tbuckley/cabot-search huggingface dataset:
Disruption of protocadherin function and correlation with metastasis and cancer progression in TCGA patients.
Authors: James Shima, Joseph Delaney, Anita Umesh, Jenny Park, Gregory Wall, Qiaojuan Su, Mamatha Shekar, Ilya Kupershmidt
Journal: Journal of Clinical Oncology (2012)

70 Background: Protocadherins (PCDH) are a large family of calcium-dependent cell–cell adhesion molecules involved in tissue morphogenesis. Inactivation of PCDH locus genes are implicated in a number of oncogenic processes—hypermethylation of the PCDH gamma locus is present in Wilms’ tumors and arises after tumor development and the epigenetic silencing of PCDHGA11 occurs in the course of parenchymal invasion by astrocytomas. Assessment of PCDH function may help guide treatment decisions and provide a marker for metastasis in specific cancers. Methods: Identification of altered PCDH locus genes in TCGA patient samples was performed using the NextBio Clinical platform which provides access to the genomic and clinical data available in the TCGA dataset. The NextBio Research platform was used to correlate curated public experimental data and identify deleterious genomic changes associated with the PCDH locus and disease. Results: A nearly 3-fold increase in the frequency of potentially detrimental somatic mutations in PCDHGB4 was observed in breast cancer patients with extensive lymph node metastases (N3) compared to those with a lower degree of lymph node metastasis (N0-N2) (p value = 0.015). No other cancers appeared to have genomic changes deleterious to PCDHGB4 function, including ovarian and uterine cancer. Using the NextBio Research platform, breast cancer was found to be the 3rd most correlated disease with PCDHGB4, strongly correlating with RNA downregulation, DNA hypermethylation, and copy number loss. Other deleterious genomic changes in the PCDH locus were identified in ovarian (PCDHG), renal (PCDHA), and lung (PCDHA) cancers. Conclusions: Using the NextBio Clinical and Research platforms to analyze available TCGA data, disruption of PCDH function was found to correlate with increased metastasis only in certain cancers and with specific locus-disease pairings. Examination of PCDH locus perturbations may provide insight into a patient’s risk of developing metastatic disease. Further examination of the tissue specific alteration in PCDH genes may also aid in identifying unique cell adhesion pathways leading to metastasis in distinct tissues.
Outcome of phyllodes tumors of the breast: A series of consecutive cases.
Authors: P. Khosravi-Shahi, Y. Jerez, R. Mondejar, G. Tapia, M. P. Lopez, M. Martin
Journal: Journal of Clinical Oncology (2010)

e20506 Background: Phyllodes tumors of the breast (PTB)are rare tumors. PTBs exist in benign (B), borderline, and malignant (M) subtypes. Local recurrences (LR) are the most common site of recurrence. Treatment consists of local excision (LE), with free margins of resection (MR),or mastectomy (MM). Methods: We conducted a retrospective analysis of all patients (ps) treated at our Institution between 2000 and 2008. Primary end-point was disease-free survival (DFS), and 2o endpoints were overall survival (OS), site of first recurrence(SFR), and prognostic factors. Results: We included a total of 16ps (100% women). Four ps (25%) had BPTB, and 75% had MPTB. Median age was 48 years (range 21-81), 62.5% were postmenopausal, 93.8% unifocal tumor, median size (T) was 3.6cm (range 1,3-19), 31.2% had T>4.5 cm, median mitosis/HPF was 10 (62.5%>10mitosis/HPF), 31.2% had necrosis, 18.8% infiltration of the skin, and 6.3% positive-MR; 31.2% were treated with LE and 68.8% with MM. End-Points: With a median follow up of 97m, median DFS was not reached (NR). The probability of DFS at 5 years was 66%. There had been a total of 5 (31.2%) DFS-events, all in MPTB-subgroup (41,7%). Hence, 100% of BPTB were alive without any events. In MPTB-subgroup 5-years-DFS was of 50%, and median DFS was of 60m. Median OS was NR in the total population and was 62m in MPTB ps. Five-years- DFS were 66% and 50% in total population and MPTB-subgroup, respectively. All the ps with a relapse had died: 4 (80%) due to disease-progression and 1 due to sepsis related to treatment. The most common SFR was LR (60%), followed by lung (20%) and bone (20%) metastases. In univariate analysis, T> 4.5 cm (p = 0.004) and positive-MR (p = 0.038) were adverse prognostic factors, associated with increased risk of relapse and death. Neither age nor menstrual status or necrosis or number of mitosis or type of treatment were associated with a significant increase in relapse. Multivariant analysis with IHC markers will be presented in the Meeting. Conclusions: BPTB is associated with a good prognosis after adequate surgery. However, MPTB has a high risk of relapse and death after surgery, and this risk increases with T>4.5 cm and positive-MR. In this subgroup of ps, the value of adjuvant chemotherapy and/or radiation should be evaluated. No significant financial relationships to disclose.
