tbuckley/cabot-search huggingface dataset:
Criteria for a prophylactic gastrostomy in head and neck cancer patients receiving concurrent radiochemotherapy.
Authors: Christiane Matuschek, Edwin Boelke, Caroline Geigis, Thomas Hoffmann, Wilfried Budach
Journal: Journal of Clinical Oncology (2014)

e17002 Background: Concurrent chemoradiation for head-and-neck cancer (HNC) may lead to increased rates of long term dysphagia as a severe side effect. Percutaneous endoscopic gastrostomy (PEG) may be indicated in numerous situations in HNC patients undergoing chemoirradiation when normal nutrition becomes impossible. It is still under debate, which predictive factors for prophylactic PEG tube insertion are useful. Methods: From an institutional database, 101 patients (72 male, 29 female, mean age 59.5 years) with concurrent radiochemotherapy for HNC were included in this study. Clinical factors (ECOG performance status, age, TNM stage), administration of chemotherapy and several organ-at-risk dosimetric parameters (oropharynx + 1cm margin, superficial pharyngeal constrictor muscle, larynx, oral cavity) were correlated with the need for tube feeding or parenteral nutrition for more than 4 days using a multiple logistic regression model. Results: Whereas several dosimetric and clinical factors were significant predictors for the need of artificial nutrition on univariate analysis, on multivariate analysis only three factors remained independently significant: Mean dose to the oropharynx + 1 cm circumferential margin, ECOG performance state and the use of chemotherapy. Conclusions: Using a multiple logistic regression model we could distinguish HNC-patients with different risk factors for the need of additional feeding during radiochemotherapy.
Can PET/CT substitute for bone scintigraphy in assessment of bone metastases in lung cancer patients?
Authors: H. Watanabe, S. Monzawa, S. Adachi, A. Hamanaka, Y. Kitamura, K. Izaki, M. Okada, M. Satouchi, S. Negoro, Y. Takada
Journal: Journal of Clinical Oncology (2006)

7203 Background: Bone is a frequent site of lung cancer metastasis. However, false positive lesions detected by conventional bone scintigraphy often become problematic. We compared the efficacy of whole-body [18F]-2-Fluoro-2-deoxy- D- glucose PET/CT imaging and conventional bone scintigraphy for assessment of bone lesions in lung cancer patients on an individual patient basis. Methods: The study population comprised 106 consecutive patients with suspected or proven lung cancer (73 men and 33 women; age range: 40 to 85 years) who underwent both whole-body PET/CT imaging and conventional bone scintigraphy using 740 MBq of Tc-99m hydroxymethylene diphosphonate for cancer staging. Diagnostic radiologists interpreted and assessed all images on a patient-by-patient basis. Clinical information and the findings of follow-up imaging studies were used as the gold standard for the identification of bone metastases. Results: On the basis of the gold standard, 11 of the 106 patients were identified as having bone metastases. Bone scintigraphy showed a sensitivity of 67% (7/11) while that of PET/CT was 100% (11/11) for detection of bone metastases. Seven of these 11 patients were deemed positive based on both bone scintigraphy and PET/CT. Bone metastases not identified on bone scintigraphy were detected on PET/CT in another four patients. For 39 of 95 patients without bone metastases, the assessment was false-positive for bone scintigraphy but negative for PET/CT. In two of the 39 patients, CT images of PET/CT could identify a benign fracture causing a false positive finding for bone scintigraphy. Conclusions: PET/CT might actually substitute for bone scintigraphy in lung cancer patients because of its superior ability to detect unsuspected bone metastases and to differentiate bone metastases from false positive lesions detected by bone scintigraphy. No significant financial relationships to disclose.
Could any pT1a,bN0M0 hormone-responsive, invasive breast carcinomas be safely treated without endocrine therapy?
Authors: Christophe Perrin, Jean-Sebastien Frenel, Julien Edeline, Marie Robert, Patrick Tas, Claudia Lefeuvre-Plesse, Carole Gourmelon, Fanny Le Du, Mario Campone, Pierre Kerbrat
Journal: Journal of Clinical Oncology (2015)

