tbuckley/cabot-search huggingface dataset:
Phase I trial of molecularly targeted, radiolabeled somatostatin analog in children and young adults with recurrent or progressive solid tumors
Authors: M. S. O’Dorisio, S. Michael, Y. Menda, D. Bushnell, M. Madsen, G. Khanna, M. Connally, J. W. Babich, T. M. O’Dorisio
Journal: Journal of Clinical Oncology (2008)

10029 Background: Somatostatin receptors are highly expressed in several pediatric solid tumors, including neuroblastoma, medulloblastoma and neuroendocrine tumors. We hypothesize that molecularly targeted somatostatin analog, 90Y-DOTA- tyr3-Octreotide which binds with high affinity to somatostatin receptor type 2 (sst2), will be an effective therapy for pediatric malignancies that express sst2. Methods: A Phase I, dose/toxicity trial of 90Y-DOTA-tyr3-Octreotide was conducted at 30 (cohort 1), 40 (cohort2), and 50 (cohort 3) mCi/m2 with concomitant Aminosyn II infusion. Subjects received 3 cycles of treatment, 6 weeks apart. Eligibility criteria included: recurrent or progressive malignancy with at least one Octreoscan positive lesion; age 2–25 yrs; bone marrow cellularity >40%; GFR >80 ml/min/m2; no radiation therapy for 3 months; no chemotherapy for 30 days. Escalation was based on 3/3 or 4/6 subjects with no dose limiting toxicity. Additionally, subjects were limited to <21Gy calculated radiation dose to kidneys, including any previous external beam radiotherapy received prior to 90Y-DOTA-tyr3- Octreotide dosing. Results: Twelve subjects completed 3 cycles (5, 3 and 4 subjects in cohorts 1,2, 3, respectively). Diagnoses included gastrinoma (3), foregut carcinoid (3), neuroblastoma (2), paraganglioma (2), MENIIb, and anaplastic astrocytoma. Five subjects (38%) had a PR (>50% decrease in target lesion); four subjects had a positive response (>25%<50% decrease in target lesion); three subjects had stable disease for > 4 months; seven subjects remain alive without progression 2 months to 3.5 years after completion of therapy. Four subjects withdrew from the study after one cycle and had progressive disease within 6 weeks. No dose limiting toxicities were observed; specifically, no Grade III or greater renal or hematologic toxicity was observed. Conclusions: Based on intent to treat, 53% of children and young adults with recurrent, sst2 positive tumor had a positive response to 90Y-DOTA-tyr3- Octreotide. PR was obtained in at least one subject at each dose level. No dose limiting toxicities were observed with 50 mCi/m2, the recommended dose for Phase II studies. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Molecular Insight Pharmaceuticals Milecular Insight Pharmaceuticals, Novartis Pharmaceuticals, Inc. Molecular Insight Pharmaceuticals
Quantification of the impact of multifaceted improvements in patient safety culture: A case study from academic medical center radiation oncology department.
Authors: Bhishamjit S. Chera, Lukasz Maszur, Prithima Mosaly, Marianne Jackson, Kinely Taylor, Katharin Burkhardt, Sha Chang, Dana LaChapelle, John Rockwell, Seth Miller, Timothy Zagar, Ellen Jones, Jessica A. Church, Robert D. Adams, Lawrence Bruce Marks
Journal: Journal of Clinical Oncology (2012)

205 Background: We have systematically been incorporating several safety initiatives (based on process-engineering and Lean methodologies) into our academic radiation oncology clinic. We herein quantify the impact of these initiatives on prospectively collected, clinically meaningful metrics. Methods: The data from five quality improvement initiatives are presented. For each, data was collected prospectively: operational metrics recorded before and after implementation of the initiative were compared using descriptive statistics and unpaired student t-test. Each initiative focused on a specific safety/process concern in our clinic. Results: 1) Workload levels for nurses assisting with brachytherapy were too high (NASA task load index scores &gt;55-60, suggesting, “overwork”). Changes in work flow and procedure room layout reduced workload scores to more acceptable limits (&lt;55). 2) The rate of treatment therapists being interrupted was reduced from a mean of 4 (range 1-11) times per patient treatment to a mean &lt; 1 (range 0-3, p&lt;0.001) after implementing standards for electronic communication and placement of monitors informing patients and staff of the treatment machine status (e.g., delayed, on time). 3) The rates of replans by dosimetrists was reduced from 11% in 2010 to 6% in 2011 though a more systematic pre-treatment peer review process. 4) Standardizing nursing/resident functions reduced patient wait times by ≈ 45% (14 min). 5) Standardizing pre-simulation instructions from the physician within the EMR reduced the number of patients experiencing delays on the simulator (from approximatley &gt;50% to &lt;10%). Conclusions: Process engineering and Lean methodologies can be successfully applied in an academic radiation oncology department to yield measurable improvements in operations likely improving quality/safety.
