tbuckley/cabot-search huggingface dataset:
Prospective phase 1 study assessing feasibility of IMRT and IGART to deliver simultaneous integrated high-dose tumor boost (up to 70 Gy) for the radical treatment of localized muscle-invasive bladder cancer.
Authors: Shaista Hafeez, Karole Warren-Oseni, Helen McNair, Vibeke Hansen, Fiona McDonald, Susan Lalondrelle, Alan Thompson, Pardeep Kumar, Victoria Harris, Melissa Tan, Kabir Mohammed, Karen Thomas, Kelly Jones, David Paul Dearnaley, Alan Horwich, Robert Anthony Huddart
Journal: Journal of Clinical Oncology (2015)

307 Background: Advances in IGART offer individualized solutions to improve target coverage and reduce normal tissue irradiation allowing opportunity to increase radiation tumour dose and spare normal bladder. Methods: A library of 3 IMRT plans were created (small, medium and large) from planning CT scans performed at 30 and 60 minutes; treating whole bladder to 52 Gy and tumour to 70 Gy in 32 fractions. Where normal tissue dose constraints were not met consideration was made to boosting tumour to lower dose (68 Gy-64 Gy). Cone beam CT (CBCT) imaging was performed prior to each fraction. Appropriate PTV was selected from the library for treatment delivery. Post treatment CBCT was acquired weekly in order to assess intra-fraction filling and coverage. Results: 22 patients have been planned using this technique. All have met tissue constraints for treatment to 70 Gy. 21 patients have completed radiotherapy, 18 completed treatment to 70 Gy; 1 patient was planned and treated to 68 Gy prior to dose escalation using this technique; 1 patient was treated to a total dose of 65.6 Gy because dose limiting toxicity occurred before dose escalation. 572 CBCTs have been evaluated. Treatment was delivered using small, medium, and large plans in 35%, 52%, and 13% cases respectively. Mean intra-fraction filling was 14 cm 3 (SD 16.3, range 0.23-107.9). Mean time between pre- and post-CBCTs was 13 min (SD 2.1, range 9-18). Mean D 98% as assessed on post-radiotherapy CBCT was 98.7% (SD 1.78, range 89.9-100%). At median follow-up of 8 months (range 1-24 months), 18 patients remain alive and disease free. 2 superficial recurrences and 3 deaths from metastatic bladder cancer have occurred. No muscle invasive recurrences have occurred within this cohort. Using this technique one patient has experienced late toxicity (grade 3 cystitis) 5.3 months after radiotherapy (now resolved). Conclusions: IGART using IMRT to delivery a simultaneous integrated tumour boost is feasible with acceptable toxicity. Trial recruitment continues at 70 Gy and will be evaluated in a randomised trial (RAIDER). Clinical trial information: NCT01124682.
Racial disparities in quality metrics of muscle invasive bladder cancer (MIBC).
Authors: Stephanie A. Mullane, Christian Meyer, Toni K. Choueiri, Mark A Preston, Paul L. Nguyen, Joaquim Bellmunt, Quoc-Dien Trihn
Journal: Journal of Clinical Oncology (2016)

442 Background: There is conflicting evidence regarding MIBC treatment and outcomes. Our aim was to assess the variation in four quality metrics (neoadjuvant chemotherapy, time to treatment ≤ 3 months, ≥ 10 lymph nodes removed, use of continent urinary diversion) according to race. Methods: Using the National Cancer Database (NCDB), we identified 17,944 MIBC patients undergoing radical cystectomy. Race was stratified into non-Hispanic White (nHW), African-American (AA), Asian (A) and Hispanic/Latino (H). Uni- and multivariable analyzes examined the association between race and receipt of quality metrics, accounting for baseline characteristics. Cox regression model was used to calculate differences in overall survival(OS). Results: Baseline characteristics (insurance status, income, education, age, sex, facility type, Charlston Comorbidity Index) were significantly different between races. We did not observe any difference in the number of quality metrics received ( ≤ 1 vs ≥ 2) according to race (p = 0.161). However, there were significant differences for time to treatment and diversion type (p = 0.002, 0.012). Blacks had a significantly worse OS after adjustment for significant confounders (OR: 1.224, CI: 1.113-1.347). Conclusions: Even after accounting for treatment disparities, AA have a worse OS, warranting further investigation into potential biologic and epidemiologic factors affecting race and MIBC.
Observational study to evaluate the pattern of trastuzumab (T) use and survival outcomes in HER2-positive (HER2+) early breast cancer (EBC): Regional Southern Italy experience.
Authors: V. Adamo, G. R. R. Ricciardi, B. Adamo, B. Agostara, M. Caruso, V. Gebbia, N. Gebbia, G. Lavenia, G. L. Banna, A. Mafodda, R. Rossello, A. Butera, S. Spada, N. Borsellino, A. Mangiameli, M. Campiglio, G. Tuccari
Journal: Journal of Clinical Oncology (2011)

