tbuckley/cabot-search huggingface dataset:
Use of Tegwondo, a near-continuous temozolomide regimen, in high- and low-grade gliomas.
Authors: H. M. Strik, H. C. Bock, C. Marosi
Journal: Journal of Clinical Oncology (2011)

2084 Background: We report here updated results on safety and efficacy of a near-continuous 5/7-day application (“Tegwondo”) of temozolomide (TMZ) for high- and low-grade gliomas. Methods: 47 glioma patients received 292 cycles of TMZ with individual dose adaptation: 24 patients with glioblastoma (GBM), 16 pts. with WHO III gliomas and 7 pts. with low-grade gliomas received near-continous TMZ day 1-5/7, initially at 100mg/m2 Results: Toxicity was: hematotoxicity grade ¾ (asymptomatic): 7/47 (15%); nonhematological (infections) ¾°: 4/47 Pts. (4%). Only in 2/47 patients, haematological toxicity required treatment (platelet transfusion, G-CSF). GBM-pts. (n=24) had a mean age of 55y and received a median number of 5 cycles of chemotherapy. Efficacy was: 1 complete remission (CR, 4%), 11 stable diseases (SD, 46%) and 12 progressive diseases (PD, 50%) at ≥3 months. Patients with WHO-grade 3 gliomas had a median age of 47 years. They received a median of 6 (2-12) cycles of temozolomide and achieved 1/16 CR (6%), 5 partial remissions (PR, 31%), 5 SD and 1 minimal response (MR, together 38%), and 4/16 PD (25%). Patients with low-grade gliomas had a mean age of 44 years and received a median number of 6 cycles of chemotherapy. SD for at least 1year was achieved by 5/7 pts. (71%), PR by 2/7 pts. (29%). Conclusions: We previously reported rechallenge of gliomas with dose-dense temozolomide day 1-21/28 and 1-5/7. In this series, patients were exclusively treated with the 1-5/7 (“Tegwondo” = TEmozolomide Glioma WOrkiNgday DOse-dense regimen”) schedule starting at 100 mg/m2 with individual dose adaptation. This regimen was well tolerated and could be handled easily. Of note, activity was also seen in low-grade gliomas. This may be explained by the near-continuous application of chemotherapy that provides a long-lasting presence of chemotherapy in a tumor with a low proliferation rate. We conclude that the application of temozolomide with this regimen is feasible, well tolerated and is an alternative for glioma patients with critical blood counts and with lower grades of malignancy. In view of the safe application, we consider this regimen also to be an ideal basis to be combined with other antineoplastic agents.
A new digital classification schema to detect treatment variances and enable value-based payment reforms.
Authors: Andrew Pecora, Eric V Schultz, Kelly Choi, William Kea, Augie Smith, Cindy Kim, Matthew Axelrod, Teresa Fletcher, Matthew Love, Ruth Pe Benito, Samira Daswani, Sukhi Kaur, Kathyrn Tanenbaum, James Schaffer, Ali Hasan, Dilip Raj, Kumar Bharath Prabhu, Kiran Suryadevara, Ryan Callahan, Stuart L. Goldberg
Journal: Journal of Clinical Oncology (2016)

28 Background: Value based payment reforms which improve the outcome to cost ratio (paying for outcomes not for services) require detailed information on both elements. Although the digitalization of medicine via the EHR may facilitate data collection, the imprecise ICD9 and ICD10 schemas hinder analysis (eg: all breast cancers are ICD9 174.9). A more precise classification schema that accounts for biologic variances to allow analysis (and reduction) of treatment variances is needed. Methods: We have developed a digital classification (COTA Nodal Address) based on known clinically relevant prognostic variables. (eg: breast cancer variables include stage, tumor size, hormone status, her2 neu status, etc.). The digital classification also accounts for therapy status (neoadjuvant vs adjuvant, etc.) and line (1 st or 2nd treatment, etc.). Results: Using breast cancer as an example, there are &gt; 2975 unique CNA phenotypes that encompass prognostic and treatment status variables. However, in a series of 1204 patients in a community setting only 114 CNAs have been utilized, suggesting biologic disequilibrium. Two phenotypes accounted for the top 25% of cases, 6 for the top 50% and 16 for the top 75%. Early stage, small tumor, hormone receptor positive were most common. The CNA classification uncovered treatment variances among patients with similar phenotypes. In an ongoing episodes of care payment program, young breast cancer patients with early stage, good performance status, hormone positive, her2 neu negative, very small tumors (with similar extended attributes) received varying adjuvant treatment strategies (hormone alone 46% , non-anthracycline 35%, anthracycline chemotherapy 4%, observation 1%). Conclusions: Unlike ICD9/10 systems, a digital classification schema that precisely segregates cancers into unique cohorts based on complete biologic characteristics can rapidly identify behavioral variances at scale that drive differences in outcomes and costs. Using the breast cancer model, we have noted demographic disequilibrium in cancer presentations (potentially a factor of both biology and screening practices) and major variances in treatment strategies (with impact on outcomes/ costs).
