tbuckley/cabot-search huggingface dataset:
Incidental PSMA Uptake in an Undisplaced Fracture of a Vertebral Body
Authors: Shankar Vamadevan, Ken Le, Choung Bui, Robert Mansberg
Journal: Clinical Nuclear Medicine (2017)

A 50-year-old man with recently diagnosed prostate cancer was referred for Ga-prostate-specific membrane antigen (PSMA) PET/CT with elevated prostate-specific antigen. PET/CT demonstrated increased PSMA uptake in an undisplaced transverse fracture of the L1 vertebral body. This case illustrates that PSMA uptake can occur in a transverse vertebral body fracture and is a benign cause of PSMA uptake.
Second-line sequential therapy in patients with metastasized renal cell carcinoma (mRCC): Retrospective comparison of common treatment options following failure of receptor tyrosine kinase inhibitor therapy.
Authors: S. Weikert, C. Seidel, J. Busch, L. Weinkauf, K. Miller, V. Gruenwald
Journal: Journal of Clinical Oncology (2011)

e15059 Background: Everolimus (EV) is an efficacious treatment option after failure of receptor tyrosine kinase inhibitor (rTKI) therapy in mRCC patients. However, the best sequence of targeted therapy options has not been sufficiently defined. The objective of this study was to describe the clinical activity of sequence options in 2nd line treatment, i.e. rTKI followed by EV vs. rTkI followed by another rTKI. Methods: Retrospective study of 108 patients receiving rTKI or everolimus treatment after progression on first-line rTKI therapy at 2 German academic centres. Sequence of systemic targeted treatment consisted of an rTKI-rTKI-sequence (n=46; sunitinib-sorafenib, n= 35; sorafenib-sunitinib, n=11) or an rTKI-EV sequence (n=62). Median progression free survival (PFS) and median overall survival (OS) were determined for the two sequence treatment options using the Kaplan-Meier method. Response to treatment was assessed according response evaluation criteria in solid tumors (RECIST) 1.0. Results: Sequence treatement groups (rTKI-rTKI vs. rTKI-EV) did not significantyl differ by gender, MSKCC prognostic group, or ECOG performance status. Best response to 2nd line therapy included partial response (EV: n=2, 3%; rTKI: n=5, 11%; p=.11) and stable disease (EV: n=30, 48%; rTKI: n=15, 33%; p=.21) for a disease control rate of 51.5% (EV) and 43.4% (rTKI), respectively. The estimated 2nd line PFS was 3.6 months (92% CI: 1.8 – 5.4) for Everolimus and 4.0 months (3.2 – 4.9) for rTKI sequential therapy. The estimated OS was longer for the group of patients receiving the rTKI-EV sequence (43 months; 95% CI: 33.9 – 52.1) than for those receiving the rTKI-rTKI sequence (29 months, 95% CI: 18.6 – 39.5; p = .03). However, the rTKI-rTKI group was characterized by a relatively short first-line PFS (6.6 months compared to 10.6 months of the rTKI-EV group) which may at least in part explain the observed OS difference. Conclusions: Common sequence treatment options may have comparable efficacy in terms of PFS and response rate. The observed differences in OS await further confirmation in prospective randomized trials.
The incidence of secondary pelvic tumors after previous (chemo)radiation for rectal cancer.
Authors: Anouk J.M. Rombouts, Niek Hugen, Marloes A. G. Elferink, Ton Feuth, Philip M. Poortmans, Iris D. Nagtegaal, Johannes H.W. de Wilt
Journal: Journal of Clinical Oncology (2016)

