tbuckley/cabot-search huggingface dataset:
Assessment of molecular determinants of development and treatment efficacy in radiation induced sarcoma (RIS). EORTC STBSG Translational Research Project 01/01
Authors: P. Hohenberger, U. Schneider, P. Hoogendorn, O. S. Nielsen, J.-Y. Blay, J. T. Hartmann, M. Peiper, I. Judson
Journal: Journal of Clinical Oncology (2005)

9008 Background: Radiation-induced sarcomas (RIS) is a challenging problem with few data available. We analysed characteristics of tumor biology to obtain a molecular profile of the RIS and correlated the findings with treatment outcome. Methods: 207 pts with sarcomas within an irradiation field were registered from 11 countries. All tumors were biopsy-proven. In 107 pts, paraffin blocks were available. We collected data on the primary disease radiation (RT) had been applied for, dose and type of RT, location of the tumor, type, grade, and response to treatment of the RIS, long-term tumor control and survival. Two pathologists used a four-eye principle for histological re-classification (H&E, EVG, actin, desmin, S-100) and analysis of a molecular profile by cyclins A, E, B1 nu/cy and D1; checkpoint proteins p53, p21, RB; resistance genes MdR-1, LRP, MRP-5; CD31/34; CD117; Ki-67/MIB-1. SPSS was used for statistical analysis. Results: Re-classification resulted in different subtyping in 36%. Osteosarcoma (OSa, 30%), leiomyosarcoma (LMS, 13%), angiosarcoma (10%), and MFH (9%) were the most frequent subtypes whereas 13% could not be classified (NOS). RT dose delivered ranged from 30 Gy to 260 Gy and latency from 7 to 42 yrs. No correlation between RT dose and latency could be found, however, LMS showed a significantly longer latency (p<0.03). Angiosarcoma were only found following RT for breast cancer (BC), however, BC pts. treated with telecobalt developed OSa as their RIS. Systemic chemotherapy (ADM based, COSS) was applied in 84 pts (RR 41%, 7 pts with pCR); LRP was significantly more present in STS than in OSa (p<0.002) but failed to show prognostic value for response. Median survival was 2.2 years. R0 resection after chemotherapy gave the most favourable outcome. Multivariate analysis correlated cyclines/RB significantly with survival. Conclusions: Intergroup collaboration allowed to collect the largest series of RIS worldwide. A molecular profile of subgroups as angiosarcoma after breast cancer could be obtained. Systemic chemotherapy seemed to be effective, however, R0 resection after chemotherapy resulted in best survival. No significant financial relationships to disclose.
A randomized trial of 79.2Gy versus 70.2Gy radiation therapy (RT) for localized prostate cancer.
Authors: Jeff M. Michalski, Jennifer Moughan, James Purdy, Walter Bosch, Jean-Paul Bahary, Harold Y. Lau, Marie Duclos, Matthew Parliament, Gerard Morton, Daniel A. Hamstra, Michael J. Seider, Michael Lock, Malti Patel, Hiram Alberto Gay, Eric Vigneault, James Dignam, Howard Mark Sandler
Journal: Journal of Clinical Oncology (2015)

