tbuckley/cabot-search huggingface dataset:
ARN-509 in men with high-risk nonmetastatic castration-resistant prostate cancer (CRPC).
Authors: Matthew Raymond Smith, Emmanuel S. Antonarakis, Charles J. Ryan, William R. Berry, Neal Shore, Glenn Liu, Joshi J. Alumkal, Celestia S. Higano, Edna Chow Maneval, Dana E. Rathkopf
Journal: Journal of Clinical Oncology (2013)

7 Background: ARN-509 is a novel second-generation anti-androgen that binds directly to the ligand-binding domain of the androgen receptor, impairing nuclear translocation and DNA binding. The Phase II portion of a multicenter Phase I/II study is evaluating the activity of ARN-509 in 3 distinct patient populations of men with CRPC (high risk non-metastatic CRPC, metastatic treatment-naïve CRPC, and progressive disease after abiraterone acetate). Preliminary results for the cohort of patients with high-risk non-metastatic CRPC are presented here. Methods: All patients had CRPC, no radiographic evidence of metastases (pelvic lymph nodes &lt;3 cm below the iliac bifurcation were allowed), and high risk for disease progression based on PSA value ≥ 8 ng/mL within 3 months of enrollment and/or PSA doubling time ≤ 10 months. Patients received ARN-509 at the recommended Phase II dose of 240 mg/day, previously established in Phase I (Rathkopf et al, GU ASCO 2012). The primary endpoint was PSA response rate at 12 weeks according to the Prostate Cancer Working Group 2 Criteria. Secondary endpoints included safety, time to PSA progression and 1-year metastasis-free survival. PSA assessments were collected every 4 weeks and tumor scans were performed every 16 weeks. Results: Forty-seven patients were enrolled between November 2011 and May 2012. The median age was 71 years (range 51 to 88) and at baseline, patients presented with ECOG performance status 0 (77%), Gleason Score 8-10 (32%), and median PSA of 10.7 ng/mL. All patients received prior treatment with a LHRH analog with or without a first-generation anti-androgen. At a median treatment duration of 20 weeks, three patients discontinued the study. The most common treatment-related adverse events (AE) were fatigue (30%), diarrhea (28%), nausea (17%), rash (13%), and abdominal pain (11%). The incidence of Grade 3 AEs was 6.4%, and no seizures have been observed to date. The 12-week PSA response was 91% and the time to PSA progression has not been reached. Conclusions: In men with high-risk non-metastatic CRPC, ARN-509 is safe and well tolerated with promising preliminary activity based on high PSA response rates. Clinical trial information: NCT01171898.
Romiplostim for the treatment of a megakaryocytic thrombocytopenia secondary to remission-inducing immunomodulation in a patient with relapsing acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation.
Authors: L. Volodin, V. K. Bhanderi, J. Shahan, C. Leary, G. Jean, J. Comeau, J. Cotelingam, G. C. Hildebrandt
Journal: Journal of Clinical Oncology (2011)

6609 Background: Amegakaryocytic thrombocytopenia (AmegTP) is a rare immune mediated cause of thrombocytopenia (TP). We report a 57 y.o. woman who developed AmegTP as a result of immune modulation with interferon-α (IFN-α) and GM-CSF for acute B lymphoblastic leukemia (B-ALL) recurrence after allogeneic hematopoietic stem cell transplantation (HSCT). Results: B-ALL relapse was documented on day +71 post HSCT both extramedullary (subcutaneous scalp nodule) and with leukemic cells comprising 10% of bone marrow (BM) cellularity. Donor unavailability did not allow for 2nd HSCT or donor lymphocyte infusion. Immunosuppression was stopped immediately. On day +80, IFN-α (1-3x10E6 units) and GM-CSF (500μg) were commenced three times a week in order to augment graft versus leukemia responses. The nodule resolved within 3 weeks and BM analysis on day +97 showed a hypocellular marrow but no evidence of disease. IFN-α was stopped on day +101 due to pancytopenia. GM-CSF (if ANC <1/nl) and transfusion support were continued. TP persisted and transfusion refractoriness evolved. BM analysis on day +125 confirmed remission with 35% overall cellularity, spotty aplasia and absent megakaryocytes, consistent with AmegTP. A positive ANA screen suggested an immune-mediated cause. The patient received 1 course of high dose methylprednisolone plus IVIG (1g/kg). Parallel, a thrombopoietin receptor agonist (TRA) Romiplostim was started on day +127 at 1μg/kg and then increased by 1μg/kg every 7 days. No platelet transfusions were required after day +181 at a Romiplostim dose level of 8μg/kg, and platelets increased to 54/nl at a max. dose of 10 μg/kg. BM analysis on day +205 confirmed remission with normal myelo- and erythropoiesis and adequate maturing megakaryocytes. Conclusions: The observed supportive effects of Romiplostim on megakaryocyte expansion and proliferation in the context of AmegTP in our patient support the need for further studies on the efficacy and safety of TRAs in the post-HSCT setting.
Defining early-onset kidney cancer: Implications for genetic counseling.
Authors: Brian Shuch, Srinivas Vourganti, Lindsay Middleton, W. Marston Linehan
Journal: Journal of Clinical Oncology (2013)

