tbuckley/cabot-search huggingface dataset:
Validation of a gastric cancer nomogram using a U.S. cancer registry.
Authors: Lee Joseph McGhan, Amylou C. Dueck, Barbara A. Pockaj, Richard J. Gray, Sanjay Prakash Bagaria, Nabil Wasif
Journal: Journal of Clinical Oncology (2012)

13 Background: A Memorial Sloan Kettering Cancer Center (MSKCC) nomogram predicts disease−specific survival (DSS) following R0 resection for gastric adenocarcinoma using patient and tumor factors, with predictive ability superior to that of the current AJCC staging system. However, validation has only been performed in high−volume, specialized institutions. The goal of this study is to compare nomogram-predicted survival with actual survival by using a population database with the largest sample size reported to date. Methods: A retrospective review of all gastric cancer patients from Surveillance, Epidemiology and End Results (SEER) registry data from 1988 to 2000 was conducted. Data for patient age, tumor size, gender, primary location of tumor, Lauren histology, depth of tumor invasion, and % (+) and (-) lymph nodes was entered into the nomogram calculator for each patient. Nomogram-derived 5−year DSS was compared with actual DSS survival using Cox proportional hazards regression and Kaplan-Meier estimates. Results: 4,700 patients were identified. Mean patient age was 68.7 years (SD 12.3), and mean tumor size was 4.8 cm (SD 2.7). The commonest tumor location was the body/middle third of stomach (1519, 32%), followed by the gastro−esophageal junction (1381, 29%) and the antrum (1376, 29%). The majority of patients (76%) had intestinal histology. The estimated proportion of patients surviving 5 years was 23%, 48%, 58%, and 82% for survival groups defined by nomogram likelihoods of 5−year DSS of 0−25%, 26−50%, 51−75%, and 76−100%, respectively. Relative to patients in the 76−100% 5−year nomogram group, patients in the 0−25%, 26−50%, and 51−75% group had significantly higher likelihood of death with hazard ratios of 7.0 (95% CI 6.1−8.0), 3.3 (95% CI 2.8−4.0), and 2.6 (95% CI 2.2−3.0), respectively (all p&lt;0.001). Median follow-up was 9.1 years (range, 0−18). The concordance index (c−index) for the 5−year nomogram score was 0.68 (95% CI 0.67−0.69). Conclusions: There is good discrimination of survival between nomogram-predicted survival groups. Our results validate the use of the MSKCC nomogram in the setting of the general population, outside of specialized institutions, for predicting DSS following resection of gastric adenocarcinoma.
Results from Ion AmpiSeq Cancer Panel in 200 cases of gastric and gastroesophageal junction cancer.
Authors: Howard John Lim, Christian K. Kollmannsberger, Sharlene Gill, Esther Kong, Ying Ng, Amy Lum, Michelle Woo, David Huntsman, Stephen Yip
Journal: Journal of Clinical Oncology (2013)

39 Background: We used the Ion AmpiSeq Cancer panel which contains multiplex PCR primers covering 739 potential cancer- related mutations in 46 genes to profile 200 gastric and gastroesophageal cancers. Methods: The assay requires only 10ng of genomic DNA isolated from formalin-fixed paraffin-embedded (FFPE) archival tissue blocks. Samples were retrieved from biopsies from either the primary or metastatic lesion. All samples generated usable DNA and the resultant amplicons were sequenced on the Ion Torrent PGM platform to achieve in depth coverage of potential mutations. Results: Mutations in the tumour suppressor gene TP53 (39.5%) are most commonly identified in our cohort which is consistent with known mutation profiling of gastric carcinoma. We have also identified mutations in MET (8%), PIK3CA (7.5%), KRAS (4%), BRAF (4%) in addition to other known oncogenes. Lastly, We identified two cases with hotspot mutations in IDH1 (R132H and R132C), hotspot mutation traditionally associated with glioma and acute leukemia, which suggest novel role(s) of this mutant protein in the pathogenic progression of this cancer. Conclusions: These findings might predict response to targeted therapeutic agents or have prognostic implications. This study highlights the potential of focused profiling of cancer related genes using the Ion Torrent platform and its advantage of utilizing small amount of DNA from archival pathology specimens.
Resectability assessment of enhanced CT and contrast-enhanced endoscopic ultrasonography for the periampullary neoplasm.
Authors: Pengfei Yu
Journal: Journal of Clinical Oncology (2016)

