tbuckley/cabot-search huggingface dataset:
A phase I/IIa trial of prostate specific membrane antigen (PSMA) positron emission tomography (PET) imaging with <sup>89</sup>Zr-Df-IAB2M in metastatic prostate cancer (PCa).
Authors: Michael J. Morris, Danny Francisco Martinez, Jeremy C. Durack, Susan F. Slovin, Daniel Costin Danila, Joseph A. O' Donoghue, Nicole Andrea Parada, Serge K. Lyashchenko, Jorge A. Carrasquillo, Shutian Ruan, Jason Stuart Lewis, Jennifer Keppler, Anna M. Wu, Victor E. Reuter, Wolfgang Weber, Howard I. Scher, Steven M. Larson, Neeta Pandit-Taskar
Journal: Journal of Clinical Oncology (2016)

287 Background: There is a pressing need for improved imaging biomarkers to identify disease distribution and response in both localized and advanced prostate cancer patients. PSMA-directed imaging is undergoing analytic and clinical validation for these contexts of use. IAB2M is an anti-PSMA recombinant minibody (Mb) derived from huJ591. We have previously reported on 28 pts imaged with IAB2M(Pandit-Taskar et al, SNM 2015). Here we report the lesion targeting and uptake (SUV) of the Mb and correlation with pathology of biopsied lesions on the full complement of the 38 pts examined in this trial. Methods: 38 pts with progressive metastatic PCa received escalating amounts of the Mb (16 pts at 10mg, 16 pts at 20mg, 6 pts at 50mg) in a phase I/IIa trial. All pts underwent standard imaging (SI) using CT, bone scintigraphy (BS), FDG PET, followed by imaging with 5 mCi of IAB2M. Whole body PET/CT scans were performed and evaluated for lesion targeting and SUVmax. Biopsy (bx) locations were selected by a consensus panel prioritized on the basis of: IAB2M &amp; FDG positivity, IAB2M &amp; FDG mismatch, and CT or BS positivity &amp; any PET mismatch. Results: A total of 556 lesions (410 bone, 146 soft tissue) in 38 pts were detected by SI or IAB2M. In bone, IAB2M detected 344 lesions (83.9%), CT 209 (51%), BS 211 (51.5%), and FDG 109 (26.6%). For soft tissue, IAB2M detected 119 (81.5%), CT 83 (56.8%), and FDG 79 (54.1%). The SUV for bone lesions ranged from 2.1-60.4 for 10mg Mb, 1.7- 33 in 20mg Mb, and 2.3-17.5 in 50mg Mb. For soft tissue lesions, SUV range was 3.1-45.4, 2.1-20, and 1.9-13.8 respectively. 28 bxs (13 bone, 15 soft tissue) were obtained from 27 pts; 27 bxs were evaluable (1 was non-diagnostic). 20/27 (74.1%) bxs were pos for PCa; 20/24 (83.3%) IAB2M pos lesions were path pos and 3/3 (100%) IAB2M neg lesions were neg on path. All imaging and path correlated (true pos + true neg) in 23/27 (85.2%) bxs. Conclusions: PET imaging with IAB2M has demonstrated higher lesion detection when compared with SI. IAB2M’s high concordance with path suggests pos findings represent bx confirmed PCa. Further studies to examine biochemically recurrent prostate cancer are planned. Clinical trial information: NCT01923727.
The Emerging Role of RH Genotyping in Chronically Transfused Sickle Cell Disease Patients
Authors: Ross Fasano, Alessandro Monaco, Emily Riehm Meier, John Otridge, Hallie Lee-Stroka, Philippe Pary, Harvey G. Klein, Francesco M. Marincola, Naomi L.C. Luban, David Stroncek
Journal: Blood (2008)
Phase I Study of Sapacitabine, an Oral Nucleoside Analogue, in Patients with Advanced Leukemias or Myelodysplastic Syndromes (MDS).