491 Background: The aim of this study was to analyze the association between radiotherapy (RT) for rectal cancer and the development of second primary tumors. Methods: Data on all surgically treated, non-metastasized primary rectal cancer patients diagnosed between 1989 and 2007 were retrieved from a population-based cancer registry and retrospectively reviewed. To estimate the cumulative incidence of a second tumor, Fine and Gray’s competing risk model was used with death as a competing event. Standardized incidence ratios (SIR’s) were calculated for comparison with the incidence of primary tumors in the general population, taking in account sex, age and calendar year. Results: The cohort consisted of 29,214 patients of which 15,454 patients had undergone (chemo)RT. Median follow-up was 6.2 years (range 0-24). 3655 patients were diagnosed with at least one second primary tumor of which 808 patients had pelvic tumors. The SIR for any second tumor was 1.14 (95% confidence interval [CI] 1.10-1.17), resulting in 23.3/10,000 excess cases per year. RT reduced the cumulative incidence of second pelvic tumors compared to patients who received no RT (SHR 0.70, 95% CI 0.61-0.81). Second pelvic tumors were more common in patients who underwent post-operative RT than in patients who underwent pre-operative RT (SHR 1.37, 95% CI 1.10-1.70). Organ-specific analyses showed that second prostate tumors were less common in patients who received RT compared to patients who received no RT (SHR = 0.51, 95% CI 0.43-0.62). RT also reduced the risk for a second primary tumor in the rectum(sigmoid) compared to patients who did not receive RT (SHR 0.59 95% CI 0.37-0.94). Patients who received post-operative RT had higher chances of developing a second rectum(sigmoid) tumor then patients who received pre-operative RT (SHR 2.25, 95% CI 1.07-4.73). Patients without RT had worse overall survival than patients who received RT (hazard ratio 1.22, 95% CI 1.19-1.26). Conclusions: In this nationwide study, patients with previous rectal cancer had a slightly increased chance of developing another primary tumor compared with the general population. We found a protective effect of RT on the development of secondary pelvic tumors, predominantly for prostate cancer.
Survival determinants with matched targeted therapies in <i>BRAF</i> mutant metastatic colorectal cancer (mCRC).
Authors: Enrique Sanz-Garcia, Ana Maria Martinez, Elena Elez, Guillem Argiles, Julieta Grasselli, Teresa Macarulla, Jaume Capdevila, Maria Alsina, Tamara Sauri, Cinta Hierro, Ignacio Matos, Helena Verdaguer, Analia Azaro, Stefania Landolfi, Javier Hernandez-Losa, Jordi Rodón, Paolo Nuciforo, Ana Vivancos, Rodrigo Dienstmann, Josep Tabernero
Journal: Journal of Clinical Oncology (2016)

649 Background: BRAF mutation (mt) occurs in 5-8% of mCRC and is associated with poor prognosis. Matched targeted therapies for this population are increasingly available in clinical trials. Methods: From Nov 2010 to June 2015, a total of 32 chemorefractory BRAF mt mCRC patients (pts) were enrolled in phase I trials with anti-BRAF matched therapy at Vall d´Hebron Institute of Oncology. BRAF mt was determined by real-time PCR (50%), mass spectrometry (Sequenom, 28%) or next-generation sequencing (Amplicon MiSeq, 22%). All demographic, treatment and survival data were retrospectively analyzed. Results: Median age was 60.4 years (range 42.8-73.5), 62% had right-sided CRC primaries and 59% were stage IV at diagnosis. Median treatment lines before matched therapy was 2 (range 1-4). Co-existing RNFA43, PI3KCA and GNAS mt were found in 4, 2 and 1 pts, respectively. Median time from diagnosis to start of anti-BRAF therapy was 18.6 months (m) (CI95% 14-36) and median time from diagnosis of mCRC to death was 28.4m (CI95% 25-50). A total of 41 anti-BRAF matched therapies were delivered, 9 pts received more than 1 regimen. BRAF inhibitor (inh) monotherapy was delivered in 34% of cases; BRAF plus MEK/EGFR/WNT/PI3K/CDK inh doublets or triplets to 37% and 29% pts, respectively. Survival from start of anti-BRAF to death was 8.9m (CI95% 7-15), without significant differences if 1 or more than 1 anti-BRAF regimen was given (HR: 0.82, p=0.6). Partial responses were observed in 7 cases (17%, 4 doublets and 3 triplets) and complete response in 2 cases (5%, 1 doublet and 1 triplet). Median time on treatment (ToT) with anti-BRAF therapy was 2.83m (CI95% 2-5.5). Of note, ToT was significantly longer for triplets compared to mono/doublets: 5.5m (CI95% 2.7-not reached) vs. 1.9m (CI95% 1.6-3.7; HR: 0.46 [CI95% 0.2-1.0], p=0.05). Median BRAFmt allele fraction (adjusted for tumor purity) was 0.25 (0.13-0.68); no correlation with ToT on anti-BRAF therapy was observed (p=0.36). Conclusions: In a selected BRAF mt population enrolled in early trials with anti-BRAF matched therapy at our institution, survival in the metastatic setting was remarkably high. Triplet matched therapies seem to control disease for longer time than mono/doublets.
Phase I dose-escalation trial of a recombinant HER2 vaccine in patients with Stage II/III HER2+ breast cancer
Authors: S. Limentani, T. Dorval, S. White, G. Curigliano, M. Campone, N. Disis, M. Piccart, M. Cheever, C. Gérard, V. G. Brichard
Journal: Journal of Clinical Oncology (2005)