Safety and Efficacy of Bortezomib (VELCADE™) in 104 Patients with Relapsed and/or Refractory Multiple Myeloma Who Have Received at Least Two Previous Lines of Therapy: Impact of Cytogenetics on Response from a Canadian Cohort.
Authors: Joseph R. Mikhael, Donna E. Reece, Andrew Belch, Nizar J. Bahlis, Deepa Sharma
Journal: Blood (2006)
Effect of surgeon education on lymphadenectomy in colon cancer.
Authors: S. E. Young, A. L. Cohn, G. Sellers, J. M. Gomez, H. Shapiro, K. Birdsey, A. Spaulding
Journal: Journal of Clinical Oncology (2011)

423 Background: The most important determinant of prognosis for localized colon cancer is metastatic lymph node involvement. The American Joint Commission on Cancer and the College of American Pathologists have recommended examination ≥ 12 lymph nodes to ensure adequate staging. We hypothesized that surgeon education would improve the extent of lymphadenectomy in patients being treated for colon cancer. A large community based metropolitan health care system served as a model for testing this hypothesis. Methods: 906 patients comprising AJCC stage I (n=265), stage II (n=304), and stage III (n=337) colon cancers were evaluated. Surgical approach was either open (n=567), laparoscopic (n=310), or unknown (n=29). Lymphadenectomy results obtained from post-operative pathology reports were tracked across four separate time periods: era 1 (1/1/02-1/31/04), era 2 (1/1/05-1/31/06), and era 3 (1/1/07-1/31/07). Results were then compared against a study endpoint measurement of 2008, era four. Results: Upon analysis and comparison of individual era results, a significant improvement in lymphadenectomy (percentage of patients with ≥12 nodes harvested) was noted for all AJCC stages (p-values compare era 4 versus era 1): I (34.2% vs. 59% vs. 65% vs. 69%, P=0.0001), II (62% vs. 76% vs. 90% vs. 91%, P=0.0004), and III (55% vs. 72% vs. 84% vs. 86%, P&lt;0.0001; see table). Surgical approach was not a significant factor. Neither age nor sex was significant. Conclusions: Through physician education, we were able to increase awareness of optimal staging practice for lymphadenectomy in colon cancer. This resulted in significantly improved patient outcomes within a large metropolitan health care system. No significant financial relationships to disclose.
Single-institution experience comparing double-barreled wet colostomy to ileal conduit for urinary and fecal diversion.