Authors: Hagop Kantarjian, Guillermo Garcia-Manero, Stefan Faderl, Jorge Cortes, Zeev Estrov, Patricia Boone, Iain Stuart, Robert Westwood, Simon Green, Judy H. Chiao, Willilam Plunkett
Journal: Blood (2007)
Outcomes of Down-Syndrome Associated Acute Lymphoblastic Leukemia in Adults: A Single Center Retrospective Review
Authors: Sita D. Bhella, Eshetu G Atenafu, Joseph Brandwein, Vikas Gupta, Johann Hitzler, Dina Khalaf, Andrzej Lutynski, Aaron D. Schimmer, Andre C Schuh, Amr Rostom, Anna Rydlewski, Karen W.L. Yee, Mark D. Minden
Journal: Blood (2015)
Impact of hereditary multigene panel testing for cancer survivors.
Authors: Nimmi S. Kapoor, Jennifer Swisher, Rachel E. McFarland, Mychael Patrick, Lisa D. Curcio
Journal: Journal of Clinical Oncology (2016)

261 Background: Recently, genetic testing for hereditary cancer syndromes has seen numerous advances in testing spectrum, capability, and efficiency. This may have important implications for cancer survivors and their families. The purpose of this study is to evaluate the impact of reflex genetic testing with newer multi-gene panels on patients with prior negative BRCA1/2 tests. Methods: Data was collected retrospectively from patients who underwent multi-gene panel testing at one of three sites from a single institution between 8/2013-6/2015. Those with a personal history of breast or ovarian cancer and a prior negative BRCA1/2 test were included. Results: Of 914 patients who underwent multi-gene panel tests, 187 met study inclusion criteria. Ten patients (5.3%) were found to carry 11 pathogenic mutations, including 6 patients with mutations in CHEK2, 2 patients with mutations in PTEN, and 1 patient each with mutations in the following genes: BARD1, NF1, and RAD51C. One patient had two pathogenic mutations identified—CHEK2 and BARD1. Of 10 patients with mutations, 9 had a personal history of breast cancer diagnosed at a median age of 43 (range 35-52) and 1 had ovarian cancer diagnosed at age 65. A majority of mutation carriers underwent panel testing years after their cancer diagnosis (median 6 years, range 0.5-32 years) and none with delayed testing had undergone prophylactic contralateral mastectomy prior to the discovery of their gene mutation. All patients with mutations had a family history of at least one cancer, with most having a variety of cancer diagnoses in multiple relatives. Positive panel testing results altered clinical management in most patients, including addition of breast MRI, colonoscopy, or thyroid ultrasound depending on the gene mutation. After discovery of a PTEN mutation 19 years after her initial cancer treatment, one woman underwent bilateral prophylactic mastectomy and was found to have occult ductal carcinoma in situ. Conclusions: Cancer survivorship must incorporate advances in technology that may be beneficial even years after treatment has ended. Multi-gene panel testing can be applied in survivorship settings as a useful tool to guide screening recommendations.
Phase I study of vincristine, irinotecan, and <sup>131</sup>I-MIBG for patients with relapsed or refractory neuroblastoma: A New Approach to Neuroblastoma Therapy (NANT) study.