Assessing 2-month clinical prognosis in patients with solid tumors: First results of PRONOPALL study.
Authors: H. P. Bourgeois, S. Traoré, P. Solal-Celigny, O. Dupuis, P. Maillart, O. Capitain, R. Delva, P. Soulie, M. Marcq, E. Boucher, G. Ganem, E. Bourbouloux, J. Baudon, M. Kaassis, M. Zinger, C. Lafond, V. Berger, P. Mussault, P. Ingrand, F. Grude
Journal: Journal of Clinical Oncology (2011)

6047 Background: in 2008, we published in our results of a prognostic score defined by 4 factors (Karnofsky index, number of metastatic sites, serum albumin and LDH levels) in a population of 177 hospitalized patients in two hospitals (Assessing 2-Month Clinical Prognosis in Hospitalized Patients With Advanced Solid Tumors - Anne-Claire Barbot, Pascale Mussault, Pierre Ingrand and al. J Clin Oncol - vol 26, p 2358-2543. 2008.). Albumin cutoff is 33 g/l and LDH cutoff is 600 ui/l. This score defined 3 different patients populations: A: low score (0 to 3), B: intermediate score (4 to 7) and C : high score (8 to 10). The survival rates at 2 months were 92.2% ± 3.8 (population A), 42.7% ± 5.2 (population B) and 8.3% ± 4.6 (population C). Methods: In order to validate this score, we decided to start a second study in a large multicentric trial with a high proportion of out-patients. Results: Between October 2009 and October 2010, 302 patients were included from 16 institutions. Inclusion criteria: adults patients with a solid tumor in palliative setting and with one or more of the three following criteria: life expectancy less than 6 months, PS ≥ 2, evidence of progressive disease during palliative chemotherapy. All patients signed an informed consent. At this time,146 (48%) patients are evaluable for this first analysis. 13 patients are not eligible. Median age 64 years [37-87], women 60%, men 40%. PS 0-1 (43%), PS 2 (40%), PS 3-4 (17%). The most frequent primary sites: breast (39%), colon/rectum (23%), lung (15%), pancreas (10,5%), others (12,5%). One metastatic site (31%), two (37%), more than two (33%). Median LDH level: 362 ui/l [118-1,314]. Median level of serum albumin was 36 g/l [20-54]. According the prognostic score, the 2-month survival rate and the median survival were 87% and 306 days [195-417] (population A, 72 patients), 60% and 75 days [53-97] (population B, 62 patients) and 18% and 15 days [7-23] (population C, 12 patients). These three populations are statistically different (p<0.0001). Conclusions: PRONOPALL confirms the three prognotic profiles defined by combination of theses four factors and is useful in daily practice.
Association between intratumoral HER2 heterogeneity (IHH) and trastuzumab (T-mab) efficacy in HER2 positive–gastric cancer (GC).
