tbuckley/cabot-search huggingface dataset:
Reply: Software-assisted Computed Tomography Quantification of Airway Remodeling in the Normal Aging Process
Authors: Carlos H. Martinez
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

We think that small airway obstruction related to age is, indeed, most relevant in this elderly population.In fact, as the authors rightly pointed out, this phenomenon impacts functional analysis and could also contribute to disability among the oldest people.Quantitative CT imaging offers new insight into the scope and limits of lung and airway abnormalities, especially at the level of the small airways, which play a major role in obstructive diseases, while remaining beyond the zones that most pulmonary function tests evaluate.Furthermore, it is particularly noteworthy that this finding could be assessed using different technical approaches, such as Parametric Response Mapping or expiratory-to-inspiratory ratios of mean lung density.The variability related to age could be factored into clinical research using quantitative CT imaging.Also, the limits between normality and disease should now be assessed, as done by functionalists (5), and updated using a large range of the population to put forward radiomics as a reference tool to monitor small airway diseases.
High CD79b Expression Predicts a Poor Outcome in B-Cell Chronic Lymphocytic Leukemia (B-CLL).
Authors: Giovanni Del Poeta, Maria Ilaria Del Principe, Antonella Zucchetto, Francesco Buccisano, Cristina Simotti, Luca Maurillo, Laura Giannì, Pietro Bulian, Adriano Venditti, Angela Coletta, Pasquale Niscola, Paolo de Fabritiis, Valter Gattei, Sergio Amadori
Journal: Blood (2008)
Treatment of borderline resectable (BR) and locally advanced (LA) pancreatic cancer in the era of FOLFIRINOX and gemcitabine plus <i>nab</i>-paclitaxel: A multi-institutional study.
Authors: Kamran Idrees, Alexander A. Parikh, Lauren McLendon Postlewait, Sharon M. Weber, Clifford Suhyun Cho, Ahmed I. Salem, Robert C. G. Martin, Charles Raben Scoggins, Hong Jin Kim, Jacquelyn Carr, Heather Stuart, Brent Xia, Syed Ahmed, Daniel Erik Abbott, Shishir Kumar Maithel, David A. Kooby, Nipun B. Merchant
Journal: Journal of Clinical Oncology (2016)

451 Background: FOLFIRINOX or Gemcitabine+nab-Paclitaxel (Gem/nPac) has superior overall survival (OS) compared with gemcitabine alone in pts with Stage 4 pancreatic cancer (PC). Based on these results, FOLFIRINOX or Gem/nPac has been utilized in neoadjuvant (NA) setting for BR and LA PC. This report describes our multi-institutional experience with NA treatment with FOLFIRINOX or Gem/nPac followed by surgical resection. Methods: Pts with BR and LA PC who received NA FOLFIRINOX or Gem/nPac and underwent surgical resection between 2011 and 2015 at 7 high volume pancreas centers were reviewed. Pre-operative chemoradiation therapy (pCXRT) was administered selectively based on radiographic response (RR). Near-complete (minimal residual disease) or complete pathologic response (PR) was categorized as marked PR. Results: 86 pts received either NA FOLFIRINOX (69%) or Gem/nPac therapy (31%) for BR (67%), LA (32%) PC. pCXRT was administered in 71% of pts. Pts received a median of 4 cycles of FOLFIRINOX (range 1-28) and 3 cycles of Gem/nPac (range 2-13). No grade 4-5 toxicities were noted. The majority of pts underwent pancreaticoduodenectomy (84%) and vascular resection was performed in 53% - 40 with venous resection and 6 with arterial resection. R0 resection rate was 86% with no difference between two treatment groups (p = 0.9). Reduction in CA 19-9 or RR did not correlate with pathological response (p = 0.8). A marked PR was seen in 12 pts – 13.6% vs. 15.4% for FOLFIRINOX and Gem/nPac, respectively (p = 0.8). Adjuvant chemotherapy or CXRT was administered in 44% of pts. With a median follow up of 20 months (mo), OS was 27.4 mo with median OS in marked PR was 53 vs. 25 mo in moderate PR/non-responders (p = 0.04). Recurrence was noted in 45 pts – 49% had distant recurrence, 20% had local recurrence and 31% had both. Conclusions: Neoadjuvant FOLFIRINOX or Gem/nPac therapy in conjunction with aggressive surgical resection in BR and select LA PDAC pts result in significant long-term survival especially in marked pathologic responders. Further, optimization of treatment protocols in the neoadjuvant and adjuvant setting is warranted since recurrence rates are high.
Surrogacy analysis of prostate-specific antigen (PSA) decline for improved overall survival (OS) with enzalutamide (ENZ) in AFFIRM.
Authors: Andrew J. Armstrong, Fred Saad, Neal D. Shore, Karim Fizazi, De Phung, Carl Frank Dmuchowski, Mohammad Hirmand, David Forer, Howard I. Scher, Johann S. De Bono
Journal: Journal of Clinical Oncology (2016)

