54.5% in the TN and HER2-positive subtypes, when compared with 7.7% in luminal subtype (P= 0.044). LPBC group had a significantly higher pathological complete response (pCR) rate of 62.5% (5/8), compared with 5.3% (1/19) for non-LPBC group (P= 0.004). LPBC showed the modest correlation with pCR in luminal (100% (1/1) vs. 0% (0/12), P= 0.077) and HER2-positive subtypes (66.6% (4/6) vs. 25% (1/5), P= 0.175). In TN subtype, neither LPBC nor non-LPBC showed pCR. After a median follow-up of 24.3 months, patients with any TILs were significantly associated with better disease-free survival (DFS) than those without TILs (24.3 vs. 23.6 months, P= 0.016). The most significant impact of TILs on DFS was observed in HER2-positive subtype (23.2 vs. 15.2 months, P= 0.046), whereas TILs did not associate with DFS in luminal and TN subtypes. Conclusions: The presence of TILs was a significant predictor for response to NAC and would provide useful information of prognosis in breast cancer.
Is the apical margin real? An analysis of postprostatectomy PSA failure by site of involved margin.
Authors: John Morgan Watkins, Michael Laszewski, Mark Rodacker, Patricia L. Watkins, James Kyle Russo
Journal: Journal of Clinical Oncology (2015)

105 Background: Though an involved margin at prostatectomy has been associated with elevated rates of PSA relapse, there has been an absence of consensus regarding the risk of relapse specific to the site(s) of margin involvement. Specifically, the apical margin has been sometimes considered "lower risk," based upon historical series. The present study seeks to determine the rate of PSA relapse in patients who had undergone prostatectomy with involved surgical margin, without immediate post-operative (adjuvant) therapy, with comparison of relapse rates by site of involved margin. Methods: A retrospective database review was performed, including patients with clinically localized prostate cancer and pre-operative PSA &lt;30, who had undergone prostatectomy, with site(s) of involved margin characterized. Slides were re-reviewed by a pathologist for verification of site of margin involvement. Patients were excluded if seminal vesicle invasion or lymph node involvement was noted in the surgical specimen, if any adjuvant therapy was delivered prior to relapse, or if post-operative follow-up with PSA was &lt;12 months. Relapse was defined as &gt;0.2 and rising after prostatectomy. Log-rank analysis was employed for comparison of disease control between groups; the Kaplan-Meier method was employed to construct survival curves and estimate 5-year disease control. Results: Between 2002 and 2010, 155 patients were identified for inclusion in the present analysis. Of these, 105, 37, and 7 patients had 1, 2, and &gt;2 sites of margin involvement, respectively. The apex was the sole site of margin involvement for 70 patients. At a median follow-up of 68 months (range 22-145), 62 patients (40%) had experienced PSA relapse. There was no statistically significant difference in risk of PSA relapse by site of margin involvement or number of foci of margin involvement. The 5-year estimates for PSA relapse for margin involvement of the apex only, other site only, or both were 40.5%, 33%, and 49.1%, respectively. Conclusions: Involvement of the apical margin is associated with a high rate of early PSA relapse, similar to rates noted when other site(s) of margin involvement are noted.
Concurrent chemotherapy and radiotherapy in locally advanced cervical carcinoma (LACC): Anályis of two different radiosensitizer schedules
Authors: D. de Dios, A. Alvarez, G. Cinat, H. Porcella, S. Gianni, A. Gandur Quiroga, V. Cuartero, C. Nicolas, B. Roth, P. Menendez, E. Mickiewicz
Journal: Journal of Clinical Oncology (2005)

5113 Background: Compare, retrospectively, the results in terms of toxicity, clinical overall response, disease free survival (DFS) and survival (S) at 2 years of two different CH schemes: A) Gemcitabine(G) + Cisplatin C vs. B) C alone, both combined with accelerated R, in LACC patients(pts). Methods: 102 pts with LACC, stages(st) II and III, who were treated in our Institution between 4/99 and 12/03. Group(Gr) A (37 pts,st.II, 16 III) received G 20 mg/m2/d twice weekly and C weekly, 30 mg/m2 for 5 weeks.Gr B (26 pts st II and 23 st III) received only C with the same schedule as de former. External R was administered in 23 fractions during 5 weeks(total dose 40–50 Gys) with two brachytherapy insertions at the end of week 3 and 5, giving 85–90 Gys to point A.Both Grs received the same R treatment, and had similar prognostic factors. Results: The median duration of treatment for Gr A was of 41 days(SD:11) vs 48 days for Gr B (SD 27). Haematologic toxicity was most frequently found in Gr A, (35 vs 21pts, p=0.01) with one neutropenia G4; Gastrointestinal toxicity G2/3 was seen in 29/53 in Gr A, and 17/49 in Gr B.Also 1 pt with anemia G4 was seen in the last Gr.No differences were seen between both Gr in relation to treatment interruptions or delays due to toxicity (seen in 5% of the pt).There were no statistical differences in terms of response rate GrA, 46 CR and 1 PR and Gr B 44 CR and 4 PR (88,6% & 97,95% respectively p=0,1) between both Grs.The median follow-up was of 31 months (r: 2–53, P75 22m)for Gr A and 16 months (2–51, P75 38m) in Gr B.DFS at 24 months was 86% in both GRS, with a median DFS of 36 m.Two years S was 84% in Gr A and 79% in Gr B.Median S was 47 m for Gr A and 49 in Gr B(P=0.7). Conclusions: Low dose G plus C in combination with concurrent R could not improve response rate for S, when compared to C alone, in patients with LACC, but had a worse toxicity profile. No significant financial relationships to disclose.
Management of metastatic prostate cancer patients in first line: Audit of real-life practices.
Authors: Anthony Turpin, Laetitia Lemoine, Jean François Berdah, Christophe Massard, Stephane Culine, Eric Bauvin, Nicolas Penel
Journal: Journal of Clinical Oncology (2016)