4 Background: RTOG 0126 is a phase III trial for localized prostate cancer (PC) testing whether dose escalation to 79.2Gy with 3DCRT or IMRT will improve overall survival (OS). Methods: Stage cT1b-T2b with Gleason Score (GS) 2-6 and PSA ≥ 10 and &lt;20 or GS 7 and PSA &lt;15 were eligible and randomized to receive 79.2Gy or 70.2Gy. No androgen withdrawal was used. Treatment was 3DCRT or IMRT to 79.2Gy in 44 fractions or 70.2Gy in 39 fractions. The objective was to detect a 23% reduction in mortality hazard (HR=0.77) for 79.2Gy. ASTRO and Phoenix definition was used for biochemical failure (BF). Time to local progression (LP), distant metastases (DM), PC death, and late GI/GU toxicity was calculated from date of registration. OS was estimated by Kaplan Meier and arms compared with log rank test. BF, LP, DM, time to late GI/GU, and PC death were estimated by cumulative incidence method and arms compared with Gray’s test. Results: 1,532 men were randomized, 763 to 79.2Gy and 769 to 70.2Gy. 1,499 were eligible, 751 and 748 in the 79.2Gy and 70.2Gy arms respectively. Median age was 69, 70% had PSA &lt; 10 ng/ml, 84% with GS 7, 57% had T1 disease, and 66% used 3D-CRT. With a median of 7.0 years follow up, the 5 and 10-yr rates of OS are 88% and 67% with 79.2Gy and 89% and 66% with 70.2Gy (p=0.87; HR (95%CI)=0.98 (0.79,1.21)). The ASTRO (Phoenix) BF rates at 5 and 10 yr are 25% (16%) and 30% (26%) with 79.2Gy and 40% (21%) and 45% (43%) with 70.2Gy (both p&lt;0.0001). The 5 and 10-yr rates of LP are 1% and 4% with 79.2Gy and 2% and 8% with 70.2Gy (p=0.0059; HR (95%CI)=0.46 (0.27,0.81)). The 5 and 10 yr rates of DM are 2% and 5% with 79.2Gy and 3% and 8% with 70.2Gy (p=0.026; HR (95%CI)=0.57 (0.35,0.94)). The high dose arm had lower rate of salvage therapy, 13.5% vs 21%, p=0.0002. The 10 yr rates for time to late grade ≥ 2 GI/GU are 22%/15% with 79.2Gy and 16%/10% with 70.2Gy (p=0.0063/p=0.001). Time to late grade ≥ 3 GI was higher for the 79.2Gy arm (p=0.035) but time to late grade ≥ 3 GU toxicity was not (p=0.14). Conclusions: Despite significant improvement in BF, DM, and LP rates, dose escalation did not improve OS. Patients receiving high dose radiation experience more late toxicity. Clinical trial information: NCT00033631.
Triple detection method for sentinel lymph node detection
Authors: S. Lee, J. Yang, S. Nam, J. Lee, W. Kim, J. Choi, G. Kim, G. Kim
Journal: Journal of Clinical Oncology (2009)

e11605 Background: Sentinel lymph node biopsy is widely accepted method to determine nodal stage of breast cancer. There are several reported method for detecting sentinel lymph node. The aim of this study was to show the new detection method of sentinel lymph node and show the effectiveness of this method. Methods: We did prospective study and enrolled 25 patients who underwent partial mastectomy and sentinel lymph node biopsy. We injected indigocyanine green (green dye) at peritumoral lesion, indigocarmine dye (blue dye) in subareolar area and radioisotope (Tc-99m) injection. Sentinel lymph nodes are identified by color change or radioisotope uptake, and classified by each color (blue or green) and radioisotope uptake. We compared the detection rate from our study with that from the previous studies. Results: Sentinel lymph nodes were detected in all patients (25/25). Green color stained sentinel lymph nodes were identified in 18 patients (18/25), blue color stained sentinel lymph nodes were identified in 15 patients (15/25) and radioactive lymph nodes were identified in 19 patients (19/25). Conclusions: The triple mapping method showed higher detection rate than the previous studies and this method is recommendable to detect sentinel lymph node. No significant financial relationships to disclose.
Long-term outcomes after neoadjuvant trastuzumab and chemotherapy for HER2+ breast cancer.