342 Background: Approximately 1-4% of renal cell carcinoma (RCC) is hereditary. No guidelines exist for patient selection for RCC genetic counseling. We evaluate how age of onset could guide referral for genetic testing. Methods: We analyzed the age distribution of RCC cases in the Surveillance and Epidemiology and End Results (SEER-17) program and from our institutional hereditary kidney cancer population. The age distributions were compared by sex, race, histology, and hereditary syndrome. Models were established to evaluate the specific age thresholds for genetic counseling. Results: The median age of RCC in SEER-17 was 64 years old with the distribution closely approaching normalcy. Statistical differences were observed by race, sex, and subtype (p &lt; 0.05). The bottom decile overall was 46 years of age and slightly differed by sex, race, and histology. The mean and median age of 608 cases of hereditary kidney cancer was 39.3 and 37 years old. While age varied by specific syndrome, 70% of the hereditary cases lied below the bottom age decile. Modeling demonstrated that age alone could limit the number of patients for counseling and that the 10 th percentile maximized sensitivity and specificity. Conclusions: Besides associated clinical manifestations and personal/family history, early age of onset in RCC could be a sign of a hereditary kidney cancer. In the absence of clinical signs, an age of onset ≤46 should trigger referral for genetic counseling and may serve as a useful cutoff when establishing genetic testing guidelines.
A pilot study of an exercise intervention for AML patients undergoing induction chemotherapy.
Authors: S. O'Neill, K. Fisher-Schlombs, H. Breunis, S. N. Culos-Reed, H. D. Klepin, J. Brandwein, G. A. Tomlinson, S. M. H. Alibhai
Journal: Journal of Clinical Oncology (2011)

e19555 Background: Induction chemotherapy (IC) to treat acute myeloid leukaemia (AML) requires 4-5 weeks of hospitalization, leading to deconditioning, declines in quality of life (QOL) and significant fatigue. Four exercise studies have demonstrated improved fitness, strength, QOL, and fatigue in AML patients undergoing IC, but were limited by small sample sizes, recruitment of mostly younger adults and lack of safety data. Objectives: 1) To determine recruitment, retention and participation of AML patients in an exercise intervention during hospitalization for IC; 2) to provide efficacy estimates on physical fitness and QOL outcomes; 3) to examine safety of the exercise program. Methods: Patients presenting with newly diagnosed or relapsed AML scheduled to undergo IC at Princess Margaret Hospital were recruited. Subjects were approached 4-5 days per week to perform 30 minutes of individualized, supervised aerobic and resistance exercises. QOL was measured with the EORTC QLQ-C30 and fatigue with the FACT-F subscale. Fitness measures included VO2max, grip and leg strength, and 6-minute walk test. Outcomes were assessed at baseline and post-induction with descriptive statistics and paired t-tests. Results: Over 6 months, 35 of 47 eligible subjects were enrolled (mean age 56.4 y, SD 12.9). Recruitment was high (74%), retention was excellent (1 drop-out), adherence was very good (80%) and the intervention was safe (1 possible grade II toxicity in 600+ patient-days of follow-up). Preliminary efficacy estimates suggest benefits in QOL and physical fitness outcomes (Table). Conclusions: Exercise is a safe, promising intervention for improving fitness and QOL in AML patients undergoing curative treatment. Next steps are to conduct a randomized phase II trial and to examine impact of exercise on treatment tolerability. Changes in mean (SD) fitness and QOL measures between baseline and 1 month (n=35). Time point Fitness measures Baseline 1 mo P value 6-min walk test (ft) 962.5 (286) 1175.6 (365) 0.012 VO2 max (METS) 6.9 (1.8) 7.2 (1.7) 0.48 Timed 10 chair stands (s) 33.0 (26.0) 27.9 (11.5) 0.46 Grip strength (kg) 23.9 (11.0) 19.9 (11.4) 0.008 Quality of life Global QOL 45.3 (26.7) 49.0 (21.6) 0.31 FACT-F 31.5 (13.1) 32.5 (11.9) 0.35
Role of estrogen-related receptor alpha (ESRRA) in oral squamous cell carcinoma.
Authors: K. S. Gopinath, S. Swamy, A. Nagashri, K. G. Srinivas
Journal: Journal of Clinical Oncology (2011)