333 Background: Docetaxel and new hormonal therapies (NHT, abiraterone and enzalutamide) are both appropriate options in management of castration resistant prostate cancer (CRPCa) patients in first line therapy. There is no reliable guidance for choosing the best option. We have carried out an audit of real life practice among French physicians. Methods: We used an online software and built a questionnaire with 22 closed questions. With the help of French regional networks in Oncology and GETUG (Groupe d’étude des tumeurs urogénitales), this questionnaire has been sent to 481 physicians treating patients with CRPCa. All the answers were declarative, individual and, anonymized. The descriptive analysis was based on percentages and their 95% confidence intervals in the case of categorical variables, and the median and extreme values in the case of continuous variables. Results: From March to July 2015, 101 physicians (20,9%) completed the questionnaire: 49 medical oncologists, 29 radiation-oncologists, 21 urological surgeons and two other specialists from 22 French regions. The selection criteria for choosing docetaxel first were: presence of visceral metastases (78.2%), heavy tumour burden (68.3%), aggressive tumour disease (67.3%), short-term efficacy of the castration (65.4%). The selection criteria for the NHT were: long-term efficacy of castration (67.3%), higher age (67.3%), low tumour grade (56.4%) and absence of symptoms (53.5%). Under Docetaxel, 1 st tumour re-assessment was done mainly after 3 (1-6) cycles, this assessment included PSA, thoraco-abdominopelvic CT and bone scintigraphy in respectively 96%, 68% and 58% of cases. Physicians assessed PSA level every cycle in 40.8% of cases and every 3 cycles in 41.8%. Under NHT, tumour reassessment was done mainly after 3 months of treatment (1-6) and included PSA, thoraco-abdominopelvic CT and bone scintigraphy, in respectively, 90%, 58%, and 62% of cases. Physicians assessed PSA level every 3 months in 50.5% of cases and monthly in 29.3%. Conclusions: This is the first descriptive study depicting real-life practice in French physicians treating CRPCa. Practices are heterogeneous. Guidelines for management of CRPCa are needed.
Trends in use of intravenous bisphosphonates in patients with prostate cancer and newly diagnosed metastases to bone in two large U.S. integrated health systems.
Authors: Lois Lamerato, Andrew Glass, Kathryn E. Richert-Boe, John Edelsberg, Greg G. Wolff, Natalie Czapski, Tracy Dodge, Andrea Lopez, Karen Chung, Akshara Richhariya, Gerry Oster
Journal: Journal of Clinical Oncology (2013)

192 Background: Bone is a common site of metastatic involvement in patients (pts) with prostate cancer (PC). Bony metastases (mets) are associated with skeletal complications, which can cause significant morbidity and mortality. Intravenous bisphosphonates (IV BPs) have been proven to reduce the incidence and onset of skeletal complications. Patterns of use of IV BPs in clinical practice in pts with bone mets due to PC are largely unknown. Methods: Using the tumor registries and electronic data stores at two large US integrated health systems that serve a total of approximately 1.3 million persons, we retrospectively identified all pts aged ≥18 yrs with primary PC and newly diagnosed bone mets between 1/1/95 and 12/31/09. Information on all administrations of IV BPs between date of diagnosis of bone mets and death, loss to follow-up, or end of study was extracted from administrative data stores and electronic medical records, which also were reviewed by trained medical abstractors for evidence of skeletal-related events (SREs) (spinal cord compression, pathologic fracture, surgery to bone, radiation to bone). Results: We identified a total of 461 pts with primary PC and newly diagnosed bone mets. Mean (SD) age was 72.8 yrs (10.7 yrs); 75% were Caucasian, and 21% were African-American. Median duration of follow-up after diagnosis of bone mets was 1.3 yrs. One-fifth (20.2%) of study subjects received IV BPs (92% zoledronic acid, 8% pamidronate) during follow-up--10.8% prior to, and 9.3% after, first on-study SRE. Median time from diagnosis of bone mets to first administration of IV BPs was 1.7 yrs, and the median number of administrations was 3. The percentage of study subjects receiving IV BPs increased steadily over the 15-yr study period--from 7.5% among those newly diagnosed with bone mets in 1995-1999, to 19.8% among those newly diagnosed with bone mets in 2000-2004, to 27.5% among those newly diagnosed with bone mets in 2005-2009. Conclusions: Despite a high risk of SREs in pts with PC and bone mets, most such pts still do not receive IV BPs.