Class I HDAC expression patterns are highly prognostic in human gastric cancer
Authors: M. Ebert, W. Weichert, A. Röske, V. Gekeler, M. Dietel, C. Denkert, C. Röcken
Journal: Journal of Clinical Oncology (2008)

11114 Background: Although histone deacetylases (HDAC) are known to play a key regulatory role in cancer cells and HDAC inhibitors (HDI) have entered late phase clinical trials for the treatment of a variety of cancers, still little is known on the expression patterns of HDAC isoforms in tumours. Methods: Two cohorts of 143 (training cohort) and 150 (validation cohort) gastric cancer patients from two single institutions and a total of 3223 tissue spots were investigated for the expression of class I HDACs 1, 2 and 3. Expression patterns were grouped (gHDAC: none, one or two, all positive) and correlated with clinico-pathological parameters and patient survival. Results: 36.3% (training cohort) and 21.3% (validation cohort) of gastric cancers showed nuclear expression of all three HDAC isoforms, 42% and 43.4% expressed one or two isoforms in the nuclei while 21.7% and 35.3% were scored negative for all three proteins. gHDAC in both cohorts was higher when lymph node metastases were present (p<0.005). In multivariate analyses, gHDAC expression and HDAC2 expression were associated with shorter survival in the training (gHDAC: hazard ratio (HR)=4.2, p=0.025, HDAC2: HR=3.6, p=0.010) and in the validation cohort (gHDAC: HR=2.2, p=0.043, HDAC2: HR=1.7, p=0.022), independent of standard clinical predictors. Conclusions: HDAC expression correlates significantly with nodal spread and is an independent prognostic marker for gastric cancer. In addition, we hypothesize that immunohistochemical detection of HDAC as a companion diagnostic tool may predict treatment response to HDI thereby enabling a selection of patients for this specific targeted therapy in gastric cancer. No significant financial relationships to disclose.
A palliative radiation oncology consult service’s impact on care of advanced cancer patients with symptomatic bone metastases.