Authors: A. Gropper, H. J. Burstein, L. Harris, K. S. Anderson, J. M. Gold, W. J. Younger, C. A. Bunnell, J. S. Najita, E. P. Winer, E. L. Mayer
Journal: Journal of Clinical Oncology (2011)

e11074 Background: Neoadjuvant chemotherapy (C) plus trastuzumab (H) improves pathologic complete response (pCR) rate over C alone. Whether pCR after CH is predictive of survival is not known. We evaluated long-term (LT) follow-up of survival and cardiotoxicity outcomes from neoadjuvant trials of CH for HER2+ breast cancer. Methods: Patients (pts) with HER2+ stage II-III breast cancer were enrolled on 2 neoadjuvant phase 2 trials between 1999-2003. Treatment consisted of either 12 wks paclitaxel/H (TH) with optional adjuvant C, or 12 wks vinorelbine/H (NH) with optional adjuvant C+/-H x 40 wks. pCR was defined as absence of invasive disease in breast and lymph nodes at surgery. LT follow-up on recurrence, survival, and cardiotoxicity endpoints was performed through chart review. Results: Of 88 enrolled pts, 78 were confirmed HER2+ and completed CH without progression (TH 32 pts, NH 46 pts). Median age was 45y. 63% were hormone receptor (HR) +, 37% HR-. 15 (19%) had pCR at surgery, 7 (22%) with TH, and 8 (17%) with NH. Optional adjuvant anthracycline-based C was received by 99% of pts, with adjuvant H in 72% of NH pts. Median duration of follow-up is 8.3y (10.2y, TH, and 7.8y, NH). 22 pts have recurred (5 local, 15 distant, and 2 both sequentially) and 15 have died from breast cancer for a total of 21 disease-free survival (DFS) events. In pts with pCR, 4-year DFS was 93.3% (95% CI 61-99); in those without pCR, 75.4% (CI 63-84). Without adjuvant H, 4-year DFS in pts with pCR had too few events to estimate, in those without pCR 72.2% (CI 55-84). In patients who received adjuvant H, 4-year DFS in those with pCR was 85.7% (CI 33-98), in those without pCR 80.4% (CI 59-91). Of 27 pts with ejection fraction (EF) recorded during follow-up, 1 experienced symptomatic cardiac toxicity while receiving H for metastatic disease. Conclusions: LT prognosis in this cohort with stage II-III HER2+ disease and neoadjuvant CH exposure was favorable, and LT cardiotoxicity was rare. Trends suggest pts with pCR experience better outcomes than those without pCR. However, adjuvant H may confound the interaction between neoadjuvant response and LT DFS. For HER2+ tumors, as for ER+ tumors, the prognostic value of pCR may be limited by the availability of effective adjuvant therapies.
LUME-Colon 1: A double-blind, randomized phase III study of nintedanib plus best supportive care (BSC) versus placebo plus BSC in patients with colorectal cancer (CRC) refractory to standard therapies.
Authors: Heinz-Josef Lenz, Josep Tabernero, Takayuki Yoshino, Zohra Oum'Hamed, Soetkin Vlassak, Mouna Sassi, Eric Van Cutsem
Journal: Journal of Clinical Oncology (2015)

TPS794 Background: Clinical studies with anti-VEGF agents, such as regorafenib (R), demonstrate that angiogenesis is critical to CRC tumor growth and metastasis. R has provided proof of principle in patients with refractory CRC, but is associated with a specific safety profile; there is a need for an effective alternative treatment with a different safety profile. Nintedanib (N) is a triple angiokinase inhibitor of VEGF, PDGF, and FGF signaling that has shown clinical benefit and a manageable safety profile in trials in several tumor types, including NSCLC, ovarian cancer, and renal cell carcinoma. In a recent Phase I study of N in CRC, one patient had a confirmed partial response, and a clinically relevant anti-angiogenic effect was observed in 67% of patients. These findings and a manageable safety profile provide a rationale to examine N in refractory CRC. The objective of this study (NCT02149108; 1199.52) is to evaluate the efficacy and safety of N in patients with refractory CRC after failure with standard chemotherapy and biologic agents. Methods: 764 patients worldwide (≥18 years of age, ECOG-PS 0–1, and histologically/cytologically confirmed CRC adenocarcinoma unamenable to surgery and/or radiotherapy) will be randomized 1:1 to receive either N (200 mg bid) + BSC or placebo (bid) + BSC in 21-day courses until disease progression or undue toxicity. The study is powered to distinguish a clinically meaningful effect in the co-primary endpoints PFS and OS. Secondary endpoints are objective tumor response and disease control. Patients will be stratified at randomization based on previous R treatment (yes vs. no), time from onset of metastatic disease to randomization (&lt;24 months vs. ≥24 months), and region. PFS and OS will be evaluated by the log-rank test to determine the effect of N independently at the two-sided alpha level of 0.05. Other assessments include frequency and severity of adverse events and changes in laboratory parameters to measure safety; health-related quality of life; and biomarker analyses that will focus on exploring predictive biomarkers and drug resistance mechanisms. Results are expected in 2016. Clinical trial information: NCT02149108.