Authors: S. G. DuBois, L. Chesler, S. G. Groshen, R. Hawkins, F. Goodarzian, G. A. Yanik, C. F. Stewart, Y. P. Mosse, J. M. Maris, J. Villablanca, K. K. Matthay
Journal: Journal of Clinical Oncology (2011)

9513 Background: 131I-metaiodobenzylguanidine (MIBG) is a targeted radiopharmaceutical with activity in neuroblastoma. Irinotecan is a radiosensitizer with activity in neuroblastoma. This phase I study aimed to determine the recommended phase II dose (RP2D) of MIBG together with vincristine and irinotecan. Methods: Patients 1-30 years old with relapsed or refractory MIBG-avid neuroblastoma were eligible. All patients had autologous hematopoietic stem cells (PBSCs) available and met standard phase 1 requirements. Prior vincristine and irinotecan, but not prior MIBG, were allowed. Patients received cefixime (8 mg/kg/day) on days -5 to +21. Irinotecan (20 mg/m2/dose IV) was given on days 0-4 and 7-11, with vincristine (1.5 mg/m2) on days 0 and 7. MIBG was given on day 1 following a 3+3 phase I design with dose levels of 8, 12, 15, and 18 mCi/kg, with 6 additional patients treated at the RP2D. PBSCs were administered to 1 patient at 8 mCi/kg for myelosuppression and on day 13 for all patients at > 12 mCi/kg. Results: 24 evaluable patients (median age 6.7 years; range 1.9 – 24.8) received 33 courses. Myelosuppression and diarrhea were the most common toxicities. 70% of courses were associated with diarrhea (grade 3 in 6 courses). No dose limiting toxicities (DLTs) were seen at dose levels 8 and 12 mCi/kg. At 15 mCi/kg, 1 patient had DLT of grade 3 diarrhea. At 18 mCi/kg, 1 patient had DLT with hallucinations and hyponatremia. One patient had protocol-defined DLT with prolonged ALT elevation that was not deemed clinically dose limiting. 18 mCi/kg was declared the RP2D and 6 additional patients enrolled, with 1 DLT (ALT and AST elevation). 7 patients received 2-3 courses to cumulative doses of 24-36 mCi/kg without DLT. The objective response rate was 25% (95% CI: 11-46%), with 3 complete responses, 1 very good partial response, and 2 partial responses. The response rate among 12 patients treated with 18 mCi/kg was 25% (2 complete responses and 1 very good partial response). Conclusions: MIBG is tolerable and active at doses of 18 mCi/kg with vincristine and irinotecan. Further studies are planned to determine this regimen’s role in frontline therapy for high risk patients.
Randomized phase II trial evaluating the optimal sequencing of sipuleucel-T and androgen-deprivation therapy (ADT) in patients (pts) with biochemically recurrent prostate cancer (BRPC).
Authors: Emmanuel S. Antonarakis, Adam Kibel, Robert Claude Tyler, Candice McCoy, Yang Wang, Nadeem A. Sheikh, Charles G. Drake
Journal: Journal of Clinical Oncology (2013)

34 Background: ADT is a standard therapy for pts with BRPC after failure of primary therapy, and has known immunomodulatory effects. Sipuleucel-T is an autologous cellular immunotherapy that targets prostatic acid phosphatase (PAP) and is FDA approved for minimally or asymptomatic metastatic castrate-resistant prostate cancer. Here we report interim data from a phase 2 trial evaluating the optimal sequencing of sipuleucel-T and ADT by examining immune response markers in pts with BRPC at high risk for metastases (i.e., PSA doubling time ≤12 mo). Methods: Men were equally randomized to Arm 1: sipuleucel-T followed by ADT (started 2 wk after the final sipuleucel-T infusion); or Arm 2: ADT followed by sipuleucel-T (started after 3 mo of ADT). In both arms pts received 3 infusions of sipuleucel-T and 12 mo of ADT (2 × 45 mg leuprolide injections at 6 mo intervals). The primary endpoint was antigen-specific immune responses (ELISPOT to PA2024 [PAP-GM-CSF]). Secondary endpoints included safety and product parameters (CD54 upregulation, CD54 + and total nucleated cell counts). Results: 68 pts were randomized over 9 mo. Baseline characteristics were balanced across arms. Product parameters, evaluated in 31 and 17 pts in Arms 1 and 2, respectively, were similar between arms at the time of this analysis (26 Sept 2012). Antigen presenting cell activation patterns indicated a prime-boost effect (increased CD54 upregulation at infusions 2 and 3). Analysis of serum samples suggested that there were no differences between the arms in cellular (n=20; n=10) or humoral (n=22; n=13) immune responses to PA2024 or PAP (p&gt;0.05). Similar anti-tetanus titers were seen in both arms, indicating equivalent immunocompetence. To date, the combination of sipuleucel-T and ADT appears to be well tolerated with only 1 serious adverse event seen (vertigo, Arm 2). Conclusions: Preliminary data suggest that in men with BRPC, sipuleucel-T results in a similar prime-boost pattern of immune activation, and antigen-specific cellular and humoral responses, independent of ADT. Sipuleucel-T plus ADT appears to be well tolerated in these pts. Updated results will be presented. Clinical trial information: NCT01431391.