e11043 Background: HER-2 have shown to be over-expressed in 20-25 % of primary breast cancer, and is associated with poor prognosis. Several large, randomized studies have reported a significant reduction in the risk of recurrence when trastuzumab is administered with chemotherapy in EBC HER2+ cancer. The aim of this study is to identify the pattern of use of T and survival outcomes in HER2+ EBC in Sicily. Methods: This observational, multicenter, retrospective study was conducted in 11 oncology centers in Sicily during 2006-2010. Inclusion criteria: age ≥18 years, surgery for early breast cancer, diagnosis of invasive disease, HER2-positivity as defined by current guidelines, and treatment with T. Results: 569 patients (pts) were included. Surgical outcomes: quadrantectomy 58.1%, mastectomy 33.7% and tumorectomy 8.2%. Tumor stage: T1 50.6%, T2 37.9% and T3 11.5%. Histology: invasive ductal carcinoma 94.7%. Histological Grade: G3 55.6%. Node status: N0 52.6%, N1 27.3%, N2 12.5%, N3 6.7% and Nx 0.9%. Hormonal status: estrogen receptor positive 60.1% and progesterone receptor positive 47.3%. Proliferation: Ki67 ≥10% in 82.4%. Neoadjuvant and adjuvant T was administered in 11.9% and 93.4% pts, respectively. Sequential administration of T after adjuvant chemotherapy was the most common schedule. Cytotoxic agents used: anthracyclines 76.04%, taxanes 33.02% and both agents in combination 26.8%. Relapses were observed in 5.6% pts. The main metastatic sites were: liver 18.75%, bone 12.5%, lung 12.75%, brain 12.75%, locoregional and contralateral 12.5% and lymph nodes 9.4%. N positivity and hormone receptor negativity are significantly associated to relapse. Cardiac toxicity (LVEF reduction >10%) was observed in 3.5% pts. DFS at 25 months of FU was similar to that of HERA DFS at 23.5 months of FU. Conclusions: Our study confirms the efficacy and safety of T in early HER2+ breast cancer, although includes a better prognostic population. These data indicate a satisfactory level of adherence to the international guidelines in the management in HER-2 positive EBC, showing a significant improvement in DFS when T was added to adjuvant chemotherapy.
Synaptic Vesicle Endocytosis Occurs on Multiple Timescales and Is Mediated by Formin-Dependent Actin Assembly
Authors: Tolga Soykan, Natalie Kaempf, Takeshi Sakaba, Dennis Vollweiter, Felix Goerdeler, Dmytro Puchkov, Natalia L. Kononenko, Volker Haucke
Journal: Neuron (2017)
Oncological outcomes in high-risk prostate cancer after radical prostatectomy based on Gleason score: USC experience with 3,755 cases.
Authors: Hooman Djaladat, Weichen Xu, Jie Cai, Gary Lieskovsky, Siamak Daneshmand
Journal: Journal of Clinical Oncology (2015)

60 Background: Gleason score is an important predictor of oncological outcomes after radical prostatectomy. However, it remains unclear whether there is a difference in outcomes between Gleason score (GS) 8 and 9-10 disease. We compare oncological outcomes after open radical prostatectomy for prostate cancer patients with GS of 8 versus 9-10. Methods: Of 3,755 radical prostatectomy patients (1987-2008), 360 patients with final pathology of GS 8, 9 or 10 and N0M0 were included. No significant differences between age, race and surgical margins between the two groups. Impact of GS on outcomes was controlled for preoperative PSA, pathological stage, use of adjuvant radiation therapy and use of neoadjuvant/adjuvant hormone deprivation therapy in multivariable analyses. Outcomes of interest were biochemical recurrence free survival (BCRFS), clinical recurrence free survival (CRFS) and overall survival (OS). Kaplan Meier plots, log rank tests and multivariable Cox regression model were used to analyze the data. Results: Median follow-up for GS 8 and GS 9-10 were 10.0 years and 8.6 years, respectively (p=0.43). Conclusions: Long term follow up after radical prostatectomy reveals significant differences in BCRFS and CRFS but not OS between patients with GS 8 vs. 9-10 prostate cancers. Further studies may examine sub-stratification of GS 8 tumors into a lower risk category than GS 9-10 tumors. [Table: see text] [Table: see text]
Acupuncture for hot flashes for prostate cancer patients
Authors: M. Hayes, C. Reeder, T. M. Beer
Journal: Journal of Clinical Oncology (2009)