Authors: Sanders Chang, Cardinale B. Smith, R. Sean Morrison, Kenneth Rosenzweig, Kavita Vyas Dharmarajan
Journal: Journal of Clinical Oncology (2015)

110 Background: Single-fraction and ≤ 5 fraction radiation treatment (SF-RT and Hypo-RT, respectively) is underutilized despite strong evidence regarding its efficacy in symptom management. Established in 2013, the Palliative Radiation Oncology Consult Service (PROC) is a specialty service designed to provide individualized, efficient treatment for advanced cancer patients by a radiation oncology team with a dedicated palliative care focus. We assessed the impact of this new model of care on use of SF-RT, hypo-RT, pain improvement, palliative care utilization, and hospitalization among patients treated with palliative radiation (PRT) for painful bone metastases. Methods: We searched electronic charts of advanced cancer patients who had PRT for symptomatic bone mets from Dec 2010 to April 2015, extracting PRT details, demographics, cancer type, pain pre- and 1 month post-PRT, comorbidities (summarized using Charlson comorbidity index [CCI]), palliative care consults, and hospitalization. Comparisons were made before and after PROC using chi-square or t-tests. Multivariable logistic regression estimated the likelihood of SF-RT or hypo-RT, controlling for age, gender, cancer type, treatment site, and CCI. Results: We identified 334 patients, described in the table below. Patients were more likely to have SF-RT (OR 2.2, 95% CI [1.2-3.8], p = 0.007), or hypo-RT (OR 3.0, 95% CI [1.8-4.7], p &lt; 0.001) after establishment of PROC. Conclusions: Establishment of a PROC service nearly doubled utilization of SF-RT and hypo-RT while maintaining pain improvement, and was associated with an increased use of palliative care consult services, decreased inpatient PRT use, and decreased length of stay. A dedicated service combining palliative care principles and radiation oncology improved quality of palliative cancer care. [Table: see text]
MFOLFOX6 with oxaliplatin stop-and-go strategy and oral S-1 maintenance therapy in advanced colorectal cancer: CCOG-0704 study.
Authors: G. Nakayama, Y. Kodera, H. Yokoyama, N. Okuda, T. Fujii, A. Nakao
Journal: Journal of Clinical Oncology (2011)

569 Background: In metastatic colorectal cancer (mCRC), a combination of leucovorin and fluorouracil with oxaliplatin (FOLFOX) is one of the standard first-line regimen. The cumulative neurotoxicity of oxaliplatin often requires therapy to be stopped in patients who are still responding. The aim of this study was to evaluate modified FOLFOX6 (mFOLFOX6) with the intermittent oxaliplatin treatment and maintenance therapy with S-1, oral fluoropyrimidine derivative, in the first-line treatment of mCRC. Methods: Thirty patients with untreated mCRC were treated with six cycles of mFOLFOX6 (oxaliplatin 85 mg/m 2 , leucovorin 200 mg/m 2 , 5-fluorouracil bolus 400 mg/m 2 and 5-fluorouracil continuous 2400 mg/m 2 , every 2 weeks) followed by maintenance therapy with oral S-1 (S-1 80- 120mg/body days 1-28, every 6 weeks). Reintroduction of mFOLFOX6 was scheduled after four cycles of S-1 or tumor progression. The primary study end point was duration of disease control (DDC). Results: Twenty of the 30 patients (66.7%) who achieved responses or stabilizations received S-1 maintenance therapy. mFOLFOX6 was reintroduced in thirteen patients (43.0%). Median DDC was 9.3 months. Median progression-free survival (PFS) was 7.9 months. Overall response rates and disease control rates were 40.0% and 86.6% for the initial mFOLFOX6, 25.0% and 55.0% for S-1 maintenance therapy and 23.1% and 76.9% for mFOLFOX6 reintroduction. Twenty-eight patients (93.3%) had peripheral neuropathy during treatment, but grade 3 neurotoxicity was observed in only 1 patient (3.3%). Conclusions: The planned oxaliplatin stop-and-go strategy with oral S-1 maintenance therapy was feasible first-line treatment for Japanese mCRC patients. Further prospective randamized control study is warranted. No significant financial relationships to disclose.