550 Background: Overtreatment is a daily concern in the adjuvant setting for breast carcinoma. Most of Hormone Responsive (HR+) pT1a,bN0 breast cancers have an excellent prognosis. The aim of this study was to identify a subset of patients in whom abstention of adjuvant endocrine therapy would be safe. Methods: In this bicentric retrospective study, we analysed the prognosis of consecutive patients treated for HR+ pT1a,bN0M0 breast cancer, focusing on the population without adjuvant endocrine therapy. Log rank test was used for univariate analysis and a cox model was used for multivariate analysis. Results: 885 patients with HR+ pT1a,bN0M0 breast carcinoma were treated between 1997 and 2007. Local treatment involved either mastectomy or breast conserving surgery followed by breast radiotherapy. 227 patients (25.6%) did not receive any adjuvant endocrine therapy. Comparatively to the group treated with endocrine therapy, these patients were significantly younger ( < 50 years old patients), with less grade II or III and less ductal histology. After a median follow-up of 6.4 years, 5 years-invasive disease free survival (IDFS) was significantly lower (89.8%) in the no endocrine therapy group than in the endocrine therapy group (94.6%) with log-rank p = 0.005. Distant Disease Free Survival (DDFS) and Overall Survival (OS) were not significantly different with numerically better results in the no-endocrine therapy group. In multivariate analysis, avoidance of endocrine therapy, grade II-III and young age (under 50 years old) were independent adverse prognostic factors for IDFS. Conclusions: In pT1a,bN0 HR+ patients, avoiding adjuvant endocrine therapy was slightly deleterious for IDFS but DDFS and OS were not affected. Discussion about risk/benefit ratio is crucial before proposing adjuvant endocrine therapy in this setting.
Mutations in NRAS codon 61, KRAS codon 146, and BRAF V600E as prognostic factors in patients who received anti-EGFR antibody for metastatic colorectal cancer.
Authors: Naoki Takahashi, Yasuhide Yamada, Hirokazu Taniguchi, Kohei Akiyoshi, Yoshitaka Honma, Satoru Iwasa, Ken Kato, Tetsuya Hamaguchi, Yasuhiro Shimada
Journal: Journal of Clinical Oncology (2012)

e14126 Background: Previous studies showed that gene mutations (NRAS, BRAF, PIK3CA) are associated with a poor prognosis or resistance of anti-EGFR antibody in metastatic colorectal cancer (mCRC) patients with wild type (WT) of KRAS codon 12/13 (KRAS-WT). However the significance of these biomarkers has not been clarified. In addition, EGFR immunohistochemistry (IHC) and EGFR gene amplification to evaluate the efficacy of anti-EGFR antibody treatment has not been reported for mCRC. Methods: We evaluated tumor response and survival in patients who received anti-EGFR antibody by mutation analysis of KRAS, NRAS, BRAF, and PIK3CA in KRAS-WT patients with mCRC. Tumor DNA samples are obtained from patients treated in our hospital with anti-EGFR antibody between August 2008 and August 2011. Results: A total of 117 patients were enrolled in this analysis, including 100 KRAS-WT patients. Seventy-one patients (60.7%) were all WT for KRAS, NRAS, BRAF, and PIK3CA, and 46 patients (39.3%) had at least 1 mutation or had insufficient DNA samples to analyze. Mutations of KRAS codon 61 (2 patients), KRAS codon 146 (5), BRAF V600E (2), PIK3CA exon9 (8), NRAS codon 12/13 (2), and NRAS codon 61 (5) were detected. No patients had a mutation of PIK3CA exon 20. Patients with at least 1 mutation had no response. Mutations of NRAS codon 61, KRAS codon 146, and BRAF V600E were associated with a shorter progression free survival (PFS) compared with all WT patients (p=0.049, p=0.004, p=0.036, respectively). Twelve patients (12% of KRAS-WT patients) with a mutation of NRAS codon 61, KRAS codon146, and BRAF V600E had poor prognosis compared with the other KRAS-WT patients (PFS, 6.4 vs 2.0 months, p&lt;0.001; overall survival (OS), 13.7 vs 7.9 months, p=0.012). In all WT patients, moderate to strong EGFR IHC was associated with a better response rate than negative and weak IHC (p=0.046). Conclusions: Mutations of NRAS codon 61, KRAS codon 146, and BRAF V600E could be a strong prognostic factor of anti-EGFR antibody in patients with mCRC. Combination of IHC and DISH of EGFR could identify patients with a tumor response to anti-EGFR antibody in patients that are all WT for KRAS, NRAS, BRAF, and PIK3CA.
Reply from Authors re: Alberto Bossi, Nicolas Mottet, Pierre Blanchard. Choline Positron Emission Tomography/Computed Tomography for Selection of Patients for Salvage Strategies After Primary Local Treatment of Prostate Cancer and Rising Prostate-specific Antigen: Ready for Prime Time? Eur Urol 2017;71:349–50
Authors: William P. Parker, R. Jeffrey Karnes, Lance A. Mynderse, Val J. Lowe, Mark A. Nathan, Eugene D. Kwon, Brian J. Davis
Journal: European Urology (2016)
It is not all about mating: Attractiveness predicts partner value across multiple relationship domains
Authors: Adar B. Eisenbruch, Aaron W. Lukaszewski, James R. Roney
Journal: Behavioral and Brain Sciences (2017)