2520 Background: Therapy with monoclonal antibodies against HER2 is effective in some patients with HER2+ Stage IV breast cancer. However, many patients do not respond to antibody therapy, and patients who do respond ultimately relapse. The current vaccine is designed to elicit a T-cell response in addition to a polyclonal Ab response and may therefore have a different spectrum of efficacy. Methods: The vaccine formulation contains a truncated recombinant HER2 protein (dHER2) combined with a new potent GSK immunological adjuvant. dHER2 includes the extracellular domain (ECD) and a part of the intracellular domain (ICD) of the HER2 protein. The trial’s objective is to evaluate safety and immunogenicity. Three dose levels of dHER2 protein were tested: 20, 100 and 500 mcg. Three cohorts of 15 patients with Stage II or III breast cancer were enrolled sequentially. Patients received 6 vaccinations over 14 weeks. Results: All patients receiving the 20- and 100-mcg doses have completed the course of 6 vaccinations, and those in the 500-mcg cohort will have done so by March 2005. To date, the vaccine has been well tolerated overall and showed minimal toxicity. Grade 3 fatigue and Grade 3 neutropenia were recorded once each, in different patients who continued treatment. No symptomatic cardiac dysfunction was observed. Ab responses against dHER2, ICD and ECD were elicited. After 4 vaccinations, 2/12 patients in the 20-mcg and 9/14 in the 100-mcg cohort responded to the ECD. Results in the 500 mcg cohort are pending. The function of the anti-ECD antibodies will be assessed by inhibition of growth in vitro of breast-cancer cell lines and by analysis of the HER2 signaling pathways. Conclusions: The dHER2 vaccine appears to be safe in the small number of patients tested. Ab to the ECD and the ICD are induced in a dose-dependent manner, suggesting that the higher-dose vaccine may be required for future Phase II and III studies. Detailed data on antibody and T-cell responses will presented. No significant financial relationships to disclose.
Correlation between standardized uptake value in pre- and post-neoadjuvant chemoradiotherapy and tumor regression grade in patients with locally advanced esophageal cancer.
Authors: Kathryn Baksh, Khaldoun Almhanna
Journal: Journal of Clinical Oncology (2014)

150 Background: A multimodality approach with neoadjuvant chemotherapy and radiation is the standard of care in the United States in the treatment of patients with locally advanced esophageal cancer. It is well established that neoadjuvant chemoradiotherapy (CRT) in these patients can facilitate downstaging, correlating with pathologic response, and improving overall survival. Our clinical practice involves the use of positron emission tomography (PET) to assist with staging in patients prior to undergoing neoadjuvant CRT and surgery. While there has been evidence showing correlation between tumor regression grade (TRG) and increased overall survival in these patients, the relationship between standardized uptake values on PET scans and TRG has not been discerned. The purpose of this study was to determine whether pre and post-chemoradiotherapy SUV on PET scans correlate with TRG in esophageal cancer patients receiving neoadjuvant chemoradiotherapy. Methods: A retrospective review of 56 patients with stage II-III esophageal cancer treated with neo-adjuvant CRT followed by surgery was performed. Pre- and post- treatment PET scans were reviewed. Maximum SUV at the site of the primary tumor was recorded. Upon completion of surgery, tumor regression grade was determined by a specialized pathologist. Spearman correlation was used to compare pre, post, and change in max SUV, to the 4 level TRG variables. Results: The median follow-up was 24 months. No significant correlation was found between pre-treatment or post treatment SUV and TRG with p value of 0.73 and 0.94 respectively. There was no significant correlation between decreased FDG uptake following CRT and TRG with p value of 0.82. Consistent with previous data, TRG predicted the therapeutic efficacy and prognosis for patients with locally advanced esophageal carcinoma treated by neoadjuvant chemotherapy. Conclusions: Our results are preliminary and retrospective in nature. A larger sample is needed to confirm these findings. Decreased FDG uptake in sequential PET scans strongly correlates with tumor response, but is not accurate enough to predict pathological response.
LICC: L-BLP25 in patients with colorectal carcinoma after curative resection of hepatic metastases—A randomized, double-blind, placebo-controlled, multicenter, multinational, phase II trial.
Authors: C. C. Schimanski, P. R. Galle, H. Lang, M. Schoen, M. H. Moehler
Journal: Journal of Clinical Oncology (2011)