e16125 Background: Hot flashes are a common adverse effect of androgen suppression therapy (AST) for prostate cancer. We sought to determine the effect of acupuncture on hot flash frequency and intensity, quality of life, sleep quality, and biomarkers. Methods: Men on AST who had a hot flash score (HFS) (J Clin Oncol. 2001;19:4280–4290) &gt; 4 were treated with acupuncture with electro-stimulation twice weekly for 4 weeks and once per week for an additional 6 weeks. The treatment plan included the following points: bilateral gallbladder 34, bladder 15, 23, and 32 and unilateral governing vessel 20, heart 7, pericardium 6, liver 2, and spleen 6. Continuous low intensity electro-stimulation at 2 Hz was used to connect bladder 23 inferiorly to bladder 32. Needles were retained for 30 minutes with manual stimulation at 10-minute intervals. The primary endpoint was a 50% reduction in the HFS after 4 weeks of therapy. Hot Flash Related Daily Interference Scale (HFRDIS) (J Pain Symptom Manage. 2001;22:979–989), Pittsburgh Sleep Quality Index (PSQI) (Psychiatry Res. 1989;28:193–213), Short Form Health Survey-36 (SF-36) (Med Care. 1992;30:473–483), blood serotonin, plasma CGRP, and urinary 5-HIAA were also examined. Results: 22 men were enrolled between September 2003 and April 2007 and were eligible and evaluable. After 4 weeks of therapy, 9 of 22 patients (41%, 95%CI 21 to 64%) had &gt; 50% reduction in hot flashes. 12 of 22 patients (55%, 95%CI 32 to 76%) met this response definition after 7 weeks of treatment. No patients had a significant increase in the HFS on therapy. Hot flash related quality of life, measured by HFDIS, improved in all patients and sleep quality, measured by PSQI, improved in hot flash responders. Hot flash related biomarkers including serotonin, 5-HIAA, and CGRP were examined before and after treatment. Conclusions: Multiple placebo-controlled trials have demonstrated that 25% of patients respond to placebo treatment for hot flashes. 41% of patients responded by week 4 and 55% by week 7 in this pilot study providing evidence of a potentially meaningful benefit with acupuncture therapy. Hot flash-related quality of life was also significantly improved with acupuncture treatment. Further studies of acupuncture for hot flashes in men undergoing hormonal treatment for prostate cancer are warranted. No significant financial relationships to disclose.
Clinical significance of serum alkaline phosphatase level in advanced pancreatic cancer.
Authors: I. Ohno, S. Mitsunaga, K. Nakachi, S. Shimizu, H. Takahashi, H. Okuyama, Y. Kojima, A. Ochiai, T. Okusaka, M. Ikeda
Journal: Journal of Clinical Oncology (2011)

183 Background: Alkaline phosphatase (ALP) is an enzyme that is elevated by various hepatobiliary diseases. Generally its elevation is thought to indicate bile stasis. There are some reports that show ALP is an important prognostic factor for several cancers such as colon, lung, and gastric cancer. Often it is speculated that ALP elevation indicates bile stasis caused by liver metastasis. However, the significance of ALP elevation in advanced pancreatic cancer (APC) patients is not well evaluated. The aim of this study was to determine the significance of elevated serum ALP as a prognostic factor in patients with APC even without jaundice and liver metastasis. Methods: Serum ALP levels were measured in 393 patients with APC receiving gemcitabine monotherapy before treatment, and according to those levels, patients were subgrouped (ALP&lt;upper normal limit (UNL), UNL-500 U/L, 501-700 U/L, 701-1000 U/L, 1000U/L &lt; ALP). The clinical data of each group were analyzed to see characteristics of elevated ALP patients. The relationship between ALP level and survival, response were also examined. Results: The elevated ALP group included poor performance status (PS&gt;1) patients (41.3%, p=0.001), and associated with low serum albumin (3.31±0.38, p&lt;0.01). The elevated ALP group (median survival time (MST) 112 days) showed significantly worse prognosis and lower disease control rate compared to the normal ALP group (MST 217days) (p&lt;0.001, p&lt;0.001). Multivariate analysis revealed ALP (p&lt;0.001), CRP (p&lt;0.001), ascites (p&lt;0.001), distant metastasis (p=0.003), white blood cell count (p=0.005), PS (p=0.020), AST (p=0.020), and ALT (p=0.020) were independent prognostic factors. Similar results were seen in liver metastasis free patients without jaundice. Conclusions: Elevated serum ALP level correlated with poor performance status and low serum albumin. ALP was also the independent prognostic factor in liver metastasis free APC patients without jaundice. No significant financial relationships to disclose.
Measuring compliance to capecitabine in colon cancer: A comparison of administrative data and medical records.
Authors: Adam Amlani, Aalok Kumar, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2015)