Abstract An account of the “beauty premium” based only on mating motivations overlooks adaptationist models of social valuation that have broader explanatory power. We suggest a broader approach based on evolved preferences for attractive partners in multiple cooperative domains (not just mating), which accounts for many observations of attractiveness-based preferential treatment more comfortably than does the target article's mating-specific account.
Efficacy of additional chemotherapy following failure of currently approved therapies in patients with castration-resistant prostate cancer.
Authors: Luca Campedel, Paul Blanc-Durand, Sandra Assoun, Cristian Mateescu, Morgan Roupret, marc-Olivier Bitker, Christophe Vaessen, Jerome Parra, Eva Comperat, Haide Angele Boostandoost, Gabriel G. Malouf, Jean-PHilippe Spano
Journal: Journal of Clinical Oncology (2017)

274 Background: Approved therapies for patients with castration resistant prostate cancer (CRPC) include next generation androgen receptor inhibitors as well as taxanes which are given sequentially. After failure of these drugs, physicians may use additional chemotherapy such as carboplatin, paclitaxel, mitoxantrone and vinorelbine. The clinical benefit of these drugs in this setting remains fully unknown. Methods: A retrospective monocentric study of patients treated for CRPC was performed. Presence of metastasis and visceral involvement at diagnosis and at castration resistance, time between start of hormonotherapy and castration resistance were recorded as well as several clinical and biological parameters at start of CRPC first line. The cohort was divided into two groups according to the use of additional chemotherapies following failure of currently approved therapies. Results: Fourty subjects out of 138 cases (28.9%) fulfilled the inclusion criteria. At diagnosis, median patients age was 68 years (range, 53-86), median Gleason grade was 8 (6-10) and 53% of them harbored distant metastasis. At castration-resistance stage, 93% were metastatic including 27% out of them wihich harbored visceral involvement. Median overall survival (OS) of patients since castration-resistance was 34.9 months (range, 7.4-88.0). The two groups were comparable in terms of age, PSA level, and Gleason grade. Median OS for patients in the additional chemotherapy group (n = 16) was 42.4 months as compared to 37.3 months in the non additional treatment group (n = 24), with no statistical difference (p = 0.961). Main treatments administered consisted of carboplatin (n = 6), paclitaxel (n = 4) and mitoxantrone (n = 4). PSA response rate (decrease &gt; 50%) obtained with use of additional treatment was 12%. Median progression-free survival was 1.9 months (range, 0.7-13.1) and median overall survival was 4.2 months (range, 2.2-17.8). Conclusions: Our retrospective study suggests that additional treatment after standard treatment failure for CRPC is associated with limited benefit. Further studies are needed to clarify the role of new agents therapies in this setting.
Is vinorelbine pharmacokinetics modified in Asian patients when compared to caucasian patients?
Authors: Pierre Ferre, Zhimin Shao, Zefei Jiang, Dafang Zhong, Chen Xiaoyan, Jean-Philippe Burillon, Aurélie Petain, Grégoire Zorza, Li Zhang
Journal: Journal of Clinical Oncology (2012)