199 Background: To evaluate the efficacy of enhanced CT and contrast-enhanced endoscopic ultrasonography (CE-EUS) for assessment of the resectability of periampullary neoplasm. Methods: a prospective analysis of 93 patients with periampullary neoplasm underwent CT and CE-EUS was conducted to compare the imaging data with the surgical and pathological findings, in order to evaluate their efficacies for the resectability assessment. Results: There was no significant difference in sensitivity and specificity between CT and CE-EUS in adjacent organ invasion, lymph node metastasis and liver metastasis (p &gt; 0.05). For the diagnosis of periampullary neoplasm and assessment of vascular invasion, CE-EUS was better than CT (94.6% vs 84.1%,P = 0.023; 96.2% vs 85.9%, P = 0.041). Logistic regression showed that the accuracy of CE-EUS in determining adjacent organ invasion was correlated with the tumor size, and vascular invasion was correlated with the tumor location and size. Conclusions: CE-EUS has advantages in the assessment of the resectability of periampullary neoplasm, especially for the assessment of vascular invasion, and can be used as a supplementary Imaging technology to the enhanced CT.
Multicenter phase II trial of neoadjuvant chemotherapy with mFOLFOX6 for stage II/III rectal cancer with a T3/T4 tumor FACT trial.
Authors: Toshiyuki Enomoto, Yoshihisa Saida, Kazuhiro Takabayashi, Jiro Nagao, Junichi Koike, Kimihiko Funahashi, Kazuhiko Yoshimatsu, Hajime Yokomizo, Hayato Kan, Takeshi Yamada, Hideyuki Ishida, Keiichiro Ishibashi, Kenji Katsumata, Hirotoshi Hasegawa, Keiji Koda, Takumi Ochiai, Kazuhiro Sakamoto, Shimpei Ogawa, Michio Itabashi, Shingo Kameoka
Journal: Journal of Clinical Oncology (2015)

713 Background: The efficacy and safety of neoadjuvant chemotherapy with mFOLFOX6 for stage II/III rectal cancer patients with a T3/T4 tumor is still unknown. Methods: Inclusion criteriain this study are as follows: Stage II/III (Ra/Rb) rectal cancer patients with a T3/T4 tumor. The primary endpoint is preoperative response rate, and the secondary endpoints are histological effect, R0 resection rate, pCR rate, down-staging rate, neoadjuvant therapy completion rate, toxicity, the incidence of postoperative complications, and 3-year disease-free survival. Computed tomography was performed after 4 courses of mFOLFOX6. Patients with disease progression (DP) underwent resection of the primary lesion, while those without DP received another 2 courses of treatment. Treatment was discontinued when resection was not possible in patients with DP. Results: Registered patients totaled 53 with a mean age of 60 (38–77). The number of patients with T3 and T4 tumors was 42 and 10, and patients at stages II and III were 10 and 42, respectively. One patient withdrew due to consent retraction. Median relative dose intensity of mFOLFOX6 therapy was 93.2% for L-OHP, 5-FU, and l-LV. Treatment completion was achieved in 96.2% and 84.6% for 4 and 6 courses, respectively, and withdrawal was due to patient’s discretion, not adverse events. Preoperative response rate was 51%. Surgery was performed in 78.8% of patients. Serious (grade ≥3) toxicity included neutropenia (n=5), leukopenia (n=1), thrombocytopenia (n=1), febrile neutropenia (n=1), nausea (n=1), vomiting (n=1), and peripheral neuropathy (n=2). The rates of R0 resection, pCR, and sphincter preservation were 91.0%, 10.3%, and 82.9%. The down staging rate was calculated as 2%. The median follow-up after surgery was 18.0 months. Median DFS was 17.3 months, and 1-year disease-free survival was 78.8%. Median OS was 22.0 months, and 1-year overall survival was 95.7%. Postoperative complications included suture failure (n=3), wound infection (n=2), pneumonia (n=1), and intestinal obstruction (n=1). Conclusions: Neoadjuvant chemotherapy using mFOLFOX6 is a safe and efficacious treatment option for rectal cancer, especially locally advanced disease. Clinical trial information: UMIN000006583.
Improvements in communication and engagement of advance care planning in adults with metastatic cancer through a targeted team approach.
Authors: Sabrina Q. Mikan, Lalan S. Wilfong, Margaret Rhoads, Mary Ann Cagle, Cynthia B. Taniguchi
Journal: Journal of Clinical Oncology (2016)