Authors: Takeru Wakatsuki, Noriko Yamamoto, Keisho Chin, Mariko Ogura, Eiji Shinozaki, Mitsukuni Suenaga, Masato Ozaka, Satoshi Matsusaka, Daisuke Takahari, Takashi Ichimura, Yosuke Kumekawa, Izuma Nakayama, TOMOHIRO MATSUSHIMA, Nobuyuki Mizunuma, Takeshi Sano, Toshiharu Yamaguchi, Yuichi Ishikawa
Journal: Journal of Clinical Oncology (2015)

92 Background: ToGA study showed superiority of adding T-mab to standard chemotherapy and a positive correlation between HER2 expression levels and the T-mab efficacy. In gastric cancer IHH is frequently recognized but its clinical impact on T-mab efficacy is unclear. Methods: Patients who were treated with T-mab and had surgical specimens available for IHC test were retrospectively examined. When all tumor cells overexpressed HER2 protein by IHC, the tumor was defined as non-HER2-heterogeneous. The others were defined as HER2-heterogeneous. Progression-free survival (PFS) and overall survival (OS) were estimated using by Kaplan-Meier methods and compared by the log-rank test. The level of significance was set to p&lt;0.05 and all statistical tests were two-sided. Results: 23 patients were enrolled. Their median age was 68 years and 83% were male. PS 0, GEJ cancer, intestinal type histology, visceral metastasis (lung or liver), and previous chemotherapy were found in 57%, 35%, 83%, 57%, and 57% of them, respectively. After a median follow-up of 11.3 months, the median OS, PFS, and overall response rate were 14.4 months, 10.8 months, and 62.5%, respectively. All tumors were IHC3+, and 13 were non-HER2-heterogeneous and 10 were HER2-heterogeneous. There was no significant difference in clinicopathological features between the two groups. Median PFS in non-HER2-heterogeneous group (21.9 months) was significantly longer than that in HER2-heterogeneous group (8.6 months), (HR: 0.24 [0.06-0.91], P=0.024). Median OS in non-HER2-heterogeneous group was not reached while that in HER2-heterogeneous group was 12.9 months (HR: 0.29 [0.06-1.42], P=0.102). A higher rate of response to T-mab was seen in non-HER2-heterogeneous group than in HER2-heterogeneous group, though the difference was not statistically significant (75% vs. 50%, p=0.608). Conclusions: IHH might have robust clinical impact on T-mab efficacy for HER2 positive GC. These findings should be validated by independent large cohorts and further molecular correlative analyses are warranted.
Phase II study of neoadjuvant chemotherapy with gemicitabine and pemetrexed (NeoGP) in resectable non-small-cell lung cancer (NSCLC): MCC 13726
Authors: K. E. Sommers, L. A. Robinson, A. Sharma, A. Cantor, C. C. Williams, A. A. Chiappori, E. B. Haura, G. R. Simon, S. Antonia, G. Bepler
Journal: Journal of Clinical Oncology (2005)

7314 Objective: We are assessing the efficacy of a non-platinum-containing doublet chemotherapy consisting of gemcitabine and pemetrexed as induction therapy (NeoGP) prior to surgical resection in patients with pathological stage IB-IIIA and selected IIIB NSCLC. The primary clinical endpoint is radiographic disease response rate. The secondary endpoints are overall and disease-free survival, pathologic response rate, treatment-related toxicity, and surgical respectability and outcome. Methods: All patients have clinical staging with computed tomography of the chest and upper abdomen, whole body FDG positron emission tomography, magnetic resonance imaging of the brain, and pathological staging with a mediastinoscopy; and they have to have medical and surgical resectable disease. Chemotherapy consists of G (1,500 mg/m2) and P (500 mg/m2) administered on days 1, 15, 29, and 43. Imaging studies were repeated between days 50–63. Disease response is determined by RECIST criteria, and patients with resectable disease are offered surgery between days 64–77. Patients are followed every 3 months for 2 years after resection with imaging studies. Results: From 4/04 to 11/04, 32 patients were enrolled. After completion of staging, 13 were ineligible because of the extent or histopathology of their disease. Of the 19 eligible patients 10 were women; the median age was 67 (range 42–77 years); the pathologic disease stages were IB in 5, IIA in 1, IIB in 6, IIIA in 6, and IIIB in 1 patient. None of the patients had disease progression, and the response rate is 50%. Chemotherapy dose reductions or adjustments for ≥ grade 3 toxicities were required in 2 patients. Six patients have had thoracotomy, and tumor resection was complete in 5 and incomplete in 1. There have been no deaths or unexpected morbidities related to surgery or chemotherapy. Conclusions: NeoGP appears to be equally as efficacious as platinum-containing chemotherapy doublets in terms of radiographic response rates. However, 1-year and 2-year survival rates and the median survival time are required to better compare this regimen with platinum-containing doublets. No significant financial relationships to disclose.