e16009 Background: Oral squamous cell carcinoma (OSCC) is one of the most common malignancies world over with one of the lowest rates of survival which has remained unchanged over the past many decades. Given this scenario, it is imperative to identify new therapeutic targets and molecular biomarkers to aid in better estimation of prognosis and treatment. Methods: Oligonucleotide based comparative genomic hybridization (aCGH) analysis in our laboratory has revealed that 3/8 OSCC samples show amplification of the gene ESRRA (estrogen related receptor alpha) located at chromosome 11q13.1. ESRRA is a member of the orphan nuclear receptor super family and is closely related to estrogen receptor (ER) alpha. ESRRA is known to modulate gene expression of a number of genes such as EGFR, VEGF etc. The transcriptional activity of ESRRA is regulated through the EGFR pathway. Recently many reports suggest the potential involvement of ESRRA in several tumors such as breast, prostate and ovarian cancer. Given this scenario, we wanted to study the role of ESRRA in OSCC. Real-time RT-PCR and western blot analyses showed that ESRRA is significantly up-regulated both at the transcript and protein levels in OSCC samples and precancerous lesions. Results: The expression profile of ESRRA is correlated well with aggressiveness of the cancer, suggesting that ESRRA may play an important role in the proliferation and metastasis of cancer. Conclusions: Treatment of cancer cell lines with the specific inhibitor XCT790 of ESRRA showed a significant decrease in cell viability. Treating the cells with XCT790 has provided an important insight into the unique interaction between ESRRA and EGFR which is a specific target of ESRRA. These preliminary results suggest that ESRRA might have a potential involvement in the progression of OSCC. This work is financially supported by CSIR and DBT, New Delhi.
Weekly paclitaxel (P) in patients with advanced non-small cell lung cancer (NSCLC)
Authors: K. Nakagawa, M. Fukuoka, N. Saijo
Journal: Journal of Clinical Oncology (2005)

7336 Background: Weekly schedule of P administration (WP) has already been extensively used especially for breast cancer due to its mild toxicity profile with the better feasibility than conventional tri weekly schedule of P administration.(TP). The present study was conducted to evalutate that WP may produce the same efficacy or toxicity profile for NSCLC as well as breast cancer. Patients and Methods: A single arm phase II study of WP was conducted to evaluate efficacy and safety in patients with advanced NSCLC. The present results were historically compared with the previous data of TP in the same trial group in Japan. Eligibility included < 75 years old, histologically or cytologically proven NSCLC, stage IIIB or IV, chemotherapy naive, and performance status (PS) of 0 to 2. Patients received Paclitaxel 100mg/sqm per week for 6 consecutive weeks followed by 1 week treatment off (1 course includes 7 weeks). On the other hand, patients in the historical TP group received P 210mg/sqm in every 3-weeks and continued > 3 cycles without tumor progression or severe toxicity. Results: From December 2002 to November 2004, 53 pts were eligible among 54 enrolled into the present study. All were previously untreated. Median age was 66 years (range 45–74 years), and thirty-six pts (66.7%) were male. Forty-five pts (88.7%) were stage IV disease and fifty pts (92.6%) were good PS of 0–1. Histological backgrounds are: Adenocarcinoma(Ad): 37pts (68.5%), Squamous Cell Carcinoma(Sq): 12pts (22.2%), and Large Cell Carcinoma: 4 pts (7.4%). Eighteen pts achieved partial response (PR) in RECIST criteria with 34.0% of response rate (RR), which is almost similar to RR in the historical TP group (42 of 120 pts, 35% of RR). To date, 23 of 53 pts in the present study have been analyzed for toxicity by the interim evaluation committee. Significantly low frequency of grade 3–4 neutropenia (26.1%) was observed in WP as compared with TP (26.1 vs. 77.5%, p<0.001). Other major toxicities including peripheral neuropathy (PNP) seemed to be almost same between the two groups (all grade PNP: P and TP group; 68.9% and 70.8%, respectively). Conclusion: WP may result in the same efficacy with mild toxicity as TP in patients with advanced NSCLC. No significant financial relationships to disclose.
Association between chronic myeloid leukemia (CML) treatment responses and patient satisfaction, functioning, and quality of life (QOL): Patient survey results.
Authors: S. Goldberg, V. K. Bollu, R. Morlock, A. Niyazov, A. Guo, E. Jabbour
Journal: Journal of Clinical Oncology (2011)