e13036 Background: Pharmacokinetics (PK) of vinorelbine (VRL) has been extensively studied through a series of clinical studies, mainly conducted in Caucasian patients. Interethnic differences in drug disposition may however induce interethnic variation in drug exposure. Consequently, the PK of VRL was assessed in Asian patients during two clinical studies conducted in China, and compared to previous knowledge from non-Asian patients. Methods: Two phase II studies were conducted in China using VRL on Day 1 and 8 in combination on Day 1 with iv cisplatin for lung cancer (NSCLC) or with epirubicin for breast cancer (ABC). Patients were randomized within each study to receive either iv VRL (25 mg/m2 on cycle 1) or oral VRL. PK samples were obtained from subgroups of patients, and blood VRL and its active metabolite DVRL were quantified through LC-MS/MS. Bayesian PK parameters were calculated and VRL monotherapy results (iv 25 mg/m²; oral 60 mg/m²) were compared to historical single agent data from Caucasian patients. A population PK analysis (Variol P. et al. Eur J Clin Pharmacol, 2002: 58) was conducted to investigate for a potential effect of ethnicity. Results: VRL PK was evaluated in 38 NSCLC and 43 ABC Asian patients. Blood VRL and DVRL concentrations profiles were consistent with those from European studies. In Asian patients, mean Cltot/F (oral VRL) was 138 ± 56.5 and 179 ± 87.3 L/h for NSCLC and ABC, and mean Cltot (iv VRL) was 34.6 ± 8.82 and 41.2 ± 13.5 L/h for NSCLC and ABC. Those results did not differ from a reference European study (Bourgeois H. et al. Cancer Chemother Pharmacol, 2007: 60) (n = 48), for which mean clearance was 144 ± 66.6 and 42.8 ± 12.2 L/h for oral and iv VRL. The population PK analysis (n = 222 and 111 patients for oral and iv route) did not evidence ethnicity as a significant covariate on both clearance and oral bioavailability. Conclusions: The PK results reported from 81 Asian patients having received iv or oral monotherapy VRL treatment are consistent with previous data from European PK studies. This is in line with the metabolism knowledge of VRL, mainly involving esterase and CYP3A4 enzymes, which are not described as highly functionally polymorphic in Caucasian and Asian population.
Moxetumomab pasudotox and minimal residual disease in hairy cell leukemia.
Authors: Robert J. Kreitman, Evgeny Arons, Katherine Still, Martin S. Tallman, Maryalice Stetler-Stevenson, Constance Yuan, David JP FitzGerald, Ira Pastan
Journal: Journal of Clinical Oncology (2015)

7079 Background: Moxetumomab pasudotox is a recombinant immunotoxin containing truncated Pseudomonas exotoxin fused to an anti-CD22 Fv, reported to achieve 46% complete remissions in 28 relapsed/refractory hairy cell leukemia (HCL) patients treated with 5-50 ug/Kg every other day for 3 doses (QOD x3) per cycle. As a secondary endpoint of this phase I study, minimal residual disease (MRD) was studied in the original cohort and in an additional 21 patients enrolled at the highest dose level, amounting to 33 patients at 50 ug/Kg QOD x3. Methods: MRD studies included immunohistochemistry (IHC) of bone marrow biopsy (BMBx) and flow cytometry (FC) of blood and bone marrow aspirate (BMA). Real-time quantitative (RQ)-PCR, previously reported to detect 1 HCL cell in 106normal, used immunoglobulin rearrangement (IgH)-specific primers, when patient HCL IgH sequencing was possible. Results: Elimination of MRD by BMA FC, BMBx IHC and blood FC was achieved in 13 of 46 evaluable patients, 12 (36%) of 33 at 50 ug/Kg x3 and 1 (33%) of 3 at 40 ug/Kg QOD x3, vs 0 of 10 at lower doses (p = 0.04). Of 36 patients at 40-50 ug/Kg, those MRD-negative included 5 by blood FC, 1 by BMBx IHC, 5 by both blood FC and BMBx IHC, and 13 by all 3 studies. The median time to resolution of MRD in these 13 patients was 84 days, just prior to cycle 4. Of these 13 MRD-free patients, 11 (85%) remain MRD-free for 28-72 (median 45) months, and all 13 remain MRD-free in blood. In contrast, 7 of 10 patients MRD-free by blood but not BMA FC eventually became MRD+ in blood (p = 0.0005). RQ-PCR was more sensitive than BMA FC; of 19 patients evaluable for RQ-PCR, 5 of 6 MRD-free by BMA FC were also MRD-free by BMA RQ-PCR. Conclusions: Moxetumomab pasudotox can eradicate MRD in multiply relapsed HCL patients. We are aware of no other non-chemotherapy option with documented multi-year MRD-free BMA FC in a significant fraction of HCL patients. BMA MRD eradication is associated with lack of HCL progression in blood. Additional testing with RQ-PCR will determine if this more sensitive test is associated with outcome and can be used to help determine the optimal number of cycles. This study of investigator reported data was sponsored by MedImmune and supported by NCI’s Intramural Research Program and the Hairy Cell Leukemia Foundation. Clinical trial information: NCT00462189.
Lesion-specific patterns of response and progression with anti-PD-1 treatment in metastatic melanoma (MM).
Authors: Megan Kate Lyle, Jenny HJ Lee, Alexander M. Menzies, Matthew MK Chan, Arthur Clements, Matteo S. Carlino, Richard Kefford, Georgina V. Long
Journal: Journal of Clinical Oncology (2014)