266 Background: ENZ significantly increased OS for men with metastatic castration-resistant prostate cancer (mCRPC) vs. placebo and significantly decreased PSA levels. However, the prognostic significance and role of PSA falls as a surrogate for OS are not established. Methods: Men in the AFFIRM trial were grouped by maximal unconfirmed PSA decline during the 1st 90 days of treatment in a post-hoc analysis. Each PSA decline criterion was assessed for surrogacy for OS by the proportion of treatment effect (PTE)-explained and Prentice criteria. We also assessed the association of PSA decline with OS, progression-free survival (PFS), and pain response. Results: ENZ improved OS (hazard ratio 0.63, p &lt; 0.001) and was associated with higher rates of PSA declines when compared to placebo (odds ratio &gt; 19.0, p &lt; 0.001). Greater declines in PSA were associated with longer OS, PSA PFS, radiographic PFS, and higher pain response when compared with no PSA decline or PSA increase (table). All decline measures from baseline were highly prognostic for OS and several ( &gt; 0%, ≥ 30%, ≥ 50% declines) explained a proportion of the treatment effect (PTE 1.07–1.29, 95% CI lower bounds &gt; 0.63), in which treatment was no longer significant after adjustment for the decline measures (p &gt; 0.20). Full surrogacy was not demonstrated. Conclusions: In AFFIRM, &gt; 0, ≥30%, and ≥50% PSA declines within 90 days of treatment fulfilled Prentice surrogacy criteria 1–3. Prentice 4, equivalency of survival adjusting for PSA decline outcomes, could not be demonstrated. PSA declines are associated with longer PFS and improved pain response. External prospective validation is needed. Clinical trial information: NCT00974311. [Table: see text]
A phase I/II study of S-1 plus cisplatin alternating with S-1 plus docetaxel in patients with advanced gastric cancer (AGC).
Authors: A. Hosokawa, K. Ogawa, S. Kajiura, Y. Tsukioka, T. Kobayashi, N. Horikawa, Y. Kobayashi, A. Yoshioka, S. Sumi, T. Sugiyama
Journal: Journal of Clinical Oncology (2011)

101 Background: S-1 plus cisplatin has been regarded as standard first-line chemotherapy for patients with AGC in Japan, and S- 1 plus docetaxel showed promising results for AGC in clinical trials. To investigate the usefulness of S-1 plus cisplatin alternating with S-1 plus docetaxel as first-line treatment in patients with AGC, we conducted a phase I/II study to determine the maximum tolerated dose (MTD), the recommended dose (RD), preliminary efficacy and toxicity. Methods: Eligibility criteria included pathologically confirmed AGC; no prior chemotherapy; Age 20 to 74, ECOG performance status (PS) of 0 to 2; adequate organ function; and written informed consent. Cisplatin was administered on day1 and the dose was escalated by 10 mg/m 2 from starting dose of 40 mg/m 2 in phase I part. S-1 was given orally at 80 mg/m 2 on day1-14. Docetaxel was administered at 40 mg/m 2 on day 22 in combination with S-1 80 mg/m 2 on days 22-35. The treatment was repeated every 6 weeks. The RD was studied in every 3-6 patients cohort and determined according to the pre-defined DLTs. Primary endpoint of phase II was the response rate (RR). Results: Between Aug 2006 and Jul 2010, 33 pts were enrolled. Nine patients entered the phase I part and 24 enrolled in phase II part. In the phase I part, the MTD of cisplatin was presumed to be 50 mg/m 2 , because 50% of patients (3/6) developed DLTs. Therefore, the RD of cisplatin was estimated as 40 mg/m 2 , and the 27 patients received the treatment at RD level. Patients characteristics were as follows: median age=65 years (range 48-74), Male: female=21:6, PS 0:1:2=11:16:0, diffuse: intestinal=19:8, initially unresectable: recurrent=24:3. The RR was 59.2% (95% CI, 40.7-77.7). Median follow-up period was 14.6 months, median PFS was 7.9 months, and median survival time was 17.2 months, although survival data remain to be confirmed. Major grade 3/4 toxicities were neutropenia (63%), leucopenia (41%), and anemia (33%). These toxicities were tolerable and manageable. No treatment-related death was observed. The updated analysis will be presented at the meeting. Conclusions: This alternating treatment seems to be effective and well tolerated in the first-line treatments in patients with AGC. No significant financial relationships to disclose.
Multidisciplinary approach to patients with recurrent colorectal liver metastases.
Authors: Luca Vigano, Guido Costa, Tiziana Comito, Vittorio Pedicini, Dario Poretti, Marta Scorsetti, Luigi Solbiati, Guido Torzilli
Journal: Journal of Clinical Oncology (2016)