Outcome for children ≤3 years of age with malignant brain or spinal cord tumors treated with high dose chemotherapy with peripheral blood stem cell rescue
Authors: H. K. Thorarinsdottir, B. Rood, D. Lafond, E. Perez, B. Loechelt, N. Kamani, R. Packer, T. MacDonald
Journal: Journal of Clinical Oncology (2005)

8552 Background: Children ≤3 years of age (yo) with malignant brain tumors have a dismal prognosis. In a POG study starting in 1986 (NEJM Jun ’93), 102 patients had a 1 and 2 year progression free survival (PFS) of 41% and 39% respectively after chemotherapy using repetitive 28 day cycles of cyclophosphamide plus vincristine, followed by cisplatin plus etoposide. In an attempt to delay or obviate radiation therapy and improve outcome, our institution has treated children ≤3 yo with newly diagnosed malignant brain tumors with high dose chemotherapy (HDC) followed by peripheral blood stem cell (PBSC) rescue. Methods: Since August 1998, 14 children (age 4–38 mos) with malignant brain and spinal cord tumors have been treated at our institution. All patients received 3 cycles of induction chemotherapy (cisplatin 3.5 m/kg -day 0, cyclophosphamide 60 mg/kg -day 1 and 2, etoposide 2.5 mg/kg -day 0 to 2, vincristine 0.05 mg/kg, day 0, 7, 14) followed by 3 cycles of HDC (carboplatin 17 mg/kg and thiotepa 6mg/kg day 0 and 1) with PBSC rescue after each cycle. Histology included 9 medulloblastoma/PNET (6 post. fossa/brainstem, 3 supratentorial; 7 M0, 1 M1 and 1 M3), 4 malignant glioma (2 supratentorial, 2 brainstem; 3 M0, 1 M3) and 1 ependymoma. Outcome and treatment toxicities were evaluated by retrospective chart review. Results: 3 of 14 children are currently undergoing HDC and are too early to be evaluable. 1 and 2 year PFS for the remaining 11 is 81% and 63%. 3 patients had disease progression (all M0 disease) at 8, 12, and 17 mos; 2 had received post-HDC radiation. 8 patients are alive and disease free 8 to 70 mos after completion of HDC (median 33 months). 5 of the 8 disease free patients had radiation therapy. Toxicity was primarily myelosuppression, with a total of 68 admissions for fever and neutropenia with G+ bacteremia detected in 32% of those admissions. There were no toxic deaths. Conclusions: We are encouraged by the outcome of these 14 children ≤3 years of age with malignant brain tumors treated with HDC and PBSC rescue at our institution. The treatment regimen is well tolerated. The high incidence of gram+ bacteremia supports the use of broad-spectrum antimicrobial coverage for fever/neutropenia. No significant financial relationships to disclose.
Prognostic factors and long-term outcomes of resected pancreatic adenocarcinoma: A comparison between two decades.
Authors: Pablo Emilio Serrano Aybar, Peter Tae Wan Kim, Kenneth Leung, Sean P. Cleary, Carol-anne Moulton, Paul David Greig, Steven Gallinger, Alice Chia-chi Wei
Journal: Journal of Clinical Oncology (2014)

318 Background: There have been improvements in short and long-term survival rates for patients with resected pancreatic adenocarcinoma over time The main objective of this study was to evaluate differences in long-term survival in a cohort of patients with resected pancreatic adenocarcinoma. Methods: This is a retrospective cohort study of patients who underwent pancreatic resection for pancreatic adenocarcinoma over 2 decades at a high volume academic centre. Univariate and multivariate analysis using Cox proportional hazards model were performed to evaluate prognostic factors associated with long-term survival. Time trend analyses were performed to evaluate differences between decades. Results: There were 489 patients identified, 179 patients during the early (1991-2000) and 310 during the recent decade (2001-2010). Main differences between early and recent decade were: node-positive disease rate (59% vs. 69%), number of lymph nodes collected (median 7 vs. 17), perioperative mortality (6.7% vs. 1.6%) and percentage of patients receiving adjuvant therapy (33% vs. 68%), respectively. There were no differences in sex distribution, age, margin positivity rate or tumor grade. In the multivariate analysis, node, margin status, tumor grade, adjuvant therapy and decade of resection were independently associated with overall survival for the entire cohort. Patients who received adjuvant therapy had better median overall survival: 17 [95% confidence interval (CI): 14-22] vs. 26 months (95% CI: 24-31). Median overall survival for the early and recent decade were 16 months (95% CI: 14-20) and 27 months (95% CI: 24-30, p&lt;0.001), respectively. Conclusions: Factors associated with improved long-term survival remain comparable over time: low tumor grade, node and margin negative disease. Short and long-term survival for patients with resected pancreatic adenocarcinoma has improved in the recent decade. This is due to decreased perioperative mortality and increase use of adjuvant therapy.