TPS166 Background: Distant metastases limited to the liver occur in 15-20% of all patients initially diagnosed with colorectal cancer. Complete surgical resection represents the only curative option. The 5-year survival after R0-resection of liver metastases ranges between 28 and 39%. Unfortunately, recurrence rates peak up to 70% in long-term follow-up. Adjuvant chemotherapeutic protocols did not reveal significant improvement of the situation. The primary objective of the LICC trial is to determine whether the therapeutic cancer vaccine L-BLP25 extends recurrence-free survival (RFS) time over placebo in colorectal cancer patients after resection of hepatic metastases. L-BLP25 targets the MUC1 glycoprotein, which is highly expressed in hepatic metastases of colorectal cancer. In a phase IIB trial, L-BLP25 showed acceptable tolerability and a trend toward longer survival in patients (pts) with stage IIIB locoregional NSCLC. Methods: This is a planned multinational, phase II, multicenter, randomized, double-blind trial. Planned sample size is 159 pts from 20 centers in 3 countries; accrual is planned to start in Q3 2011. Pts with colorectal adenocarcinoma after complete resection of the primary tumor and having experienced a curative-intent resection of all hepatic metastases (R0/R1, metachronous/synchronous, <6 weeks) are eligible. Pts will be randomized 2:1 to receive either L-BLP25 or placebo. Those in the L-BLP25 arm receive a single dose of cyclophosphamide (CP) (300 mg/m2) 3 days before first L-BLP25 dose, then primary treatment with sc L-BLP25 930 μg once weekly for 8 weeks, followed by sc L-BLP25 930 μg maintenance doses at 6-week (years 1&2) and 12-week (year 3) intervals until recurrence. In the control arm, CP is replaced by NaCl solution and L-BLP25 by placebo. Stratified: R0 vs. R1. Primary endpoint: RFS time between treatment groups. Secondary endpoints: overall survival (OS) time, safety, tolerability, RFS/OS in MUC-1 positive cancers. Exploratory immune response analyses are planned. Evaluation of primary endpoint is planned for Q3 2016.
FOLFERA: A randomized phase II study of irinotecan, 5-fluorouracil (5-FU), and folinic acid (FOLFIRI) with or without addition of the endothelin receptor antagonist (ETAR) zibotentan in patients with metastatic colorectal cancer after failure of oxaliplatin-containing chemotherapy.
Authors: Anne L. Thomas, Angela Claire Casbard
Journal: Journal of Clinical Oncology (2013)

406 Background: Zibotentan (Z) is an oral specific ETAR antagonist. The ETAR is over expressed in colorectal cancer, and pre-clinically, antagonism of the ETAR has been shown to enhance cytotoxicity when combined with cytotoxics such as 5-FU. This multi-center, randomized, double-blind, placebo-controlled phase II study evaluated the safety and anti-tumor activity of irinotecan and 5-FU (as the FOLFIRI regimen) in combination with Z in advanced colorectal cancer. Methods: Patients (pts) with advanced colorectal cancer who had progressed after oxaliplatin-containing chemotherapy (FOLFOX) were randomized (1:1) to receive 10 mg O.D Z/placebo (continuous dosing) with standard dose FOLFIRI for a maximum of 12 cycles. Z /placebo could be continued until progression or unacceptable toxicity in those patients with a documented response. The primary objective was progression–free survival (PFS) with secondary endpoints of safety and blood and archival tumor samples collected for translational work including circulating tumour cell (CTC) analysis. This study was run as part of the AZ/NCRN alliance, endorsed by Cancer Research UK (CRUKE/09/023) and coordinated by the Wales Cancer Trials Unit, Cardiff University. Results: A total of 111 patients were recruited: 61% men, median age of 62 years. Z was well tolerated with G3/4 toxicity balanced between both groups (34/55 patients in Z and 38/56 in placebo group). The study was terminated before the planned number of pts (122) were recruited due to lack of efficacy of the drug in two other tumour types. Median PFS was 4.0 months in the Z group and 7.4 months in the placebo group (HR=1.86, 95% CI 1.20 to 2.87, p=0.005). The CTC analysis in relation to outcome in the placebo group will be presented. Conclusions: Zibotentan does not have anti-cancer activity in combination with FOLFIRI in patients with colorectal cancer treated with previous FOLFOX. Taken in consideration with the other trial data we do not recommend the further development of zibotentan in oncology. Clinical trial information: 73199181.
A Phase II Study of the Combination Chemotherapy Consisted of Rituximab and THP-COP Regimen as First-Line Treatment for Patients with Diffuse Large B-Cell Lymphoma
Authors: Hisashi Tsurumi, Naoe Goto, Takeshi Hara, Senji Kasahara, Nobuhiro Kanemura, Junichi Kitagawa, Takeshi Yoshikawa, Toshiki Yamada, Michio Sawada, Takeshi Takahashi, Tsuyoshi Takami, Hisataka Moriwaki
Journal: Blood (2008)
Raltitrexed in the management of metastatic colorectal cancer: The COMET study.
Authors: Jérôme Desramé, Louis-Marie Dourthe, Philippe Debourdeau, Dominique Mille, Pascal Artru, Helene Albrand
Journal: Journal of Clinical Oncology (2015)