531 Background: Studies of administrative data indicate that compliance with oral anti-neoplastic agents, including capecitabine, is suboptimal. Using a population-based cohort of colon cancer, our aim was to evaluate the proportion of patients deemed non-compliant that actually had a reasonable indication for not adhering to their prescribed oral systemic therapy. Methods: Consecutive patients diagnosed with stage III colon cancer from 2008 to 2010, referred to any 1 of 5 regional cancer centers in British Columbia, Canada, and who initiated at least 1 cycle of oral adjuvant capecitabine within 12 weeks of curative resection were reviewed. Administrative data from the provincial oncology pharmacy database were analyzed to assess for non-compliance, which was defined as any prescription refill delays of &gt;/=1 week from the end date of the preceding cycle. Electronic medical records were abstracted to examine the factors, if any, which contributed to non-compliance. We compared administrative vs. medical record data to determine the level of concordance and the appropriateness of non-compliance. Results: We included 752 patients: median age was 70 years (IQR 35-87), 56% were men, and 86% had ECOG 0/1. Administrative data showed that 413 patients were non-compliant: 230 (56%) and 183 (44%) had 1 and &gt;/=2 late refills, respectively. In this group, a total of 2095 cycles of capecitabine were delivered among which 688 (33%) treatment delays occurred. No differences in baseline characteristics were observed between individuals who were compliant and those who were not (all p&gt;0.05). Of the 688 prescription delays that were ascertained from administrative data, medical records demonstrated that 30 (4%) were misclassified. From the remainder, the majority were attributable to valid reasons, including: 339 (49%) toxicities necessitating time off therapy; 170 (25%) physician discretion; 40 (6%) travel requiring adjustment to treatment schedule; and 6 (1%) patient refusal. Only 103 (15%) cases were considered as true non-compliance. Conclusions: Using administrative data alone to measure oral drug compliance without corroborating with medical records may overestimate the degree of non-adherence.
Distant recurrences of colorectal cancer: Incidence, systemic treatment, and survival in daily practice.
Authors: Yvette van Gestel, Myrthe van Herk-Sukel, Ignace de Hingh, Harm Rutten, Geert-Jan Creemers, Valery E. P. Lemmens
Journal: Journal of Clinical Oncology (2013)

441 Background: To provide population-based data on the patterns, risk factors, treatment, and survival of distant recurrences of colorectal cancer (CRC). Methods: All patients (n=6,066) diagnosed with CRC M0 in 10 large Dutch non-academic hospitals between 2003 and 2008 were included. By means of active follow-up, data on distant recurrences and systemic treatment were collected. Median follow-up was 4.4 year. Results: 1,074 (18%) patients were diagnosed with distant recurrent disease during follow-up of which 85% within 3 years. Most common affected sites were liver (60%), lung (39%), extra-regional lymph nodes (22%) and peritoneum (19%) (multiple sites possible). Male sex (female=ref (17%), 19%/HR 1.1 95%CI 1.0-1.3), advanced primary tumor stage (T1=ref (4%), T2 9%/HR 3.0 95%CI 1.8-4.9, T3 21%/HR 6.1 95%CI 3.8-9.9, T4 29%/HR 11.0 95%CI 6.7-18.1), advanced lymph node stage (N0=ref (11%), N1 29%/HR 2.8 95%CI 2.4-3.3, N2 41%/HR 4.5 95%CI 3.7-5.4), primary tumor localization (left colon=ref (17%), right colon 16%/HR 0.8 95%CI 0.7-1.0, rectum 25%/HR 1.2 95%CI 1.0-1.4), and tumor differentiation grade (well differentiated=ref [16%], poorly differentiated 26%/HR 1.4 95%CI 1.2-1.7) were associated with increased risk recurrences while chemotherapy for the primary tumor was associated with reduced risk (HR 0.8 95%CI 0.7-0.9). Recurrence rates did not differ between hospitals. 52% of patients with recurrences received systemic therapy, ranging from 34-62% between the 10 hospitals (p&lt;0.01). Half of these patients (52%) was also treated with bevacizumab, ranging from 39-73% between hospitals (p&lt;0.05). Median survival since diagnosis of recurrence was 31 months for patients with lung metastases only, 16 months for liver metastases only, 14 months for lung metastases only, and 5 months for metastases confined to the peritoneum. Conclusions: The development of distant recurrent disease was strongly related to tumor characteristics, but not correlated with hospital of primary treatment. Population-based data on distant recurrences may ultimately contribute to more accurate patient information, and more efficient follow-up schemes.
VEGF receptor 1 and heparanase expression as prognostic factors in cholangiocellular carcinoma.
Authors: E. Goekkurt, J. Stoehlmacher, D. E. Aust, P. V. Danenberg, K. D. Danenberg, S. Lehmann, U. Mogck, G. Ehninger, A. C. Hoffmann
Journal: Journal of Clinical Oncology (2011)