A feasibility study of a fully automated molecular diagnostic system for mutation analysis of colorectal cancer.
Authors: S. Kitano, J. Myers, M. Amano, M. J. Ratain, W. Liu
Journal: Journal of Clinical Oncology (2011)

e21074 Background: KRAS and BRAF mutations are strong molecular predictors for efficacy of cetuximab and panitumumab in colorectal cancer (CRC). We have developed a novel, simple, sensitive and fully automated DNA mutation detection system (Toppan Genotyping Analyzer, TGA) based on Invader Plus® technology. Here we report the validation study of our system, comparing it to DS in the detection of KRAS and BRAF mutations. Methods: Assays were set up using plasmids containing major KRAS (G12A, G12C, G12D, G12R, G12S, G12V and G13D) and BRAF (V600E) mutations. Sensitivity and accuracy of the detection method were evaluated with plasmids, as well as cancer cell lines with KRAS or BRAF mutations. DNA samples were extracted from frozen (n=31) and formalin fixed, paraffin embedded (FFPE) samples (n=36). Results: Sensitivity and accuracy assays using genomic DNA derived from cancer cell lines and plasmid DNA showed that the TGA system can detect mutations at a 5% level. The chip-based assay system allows for simultaneous analysis of 23 mutations in one hour (including the PCR process). The system was compared with two sets of DS, which had different primer sites. KRAS mutations detected in both frozen (DS1:12/31, DS2:11/31) and FFPE (DS1:7/36, DS2:8/36) samples were also successfully detected by the TGA. In the samples shown to be wild-type by DS, TGA was able to detect additional mutants in the frozen (vs. DS1:1/31, vs. DS2:2/31) and FFPE (vs. DS1:4/36, vs. DS2:3/36) samples. In addition, the frequency of BRAFmutation in frozen (1/31) and FFPE (0/36) was concordant between DS and TGA. Conclusions: In terms of detection of KRAS and BRAF mutations, TGA is a highly sensitive and accurate system compared to DS. It also possesses several other advantages including its all-in-one chip reaction, simple procedure and excellent reproducibility. The versatility in detecting mutations in DNA samples with different fixative forms makes the TGA a useful system that can be widely applied in both diagnosis and research areas. We hypothesize that TGA is superior to DS for predicting efficacy of molecularly targeted agents, since it has greater sensitivity for detection of mutations associated with drug resistance.
The added value of diffusion-weighted magnetic resonance imaging (DW-MRI) in the local staging of advanced colorectal pelvic cancer.