Clinical and pathologic profile of breast cancer in a tertiary cancer center in Saudi Arabia.
Authors: S. AlShehri, O. A. M. Abulkhair, A. Al Kushi, S. Musaad, A. Al Olayan, A. R. Jazieh
Journal: Journal of Clinical Oncology (2011)

1603 Background: Breast cancer (BC) ranked first among Saudi females, accounting for 23.6% of all cancers with highest incidences in Eastern and Riyadh Regions. Our study aimed at describing the clinical, pathological and epidemiological characteristics of BC at our institution, a leading tertiary cancer center in the region. Methods: Data were collected from records of BC patients treated at King Abdulaziz Medical City over 5 year period from 2002 to 2007, including clinical, demographic, and disease characteristics. Data was analyzed using SPSS version 18. Results: 450 pathologically confirmed BC patients were identified. The median age of diagnosis was 47.8 years (13-84). The vast majority are Saudi 81%. Most of the patients are overweight (32.5%) or obese (49.0%) whereas, over 21% of them are diabetic and 20% are hypertensive, 4.5% are nulliparous, and 59% have family history of malignancy. Only four patients have previous history of malignancy. The most frequent presenting symptom is breast lump (85%) followed by axillary lump in (11%). The mean duration of symptoms was 348 days. Around 4.5% presented with bilateral tumors and the primary site of cancer was the right upper outer quadrent in nearly 40% of patients. 93% of cases are invasive ductal carcinoma and 7.1% are invasive lobular carcinoma. 2% are insitu tumor, 28% had localized disease, 35% regional involvement and 19% with distant metastasis while 16% were unknown. Finally the ER and PR were positive in 39% and 33.5%, respectively and 29.5% had positive HER2 over expressed. 14.3% were triple negative (TNBC). Conclusions: Patients with BC present at younger age and more advanced stage. The latter fact may be related to delay in seeking medical help in a timely fashion. Public outreach programs are underway to improve female awareness about the importance of screening and early detection. Higher percentage of tumors over express HER2 neu while TNBC rate is similar to Western data. High percentage of women has positive family history, overweight, and obesity which need further evaluation as BC risk factors.
A Phase 3, randomized, double-blind, placebo-controlled study of tasquinimod (TASQ) in men with metastatic castration-resistant prostate cancer (mCRPC), secondary endpoints.
Authors: Cora N. Sternberg, Andrew J. Armstrong, Roberto Pili, Tore Nederman, Michael Anthony Carducci
Journal: Journal of Clinical Oncology (2016)

239 Background: TASQ is an oral agent with immunomodulatory, anti-angiogenic and anti-metastatic properties that targets the tumor microenvironment. It was recently reported from this study that in chemotherapy-naïve men with mCRPC, single-agent TASQ statistically significantly improved rPFS, by both central (HR (95% CI) 0.64 (0.54-0.75)) and local review, as compared to PBO but no OS benefit was demonstrated (HR (95% CI) 1.10 (0.94-1.28)). In this abstract the results of secondary efficacy endpoint analyses are presented. Methods: Men with asymptomatic to mildly symptomatic chemotherapy-naïve mCRPC and evidence of bone metastases were assigned (2:1) to receive TASQ or PBO once daily until progression or toxicity. Randomization was stratified by KPS ( ≥ 90% vs &lt; 90%), presence/absence of visceral disease, and geographic region. The secondary efficacy endpoints discussed here include a panel of radiological, PSA based and symptomatically assessed measures. Results: 1245 pts were randomized (TASQ, n = 832; PBO, n = 413) between 29 Mar 2011 and 7 Dec 2012 at 240 sites in 37 countries. Baseline characteristics were balanced between the 2 groups. In general, all radiology-based and PSA-based secondary endpoints showed statistically significant differences between TASQ and PBO in favor of TASQ. E.g. median time to radiological progression was 8.4 m for TASQ vs. 5.5 m for PBO, p &lt; 0.001, HR (95% CI) 0.628 (0.534-0.739) by central assessment. However, symptomatically assessed endpoints in general showed statistically significant differences in favor of PBO. E.g. median time to symptomatic progression was 9.5 m for TASQ vs. 11.9 m for PBO, p = 0.031, HR (95% CI) 1.171 (1.014-1.353). Grade ≥ 3 TEAEs were more common with TASQ than PBO (42.8 vs 33.6%). Conclusions: Outcome of the radiological and PSA-based endpoints favor TASQ in contrast to the symptomatically assessed endpoints, which favor placebo. Overall survival was not improved, which may be due to limited efficacy of TASQ in the studied population, toxicity, or the differential use of effective life-prolonging agents post-TASQ/placebo. Clinical trial information: NCT01234311.