Authors: R. J. Chokshi, M. P. Kuhrt, D. Arrese, L. Parks, M. Johnson, E. W. Martin
Journal: Journal of Clinical Oncology (2011)

542 Background: Patients with advanced primary or recurrent colorectal cancers that undergo total pelvic exenteration for cure or palliation require proximal urinary and fecal diversion. The most commonly used diversion technique is use of an ileal conduit (IC) and end colostomy. At our institute, the double-barreled wet colostomy (DBWC) has been shown to be have similar outcomes and technically feasible. Methods: Between 2004 and 2010, 37 patients underwent total pelvic exenteration for advanced primary or recurrent colorectal cancer. Two groups were identified based on the technique used for their urinary diversion, either by way of an IC (n = 4) or DBWC (n = 33). Demographics, periprocedural events, and outcomes were compared between the two groups. Results: The two groups were similar in the terms of age, gender, and comorbidities. Thirty-three patients (89%) underwent a DBWC and four patients (11%) underwent an IC. All of these patients underwent a total pelvic exenteration for advanced primary (27%) or recurrent colorectal cancer (73%) either for cure or for palliation. Twenty patients underwent R0 resection (54%), and 17 patients had non-R0 resection (46%). Complications, length of stay, and operative times between both groups were similar. Median survival for both groups showed no statistical difference. Conclusions: DBWC is a safe and feasible alternative to the traditional ileal conduit for urinary diversion. It provides a single stoma to care for, and an intact contralateral abdominal muscle to use as a vertical rectus abdominus musculocutaneous flap for reconstruction. This technique is easy to learn and is not associated with higher operative times, length of stay, morbidity, or mortality. [Table: see text] No significant financial relationships to disclose.
Neoadjuvant chemotherapy (NACT) in hormone receptor-positive (HR+) or triple-negative (TN) operable breast cancer (BC): A randomized study comparing standard to response–adapted sequence.
Authors: H. Cure, Q. Wang-Lopez, M. Mouret-Reynier, X. Durando, C. Jouannaud, J. Charpentier, J. Eymard, P. J. M. Chollet, C. Garbar, E. Brabencova, I. Raoelfils, F. Penault-Llorca, J. Nabholtz
Journal: Journal of Clinical Oncology (2011)

1133 Background: Achieving pathologic complete response (pCR) is the main goal in NACT. PCR rates will be studied comparatively for stage II-IIIA operable breast cancer in 264 women, randomized to receive either 3 FEC 100 then 3 docetaxel 100 mg/m2 (standard arm A) or adapted arm B beginning with 2 FEC 100. Docetaxel will be given if tumor size decreased by less than 30 or 50 percent after 2 or 4 FEC 100, respectively; otherwise FEC100 was given for 6 courses before surgery. A new classification will assess the limited residual disease in breast and nodes (LRDBN) when obtained. Methods: 140 patients, all Her 2 negative with or without HR on microbiopsies, have been randomized to date with a median age of 52 years. They were repartited according to 2 tumour phenotypes : Her2-HR+ (luminal phenotype) and Her2-HR- (TN). 107 patients post NACT were operated. Pathological response was analyzed in 98 BC (77 Luminal; 18 TN) according to: Chevallier’s (Am J Clin oncol 1993), Sataloff’s (J Am Coll Surg 1995) and Residual Disease in Breast and Nodes’s (RDBN) (Cancer J 2008) classifications. A retrospective analysis of pathology was carried out in 41 patients, who had a small residual tumor, in order to assess the “new pCR” named LRDBN, reached when 4 criterias were met: Ki 67(<5%), tumor surface residual vs initial (<5%), large tumoral fibrosis/elastosis and node metastasis (≤2mm). Results: We realized an intermediate analysis in the luminal phenotype, objective response rate was 45% in arm A versus 50% in arm B. The pCR rate was 7.5% vs 5 % for Chevallier (1 + 2 classes); 7.5% vs 12.5% for Sataloff (TANA + TANB); 2.5% both for RDBN (Class 1). 15% vs 20% patients achieved pCR in arm A and B with LRDBN. In TN subgroup, objective response rate globally was 83% and 11% for complete response; pCR global rate was 50 / 56 / 39 / 50% for Chevallier / Sataloff / RDBN / LRDBN, respectively. Conclusions: TN tumors responded better to NACT based on FEC 100 / docetaxel with a higher pCR rate than luminal phenotype. There was a tendancy to improvement of response and pCR in favor of arm B. Trial must go on to reach its final goal.