14 Background: Advance care planning (ACP) continues to be a vital part of comprehensive, person-centered cancer care. A large community oncology practice performed a targeted approach to improve patient engagement of ACP. A process improvement project with three goals was set: increasing ACP referrals, ACP counseling visits and completed Values Assessment (VA) instrument. A leadership team consisting of practice director, physician, nurse manager, and nurse practitioner was developed with ownership of roles and responsibilities. Methods: The ACP leadership team outlined workflows to be tested, followed by evaluating outcomes of each goal over 107 days. Barriers and challenges were identified; ACP education was taught to staff. NP and RNs introduced ACP to patients during ChemoTeaching. Eligible patients were identified weekly by infusion RNs on C1D1, and patients were given the VA. Desk RNs would speak with patients on C1D2 to review symptoms and VA responses. RNs would offer ACP visits to patients. Referrals were made for patients to have one-on-one counseling with NP. Staff was educated about EMR documentation by RN manager. Weekly team phone meetings were held to discuss project status. Results: During the first 53 days of the project, 20 patients were identified at C1D1, 5 VA were completed and 15 ACP visits occurred. After evaluation, weekly communication with clinical staff increased to daily huddles. Daily communication allowed for RNs to identify C1D1 patients and communicate to the full team. During the second 54 days, 94 patients were identified at C1D1, 46 VA were completed, and 27 ACP visits occurred. A 5-fold increase occurred in patient identification; a 9-fold increase in VA completion occurred, and approximately 2-fold increase occurred in ACP counseling. Conclusions: By developing a focused and concerted process on ACP, the cancer center was able to show that patient engagement in the ACP process markedly improved. A navigation process for identifying patients who would benefit from ACP counseling was vital in increasing in the counseling visits. Continual quality improvement by refining processes in the ACP program will benefit patients.
Phase II trial of docetaxel, cisplatin, irinotecan, and bevacizumab in metastatic esophagogastric cancer
Authors: P. C. Enzinger, D. P. Ryan, E. M. Regan, N. Lehman, T. A. Abrams, A. F. Hezel, P. Fidias, L. V. Sequist, L. S. Blaszkowsky, C. S. Fuchs
Journal: Journal of Clinical Oncology (2008)

4552 Background: The combination of weekly docetaxel, cisplatin and irinotecan has demonstrated a response rate of 60% in chemo-naïve patients (pts) with metastatic esophagogastric cancer (Enzinger. ProcASCO '04). The addition of bevacizumab to standard chemotherapy has improved response rates and survival in pts with metastatic colorectal, lung, and breast cancer in randomized trials. Pts with the *28 allele of the UGT1A1 gene have an increased risk of toxicity to irinotecan-containing therapy. Methods: Pts with measurable, metastatic esophagogastric cancer received bevacizumab 10mg/kg on day 1 every 3 weeks, docetaxel 30mg/m2, cisplatin 25mg/m2, and irinotecan 50mg/m2 on days 1, 8, of each 3-week cycle. Unless contraindicated, pts were urged to take aspirin 81mg daily. UGT1A1 genotyping was required of all pts entering the study. Additionally, blood samples and endoscopic biopsies of tumor were obtained at baseline and after one cycle of therapy in all consenting pts. Results: 32 pts have been enrolled: median age = 59 (32–79), male/female = 28/4, ECOG: 0/1 = 14/18, gastric/GE junction/esophageal = 12/7/13, adenocarcinoma/ squamous cell carcinoma = 29/3. Sites of metastatic disease included: lymph nodes (26 pts), liver (19 pts), peritoneum (6 pts), lung (4 pts), bone (4 pts), adrenal gland (4 pts), ovary (1 pt), other (12 pts). Grade III/IV toxicities occurring in >5 % of 32 pts included: grade III neutropenia = 7 pts (22%), grade III diarrhea = 9 pts (28%), grade III nausea = 2 pts (6%), grade 4 thromboembolic events = 3 pts (9%; none of these pts were taking aspirin). 13 of 30 pts (43%) had the *28 allele present (6/7 or 7/7); of these, 62% had grade III diarrhea and/or neutropenia; 29% of patients without the *28 allele had these toxicities. 30 patients are evaluable for response: partial = 19 (63%), stable = 9 (30%) progression = 2 (7%). Conclusions: The combination of docetaxel, cisplatin, irinotecan and bevacizumab is well-tolerated and has a promising response rate in chemo-naive patients with esophagogastric cancer. UGT1A1 testing appears to predict the risk of severe diarrhea/neutropenia in this group of patients. Supported by Genentech. No significant financial relationships to disclose.
Clinical use of personalized molecular biomarkers in patients with glioblastoma.
Authors: M. Holdhoff, J. O. Blakeley, C. Carson, C. H. Ferrigno, L. Blair, A. S. Balmanoukian, P. Burger, S. A. Grossman, L. A. Diaz
Journal: Journal of Clinical Oncology (2011)

