tbuckley/cabot-search huggingface dataset:
Biochemical and functional outcomes of brachytherapy for young men (≤50) with prostate cancer.
Authors: Daniel Shasha, Dorothy Boo, Leora Perlow, Robert Salant, Louis Benjamin Harrison
Journal: Journal of Clinical Oncology (2013)

245 Background: NCCN guidelines endorse prognostic risk grouping to select therapy, and lend equal support to surgery and radiation therapy (RT). Despite this, the optimal treatment of prostate cancer in young men remains contentious, with the majority treated surgically. This may be because there are few reports of RT outcomes with long follow-up (FU) in this cohort. Thus, we report long-term biochemical and functional outcomes after prostate brachytherapy (BT) +/- supplemental therapies in men ≤ 50 years old. Methods: With IRB approval we analyzed outcomes of 47 patients ≤ 50 yrs old (median 48, range 48-50) implanted with curative intent by a single physician (DS) at Beth Israel Medical Center (New York City) between 2000-2009. Supplemental external beam therapy (45-50.4 Gy) was delivered to patients with NCCN intermediate risk (IR) and high risk (HR) disease, and to select patients with high volume low risk (LR) disease. Androgen deprivation therapy (ADT) was used in all HR patients, for pre-implant prostate downsizing, and for biopsy demonstrating very high volume disease. Biochemical failure (BF) was defined as “nadir +2.” Genitourinary (GU), gastrointestinal (GI) and erectile functional outcomes are included. Results: Median follow up (FU) was 5.2 yrs (range: 2-11). Only 1 patient experienced BF, thus, overall freedom from BF was 97.9%. Grade 2 acute and late 2 GU toxicity were reported in 10.6 % (n = 5) and 8.5% (n = 4), respectively. Grade 2 proctitis was seen 4.3 % (n=2). Erectile function was preserved in 41 of 47 men (87.2 %) with or without phosphodiesterase-5 inhibitors. Conclusions: With median FU of 5.2 years, excellent biochemical control with minimal toxicity was achieved in men ≤ 50 years old. The finding of only a single patient exhibiting BF over the 11 years of FU in this study is highly encouraging. Erectile preservation rates were high, and acute and late GI and GU toxicity were low. These results support prostate BT as an excellent option for patients in this age group.
Volatolomics of breath as an emerging frontier in pulmonary arterial hypertension
Authors: Morad K. Nakhleh, Hossam Haick, Marc Humbert, Sylvia Cohen-Kaminsky
Journal: European Respiratory Journal (2017)

There is accumulating evidence in support of the significant improvement in survival rates and clinical outcomes when pulmonary arterial hypertension (PAH) is diagnosed at early stages. Nevertheless, it remains a major clinical challenge and the outcomes are dependent on invasive right heart catheterisation. Resulting from pathophysiological processes and detectable in exhaled breath, volatile organic compounds (VOCs) have been proposed as noninvasive biomarkers for PAH. Studies have confirmed significant alterations of the exhaled VOCs among PAH patients when compared to controls and/or patients with other respiratory diseases. This suggests exhaled breath analysis as a potential noninvasive medical application in the field of PAH. In this article, we review and discuss the progress made so far in the field of exhaled volatolomics (the omics of VOCs) as a potential noninvasive diagnostics of PAH. In addition, we propose a model including possible biochemical pathways on the level of the remodelled artery, in which specific VOCs could be detectable in exhaled breath during the early phases of PAH. We debate the different analytical approaches used and recommend a diagram including a “bottom–top” strategy, from basic to translational studies, required for promoting the field.
How is race/ethnicity associated with patient reporting of cancer pain in recently diagnosed colorectal and lung cancer?