The Prognostic Utility of the Current Risk Models in Predicting Outcomes of Patients (pts) with Higher-Risk Myelodysplastic Syndromes (HR-MDS) Treated with Hypomethylating Agents (HMA)
Authors: Amer M. Zeidan, Mikkael A. Sekeres, Guillermo Garcia-Manero, John Barnard, Najla H Al Ali, Cassie Zimmerman, Gail J. Roboz, David P. Steensma, Amy E. DeZern, Elias Jabbour, Hagop Kantarjian, Katrina Zell, Quiqing Wang, Steven D Gore, Aziz Nazha, Jaroslaw P. Maciejewski, Alan F. List, Rami S Komrokji
Journal: Blood (2014)
Neoadjuvant intensity-modulated radiotherapy (IMRT) in pancreatic adenocarcinoma: The Dartmouth experience.
Authors: M. Palmeri, J. M. Pipas, G. H. Ripple, M. McGowan, K. D. Smith, B. I. Zaki
Journal: Journal of Clinical Oncology (2011)

274 Background: Neoadjuvant chemoradiation may play a role in improving the resectability and overall survival (OS) of patients with pancreatic adenocarcinoma. IMRT allows higher radiation doses to regions within a tumor while minimizing the dose to surrounding normal structures. Methods: Eighty-one patients with pancreatic adenocarcinoma completed neoadjuvant IMRT from 2003-2008. All were staged by CT scan, endoscopic ultrasound and laparoscopy. Based on defined resectability criteria, 14 were resectable (R), 38 considered borderline resectable (B) and 29 unresectable (U). Patients were categorized into 3 groups based on their neoadjuvant treatment. All patients received concurrent IMRT with gemcitabine (50mg/m 2 ) twice weekly for 12 doses. IMRT prescription dose was 54 Gy in 28 fractions with a biologically effective dose of 64.47Gy 10 . All resected patients received intra-operative radiation (mean dose 14 Gy). Group 1 received neoadjuvant chemotherapy involving gemcitabine and docetaxel on days 1, 15, and 29 followed by IMRT. Group 2 received concurrent weekly cetuximab in addition to bi-weekly gemcitabine and IMRT. Group 3 received only concurrent gemcitabine twice weekly and IMRT. Four weeks after treatment completion, patients were evaluated with a CT scan in preparation for surgery. Results: Median OS for all patients was 22 months. The overall resectability rate after neoadjuvant IMRT was 63%. 78% of B and 39% of U patients underwent resection. 80% of all patients had an R0 resection. Median OS was 23 months for R, 28 months for B and 14 months for U patients (P = 0.002). Median OS was 18 months, 27 months and 18 months respectively for patients receiving gemcitabine-IMRT, gemcitabine-cetuximab and neoadjuvant gemcitabine/docetaxel plus concurrent gemcitabine-IMRT (P = 0.20). Median OS for R0 resections were 28 months compared to 24.3 months for patients with positive margins and 11.7 months for unresectable patients (P &lt; 0.001). Conclusions: IMRT as part of a neoadjuvant treatment strategy for pancreatic adenocarcinoma is feasible and well tolerated. Neoadjuvant IMRT rendered a significant percentage of B patients resectable with an OS comparable to patients who were R at presentation. [Table: see text]
Examination of 12-lipoxygenase (12-LOX) as a therapeutic target in non-small cell lung cancer (NSCLC): Mechanisms controlling survival and induction of apoptosis following selective inhibition.