9077 Background: Anti-PD-1 therapy has demonstrated activity in MM but current data may not fully reflect patterns of response and relapse as discerned by comprehensive lesion-specific analysis. Methods: Bidimensional measurements of every metastasis (met) ≥5mm (≥15mm short axis for lymph nodes [LN]) in MM pts enrolled in the MK3475-001 phase 1 trial at a single center were obtained on CT scan at baseline, 12 wks and thereafter. Response of each individual met was determined by change in product of longest perpendicular diameters (POD) and classified as complete (CR, disappearance or <10mm short axis for LN), partial (PR, ≥50% reduction in POD), stable (SD, neither CR/PR/PD) or progressive (PD, ≥25% increase in POD and ≥5mm in 1 axis). Overall pt response was investigator determined using standard immune related response criteria (irRC). Results: 27 evaluable pts with med. follow up of 54 wks had a total of 442 discrete mets at baseline (med. 10/pt; range 2-68/pt; med. POD 129mm2). 13/27 (48%) pts had an irRC objective response (OR), 11 (85%) by first scan. Med. time to best response in pts with OR was 24 wks. Although only 1/27 pts had CR (3.7%), 228/442 (52%) individual mets underwent CR and 81% of pts (22/27) had ≥1 CR met at first scan. CR mets were smaller than non-CR [med. POD 80 vs 246mm2(p<0.05)] but 92/244 mets (38%) ≥100mm2 reached CR. CR rate was highest in lung vs other sites combined (p<0.05) (Table). Only 1 CR met subsequently progressed. Of 12 (44%) pts who progressed only 1 had prior OR. 10 (83%) of these pts PD in new and existing mets simultaneously. No site of PD predominated; only 1 pt (8%) PD in brain. 98/442 baseline mets (22%) progressed and most (74%) had PD as best response. Of 80 new or growing mets at first scan, only 4 (5%) subsequently had OR. Conclusions: Response to anti-PD1 therapy is rare in mets that are new or growing at first scan. CR in individual mets is common, sustained, and influenced by site and size. These results have implications for the biology of PD-1 inhibition, resistance, biomarker development and patient selection. Site of met CR PR/SD/PD Lung 141 (64%) 79 (36%) Liver 20 (54%) 17 (46%) Subcut 26 (42%) 36 (58%) LN 14 (41%) 20 (59%) Soft tissue 18 (32%) 39 (68%) Other 9 (28%) 23 (72%) Total 228 (52%) 214 (48%)
Mutational burden, immune checkpoint expression, and mismatch repair in glioma: implications for immune checkpoint immunotherapy
Authors: Tiffany R. Hodges, Martina Ott, Joanne Xiu, Zoran Gatalica, Jeff Swensen, Shouhao Zhou, Jason T. Huse, John de Groot, Shulin Li, Willem W. Overwijk, David Spetzler, Amy B. Heimberger
Journal: Neuro-Oncology (2017)

Despite a multiplicity of clinical trials testing immune checkpoint inhibitors, the frequency of expression of potential predictive biomarkers is unknown in glioma.In this study, we profiled the frequency of shared biomarker phenotypes. To clarify the relationships among tumor mutational load (TML), mismatch repair (MMR), and immune checkpoint expression, we profiled patients with glioma (n = 327), including glioblastoma (GBM) (n = 198), whose samples had been submitted for analysis from 2009 to 2016. The calculation algorithm for TML included nonsynonymous mutation counts per tumor, with germline mutations filtered out. Immunohistochemical analysis and next-generation sequencing were used to determine tumor-infiltrating lymphocyte expression positive for programmed cell death protein 1 (PD-1), PD ligand 1 (PD-L1) expression on tumor cells, MMR (MLH1, MSH2, MSH6, and PMS2) protein expression and mutations, and DNA polymerase epsilon (POLE) mutations.High TML was only found in 3.5% of GBM patients (7 of 198) and was associated with the absence of protein expression of mutL homolog 1 (MLH1) (P = .0345), mutS homolog 2 (MSH2) (P = .0099), MSH6 (P = .0022), and postmeiotic segregation increased 2 (PMS2) (P = .0345) and the presence of DNA MMR mutations. High and moderate TML GBMs did not have an enriched influx of CD8+ T cells, PD-1+ T cells, or tumor-expressed PD-L1. IDH1 mutant gliomas were not enriched for high TML, PD-1+ T cells, or PD-L1 expression.To clarify the relationships among TML, MMR, and immune checkpoint expression, we profiled the frequency of shared biomarker phenotypes. On the basis of a variety of potential biomarkers of response to immune checkpoints, only small subsets of glioma patients are likely to benefit from monotherapy immune checkpoint inhibition.