Authors: Kathryn Anne Martinez, Sydney Morss Dy
Journal: Journal of Clinical Oncology (2012)

50 Background: Racial and ethnic disparities in the quality of cancer pain treatment are widely documented. The purpose of this study was to examine adjusted differences by race/ethnicity in the odds of reporting pain and differences in pain severity. Methods: This study used data from Cancer Care Outcomes Research and Surveillance Consortium (CanCORS), a nationally representative cohort study of colorectal and lung cancer patients. Patients were identified following incident colorectal or lung cancer diagnosis via rapid case ascertainment. Surveys were administered between three and five months following diagnosis. Pain was assessed via patient self-report using the Brief Pain Inventory. Control variables included sex, age, education, wealth, fatalism, marital status, survey language, self-reported health status, depression, cancer stage, and care at a Veterans Administration (VA) facility. Each control variable was first individually assessed as a potential mediator in the relationship between race/ethnicity and pain severity. Final models were fully adjusted with all control variables. Results: Among 3,216 individuals with colorectal cancer (16.4% black), 40% reported pain; among 2,545 with lung cancer (12% black), 57% reported pain. The odds of reporting pain did not differ by race/ethnicity in lung or colorectal cancer patients in adjusted analyses. None of the included covariates significantly mediated this relationship. However, among those reporting pain, pain severity was higher for black relative to white patients in both lung (p=0.002) and colorectal cancer (p=0.000). Conclusions: The odds of reporting presence of pain did not differ by race/ethnicity. However, among those reporting pain, blacks reported higher pain severity than whites in both cancer types, even after adjusting for patient and health status characteristics. Differential pain severity by race/ethnicity, particularly for black patients, may be an important consideration in assessing the quality of cancer pain management.
SmgGDS splice variants: Potential novel targets for breast cancer therapeutics.
Authors: C. Bergom, A. Hauser, E. L. Lorimer, R. Li, A. C. Mackinnon, C. L. Williams
Journal: Journal of Clinical Oncology (2011)

225 Background: Breast cancer malignancy is promoted by the small GTPases K-Ras, Rap1, RhoA, and Rac1. We recently reported that the activity of these GTPases is regulated by two splice variants of SmgGDS, named SmgGDS-558 and SmgGDS-607. SmgGDS is overexpressed in lung and prostate cancer, but its role in breast cancer is unknown. Here we examine whether SmgGDS splice variants are expressed in breast cancer and promote breast cancer malignancy. Methods: Immunohistochemical staining for SmgGDS was performed on archival human breast tumors (N=183) and normal breast tissue (N=22). Immunoblotting was used to detect SmgGDS splice variants in human breast cancer cell lines. siRNAs that silence different SmgGDS splice variants were used to examine the effects of SmgGDS knockdown on breast cancer cell spreading, cell proliferation via [ 3 H]thymidine uptake, anchorage-independent cell growth using soft agar colony assays, and NF-kB activation using luciferase reporter assays. Results: SmgGDS expression was detected in &gt;65% of DCIS and invasive lobular and ductal carcinoma, and in 100% of metastatic tumors, but was detected in only 18% of normal breast tissue specimens (p&lt;0.01). All tested cell lines expressed both SmgGDS splice variants. Silencing SmgGDS-558 or SmgGDS-607 with siRNA significantly diminished cell proliferation (100±2.0 vs. 11.3±1.0 vs. 50.5±2.2, p&lt;0.05) in MCF-7 cells, with similar results in MDA-MB-231 and T47D cells. MCF-7 soft agar colony formation was significantly decreased 71% and 49% when SmgGDS-558 or SmgGDS-607 was silenced. MCF-7 cell spreading was promoted by silencing SmgGDS-558, but not SmgGDS-607. NF-kB activation was also decreased by 30% in resting and TNF-α-treated MCF-7 and MDA-MB-231 cells by silencing either splice variant. Conclusions: SmgGDS is disproportionally expressed in human breast cancers. Reduction of SmgGDS-558 and SmgGDS-607 levels dramatically reduced breast cancer cell proliferation, soft agar colony formation, and NF-kB activation. Our results indicate that SmgGDS splice variants regulate breast cancer malignancy, most likely through their regulation of small GTPases. This study identifies SmgGDS splice variants as novel therapeutic targets in breast cancer.