6614 Background: Clinical trials have shown that newer tyrosine kinase inhibitors provide higher rates of molecular responses in CML patients. This study assessed patient’s awareness of CML treatment response categorizations and the association between treatment responses and satisfaction, functioning, and QOL. Methods: CML patients were invited to participate in an online survey through the Association for Cancer Online Resources. Respondents answered questions on demographics, CML disease history, and awareness of treatment responses. Current health status information was collected using a 5-item Likert scale question and a health status thermometer. Chi-square, Fisher’s test, and multivariate regressions were used for statistical comparisons. Results: Overall, 123 patients responded to the survey. The mean age was 63 years (range 20-86), 49% were male, and 96% had some level of college experience. Nearly all respondents reported to be currently in complete hematological response, 71% in complete cytogenetic response (CCyR) and 68% in major molecular response (MMR). The median duration of CML diagnosis was 8 years. In this well-educated population, 90% of patients were aware of the different CML treatment response categories. However, 71.5% of respondents felt CML patients need more information on the types of responses, with the desire for information to come from their physicians (67%) versus other staff (28%) or pamphlets (24%). Respondents indicated that achieving MMR generates the greatest improvement in daily functioning (86%), satisfaction with medication (87%), satisfaction with physician (79%), and outlook on life (86%). Patients achieving MMR had higher overall self- reported health status versus patients in CCyR (P = 0.032). Conclusions: From a patient’s perspective, achievement of MMR is an important milestone associated with improved satisfaction with their physician, medication, daily functioning, and outlook on life. Respondents in MMR reported higher overall self-reported health status. Additional research is needed to assess the best ways to help patients understand different response categories.
The outcome of preoperative chemotherapy followed by surgery and upfront surgery for liver metastases from colorectal cancer.
Authors: Jung Sun Kim, Sunyoung Kim, Hye Jeong Cho, Eun Kyung Shim, Jae Hwan Oh, Dae Yong Kim, Sung-Sik Han, Seoung Hoon Kim, Sang Jae Park, Ji Yeon Baek
Journal: Journal of Clinical Oncology (2013)

516 Background: Hepatic metastasectomy is the only curative option for patients (pts) with colorectal liver metastases (CRLM) but the optimal sequence of surgery and chemotherapy has not been established. We evaluated disease-free survival (DFS) in pts who were treated with difference sequences for resectable CRLM. Methods: Pts who had radiologically diagnosed with CRLM and underwent preoperative chemotherapy (preopCT) followed by surgery or upfront hepatic resection from Jan 2008 to Dec 2010, in National Cancer Center, Korea, were identified and their medical records were reviewed. Pts with number of metastatic nodules (mets) less than 6, and who were untreated for metastastic setting were analyzed. Those with tumor invasion of major intrahepatic vessels, extrahepatic metastases, or combined other advanced cancer were excluded. Results: Of 208 pts who underwent hepatic metastasectomy for suspicious CRLM, 123 pts who fulfilled the above criteria were analyzed. 34 (28%) pts received preopCT followed by surgery and 89 (72%) pts underwent upfront surgery. Postoperative chemotherapy was administered for 34 (100%) of preopCT group and 73 (82%) of upfront surgery group. Number of mets, baseline tumor marker levels, and R0 resection rate were similar between the two groups. But, early relapse was more in upfront surgery group. DFS at 3 year was 14% (95% CI 29%-34%) in preopCT group and 48% (95% CI 36%-59%) in upfront surgery group. In multivariate analysis, age &gt; 65, Charlson comorbidity index &gt; 0, mets≥3, and R1/R2 resection were significantly associated with increased risk for DFS events, while PreopCT was marginally associated with adverse outcome (Table). Conclusions: Upfront surgery, rather than preoperative chemotherapy followed by surgery, might be a favorable treatment option for resectable CRLM in terms of DFS. [Table: see text]
Overall survival (OS) of sorafenib (So) plus interleukin-2 (IL-2) versus So alone in patients with treatment-naive metastatic renal cell carcinoma (mRCC): Final update of the ROSORC trial.
Authors: Giuseppe Procopio, Elena Verzoni, Sergio Bracarda, Sergio Ricci, Laura Ridolfi, Cosimo Sacco, Rosalba Miceli, Camillo Porta, Marco Bregni, Emilio Bajetta
Journal: Journal of Clinical Oncology (2013)