2022 Background: The development of predictive and prognostic biomarkers in malignant gliomas is the subject of intense research designed to provide personalized therapies for patients with these cancers. The availability, ordering, and clinical influence of molecular tests are not well described. This study was conducted to assess the current use of available biomarkers in patients with glioblastoma (GBM). Methods: A questionnaire consisting of 13 multiple-choice and 2 open questions was distributed online to members of the neuro-oncology community in the United States using email addresses published in the 2010 meeting program of the Society for Neuro-Oncology. All answers were collected between January 5 and 16, 2011. Results: The response rate to this survey was 30.4% (320/1053). Participants who did not see GBM patients were excluded from analysis (n=73). The 247 qualified respondents saw 0-2 (22%), 3-10 (34%), 11-30 (30%), or >30 (15%) patients with GBM per month. When seeing patients with newly diagnosed GBM, participants (n=201) reported routinely ordering no molecular tests (33%), MGMT promoter methylation (46%), EGFR amplification (28%), 1p19q co-deletion (27%), EGFR expression (26%), p53 mutation (24%), PTEN mutation or deletion (21%), IDH1/IDH2 mutation (15%), EGFRvIII mutation (15%), PDGFR expression (6%), or PIK3CA mutation (1%). The following percentages of clinicians seeing >3 patients with GBM/month noted that molecular tests “always” or “almost all the time” influenced their management of patients with GBM: 1p/19q co-deletion 20% (28/142), MGMT promoter methylation 11% (17/158), EGFR expression 3% (4/134), EGFR amplification 3% (4/143), EGFRvIII mutation 3% (4/139), IDH1/IDH2 mutation 2% (3/132), p53 mutation 1% (1/133), PDGFR expression 0% (0/131), PIK3CA mutation 0% (0/126), or PTEN mutation or deletion 0% (0/133). Conclusions: An estimated two thirds of clinicians routinely order one or more molecular biomarkers for patients with newly diagnosed GBM. The most commonly ordered tests were MGMT promoter methylation, EGFR amplification, and 1p19q testing. However, the impact of the molecular test results on clinical decision making remains modest.
A novel risk stratification model for patients with brain metastasis: Incorporating with physiological signals.
Authors: Yu-Ming Wang, Tsung-Ying Ho, Eng-Yen Huang, Chong-Jong Wang
Journal: Journal of Clinical Oncology (2016)

38 Background: Brain metastasis (BM) develops in 10%-40% of patients with malignancies. Survival expectancy is critical for choosing an optimal treatment for BM patients. Previous reports have proposed different risk stratification systems based on clinical and image-related factors. Heart rate variability (HRV), a physiological factor, has also been reported as a novel prognosticator for BM patients. In this study, we proposed a novel risk stratification model for BM patients by incorporating HRV signals. Methods: Patients with BM referred to our department for palliative RT were prospective recruited. Those who were not suitable for HRV evaluation were excluded for analysis. A 5-minute ECG was acquired before treatment started for each patient for subsequent HRV signal analysis. All patients underwent WBRT for 30-37.5 Gy in 10-15 daily fractions. Local boost to gross intracranial tumors were performed selectively. The primary end-point for this study was overall survival (OS). Survival analysis was carried out by Kaplan-Meier method and factors were compared by log-rank test and cox-regression. A novel risk stratification model combining HRV index SDNN and KPS was proposed. Results: Total 62 patients were recruited from Jan 2010. The median follow-up time was 40.7 months for patients who were still alive. Only 1 patient (1.6%) met the criterion of RPA class I. The median OS for all patients was 4.5 months. Univariate and multivariate analysis revealed that SDNN ≥ 10ms and KPS ≥ 70 were independent survival prognosticators. For a selected group of patients (n = 29, Group 1, SDNN ≥ 10ms and KPS ≥ 70) the median OS was 9.9 months, which is significantly higher than the rest 33 patients (Group 2) as of 2.4 months. The 3-month/6-month OS rate in Group 1 and Group 2 were 82.8%/72.4% and 36.4%/24.2% (p &lt; 0.001). Conclusions: Using physiological factors for risk stratification is novel. Our results demonstrated that a group of patients with potential longer survival could be selected by using HRV index and KPS. This group of patients should be considered differently in treatment selection. Further studies are warranted to validate our findings and improve the quality of care in patients with BM.
Selection of targeted agent(s) based on matching differential protein expression and mutational profile in NSCLC patients.
Authors: N. Hoe, K. Park, S. Um, X. Liu, P. S. Kim, R. Kirkland, T. A. T. Lee, J. Zhou, A. Nguyen, Y. Ma, M. Ahn, S. Singh
Journal: Journal of Clinical Oncology (2011)