Characterization of patients who received prior chemotherapy for advanced breast cancer (ABC) in BOLERO-2.
Authors: Mario Campone, Fabienne Lebrun, Shinzaburo Noguchi, Kathleen I. Pritchard, Howard A. Burris, J. Thaddeus Beck, Yoshinori Ito, Denise Aysel Yardley, Thomas Denis Bachelot, Barbara Pistilli, Bohuslav Melichar, Katarina Petrakova, Francis P. Arena, Frans Erdkamp, Wael A. Harb, Jennifer Keating Litton, Ashok Panneerselvam, Mona El-Hashimy, Tanya Taran, Michael Gnant
Journal: Journal of Clinical Oncology (2013)

557 Background: In patients with hormone-receptor–positive (HR + ) breast cancer, endocrine therapy is the standard of care both in the adjuvant setting and as first-line treatment for ABC. For selected HR + patients with ABC, chemotherapy (CT) may be utilized if disease burden is high and rapid symptom control is required (Barrios CH. GAMO.2010). In the phase 3 BOLERO-2 study (NCT00863655), 1 line of prior CT in the ABC setting was allowed. This subset analysis examined disease characteristics and the efficacy of everolimus (EVE) plus exemestane (EXE) in patients who received CT for ABC prior to BOLERO-2 study entry. Methods: In BOLERO-2, 724 patients with HR + , human epidermal growth factor receptor-2–negative (HER2 – ) ABC whose disease recurred or progressed during/after a nonsteroidal aromatase inhibitor were randomized 2:1 to EVE (10 mg/d) + EXE (25 mg/d) or placebo (PBO) + EXE. The primary endpoint was progression-free survival (PFS) by local investigator review and confirmed by blinded independent central review. Results: A subset of 186 patients (26%) received prior CT for ABC: 125 in the EVE + EXE group and 61 in PBO + EXE. In this subset, 54% (67 of 186) of patients received prior CT only in the advanced setting and 46% (58 of 186) of patients received prior CT in both the neoadjuvant/adjuvant and advanced settings. Incidences of visceral metastases (67% vs 56%), multiple metastases (79% vs 66%), and ≥ 4 metastatic sites (18.3% vs 15%) were higher in ABC patients with prior CT for ABC at study entry versus those with no prior CT for ABC. Disease recurrence &lt; 6 months from initial diagnosis was recorded in 32.2% (n = 60) of prior CT patients versus 17.3% (n = 93) of patients with no prior CT. Median PFS (by local assessment) in patients who received prior CT for ABC was substantially longer with EVE + EXE versus PBO + EXE (6.1 vs 2.7 mo; HR = 0.38; 95% CI, 0.27-0.53). PFS by central review showed similar results (7.1 vs 2.8 mo, respectively; HR = 0.42; 95% CI, 0.27-0.65). Conclusions: These results demonstrate that patients with HR + , HER2 – ABC who received previous CT in the advanced setting had a higher tumor burden and derived clinically significant benefit from combination treatment with EVE + EXE. Clinical trial information: NCT00863655.
Presence of Minimal Residual Disease by Flow Cytometry After Induction Chemotherapy Is Less Predictive of Overall and Progression-Free Survival Compared to Conventional Prognostic Factors Including Cytogenetic Risk and Age
Authors: Cameron D. Griffiths, Elena Liew, Jennifer K. Grossman, Douglas A. Stewart, Joanne Luider, Iwona Auer, Adnan Mansoor, Michelle Geddes
Journal: Blood (2012)
Outcome and dose intensity (DI) in the elderly subgroup of the AGITG MAX phase III trial of capecitabine (C), bevacizumab (B), and mitomycin C (M) in first-line metastatic colorectal cancer (CRC).