Analgesic treatment and pain killer use in patients enrolled at Pain Control Center Hospice of Solofra (Italy).
Authors: Geppino Genua, Luisa M Rizzo, Mela Fasano, P. Lino Fina, Elena De Vinco, A. M. Strollo, Sergio Canzanella, S. Florio, Vincenzo Landolfi
Journal: Journal of Clinical Oncology (2014)

218 Background: We have evaluated the treatment procedures and the clinical outcome in terms of pain control on 163 consecutive patients enrolled from December 2012 to April 2014 at “Pain Control Center” of the Hospice of Solofra. Methods: The following characteristics have been evaluated: patient gender, mean hospitalization time, differentiation between cancer and non cancer patients (pt.), tumour type, medical weapon use, venous access type, parenteral feeding, transfer in intensive care units, pain killer use. Results: Of the 163 patients (96 males and 67 females, mean age 63.31 years, range: 31-90 years, mean hospitalization time: 29.85 days) 126/163 pt (77.30%) had tumour diseases and 37/163 pt. (22.69%) non cancer diseases. Cancer pt. had lung (24.6%), colo-rectal (17.46%), breast (4.76%), bladder (5.55%), gastric (5.55%), prostate (3.17), hepatocellular (4.76%), pancreas (3.96%), head and neck (4.76%), kidney (3.17%) and other site tumours (19.67%). Patients with tracheostomy were 14/163 (8.58%), with gastrostomy 11/163 (6.74%), with uretero and colostomy 21/163 (12.88%) and with active mechanical ventilator 5/163 (3.06%). The central venous accesses were already present at the moment of the hospitalization in 61/163 pt. (37.42%); during the hospitalization the central venous access were made on 48/163 (29.44%). Seventy-six out of 163 pt. (46.62%) received either total or partial parenteral feeding while 26/163 pt. (15.95%) received enteral feeding. Analgesic therapy with opioids was administered at 131/163 pt. (80.36%) as it follows: morphin in 18.32%; oxycodon/naloxon in 23.63%; codein-paracetamol in 9.16% and transdermic or transmucosal Fentanyl in 48.85% of the pt. The most intensively treated pts. were those with tracheostomy followed by uretero and colostomy. Conclusions: The results of the present study confirm the underestimation of the parenteral feeding and analgesic requirements by pts. with chronic diseases. Another interesting result of the present report is the good clinical benefit achieved with the use of oxycodon/naloxon associated or not with other pain killers. These results are on line with the guidelines that suggest the use of oral slow release opioids.
Genotyping non-small cell lung cancer (NSCLC) in Latin America (LATAM).