426 Background: Recurrence after liver resection (LR) for colorectal metastases (CLM) is common. Re-resection is the standard treatment. In unresectable patients, radiofrequency ablation (RFA) and stereotactic body radiation therapy (SBRT) have been proposed, but they did not show a clear survival benefit in comparison with chemotherapy alone. The present study aims to elucidate the outcome of patients with recurrent CLM according to the received treatment. Methods: A series of 323 consecutive patients undergoing first LR between 2004 and 2013 was considered. Of these, 206 (63.8%) had recurrence and were analyzed. Redo surgery was scheduled whenever possible. If surgery was excluded, RFA was considered for hepatic lesions, while SBRT for both hepatic and extra-hepatic lesions. Results: Among the 206 analyzed patients with recurrence, 72 underwent re-resection, 19 RFA and 14 SBRT. Liver-only recurrences were treated in 68.3% of cases (69/101, 47 surgery), pulmonary ones in 57.9% (22/38, 15 surgery) and other extra-hepatic ones in 20.9% (14/67, 10 surgery). After a median follow-up of 32 months, three-year survival after the diagnosis of recurrence (OS) was 42.2% (median 37.4 months). OS was associated with the administered treatment: at three years 70.5% if surgery, 53.8% if RFA/SBRT, and 15.0% if chemotherapy alone, p &lt; 0.0001. The same association was observed focusing the analysis on patients with a total of three lesions in the liver and/or the lung (1-3 liver/lung group, n = 86): three-year OS was 82.6% if surgery, 55.8% if RFA/SBRT, and 29.2% if chemotherapy, p &lt; 0.0001. Progression-free survival after the treatment of recurrence (PFS) was associated with the received treatment: at two years 29.0% if surgery, 14.4% if RFA/SBRT, and 2.6% if chemotherapy, p &lt; 0.0001. The same result was observed in the “1-3 liver/lung” group: two-year PFS was 32.1% if surgery, 18.3% if RFA/SBRT, and 0% if chemotherapy, p = 0.001. RFA and SBRT groups had similar OS and PFS. Conclusions: Aggressive management of recurrent CLM prolongs OS and PFS. Surgery is the best treatment option. Despite potential selection biases, RFA and SBRT should be considered in unresectable patients because they are associated with better outcome than chemotherapy alone.
A randomized, double-blind phase II trial of exemestane with or without MM-121 in postmenopausal women with locally advanced or metastatic estrogen receptor-positive (ER+) and/or progesterone receptor-positive (PR+), HER2-negative breast cancer.
Authors: V. M. Moyo, M. J. Higgins, R. Aravelo-Araujo, N. Iannotti, V. Charu, N. Dhindsa, P. E. Goss
Journal: Journal of Clinical Oncology (2011)

TPS112 Background: Resistance to endocrine therapy (ET) is a common challenge in breast cancer. In treatment regimes involving exemestane, combination therapy employing MM-121 presents the potential to overcome this obstacle. MM-121 is a fully human IgG2 molecule that blocks ligand binding to ErbB3 preventing heterodimerization of ErbB3 with other ErbB receptors. It induces internalization and degradation of ErbB3. Methods: This study is a double-blinded, randomized phase II trial of exemestane +/- MM-121. Depending on the treatment assignment, MM-121 or placebo will be administered as a 60 minute IV infusion once per week and exemestane (25 mg) will be administered orally once per day. The trial is designed to demonstrate whether MM-121 + exemestane is more effective than exemestane alone in ER+ and/or PR+ and HER2 negative breast cancer patients that have failed prior anti-estrogen therapy in the locally advanced or metastatic setting. Patients will be treated until radiologic or clinical progression of their disease is documented. 130 patients, from multiple sites globally, will be randomized in a 1:1 ratio to receive either MM-121 + exemestane or placebo + exemestane. Primary objective of the study is to determine whether the combination MM-121 + exemestane is more effective than exemestane alone based on Progression Free Survival. Secondary objectives will include overall survival, objective response rate and clinical benefit rate. Results: As of January 2011, the study is open at 9 centers and 3 patients have been enrolled.
The role of Ki-67 proliferation index vis-à-vis Oncotype DX.
Authors: S. Sahebjam, R. Aloyz, D. Pilavdzic, M. Brisson, C. Ferrario, N. Bouganim, V. Cohen, W. H. Miller, L. C. Panasci
Journal: Journal of Clinical Oncology (2011)