677 Background: Raltitrexed, indicated for palliative treatment of advanced colorectal cancer (CRC), may be useful for patients (pts) with cardiovascular (CV) risk factors, or cardiotoxicity/disease progression with prior chemotherapy (CT). The COMET study, conducted in France, described the characteristics of pts with metastatic CRC (mCRC) treated with raltitrexed, focusing on pts with cardiotoxicity or disease progression with prior 5-fluorouracil (5FU)/folinic acid. Methods: A national, multicentred, cross-sectional, non-interventional study to describe the profiles of pts with mCRC treated with raltitrexed. Pts (≥18 years) with mCRC, treated with raltitrexed as a single agent or in combination therapy, were included. Following patient consent, retrospective data were recorded during a single inclusion visit based on pt medical files; during the study, data were recorded prospectively. Results: 414 pts with mCRC were analysed; 84.8% had ≥1 prior CT, 60.9% had CV risk factors and 35.2% had CV history (angina: 11.8%; myocardial infarction: 11.8%). Overall, 79.5% of pts had received a prior 5FU-based CT. Reasons for switching to raltitrexed included short 15-min infusion duration (34.8%), treatment failure (49.8%) and acute cardiotoxicity with 5FU (8.9%). After switching, 57.2% of pts received raltitrexed as combination therapy. Mean initial dosage of raltitrexed was 2.6±0.6 mg/m 2 . Of those who had CV risk factors (n=73) or CV history (n=67), 69.0% and 72.7% received raltitrexed after CV toxicity, respectively. Of the pts treated with second-line raltitrexed and assessed with prior acute CV events (45/414), 88.9% (40/45) had no cardiac toxicity during treatment with raltitrexed. Of those (n=206) receiving raltitrexed due to treatment failure, 62.7% had received 5FU/folinic acid during their last CT. Of the pts assessed for tumour response (183/206), tumour progression was controlled with raltitrexed in 25.7% of cases (stable disease: 18.0%; partial response: 7.7%; progressive disease: 56.3%). Conclusions: Raltitrexed appears to be effective in heavily pretreated pts with mCRC and tumour progression after 5FU therapy and could be a safe therapeutic alternative to 5FU for pts with mCRC and prior cardiac toxicity.
Oncofertility and quality of life among adolescent and young adult survivors of childhood cancer.
Authors: Kenneth Tercyak, Darren Mays, Andrea Johnson, Sarah Murphy, Aziza T. Shad
Journal: Journal of Clinical Oncology (2016)

222 Background: Although infertility risks due to childhood cancer treatment are well-documented, research on the psychosocial impact of treatment-associated infertility risks among adolescent and young adult (AYA) cancer survivors is limited. This study examined AYA pediatric cancer survivors’ perceptions of oncofertility and cancer treatment-associated infertility risks and associations with patient-reported quality of life (QoL). Methods: Patients ages 12 to 25 (n= 70, M age 19.4, 74% white, 57% female, a majority leukemia/lymphoma survivors) were recruited from a pediatric hematology/oncology clinic and local pediatric cancer survivor support organizations. Patients reported knowledge and beliefs about treatment-related fertility risks and reproductive health, and oncofertility information and support needs, and completed the Pediatric Oncology Quality of Life (QoL) scale. Results: Patients’ knowledge about infertility risks and fertility preservation options was low (M 13.5, SD 8.6, range 0-42): patients’ attitudes indicated treatment-related infertility risks was important (M 21.7, SD 7.0, range 0-40), they perceived they were at-risk for infertility (M 3.8, SD 1.0 range 1-5), and expressed unmet needs for supportive resources on reproductive health (M 13.6, SD 4.8, range 1-24). Greater perceived risks of infertility (r = .34, p = .004) and importance of fertility risks (r = .34, p = .004) were associated with lower QoL. In a multivariable model adjusting for patient age and gender, beliefs that reproductive health was important was associated with lower QoL (B = .68, p = .041). Conclusions: Population data demonstrate few AYA cancer survivors have opportunities to discuss fertility preservation with providers. Our findings indicate AYA cancer survivors perceive treatment-related infertility risks as important, associated with QoL, and with needs for more information about reproductive health and fertility preservation. Care models addressing AYA survivors’ infertility risks are needed as part of the diagnosis, treatment, and long-term follow-up of these patients.