Authors: P. A. Georgiou, P. P. Tekkis, U. Patel, A. Antoniou, A. W. Darzi, D. Cunningham, D. Koh, G. Brown
Journal: Journal of Clinical Oncology (2011)

378 Background: Surgeons rely on imaging to plan exenterative pelvic surgery for locally advanced primary and recurrent rectal cancer. Accurate local staging is vital in this process, as it provides information about the extent of the disease, facilitating the planning of the operation required to achieve complete resection. DW-MR imaging is a functional radiological modality that can provide indirect informationabout the water proton mobility within biologic tissue, without the need of a contrast agent. The aim of the present study was to assess the diagnostic accuracy and added value of diffusion DW-MRI in detecting colorectal tumor invasion into seven intrapelvic compartments for planning exenterative pelvic surgery. Methods: Thirty three consecutive patients were preoperatively staged using DW-MRI to undergo exenterative surgery for locally advanced primary (n=12) and recurrent (n=21) colorectal pelvic cancer. Two radiologists reported tumor invasion for each of the seven anatomic surgical resection compartments and were blinded to histopathology and intraoperative reference standards. Accuracy, sensitivity, specificity and predictive values were calculated for the seven intrapelvic compartments. Interobserver agreement was assessed using Cohen's Kappa (k) coefficient for each compartment. Results: The sensitivity of DW-MRI when used alone was low for all the compartments except the central (92%). Its specificity was very high for all the compartment (≥89.5%). Combining DW-MRI with conventional MRI increased the sensitivity for the lateral compartment by 8.3% to 100% and the specificity for the anterior compartment below the peritoneal reflection by 9.1% to 90.9%. The overall incremental value for the lateral compartment was 3%. The interobserver agreement was either good or very good (k≥0.669; p&lt;0001) for all the compartments. Conclusions: DW-MRI can improve the diagnostic accuracy of conventional MRI when staging patients with advanced colorectal pelvic cancer. Diffusion images are cheap and easy to obtain. Therefore DW-MRI should always be used in combination with conventional MRI when considering patients for exenterative pelvic surgery. No significant financial relationships to disclose.
Phase I/II trial of combined hormonal therapy and hypofractionated accelerated radiotherapy with concomitant intensity-modulated boost for high-risk prostate cancer: Toxicity analysis.
Authors: H. Quon, D. A. Loblaw, G. Morton, E. Szumacher, C. Danjoux, R. Choo, G. Thomas, A. Kiss, A. Deabreu, P. Cheung
Journal: Journal of Clinical Oncology (2010)

4634 Background: Combined external beam radiotherapy (RT) and 2-3 years of hormonal therapy (HT) is a standard treatment option for high risk localized prostate cancer. Dose escalated RT alone has been shown to improve disease-free survival. Increased sensitivity of prostate cancer to high dose per fraction has led to hypofractionation as a method to radiobiologically escalate dose. We report on the acute and late toxicities of combining hypofractionated RT and HT. Methods: A prospective phase I/II study enrolling patients with any of: clinical T3, PSA ≥20, or Gleason ≥8. Forty-five Gy (1.8 Gy/fraction) was delivered to the pelvic nodes (4-field technique for the first 67 patients and intensity-modulated radiotherapy (IMRT) for the next 30 patients) with a concomitant 22.5 Gy boost to the prostate using IMRT, for a total of 67.5 Gy (2.7 Gy/fraction), in 25 fractions over 5 weeks. Image-guidance was performed using 3 gold seed fiducials. Common Terminology Criteria for Adverse Events v3.0 and Radiation Therapy Oncology Group late morbidity scores were used to assess acute and late toxicities, respectively. Biochemical failure was determined by Phoenix definition. Results: Ninety-seven patients were treated and followed for a median of 39 months, with 88% of patients having a minimum 24 months follow-up. Maximum toxicity scores are reported. Acute gastrointestinal (GI) toxicities were Grade 0 in 7%, 1 in 55%, and 2 in 38%. Acute urinary toxicities were Grade 0 in 3%, 1 in 52%, 2 in 40%, and 3+ in 5%. Late GI toxicities were Grade 0 in 55%, 1 in 39%, and 2 in 6%. There were no Grade 3+ late GI toxicities. Late urinary toxicities were Grade 0 in 81%, 1 in 10%, 2 in 5%, and 3+ in 4%. Most severe (Grade 3+) toxicities resolved at last follow-up with only 1 patient with Grade 3 late urinary toxicity. To date, 3 patients have failed biochemically. Conclusions: Pelvic RT with concomitant hypofractionated IMRT boost to the prostate combined with HT is well tolerated with low rates of severe late GI and urinary toxicity. Additional follow-up is necessary to evaluate biochemical control and 5 year prostate biopsy results. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca AstraZeneca AstraZeneca, sanofi-aventis