Testicular cancer in Mexico: Clinicopathologic and prognostic study with analysis of causes of death and palliative requirements.
Authors: Maria Teresa Bourlon, Ana Cecilia Ceja-Bojorge, Alejandro Noguez-Ramos, Juan Carlos Cordova-Ramos, Fidel David Huitzil Melendez, Eucario Leon Rodriguez
Journal: Journal of Clinical Oncology (2014)

e20550 Background: Clinical presentation, outcomes, palliative care (PC) requirements and causes of death have been poorly described in Mexican patients with testis cancer. Methods: Retrospective, single institution analysis of prognostic factors, morbidity, palliative interventions and causes of death of patients diagnosed from 2000-2012. Results: 132 patients, median age 28yo, 58% non-seminoma. Clinical stage I in 46%, II in 21% and III in 33%. Risk stratification in advanced patients (n=77): good 45%, intermediate 29% and poor 26%. Of advanced disease 75% showed response to 1st line cisplatin-based chemotherapy.13 patients died. 5y OS for seminoma was 92% (97, 83 and 90% for stage I, II and III). 5y OS for non-seminoma was 89% (100, 93 and 78% for stage I, II and III). Metastases were present in: retroperitoneum 49%, lung 20%, mediastinum 17%, liver 8%, non-regional lymph nodes 14% and CNS 4%. The presence of hepatic (p=.009) and SNC (p=.004) disease influenced OS. Before death patients suffered mainly from dyspnea (n=10), pain (n=4), bleeding (n=4) and seizures (n=3). Attempted supportive interventions were analgesia (n=6), transfusions (n=6), dyspnea control (n=6) and sedation (n=5). Four died during 1st line treatment because of tumor lysis syndrome, none had a PC intervention. One died of unrelated causes. Eight died with cisplatin-resistant disease (CRD): 1 died of surgery complications and 7 died with PD, mostly after a 3rd-line chemotherapy. Causes of death were bleeding (n=3), respiratory failure (n=3) and septic shock (n=1). Recognition of PC requirements occurred in only 4 of 7 patients with CRD with progressive illness; only two patients had a follow-up visit. PC interventions were given to patients considered not candidates for further chemotherapy; never as a complementary treatment. Conclusions: Despite high percentage of stage III disease, stage and histology adjusted survival was as expected. Oncologist neglect palliative care in expectation of further response to chemotherapy, even in cisplatin-refractory patients. Suffering derived from most frequent causes of death, bleeding and respiratory failure, may be alleviated with adequate palliative interventions.
Effect of chemoradiotherapy (CRT) for rectal cancer on the lymph nodes (LNs): Exploration of the number of retrieved LNs, number of metastatic LNs, and the size of LNs.