Relationship of guarana (Paullinia cupana) on anorexia in patients with advanced cancer.
Authors: Claudia Latorre Palma, Tatiana Goberstein Lerner, Andrea Thaumaturgo Lera, Manuella Oliveira, Thais Mazara de Borta, Renata Possebon Barbosa, Gisele Brito, Camila Ada Guazzelli, Felipe Melo Cruz, Auro Del Giglio
Journal: Journal of Clinical Oncology (2014)

e20532 Background: Anorexia is prevalent in cancer patients with advanced disease. There are currently some treatments for cancer anorexia-cachexia syndrome (CACS), including corticosteroids, progestogens, cannabinoids and anabolic steroids. However, none of these treatments alone increases appetite and weight with few side effects. In this pilot phase II, open label, non-randomized trial, we evaluated the efficacy and safety of guarana (Paullinia cupana) in patients with cancer and weight loss. Methods: We included advanced cancer patients with decreased appetite and weight loss of more than 5% from their baseline in the past 6 months. All of the patients received 50 mg of the crude dry extract of guarana twice a day for 4 weeks. The trial was designed in 2 phases (Simon model). We considered a positive response in the first phase to be at least 5% weight gain or a 3-point improvement in the appetite scale in at least 3 of the first 18 evaluable patients. Results: Of the 34 eligible patients, 30 were included and 18 completed the protocol. Only 1 patient abandoned the protocol due to toxicity (grade II arthralgia). There were no grade 3 or 4 toxicities. There were no significant differences in nausea, weight loss and quality of life (FACT-G). Only 2 of the 18 patients who completed the study had weight gain above 5% from their baseline, whereas 6 patients had at least a 3-point improvement in the visual appetite scale. The M.D. Anderson Symptom Inventory (MDASI) was used to evaluate several symptoms, and we observed a significant decrease in lack of appetite (p=0.02) and in somnolence (p=0.0142). Conclusions: We concluded that the weight stabilization and increased appetite we observed in this study justify further studies of guarana in this patient population. Clinical trial information: NCT01540019.
Self assessment of buccodental toxicity: Comparison of patients with metastatic renal cell carcinoma (RCC) treated with sunitinib with patients treated with chemotherapy.