Authors: M. Cathcart, V. Campbell, K. Gately, E. Kay, G. P. Pidgeon, K. J. O'Byrne
Journal: Journal of Clinical Oncology (2011)

7068 Background: Platelet-type 12-LOX is an arachidonic acid metabolising enzyme resulting in the formation of 12(S)-HETE, which stimulates tumour cell adhesion, invasion and metastasis. This study aimed to examine the expression profile and role of this enzyme in NSCLC, and determine if it is a potential target for intervention. Methods: A panel of retrospective resected lung tumours was stained for 12-LOX expression by IHC. Levels of the 12-LOX metabolite, 12(S)-HETE, were examined in 50 NSCLC serum samples, and correlated with serum VEGF. A panel of NSCLC cell lines were treated with baicalein (10 uM), a selective inhibitor of 12-LOX, or 12(S)-HETE (100 ng/ml) and cell survival/proliferation examined by BrdU. Apoptosis following 12-LOX inhibition was examined by HCS and validated by FACS and DNA laddering. The effect of 12-LOX inhibition on NSCLC tumour growth and survival was examined in-vivo using an athymic nude mouse model. Gene alterations following 12-LOX inhibition in NSCLC cell lines were assessed by qPCR arrays and validated by RT-PCR. Transient transfection methods were used to examine the effects of 12-LOX overexpression in NSCLC cells. Results: 12-LOX expression was observed to a varying degree in human lung cancers of varying histological subtypes. 12(S)-HETE levels were correlated (p<0.05) with those of VEGF. Baicalein inhibited proliferation/survival in all cell lines, while 12(S)-HETE increased proliferation. 12-LOX inhibition increased apoptosis, indicated by a reduction in f-actin content and mitochondrial mass potential. Treatment with baicalein significantly reduced the growth of NSCLC tumours and increased overall survival in athymic nude mice. qPCR array data implicated a number of apoptosis/angiogenesis genes regulating these effects, including bcl-2, VEGF, integrin A2 and A4. 12-LOX overexpression resulted in an increase in VEGF secretion, confirming qPCR observations. Conclusions: 12-LOX is a survival factor/potential target in NSCLC, and correlated with angiogenic factor expression. Selective 12-LOX targeting may have clinical benefit for the future treatment.
Sunitinib and pazopanib treatment patterns and cost outcomes in Medicare supplemental-covered patients with renal cell carcinoma.
Authors: James Harnett, Elizabeth A. MacLean, Helen Bhattacharyya, Laura A. Cisar, Caroline Hoang, Jack Mardekian
Journal: Journal of Clinical Oncology (2015)

485 Background: Few studies compare targeted treatments for renal cell carcinoma (RCC) so understanding real world treatment patterns and healthcare utilization may inform decision making. This study evaluated treatment naïve RCC patients initiating sunitinib (SUN) or pazopanib (PAZ) and the potential impact of administration schedules on duration of therapy (persistence) assessments using claims data. Methods: This retrospective cohort analysis used de-identified Truven Marketscan Medicare Supplemental claims data. Included patients were ≥20 years, diagnosed with RCC with ≥1 prescription (Rx) for SUN or PAZ between Oct. 2009–Sept. 2013 and continuously enrolled ≥6 months prior to and 12 months after index. Patient characteristics, treatment patterns, persistence, RCC-related and all-cause costs were evaluated. Chi-square, Student t-test, or Wilcoxon signed-rank test were used to compare groups (α=0.05). A generalized linear model was used to evaluate costs controlling for patient demographics and characteristics, index medication dose, persistence and index medication. As the recommendation for most patients receiving SUN is 4 weeks on, 2 weeks off, a sensitivity analysis was conducted imputing 42 days supply (DS) for SUN Rx with 28 or 30 DS. Results: 291 patients initiated SUN (76.6%) and PAZ (23.4%). There were no significant (NS) differences between groups in demographics, Charlson Comorbidity Index scores, or proportion with pre-index inpatient admission. Mean time from earliest RCC diagnosis to index was longer for PAZ compared to SUN (518 vs. 398 days, p&lt;0.05). There was NS difference in mean persistence in the non-imputed (154 vs. 175 days, p=0.20) and imputed DS (182 vs. 175, p=0.69) analyses for SUN and PAZ, respectively. Adjusted mean RCC-related ($65,993 vs. $65,254, p=0.68) and all-cause ($92,121 vs. 87,962, p=0.18) costs were NS different between SUN and PAZ cohorts, respectively. Conclusions: This analysis indicates NS differences in treatment persistence or costs for Medicare Supplemental patients with RCC initiating SUN or PAZ. Understanding the implications of SUN’s dosing schedule on DS values for persistence and other calculations is critical.
Comparison of oncologic outcomes following systemic neoadjuvant chemotherapy and radical cystectomy in patients with mixed histologic variants and pure urothelial carcinoma of the bladder.