Authors: O. Arrieta, A. F. Cardona, A. Gallo, G. F. Bramuglia, A. D. Campos-Parra, S. Serrano, C. Poleri, E. Amorin, R. Kirchuk, M. Cuello, E. Arechaga, R. Rosell
Journal: Journal of Clinical Oncology (2011)

e21155 Background: Epidermal Growth Factor Receptor (EGFR) and K-ras are key pathways in NSCLC; mutations in these genes determine a subgroup of patients with different prognosis and therapeutic approach. The frequency of mutations varies between different ethnic groups; so far, EGFR and K-ras mutations have not been described in the LATAM population. Methods: EGFR and K-ras mutation analyses were performed using DNA sequencing or Therascreen PCR-kit. Results: EGFR mutations were evaluable in 832 patients (México 295; Colombia 228; Peru 185; Argentina 124). 35.8% patients had EGFR mutations, 47.9% with E19 deletion; 48.3% with the in-frame L858R mutation. 19.8% patients had K-ras mutation (303 patients evaluated). Conclusions: LATAM NSCLC patients were more likely to harbor activating EGFR mutations and K-ras mutations were less frequent. Patient characteristics. Variable Argentina Colombia México Peru Total Number of patients 124 228 295 185 832 Mean age (±SD) 62.0 (11) 59.0 (13) 60.3 (13) 62.2 (11.1) 60.3 (12.6) Sex Female Male 68 (54.0) 56 (46.0) 152 (67.0) 76 (33.0) 166 (56.2) 129 (43.8) 91 (49.2) 94 (50.8) 477 (57.3) 355 (42.6) Histology Adenocarcinoma LCC NOS/Nondifferentiated SCC BAC No data 124 (100.0) 167 (63.2) 4 (1.8) 14 (6.1) 6 (2.6) 9 (3.9) 28 (12.3) 230 (77.9) 7 (2.4) 7 (2.4) 51 (17.3) 185 (99.5) 706 (84.8) 11 (1.3) 21 (2.5) 57 (6.8) 9 (1) 28 (3.) Smoking status Smoker/former smoker Never smoker No data 77 (62.0) 47 (38.0) 55 (24) 137 (60) 36 (16) 171 (58.0) 124 (42.0) 122 (65.9) 63 (34.1) 425 (51) 371 (44.5) 36 (4.3) Ethnicity Caucasian Mestizo Indigenous Black No data 124 (100.0) 45 (19.7) 49 (21.5) 1 (0.4) 133 (58.4) 4 (1.4) 291 (98.6) 19 (10.3) 165 (89.2) 192 (23) 505 (60.6) 1 (0.1) 133 (15.9) EGFR sensitizing mutation status Positive Negative 26 (21.0) 98 (79.0) 57 (25.0) 171 (75.0) 93 (32.0) 202 (68.0) 122 (67.7) 63 (31.7) 298 (35.8) 53 (64.18) Exon 18 (+) 3 (3.4) 3 (1.9) Exon 19 (+) 17 (65.0) 40 (70.0) 64 (73.5) 22 (11.8) 143 (47.9) Exon 21 (+) 9 (35.0) 17 (30.0) 20 (22.9) 100 (54.8) 144 (48.3) Complex mutations 6 (6.8) 6 (2.0) T90M basal (+) 5 (4.0) 9 (3.9) 3 (1.0) 17 (2.6) KRAS (+) 25 (21.9)* 35 (18.5)* 60 (19.8) * Test performed in 114 and 189 patients from Colombia and México, respectively.
Copayment assistance and adherence to prescription medication among patients with cancer.