226 Background: Cholangiocellular carcinoma (CCC) remains to be a tumor with very few treatment choices and limited prognosis. In this study, we sought to determine the prognostic role of VEGF receptor 1 (VEGFR1), heparanase (HPSE) and EGF receptor (EGFR) gene expression in patients with resected CCC. Methods: 47 formallin-fixed paraffin embedded FFPE tumor samples from patients with resected CCC were analyzed. FFPE tissues were dissected using laser-captured microdissection and analyzed for VEGFR1, HPSE and EGFR mRNA expression using a quantitative real-time RT-PCR method. Gene expression values (relative mRNA levels) are expressed as ratios between the target gene and internal reference genes (beta-actin, b2mg, rplp2, sdha). Results: VEGFR1 and HPSE expression levels were significantly associated with overall survival (OS). Patients expressing low levels of VEGFR1 displayed a median OS of 23.2 months compared to 5.3 months in patients with high VEGFR1 expression (p=0.006, logrank test). Patients with low HPSE expression had a median OS of 19.8 months compared to 10.0 months in patients with high HPSE expression (p=0.02, logrank test). EGFR and PDGFRα expression were significantly associated with HPSE and VEGFR1 expression (p=0.03 and p&lt;0.0001, respectively). Conclusions: These results suggest that VEGFR1 and HPSE gene expression levels may play a role as prognostic factors in patients with CCC. Further studies are warranted to study these associations. [Table: see text]
Assessment of IL-6, IL-8, bFGF, PDGF-BB, and VEGF-A as prognostic and predictive biomarkers for anti-VEGF in metastatic colorectal cancer (mCRC).
Authors: Timothy Jay Price, Amanda Rose Townsend, Maressa Bruhn, Chee Lee, Joe Wrin, Aravind Shivasami, Georgia Arentz, Niall C. Tebbutt, David Cunningham, Jenny Hardingham
Journal: Journal of Clinical Oncology (2014)

502 Background: There remains a need for predictive biomarkers in mCRC to better identify patients who clinically benefit from anti-VEGF therapy, in particular bevacizumab (BEV). The AGITG MAX trial compared capecitabine (C) with capecitabine (+/- mitomycin C (M)) and BEV and PFS was superior in the CB+/-M arm. Here we have taken a panel of pro-angiogenic proteins to assess whether there is a signal for a predictive factor for bevacizumab outcome in the MAX trial tissue population (TTP). Methods: Protein was isolated from FFPE tumour tissue and assayed using custom Bio-plex arrays to assess the expression levels of candidate tumour biomarkers IL-6, IL-8, bFGF, PDGF-BB and VEGF-A. As there are no accepted cutoff points for these analytes we chose the medians of distribution of each of these biomarkers as cutoff points for dichotomization into “high” v “low”. We then correlated levels of the biomarkers with objective response rate, disease-free and overall survival. Results: Total protein was isolated from FFPE tumour sections from 41.5% of patients (n=196) recruited into the MAX clinical trial and assayed for the proteins using a multiplex platform. Patients were generally balanced, tumour tissue population v intention to treat. Median follow up time is 30.2 mths. For patients receiving BEV there was no relationship between the level of IL-6, IL-8, bFGF, PDGF-BB and VEGF-A and PFS and OS. In patients treated with BEV/C vs. C alone, low tumor VEGF-A was predictive of better ORR as compared to those with a high level (ORR 53% vs 38%, p = 0.03). Multivariate analyses showed low VEGF-A expression level was a significant prognostic factor for longer progression free survival (median PFS 9.3 months low VEGF-A v 7.2 months high VEGF-A, multivariate adjusted HR 1.55 (95% CI 1.12-2.13), p = 0.008). Conclusions: We have shown that the chosen panel of pro-angiogenic proteins was not predictive for PFS or OS outcomes when B is added to C in mCRC. However low VEGF-A level did predict for higher ORR and was an independent prognostic marker for PFS in this cohort.