Authors: Einar Freyr Sverrisson, Patrick Espiritu, Timothy Kim, Shilpa Gupta, Michael Adam Poch, Philippe E. Spiess, Julio Pow-Sang, Wade Jeffers Sexton
Journal: Journal of Clinical Oncology (2014)

333 Background: Neoadjuvant chemotherapy (CT) is recommended prior to radical cystectomy (RC) in patients with muscle invasive urothelial carcinoma of the bladder (UCB), and has been shown to have modest survival benefit in clinical trials. The purpose of our study was to investigate the response and survival rates in patients with histologic variants (HV) and compare oncologic outcomes to patients with pure UCB. Methods: We performed a retrospective review of 163 patients treated with neoadjuvant CT prior to RC. Twenty-four patients with HV and 139 with pure UCB were identified. Numerous patient demographics, clinical and pathologic characteristics were evaluated including; clinical and pathologic stage, HV, lymphovascular invasion (LVI), margin status, node counts, concomitant carcinoma in situ (CIS), previous intravesical treatments, prior pelvic radiation, completeness of bladder tumor resection (TURBT), and CT regimens. Results: Patients with HV were younger (66.5 versus 71 years, p=0.04) but otherwise there were no significant differences noted between the two groups comparing previous treatments, clinical staging, margin status, node counts, CT regimens, # of neoadjuvant CT cycles, or rates of adjuvant CT administration. Of the 24 HV patients, 11 (47.8%) were downstaged to &lt; pT2 compared to 50 (64.1%) of 139 patients with pure UCB (P=0.37). pT0 rates for HV and pure UCB were 16.7% and 23%, respectively (p=0.60). Twelve (50%) of the HV group compared to 65 (46.8%) of the pure UCB patients (p=0.83), had no evidence of disease at a mean follow up after RC of 19.5 (HV) and 22 (UCB) months. Eight (33.3%) patients with HV died of disease compared to 44 (31.7%) in the UCB group, (p=1.0). There was no significant difference noted in CSS and OS between the 2 groups, although there was a trend towards higher rates of node positive disease (p=0.086) and inferior CSS (p=0.09) in patients with HV compared to patients with pure UCB. Conclusions: Our results indicate that patients with HV experience similar oncologic outcomes from neoadjuvant systemic CT compared to patients with pure UCB.
A prognostic examination of the chemotherapeutic selection for pancreatic cancer patients with peritoneal dissemination: A retrospective study from a single center.
Authors: Ryoji Takada, Tatsuya Ioka, Hironari Sueyoshi, Nobuko Ishida, Takuo Yamai, Nobuyasu Fukutake, Reiko Ashida, Kazuhiro Katayama
Journal: Journal of Clinical Oncology (2014)

331 Background: Pancreatic cancer(PC) patients(pts) with peritoneal dissemination are poor prognosis. This retrospective study evaluated the prognosis of Gemcitabine(GEM)-based current chemotherapy(G), GEM plus S-1 combination therapy(GS) and single agent of S-1 as 1 st line chemotherapy regimen in PC pts with peritoneal dissemination. Methods: This is a retrospective study of PC pts with ascites or peritoneal nodules in the CT or US image who underwent chemotherapy between 2002 and 2011. We collected data on age, sex, Performance Status(PS), tumor location, other metastasis location, status of peritoneal dissemination, CA19-9, CEA, albumin, CRP. We classified 1 st line chemotherapy regimen in G, GS and S-1, and we evaluated 1-year survival rate, progression free survival(PFS), overall survival(OS) for the 3 regimens. Results: A total of 81 pts were included. Median age were 64 (38-78), males 50%, PS 0-1 89%. The number of pts treated with G, GS, S-1 was 54, 14, 13. The 1-year survival rate of G, GS and S-1 were 20.3%, 28.5% and 53.8%. The median PFS were 106 days, 84 days and 88 days, respectively. The median OS were 196 days, 154 days, 359 days, respectively. The 1-year survival rate of S-1 was significantly better than that of G (p=0.01). Median PFS and median OS of S-1 didn’t demonstrate the superiority compared with that of G (p=0.40, p=0.08). Conclusions: We suggest the selection of S-1 as 1 st line chemotherapy regimen in PC pts with peritoneal dissemination might be effective and we need further investigation.