Authors: Kazutake Okada, Sotaro Sadahiro, Toshiyuki Suzuki, Akira Tanaka, Hiroko Okamura, Akemi Kamijo
Journal: Journal of Clinical Oncology (2012)

651 Background: For accurate staging of colon cancer, 12 or more LNs are recommended to be explored. Although the total number of LNs in rectal cancer was reported to be decreased after CRT, the number of LNs to be explored is not yet clear. We investigated the number of retrieved LNs, number of metastatic LNs, and the LN sizes within the radiation field in comparison with those outside the radiation field, to clarify the influence of CRT. Methods: The subjects were 211 patients with cStage II/III rectal adenocarcinoma who underwent radical surgery between 1991 and 2010. Of these, 111 patients underwent surgery alone (S group) and 100 patients also received preoperative CRT (40 or 45Gy) with concurrent oral UFT or S-1 (RT-group). The numbers of LNs were reviewed by pathological chart, and HE-stained specimens were examined with a digitizer to evaluate the LN sizes (short-axis, long-axis and area). Results: A total of 2049 LNs were retrieved, of which 230 were metastatic LNs. The average number of retrieved LNs was significantly higher in the S group (16±11) than that in the RT group (9±7) (P &lt; 0.0001). The number of LNs inside the radiation field was significantly higher in the S group (6±6) than that in the RT group (4±4) (P = 0.001), whereas outside the radiation field, there was no significant difference between the two groups (5±4 in the S group vs. 5±4 in the RT group). The short-axis of the retrieved LNs was significantly larger in the S group (within the radiation field: 3.5±2.1 mm in the S group vs. 3.0±1.9 mm in the RT group, P &lt; 0.0001; outside the radiation field: 4.3±2.6 in the S group vs. 3.8±2.4 in the RT group, P = 0.05). Conclusions: Preoperative CRT significantly decreased the total number of LNs compared to the surgery alone, attributable to the decrease in the number of LNs inside the radiation field. CRT reduced the size of the LNs and the degree of reduction was larger in the nodes within the radiation field than in those outside. And it was suggested that CRT also had an effect on the LNs outside the radiation field.
The high risk allele of a six-nucleotide insertion-deletion polymorphism in the <i>CASP8</i> promoter is associated with favorable outcome in multiple cancers
Authors: H. S. Bachmann, U. H. Frey, K. Riemann, K. J. Schmitz, F. Otterbach, R. Callies, H. Nückel, W. Siffert
Journal: Journal of Clinical Oncology (2008)

11073 Background: Recently, two polymorphisms in CASP8 were independently identified as factors influencing cancer susceptibility. A non-synonymous single nucleotide polymorphism (SNP) in exon 9 (D302H, rs1045485) has been associated with breast cancer risk and an insertion-deletion promoter polymorphism (-652 6N del, rs3834129) has been associated with susceptibility to multiple cancers, e.g. breast and colorectal cancer. The deletion variant of this polymorphism disrupts a Sp1 binding site and is associated with decreased mRNA expression in lymphocytes of healthy volunteers. Methods: 500 healthy blood donors and 436 patients with different malignancies (breast cancer (n=199), colorectal cancer (n=140), B-CLL (n=97)) were retrospectively genotyped for both polymorphisms. Polymorphisms were analysed for linkage equilibrium and possible association of genotypes as well as haplotypes with risk for cancer. CASP8 expression in the cDNA of 180 snap-frozen tumor samples was analysed by quantitative Real-Time-PCR. Both genotypes and haplotypes were correlated with CASP8 expression and the patients’ survival. Results: Kaplan-Meier curves revealed a significant association of the -652 6N del polymorphism with survival in breast cancer patients (p=0.002), colorectal cancer patients (p=0.042), and patients with B-CLL (p=0.046). Additionally, CASP8 expression was genotype-dependent significantly different in tumor specimens of the three malignancies: breast cancer (p=0.010), colorectal cancer (p=0.015), and B-CLL (p=0.041), respectively. -652 6N del and the second polymorphism D302H were in strong linkage disequilibrium (D´=1) and Kaplan-Meier curves revealed no independent or cooperative effect of the D302H SNP. Conclusions: The CASP8 -652 6N del polymorphism is a potential survival prognosticator as well as indicator of high risk groups within different cancers. Additionally, these results suggest that, although the exon 9 SNP is non-synonymous, only the -625 6N del polymorphism seems to be functional and of further interest. No significant financial relationships to disclose.
Timing of adjuvant chemotherapy in stage III colon cancer as a measure of quality: Reasons for noncompliance.