Authors: T. J. Price, D. Zannino, K. Wilson, J. Simes, G. A. Van Hazel, B. A. Robinson, A. Broad, V. Ganju, S. P. Ackland, N. C. Tebbutt
Journal: Journal of Clinical Oncology (2011)

3621 Background: With age the frequency of cancer and chronic disease increases. CRC is a common cancer and treatment with chemotherapy and biological agents will be a major health issue in the elderly. Methods: MAX, a three arm study of C vs CB vs CBM, found an improvement in PFS with addition of B (+/− M) to C. This analysis assesses effect of adding B (+/− M) to C on PFS, OS, RR, Dose delivered and toxicity in elderly patients (age >75y). Results: 21% were >75y. Number/Median age: C 37/78.5y, CB 32/78.7y, CBM 30/80.2y. Baseline characteristics were balanced. 88% commenced C dose of 2,000mg/m2/day, d1-14, q21 (61% for <75y). 88% ECOG 0-1. Proportion receiving all 3 chemotherapy drugs at some time (5FU/oxaliplatin/irinotecan) was 10% >75y v 20% <75y. Percentage dose and number of cycles of C, B and M received, median PFS and OS reported in table. Interaction test for OS and PFS revealed no impact of age. Gd 3/4 tox for >75y C/CB/CBM respectively was (%); vomiting 5/13/3, diarrhea 19/22/20, HT 0/3/3, thrombosis/thrombus/embolism 5/6/13, cardiac 0/6 (3 Gd5)/3. There was 1 perforation (Gd5) in C. Grade 2/3 HFS (%) was 38/59/53. One Gd 3/4 neutropenia episode in CB. Overall, toxicity rate similar to <75 y. Conclusions: DI and number of cycles of C, B and M did not differ in those >75yrs compared to those <75yrs, noting more patients were commenced on 2,000mg/m2/day if age >75 yrs. Significant improvement in PFS with addition of B to C was seen in the elderly group. There was no signal of increased toxicity, including rates of VTE/ATE for those age >75yrs. Dose delivered PFS OS <75y >75y <75y (m) >75y (m) <75y (m) >75y (m) Dose intensity (%) Ave No. of cycles Dose intensity (%) Ave No. of cycles C 94.1 9.9 93.2 6.6 5.8 5.6 - 20.0 13.4 C B 90.6 99.7 11.3 11.7 85.6 99.3 9.1 9.3 8.5 p=0.001 HR 0.65 (CI 0.5-0.84) 8.8 p=0.01 HR 0.53 (CI 0.32-0.86) 20.4 15.7 C B M 90.8 99.8 99.4 10.7 10.5 3.4 85.2 99.1 99.8 10.6 10.7 3.0 7.8 p=0.002 HR 0.66 (CI 0.51-0.86) 10.4 p=0.0002 HR 0.38 (CI 0.23-0.64) 16.1 19.9 Interaction test for age p=0.24 p=0.16
Avoiding skin creams right before radiation: Myth or sound advice?