356 Background: A randomized phase II trial evaluating So plus IL-2 versus So alone as first-line treatment of mRCC, did not show any difference in progression-free survival (PFS) (primary endpoint) between the two groups. The final overall survival analysis is here reported. Methods: In this open-label phase II study, 128 patients with mRCC were randomized to receive either oral So 400 mg bid continuous dosing plus IL-2 4.5 MIU subcutaneously administered 5 times weekly for 6 weeks every 8 weeks (Arm A), or So alone (Arm B). At relapse, most patients of the two arms underwent treatment with other targeted therapies (TTs) including sunitinib, everolimus, and axitinib. Overall survival was estimated by Kaplan-Meier method and compared by two-sided log-rank test. Results: According to Motzer criteria 55 % of the patients were low risk in both arms, and 41% and 39% were intermediate risk in Arm A and B respectively. After a median follow-up time of 58 months (interquartile range: 28-63 months), the median OS was 38 and 33 months in Arm A and B, respectively (p = 0.667). Five-year OS was 26.3% (95% CI: 15.9-43.5) for the combination arm and 23.1% (95% CI: 13.2-40.5) for single agent arm. The overall number of death was 85, 42 of whom in the So monotherapy group. Median PFS survival was 7.3 and 6.9 months for Arm A and B, respectively (p = 0.109). Overall, 49 (77%) and 48 (75%) patients in Arm A and B, respectively, received at least one subsequent targeted therapy (TTs). The most common adverse events (AEs) in both arms were asthenia, hand-foot syndrome, hypertension and diarrhoea. Grade 3-4 AEs were documented in 38% of patients treated with the combination regimen and in 25% of those undergoing single agent treatment. Conclusions: The OS results suggest an improved outcome in patients with mRCC treated with TTs which appears independent of the treatment initially administered. This prospective study, regarding use of sorafenib in first line of treatment, was associated with a surprising median OS. Clinical trial information: NCT00609401.
Factors associated with local control in inflammatory breast cancer.
Authors: Lindsay C. Brown, Miran J. Blanchard, Nadia N. Laack
Journal: Journal of Clinical Oncology (2012)

126 Background: Inflammatory breast cancer (IBC) is an aggressive breast cancer variant, with 5-yr overall survival (OS) typically reported at 40-45%. We recently presented our results with once-daily radiotherapy (RT) as a component of trimodality therapy, with 5-yr OS of 64%. Herein we report patient and treatment factors associated with locoregional control (LRC). Methods: With permission of the IRB, review of medical records at the Mayo Clinic in Rochester, MN was performed to identify patients treated with RT for IBC from 2000-2010. Patients with non-metastatic, clinically diagnosed IBC were included. OS, LRC and distant metastasis-free survival (DMFS) were assessed using the Kaplan-Meier method. First recurrence in the chest wall or regional lymph nodes was defined as a locoregional recurrence (LRR). Results: 52 women were included in the analysis. Median age at diagnosis was 54 years (range 23-83). Median follow-up for the population was 3.6 years (range 0.7 – 11.9). All patients were treated with adjuvant RT to the chest wall and draining nodal basins in once-daily fractions of 1.8-2.25 Gy (median 2 Gy), to a median of 50 Gy (range 46-60 Gy). Actuarial 5-yr LRC was 85%. LRR was associated with poorer DMFS and OS (p &lt; 0.01). Factors significantly associated with improved LRC included lack of extracapsular extension (ECE) and use of adjuvant chemotherapy (p &lt; 0.05). Factors associated with a trend towards LRC included use of bolus, absence of boost, node negativity at time of surgery and pathologic complete response (pCR). Daily bolus was employed in 90% of patients and was most commonly (68%) 1 cm in thickness. There was a trend towards improved 5-yr LRC when bolus ≥ 1 cm was employed daily (93% v. 67%, p = 0.06). Patients who received a boost to the mastectomy scar (62% of the population, median of 10 Gy, range 10-16 Gy) had poorer LRC (78% v. 100%, p = 0.08), but superior 5-yr DMFS (78% v. 34%, p = 0.035) and OS (77% v. 34%, p = 0.04). Conclusions: LRC is associated with improved OS in IBC. Lack of ECE and use of adjuvant chemotherapy are associated with improved LRC in women with IBC. Node negativity, pCR and use of daily bolus ≥1 cm in thickness are associated with a trend towards improved LRC. The impact of boost requires further analysis.