Authors: Omar M. Rashid, Karen A. Coyne, Thomas W. Ross, David Shibata
Journal: Journal of Clinical Oncology (2014)

640 Background: The Institute of Medicine's report on improving cancer care, along with the evolution of ASCO's Quality Oncology Practice Initiative, has helped to develop process measures into critical quality of cancer care indicators. One such measure relates to "receipt of chemotherapy for stage III colon cancer (CC) within 120 days of diagnosis" and is now being incorporated into processes including hospital accreditation (American College of Surgeons; ACS), managed care contracts and Center for Medicare and Medicaid Services (CMS) quality monitoring. To better understand potential pitfalls related to the strict guidelines of this measure, we sought to evaluate institutional adherence at a tertiary care cancer center and to examine the reasons for non-compliance. Methods: A retrospective review was performed of all cases of stage III colon cancer reported at a single institution from 2008 – 2012. Coding for compliance was performed using standard ACS guidelines. Results: A total of 122 eligible cases were identified and consisted of 49 (40.2%) women and 73 (59.8%) men with a median age of 58 (range 32 - 77). Overall, 15 (12.3%) cases were non-compliant with 2 (1.6%) lost to follow up. Of the non-compliant cases, 14 (93.3%) cases did go on to receive chemotherapy while 1 (6.7%) never received adjuvant treatment. Of those receiving delayed treatment, 7 were due to patient-centered factors [e.g. patient timing preference (n=4), request for chemotherapy closer to home (n=2) and lost to follow up (n=1)]. Other reasons included delays at outside facilities (n=4), postoperative complications (n=1) and insurance approval (n=1). In 2 cases, designation of date of diagnosis based on suspicion rather than definitive biopsy contributed to non-compliant status. Conclusions: Our center averaged an annual compliance with the CC adjuvant therapy measure of approximately 90%. Larger scale studies are indicated to determine whether refinements in coding guides that account for patient preferences, clear diagnosis dates and cross-facility care could better reflect quality of care, and also promote improved patient-centered multidisciplinary management.
Risk of colorectal cancer subsite in a prostate cancer cohort.
Authors: Yunxia Lu, Rickard Ljung, Mats Lindblad, Jesper Lagergren
Journal: Journal of Clinical Oncology (2012)

404 Background: Epidemiological studies imply an association between sex hormonal related factors and the risk of colorectal cancer. Methods: A prostate cancer cohort was initiated from the Swedish Cancer Register among patients diagnosed during 1961-2008. The prostate cancer patients were followed up until a diagnosis of colorectal adenocarcinoma, death, emigration or end of study (December, 31, 2008). The cohort was stratified into a group as “estrogen exposed” who were diagnosed with prostate cancer before 1980, and a group as “estrogen less exposed” who were diagnosed after 1980. The reason for this grouping was estrogen therapy was the predominant treatment strategy in Sweden before 1980 while other treatment became more common after 1980. Standardized incidence ratios (SIRs) and 95% confidence interval (CI) were estimated as the measure of relative risk compared to the general population of the corresponding age and calendar year. SIRs were estimated for total colorectal cancer and for cancer of the proximal colon, distal colon, and rectum separately. Results: Among a total of 190,485 of prostate cancer patients contributing 708,019 person-years at risk, we identified 1493 colorectal adenocarcinoma. For those diagnosed with prostate cancer before 1980 (estrogen exposed group),almost all age groups showed a decreased risk of colorectal cancer, except for cancer of the distal colon, compared to the general population. Increased risk of colorectal cancer was instead found in almost all age groups for those diagnosed after 1980 (estrogen less exposed group). SIRs of adenocarcinoma in the proximal colon and distal colon showed different patterns. After 1980, the SIR of adenocarcinoma in the distal colon among patients followed up for &gt;10 years was 1.29, (95% CI 1.02-1.60). Conclusions: This study indicates that exposure to estrogens protect against colorectal cancer, while treatment after 1980 displayed a potential increased risk of colorectal adenocarcinoma, especially in the distal colon.