Authors: Brian C. Baumann, Ioannis I Verginadis, Chuan Zeng, Carolyn Vachani, Timothy Solberg, Costas Koumenis, James M. Metz
Journal: Journal of Clinical Oncology (2015)

51 Background: Radiation dermatitis in breast cancer patients is common and often treated with topical creams. Patients are traditionally advised to avoid lotions for several hours before radiotherapy (RT) based on concern that creams might increase skin dose. With modern RT’s improved skin sparing, this recommendation may be irrelevant. We hypothesize that applying either metallic or non-metallic creams before treatment would have minimal effect on skin dose. Methods: We conducted an online, 24-question OncoLink survey of patients and providers to determine current skin cream practices. To evaluate the dosimetric effect of creams, we delivered 200 MU at 100 cm SSD and measured the dose at the surface and 2 cm depth in a tissue equivalent phantom, with or w/o 2 common skin creams, Aquaphor and silver sulfadiazine. We assessed the effect of various photon and electron energies, cream thicknesses and beam incidence on dose. The effect of creams on skin dose was also evaluated in C57BL/6 mice using γ-H2AX IHC staining. Results: 27 of 33 surveyed breast cancer patients (82%) and 43 of 45 providers (96%) either received or gave the advice to avoid applying creams prior to RT treatments. Measurements showed no difference in dose at the surface or 2 cm depth with or w/o a 1-2 mm application of either cream when using enface 6 or 15 MV photons. The same application of cream had no effect on surface dose as a function of beam incident angle from 15-60°, except for a 7% increase at 60° with the silver cream. Surface dose for 6 &amp; 15 MV beams were significantly increased with a thicker (≥3 mm) layer of cream. For 6 MV, the surface dose was 105 cGy (Aquaphor), 102 cGy (silver cream) and 88 cGy (controls). For 15 MV, the doses were 70, 60 and 52 cGy. With 6 and 9 MeV electrons, there was only a 2-5% increase in surface dose with use of creams. There were no dose differences at 2 cm depth. Irradiated skin in mice showed no difference in γ-H2AX positive foci with or w/o creams. Conclusions: This is the first dosimetric assessment of the effect of skin creams for RT dermatitis. Our findings suggest that thin or moderately applied creams, even if applied just prior to RT, have minimal impact on skin dose, regardless of beam energy or beam incidence. Applying very thick amounts of cream just prior to RT increased surface dose and should be avoided.
Pattern of occult nodal relapse diagnosed with <sup>18</sup>F fluoro-choline PET/CT in prostate cancer patients with biochemical failure after prostate-only radiotherapy.
Authors: Alexis Lepinoy, Alexandre Cochet, Adele Cueff, Luc Cormier, Etienne Martin, Philippe Maingon, Jean Francois Bosset, Francois Brunotte, Gilles Crehange
Journal: Journal of Clinical Oncology (2014)

77 Background: 11 C or 18 F-labeled choline PET/CT has led to better understanding of the lymph drainage pattern of prostate cancer. It can provide radiation oncologists with maps to guide the delivery of prophylactic pelvic radiotherapy while minimizing radiation toxicity to non-target normal tissue with intensity modulated radiation therapy (IMRT). The purpose of this study was twofold: (1) to describe the pattern of nodal relapse in prostate cancer patients with biochemical failure after prostate-only radiotherapy; and (2) to determine whether patients with 18 F-fluoro-choline (FCH) PET/CT positive nodes experienced treatment failure within the clinical target volume (CTV) defined by the RTOG guidelines (CTV RTOG ). Methods: Between July 2008 and December 2012, 83 patients with a prostate cancer had a FCH PET/CT for biochemical failure after radiotherapy. Of 65 patients with FCH-positive findings, 33 had positive nodes. This analysis included 31 patients who had undergone prior prostate-only radiotherapy or radical prostatectomy followed by local radiotherapy. Each choline FCH positive node was assigned to a lymph node station and situated with regard to the CTV RTOG . Results: Fourteen patients (45.2%) had a relapse outside the CTV RTOG . Of the 17 patients with a positive node inside the CTV RTOG, 15 had a single node (88.2%) while seven patients out of the 13 evaluable patients (53.9%) who had a relapse outside the CTV RTOG had two or more positive nodes on FCH PET/CT. Patients with FCH+ nodes outside the CTV RTOG were more likely than patients with FCH+ nodes inside the CTV RTOG to have two or more involved nodes (OR= 8.75, [95% CI: 1.38-54.80], p= 0.020). The ventral part of the external iliac station (29.0%) was the main site of relapse inside the CTV RTOG whereas relapses that occurred outside the CTV RTOG involved the proximal common iliac (19.3%) and lower periaortic nodes (19.3%) up to L2-L3. Conclusions: Nearly half of the patients had FCH+ nodes outside the CTV RTOG with a significantly higher number of nodes involved outside the CTV RTOG . Three-dimensional mapping of nodal relapses evaluated with FCH PET/CT suggests that with IMRT the upper field limit of pelvic radiotherapy could be extended to L2-L3 safely to cover 95% of nodal stations at risk of an occult relapse.