e11055 Background: Most newly diagnosed patients with invasive breast cancer have node negative disease. A key question in management of these patients is the risk/benefit ratio of adjuvant chemotherapy. Several microarray tests have been developed and are currently used to help identifying the patients who will benefit from adjuvant chemotherapy. Ki 67 proliferation index is less expensive and has been used as a prognostic and predictive factor in node positive breast cancer and neoadjuvant setting. Methods: Forty five cases of T1-2 N0 M0 (ER positive, HER2/neu negative) breast cancer were reviewed. Oncotype Dx results were available for all patients. Tumor specimens were stained for Ki 67. Results: The median of Ki 67 index was 17 (range 2-90). The median Oncotype recurrence score was 17 (range 7-60). There was a strong linear correlation between Ki67 index and Oncotype recurrence score (correlation coefficient= 0.74, P value= 0.000). This correlation was stronger in tumors with Ki 67 proliferation index of ≥ 25. Patients were divided to low risk, intermediate risk and high risk group based on expression of Ki 67. All patients in low Ki 67 group (Ki 67 of ≤ 10) had recurrence score of low or intermediate. Most patients (92%) in high Ki 67 group (Ki 67 ≥ 25) had oncotype recurrence score of high or intermediate. Furthermore, neither semi-quantitative immunohistologic expression of ER and HER2, nor nuclear grade had a significant impact on the correlation between Ki67 index and Oncotype recurrence score. Conclusions: Ki 67 proliferation index is a major but not the sole determinant of Oncotype Dx score. Immunologic expression of ER and HER-2 do not significantly impact this correlation. Ki 67 proliferation index can be used to identify patients with a high probability of having increased Oncotype Dx score and requiring adjuvant chemotherapy.
High Response Rate in Patients with De-Novo or Relapsed/Refractory Acute Myeloid Leukemia Using a Novel Strategy of Low-Dose, Prolonged Administration of Cytarabine and Thioguanine in Combination with Filgrastim in the Ambulatory Setting: A Single-Center, Retrospective Study
Authors: Christopher K Arthur, Brandon Aubrey, Matthew Greenwood, Keith Fay, Luke Coyle, Eunice Liu, Christopher Ward, Garry Soo, Naomi Mackinlay, William s Stevenson
Journal: Blood (2011)
Identification of genes with different methylation profiles between RAEB and RCMD in myelodysplastic syndrome.
Authors: S. Lee, H. Kwon, S. Kim, S. Oh, K. Kwon, J. H. Lee, Y. Lee, D. Seo, J. Han, H. Kim
Journal: Journal of Clinical Oncology (2010)

6608 Background: Myelodysplastic syndromes (MDS) are a group of clonal hematological disorders characterized by significant prognostic heterogeneity and a preleukemic condition with transformation into acute myeloid leukemia. However, the underlying genetic events remain poorly understood. Since aberrant DNA methylation might play a causative role in disease and prognosis, the study investigated the difference of DNA methylation profiles between refractory anemia with excess blast (RAEB) and refractory cytopenia with multilineage dysplasia (RCMD). Methods: Bone marrow samples from 20 patients with primary MDS (nine RAEB and 11 RCMD) and peripheral blood samples from four controls, were assessed using a commercial whole genome-wide methylation assay. Results: The microarray data revealed statistically significant hypermethylation of 69 genes in RAEB, but not in RCMD. The candidate genes mapped to five different networks, with network 1 being the top-scoring network with functions in gene expression, cancer, and cell cycle. Five network 1 genes (GSTM5, BIK, CENPH, RERG, and ANGPTL2) were associated with disease progression in malignancy. Methylation-specific polymerase chain reaction was used to detect the methylation level of candidate gene promoters in both RAEB and RCMD. Among these genes, methylated promoters of GSTM5 (55.5% and 20%, respectively), BIK (20% and 0%, respectively), and ANGPTL2 (44.4% and 10%, respectively) occurred more frequently in RAEB than in RCMD. Conclusions: Although the functions of these genes were not revealed, DNA methylation of GSTM5, BIK and ANGPTL2 might induce epigenetic silencing and contribute to the increasing blasts, resulting in progression of MDS. No significant financial relationships to disclose.
Intensity-modulated radiation therapy (IMRT): Differences in target volumes and improvement in clinically relevant doses to small bowel in rectal carcinoma.
Authors: H. Mok, C. H. Crane, T. Briere, S. Beddar, M. E. Delclos, S. Krishnan, P. Das
Journal: Journal of Clinical Oncology (2011)