Authors: M. Gilabert, M. Provansal, M. Cappiello, J. Walz, S. Brunelle, N. Salem, G. Gravis
Journal: Journal of Clinical Oncology (2011)

e15021 Background: Sunitinib is a standard of care for first-line treatment of advanced or metastatic RCC. Recently, the association of sunitinib and bisphosphonates has been described to increase osteonecrosis of the jaw (Bozas and al, Oncologie 2010). We measured the potential impact of sunitinib on buccodental toxicities. Methods: Between Oct and Dec 2010, 58 patients with metastatic RCC treated by sunitinib (S) and 52 patients treated by chemotherapy (C) agreed to fill a self administered questionnaire assessing buccodental status included varying oral hygiene/care practices, history of bisphosphonate treatment, occurence of dental or gingival pathologies during treatment, and quality of life. T-tests and Chi-square analyses were used to compare differences between the two groups. Results: Median age of the 110 pts analyzed was 62,5 years (28-84) with majority of male in group S (73%) and female in group C (67%). Smokers were more represented in group C (23.1%) than in group S (8.6%) (p = 0.036). Among 58 pts in the group S, 9 had previously received bevacizumab, and 5 Sorafenib. Among 52 pts in the group C, 13 received an adjuvant chemotherapy, 39 had metastatic chemotherapy line, and 8 combination of chemotherapy and bevacizumab. Some pts in each group received bisphosphonates: 8 in group S (13.8%) and 4 in group C (7.7%) (p= 0.306). Higher frequencies of dental and gingival toxicities in group S were observed: pain (53.7% vs 46.3%, p= 0.007), teeth instability (43.1% vs 22.5%, p= 0.037), gingival bleeding (62% vs 42.4%, p= 0.010) and cavities (51.6% vs 25%, p= 0.005). Consequently, 62% (S) vs 42.3% (C) needed to change their alimentary habits (p= 0.010). Indeed, the pts of the group S had more frequently visited their dentist within the few months following treatment to remove pathological teeth (15 patients vs 4 patients, p= 0.013). Results were similar with or without bisphosphonate treated patients. Conclusions: Sunitinib seems to increase buccodental toxicity as compared to chemotherapy with or without bisphosphonate association. This work emphasizes the need of an optimal dental care and follow-up for patients treated with sunitinib.
Early change in tumor size from waterfall plot analysis and RECIST response as predictor of overall survival (OS) in advanced, chemotherapy-refractory colorectal cancer (ACRC): NCIC CTG/AGITG CO.17 study.
Authors: G. A. Van Hazel, D. Tu, N. C. Tebbutt, D. J. Jonker, T. J. Price, C. O'Callaghan, J. R. Zalcberg, M. Taylor, A. H. Strickland, A. T. Tomiak, D. Yip, J. Simes, S. K. Yadav, M. Links, M. J. Burnell, M. Jefford, C. S. Karapetis
Journal: Journal of Clinical Oncology (2011)

3602 Background: The CO.17 trial demonstrated that the addition of cetuximab monotherapy (C) to best supportive care (BSC) improves OS and progression-free survival (PFS) in patients (pts) with ACRC. We compared tumour measurement as a continuous variable and visualized by waterfall plot vs. categorized as response based on RECIST as potential early predictors of OS benefit. Methods: Of the 572 randomized, 216 pts on C and 142 on BSC had tumor assessment at baseline and 8 weeks and are included in this analysis. Response at 8 weeks was assessed using standard RECIST criteria and categorised as partial response, stable disease or progressive disease. Continuous tumour size measurement was also assessed using waterfall plot, The absolute difference in logarithm transformed sum of the longest tumor diameters (LSLD) between 8 weeks and baseline were calculated for the entire group and the KRAS wild-type (WT) and mutant (MUT) subgroups and correlated with OS in a multivariate analysis including difference in LSLD, RECIST response and other prognostic factors as covariates. Results: The increase of tumor size (cm) from baseline of pts treated by C was significantly smaller than those that received BSC (mean difference in LSLD 0.02 vs. 0.23; p < 0.0001), and this remained significant after adjusting for baseline prognostic factors (p<0.0001). In a multivariate analysis of pts treated by C, difference in LSLD was significantly associated with OS (HR 14.84, per ln(cm) of increase, 95% CI 4.31 to 51.08; p<0.0001), whilst RECIST defined response was not. Results were similar for WT pts: HR 14.30 per ln(cm) of increase in LSLD, 95% CI 1.32 to 96.5; p=0.03. For MUT pts, neither change in LSLD nor RECIST response was associated with OS. Conclusions: Change of tumor size at 8 weeks following commencement of C using a waterfall plot analysis was a better predictor of OS than standard RECIST categories. This may be a better early signal of treatment efficacy for molecular targeted therapies in ACRC.