Autologous Bone Marrow-Derived Stem Cell Therapy in Patients with Severe Peripheral Arterial Disorders: A Pilot Study.
Authors: Zoltan Boda, Miklos Udvardy, Katalin Razso, Mariann Szarvas, Katalin Farkas, Judit Toth, Laszlo Jambor, Pal Soltesz, Zsolt Olah, Peter Ilonczai, Janos Hunyadi, Tamas Sipos, Krisztina Litauszky, Janos Kappelmayer, Zoltan Vereb, Eva Rajnavolgyi
Journal: Blood (2007)
A pilot study of adjuvant chemotherapy with cisplatin and irinotecan for high-grade pulmonary neuroendocrine carcinona (large cell neuroendocrine carcinoma and small cell lung cancer).
Authors: H. Kenmotsu, S. Niho, T. Ito, Y. Ishikawa, H. Tada, I. Sekine, S. Watanabe, M. Yoshimura, N. Yamamoto, F. Oshita, K. Kubota, K. Nagai
Journal: Journal of Clinical Oncology (2011)

7076 Background: Large cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC) are recognized as high grade neuroendocrine carcinoma (HGNEC) of the lung. In patients with completely resected SCLC, platinum-based adjuvant chemotherapy may be considered. However, the optimum chemotherapy regimen has not been determined. We conducted a multicenter phase II trial to evaluate cisplatin and irinotecan in postoperative adjuvant chemotherapy for the HGNEC. Methods: Patients with completely resected stage IA, IB, IIA, IIB or stage IIIA HGNEC received 4 cycles of cisplatin (60 mg/m2, day 1) plus irinotecan (60 mg/m2, day 1, 8, 15). This regimen was repeated every 4 weeks. Other eligibility criteria included ECOG PS 0–1, age 20, and <75 years old, adequate organ function, no prior chemotherapy or radiotherapy. Patients with UGT1A1 polymorphisms (homozygous for *6 or *28, simultaneously heterozygous *6 and *28), associated with irinotecan-related severe toxicity, were excluded. The primary endpoint was the rate of completion of chemotherapy (defined as underwent 3 or 4 cycles), and secondary endpoints were 3-year relapse free survival, 3-year survival, and toxicity. Results: 40 patients were administered with cisplatin and irinotecan between September 2007 and July 2010. Patients’ characteristics were as follows: median age (range) 65 (45-73) years; male 85%; ECOG-PS 1 60%; SCLC 40%; stage IA/IB/IIA/IIB/IIIA 32/35/0/8/5%; lobectomy 90%. The rate of completion of chemotherapy was 83% (95% C.I.; 63-91%). Toxicities: Grade (G) 3/4 neutropenia (38%/10%), G3/4 anemia (15%/10%). G3 febrile neutropenia (13%), G2 creatinine (0%), G2/3 fatigue (25%/13%), G2 anorexia (15%), G2/3 nausea (20%/10%), G2/3 vomiting (10%/5%), G2/3 diarrhea (28%/5%). No treatment related deaths were observed in this study. Conclusions: Cisplatin and irinotecan showed acceptable toxicities and favorable feasibility as postoperative adjuvant chemotherapy for HGNEC of the lung.
Effect of High Body Mass Index on the Prognosis of Diffuse Large B-Cell Lymphoma
Authors: Yukako Hattori, Naoto Tomita, Taisei Suzuki, Yasufumi Ishiyama, Kumiko Kishimoto, Satoshi Koyama, Hiroyuki Takahashi, Kazuho Miyashita, Yuki Nakajima, Kenji Motohashi, Hirotaka Takasaki, Rika Kawasaki, Chizuko Hashimoto, Katsumichi Fujimaki, Rika Sakai, Shin Fujisawa, Shigeki Motomura, Yoshiaki Ishigatsubo
Journal: Blood (2014)