e21085 Background: Treatment of nonsmall-cell lung cancer (NSCLC) with tyrosine kinase inhibitors (TKIs) shows initial response, but most tumors develop acquired resistance to TKIs due to secondary resistance mutations (T790M) and amplification of other RTKs. Patients stratified for mono therapy treatment based on genotype alone is not sufficient as other kinases contribute to survival and necessitate inhibition of multiple kinases. Methods: The Collaborative Enzyme Enhanced Reactive-immunoassay (CEER) is a multiplexed protein microarray platform requiring co-localization of two detector enzyme-conjugated-antibodies. CEER is capable of high detection sensitivity from FNA/CTC viable samples (23-35 gage needle). Lysates were prepared from frozen tissues obtained surgically from 71 Caucasian and 29 Asian patients with NSCLC. Expression and activation of EGFR, ErbB2, ErbB3, cMET, IGF1R, cKIT, Shc, PI3K, AKT, ERK, VEGFR2, Src, FAK, Stat5, JAK2, CrKL, and other pathway proteins were profiled. Genotyping on panel of mutations in KRAS, EGFR, and BRAF were performed on all samples. Results: We have observed differential expression patterns between Asian and Caucasian patients. KRAS is mutated in 30% of all the patients. In Asians, EGFR over expression is higher (27%) compared to the Caucasians (3%). Caucasian patients expressed high Her3 (58%), cMET (25%), and co expression of both cMET and HER3 (27%). VEGFR2 is highly expressed in 17% of all patients. Patients over expressing cMET, HER3, and HER2 will benefit from combination of pan-HER and cMET inhibitors. Those over expressing cMET and EGFR will benefit from cMET and EGFR inhibitors. Lastly, patients over expressing VEGFR2 and cMET will benefit from cMET and VEGFR inhibitors. A comprehensive differential biomarker prevalence for each NSCLC sub-populations for all tested RTKs and signaling proteins will be presented. Conclusions: Mono therapy and patient selection based on genotype is not an effective criteria for treatment options. Instead, a comprehensive pathway profile using FNA/CTC should guide selection of appropriate therapy (combined or sequenced), and shifts in pathway profile should be monitored for appropriate response.
Results of radiotherapy performed after unplanned surgery (without reexcision) for soft tissue sarcomas
Authors: L. Kepka, H. D. Suit, S. I. Goldberg, A. E. Rosenberg, G. P. Nielsen, T. F. Delaney
Journal: Journal of Clinical Oncology (2005)

9021 Background/Purpose: For soft tissue sarcomas (STS), some patients undergo a non-oncologic resection for presumed benign tumor, without preoperative imaging or any attempt at wide margins, a scenario we have called “unplanned surgery”. The treatment of choice in such cases is reexcision followed (if indicated) by radiotherapy. However, there are some clinical situations, when reexcision cannot be performed and patients are referred for immediate radiotherapy. The purpose was to assess the results of such an approach. Materials/Methods: Fifty patients irradiated after unplanned surgery between 1970 and 2000 were identified from a single institutional database. All had surgical margins not evaluable. Median age was 48 (range: 14–85). Tumors characteristics: location - lower extremity (68%), upper extremity (28%), other (4%); median tumor size at surgery: 5.25 cm (range: 2–20 cm); grade - G1 (28%), G2 (50%), G3 (22%); AJCC stage (2002) - I (28%), II (46%), III (26%). Median radiation dose given was 66 Gy (range: 51–88). Results: With a median follow-up of 11 years, estimated local control rate by Kaplan Meier method was 88% and 85% at 5 and 10 years, respectively. Distant control rate was 78% at 5 and 10 years (all failures occurred during first 5 years). The small number of events precluded demonstration of any statistically significant impact of tumor or treatment related variables on outcomes. There were 9 (14% of treated patients) major radiotherapy complications occurring from 1 to 21 years of f/up (5 severe peripheral neuropathies, 2 bone fractures, 1 major fibrosis, and 1 arterial injury). There was no relationship between the dose delivered and occurrence of major complications. Conclusions: Despite convincing data about the necessity for reexcision after unplanned surgery for STS, these results show that an omission of additional surgery and the immediate use of radiotherapy could be advisable for patients in whom functional, cosmetic, or medical considerations preclude further surgery. The risk for potential radiotherapy complications must also be considered in the treatment decisions. No significant financial relationships to disclose.