586 Background: In the treatment of rectal cancer, a strong dose-volume relationship exists between the amount of small bowel receiving low- to intermediate-doses of radiation and the rates of acute, severe gastrointestinal toxicity. Highly conformal treatment approaches, such as intensity-modulated radiation therapy (IMRT), may reduce dose to adjacent organs-at-risk (OAR). We performed a dosimetric evaluation of IMRT compared to 3-dimensional conformal radiation therapy (3DCRT) in standard, preoperative treatment for rectal cancer. Methods: Using RTOG consensus contouring atlas, treatment volumes were generated for ten patients treated preoperatively, with IMRT plans compared to 3DCRT plans derived from classic anatomic landmarks, as well as modified 3DCRT plans treating the RTOG consensus volume. The patients were all T3, were node-negative (N=1) or node–positive (N=9), and were planned to a total dose of 45-Gy. Bowel displacement was achieved using a carbon-fiber bellyboard apparatus with prone positioning. Results: IMRT plans had superior PTV coverage, dose homogeneity, and conformality in treatment of the gross disease and at-risk nodal volume, in comparison to 3DCRT. Additionally, in comparison to the modified 3DCRT plans, IMRT achieved a concomitant reduction in doses to the bowel, bladder, pelvic bones, and femoral heads, with an improvement in absolute volumes of small bowel receiving dose levels known to induce clinically-relevant acute toxicity. In the six patients with the highest volume of small bowel (range: 209-537-cc), the volume of bowel receiving 15-Gy was reduced from a median of 224-cc in the modified 3DCRT plans to 185-cc with IMRT. Also, the IMRT volumes were typically larger than that covered by classic 3DCRT fields, without incurring penalty with respect to adjacent OAR. Conclusions: For rectal carcinoma, IMRT, compared to 3DCRT, yielded plans with superior target coverage, homogeneity, and conformality, while lowering dose to adjacent OAR. This is despite treating larger volumes, raising the possibility of a clinically-relevant improvement in the therapeutic ratio through the use of IMRT with a belly-board apparatus. No significant financial relationships to disclose.
Capecitabine/cisplatin doublet in patients with antracycline and taxane pretreated and HER2-negative metastatic breast carcinoma.
Authors: N. Ozdemir, S. Aksoy, M. B. Akinci, D. Uncu, B. Budakoglu, H. Abali, O. B. Oksuzoglu, N. Zengin
Journal: Journal of Clinical Oncology (2011)

e11115 Background: Treatment of metastatic breast cancer patients is challenging issue. To evaluate the activity and toxicity of the combination of capecitabine and cisplatin (CapCisp) in antracycline and taxane pretreated HER-2 negative metastatic breast carcinoma (MBC) patients was the aim of our study. Methods: Patients with HER-2 negative MBC and pretreated with anthracycline and taxane who treated with CapCis combination were retrospectively evaluated. All patients received Cap 2x1000 mg/m2 on days 1-14, and Cisp 60 mg/m2 on day 1, repeated every 3 weeks. In the case of disease control without intolerable toxicity, single agent Cap was continued until progression or intolerable toxicities after Cis cessation. Results: Sixty- four female MBC patients were included the study. Median age of the patients was 43 (min-max; 20-66). Infiltrative ductal carcinoma was the most common histology (85.9%). Ten-percent of the patients had grade I, 42% grade II, and 48.0% grade III tumors. Estrogen receptor and progesteron receptor were positive in 48.4% and 51.6%, respectively. Twenty-eight percent of the patients had triple negative tumors. Almost the entire patients had this regimen as a third-line treatment. The median combination chemotherapy cycle was 6 (min-max; 2-8). Twenty-seven nonprogressive patients continued treatment with single agent Cap. Median single agent Cap cycle was 4 (min-max;1-38) after the combination chemotherapy. Disease control rate was 81.3% (complete response 6.3%; partial response 48.4%, stable disease 26.6%, progressive disease 18.8%). Median follow-up time was 10.6 months Median time to disease progression was 7 months, median overall survival was 17 months (6.9-16.1, 95% CI) since the treatment of CapCisp chemotherapy. There was no treatment related to death. The most frequent grade 3-4 toxicities were neutropenia (8.1%), nausea – vomiting (7.8%) and thrombocytopenia (6.3%). Conclusions: CapCisp doublet has an encouraging antitumor activity with acceptable and manageable toxicity in antracycline and taxane pretreated Her-2 negative metastatic breast carcinoma patients.