Authors: Leah L. Zullig, Jeffrey M. Peppercorn, Deborah Schrag, Donald H. Taylor, Xiaoyin Zhong, Gregory Samsa, Amy Pickar Abernethy, Yousuf Zafar
Journal: Journal of Clinical Oncology (2012)

57 Background: The relationship between prescription medication adherence and copay assistance is understudied and directly impacts quality of care. Methods: We conducted a cross-sectional survey study assessing patient-reported failure to take medication as prescribed (nonadherence) and application for copay assistance. Participants were enrolled between 6/2010-5/2011 from the HealthWell Foundation (a copay assistance program) and Duke Cancer Center. Eligible patients were adults receiving treatment for a solid malignancy. Nonadherence was defined as taking a less than prescribed amount of medication, not filling or partially filling a prescription, or taking medications prescribed for someone else. Adherence and receipt of copay assistance were not linked to a specific drug. Logistic regression assessed the association between medication nonadherence, copay assistance application, and financial burden. Results: Among 258 participants, 75% applied for copay assistance. 38% (n=99) reported nonadherence with medications due to cost. Compared to adherent participants, nonadherent participants were more likely to: ask their doctor for a less expensive medication than prescribed (p&lt;0.001); reduce spending on basics like food or clothing to pay for medication (p&lt;0.001); purchase an over-the-counter drug to replace a more costly prescription (p&lt;0.001); borrow/use credit to pay for medications (p&lt;0.001); and talk with doctors about treatment-related costs (p=0.014). In adjusted analyses applying for copay assistance did not change odds of nonadherence. Having a prescription drug plan (OR 6.56, 95% CI 1.69-25.53) and utilizing coping strategies (OR 2.72, 95% CI 2.03-3.65) increased odds of nonadherence; older age (OR 0.93, 95% 0.88-0.98) decreased odds of nonadherence. Conclusions: Medication nonadherence due to cost was prevalent among cancer patients whether or not they applied for copay assistance. To afford medications cancer patients adapted their lifestyles and altered their care. Future research should investigate whether underinsured patients have timely access to copay assistance programs and whether copay assistance impacts the quality of care.
The optimal time-interval to re-resection for incidentally discovered gallbladder cancer: A multi-institution analysis from the US Extrahepatic Biliary Malignancy Consortium.
Authors: Cecilia Grace Ethun, Lauren McLendon Postlewait, Timothy M. Pawlik, Stefan Buettner, George A. Poultsides, Thuy Tran, Kamran Idrees, Chelsea A Isom, Ryan C. Fields, Linda Jin, Sharon M. Weber, Ahmed I. Salem, Charles Raben Scoggins, Perry Shen, Harveshp Mogal, Carl Richard Schmidt, Eliza W Beal, Ioannis Hatzaras, Rivfka Shenoy, Shishir Kumar Maithel
Journal: Journal of Clinical Oncology (2016)

201 Background: Current recommendation is to perform re-resection for select patients with incidentally discovered gallbladder cancer. The interval time to re-resection that optimizes both patient selection and long-term survival is not known. Methods: All patients with incidentally discovered gallbladder cancer who underwent re-resection at 10 institutions from 01/2000-05/2015 were included. The interval time to re-resection was analyzed. Primary outcome was overall survival (OS). Results: Of 449pts with gallbladder cancer, 233 (52%) were discovered incidentally and underwent attempted re-resection at 3 different time-intervals from the date of original cholecystectomy: Group A: 0-4wks (49pts, 21%); B: 4-8wks (91pts, 39%); C: &gt; 8wks (93pts, 40%). All 3 groups were similar with regards to T-stage, LN involvement, grade, and post-operative complications. Group A tended to have distant disease found less frequently at the time of re-resection (11% vs 20% vs 19%; p = 0.38) and was least likely to have residual disease on pathologic analysis (29% vs 47% vs 49%; p = 0.048). Despite these findings, patients who underwent attempted re-resection between 4-8 weeks had the longest median OS (Group B: 40.4mo) compared to those who underwent early (Group A: 18.1mo) or late (Group C: 23.6mo) re-exploration (p = 0.015). A 4-8 week time interval to re-resection, presence of residual disease, advanced T-stage, LN involvement, high grade, and positive margin were associated with decreased OS on UV Cox regression (all p &lt; 0.05). Only a 4-8 week time interval to re-resection (HR 0.43, 95%CI 0.21-0.90; p = 0.02), advanced T-stage (HR 2.65, 95%CI 1.16-6.09; p = 0.02), and margin positivity (HR 2.46, 95%CI 1.16-5.22; p = 0.02) persisted on MV analysis. Conclusions: The optimal time-interval for attempted re-resection for incidentally discovered gallbladder cancer appears to be between 4-8 weeks after the date of the original cholecystectomy.