tbuckley/cabot-search huggingface dataset:
Predictive value of PET/CT for pathological complete response and survival in patients with locally advanced rectal cancer.
Authors: Eric C Sorenson, Aruj J Choudhry, Jian Qin Yu, Sanjay S. Reddy, Crystal Shereen Denlinger, Joshua E. Meyer, Jeffrey M. Farma, Elin R. Sigurdson
Journal: Journal of Clinical Oncology (2017)

697 Background: A major challenge in identifying candidates for nonoperative management of locally advanced rectal cancer is predicting pathological complete response (pCR) following chemoradiation therapy (CRT). We evaluated the ability of pre- and post-CRT PET imaging to predict pCR and long-term prognosis. Methods: We retrospectively identified patients at our institution from 2002–2015 with locally advanced rectal cancer who underwent CRT, pre- and post-CRT PET imaging, and surgical resection. Logistic regression and Kaplan-Meier estimates were used to analyze the association of PET variables with tumor pCR and survival outcomes. Receiver operator characteristic curves were generated to define optimal cutoff points for predictive PET variables. Results: 140 patients matched the inclusion criteria. The pCR rate was 28%, and median follow-up time was 48 months. On multivariable analysis, pCR was associated with lower median post-CRT SUV max (3.2 vs 5.2, p=0.009) and higher median SUV percent decrease (72 vs 58%, p=0.009). ROC curves were generated for SUV percent decrease (AUC=0.70) and post-CRT SUV (AUC=0.69) to estimate cutoff points for maximum specificity and sensitivity to predict pCR. Post-CRT SUV &lt;4.3 and SUV percent decrease of &gt;66% were equally predictive of pCR with a sensitivity of 65%, specificity of 72%, PPV of 44%, and NPV of 86%. Median 5-year OS and RFS were significantly improved for patients with post-CRT SUV &lt;4.3 (OS, 86 vs 66%, p=0.01; RFS, 75 vs 52%, p=0.01) or SUV percent decrease of &gt;66% (OS, 82 vs 66%, p=0.05; RFS, 75 vs 54%, p=0.01). Patients with stage III disease and a post-CRT SUV &lt;4.3 were in effect downstaged, with a median 5-year OS equivalent to that of patients with stage II disease (Table 1; 86 vs 86%). Conclusions: PET/CT may be a useful modality in predicting pCR and overall survival in patients undergoing CRT for rectal cancer. Inclusion of pre-CRT PET does not appear to add prognostic value for pCR compared with post-CRT PET alone. Patients with a post-CRT SUV of &gt;4.3 should not be considered for nonoperative management, as an estimated 86% of these patients will not have a pCR.
Monotherapy with a tumor-targeting mutant of <i>S. typhimurium</i> cures orthotopic metastatic mouse models of human prostate cancer
Authors: R. M. Hoffman, M. Zhao, J. Geller, H. Ma, M. Yang
Journal: Journal of Clinical Oncology (2007)

15641 Background: The evidence that bacteria have a therapeutic effect on tumors has been accumulating since the 19 th century. In recent years, there has been renewed interest to develop bacteria that target necrotic tumor areas. However, this approach requires combination with cytotoxic chemotherapy for efficacy. Toward the goal of effective tumor-targeting bacteria as monotherapy, we have developed Salmonella typhimurium leu-arg auxotrophs (A1-R), which enable the bacteria to grow in viable as well as necrotic areas of tumors but not in normal tissue. Methods: In the current study, we determined the efficacy of A1-R on metastatic PC-3 human prostate tumors orthotopically implanted in nude mice. Ten of 20 orthotopically-implanted nude mice served as untreated controls and were followed until death. Ten mice were given the S. typhimurium A1-R weekly intravenously, beginning at 2 weeks when the tumor was first externally visible due to expression of green fluorescent protein. Survival time was compared to the untreated mice. Results: Of the 10 mice with the PC-3 tumors injected weekly with S. typhimurium A1, 7 were alive and well at the time the last untreated mouse died. Four A1-R-treated mice remain alive and well 6 months following implantation. Ten additional non-tumor-bearing mice were used to determine toxicity of S. typhimurium A1-R which were injected weekly. No toxic effects were observed. Conclusions: The approach described here, where bacterial monotherapy could cure metastatic prostate tumors, is a significant improvement over other bacterial tumor-therapy strategies that require combination with toxic chemotherapy. The results also suggest the clinical potential of tumor-targeting bacteria that can grow in the viable as well as necrotic areas of the tumor. Since human prostate cancer eventually becomes non-androgen- dependent similar to PC-3 tumors, genetically-altered bacteria represent a novel potential treatment for this disease. No significant financial relationships to disclose.
Assessing bone response to cabozantinib in patients (pts) with metastatic urothelial carcinoma (mUC) using <sup>18</sup>F-Sodium Fluoride (NaF) PET/CT.
Authors: Jeffrey Lin, Liza Lindenberg, Seth M. Steinberg, Yolanda McKinney, Juanita Weaver, Deneise C Francis, Marilise Anne Berniger, Howard L. Parnes, Nicole N. Davarpanah, Peter L. Choyke, Andrea B. Apolo
Journal: Journal of Clinical Oncology (2017)

328 Background: NaF PET/CT is a radiotracer used for the assessment of bone metastases (mets). The goal of our study was to assess bone mets using NaF PET/CT imaging in mUC pts treated with cabozantinib. Methods: We conducted a single-arm phase II trial of cabozantinib in pts with mUC. Pts with known bone mets underwent a NaF PET/CT scan at baseline and every 8 weeks until progression. At each scan, we captured, the number of lesions per pt and per anatomical site, the maximum standardized uptake values (SUV), and serum alkaline phosphatase (AP). Bone responses (bone response (BR), stable disease (SD), progressive disease (PD)) were assigned to each pt based on the NaF report. Change from baseline to the time of best response for SUV, the number of lesions, and AP were compared between BR + SD vs PD were analyzed using an exact Wilcoxon rank sum test. The Kaplan-Meier method was used to determine the association of progression free survival (PFS) or overall survival (OS) with baseline SUV and number of lesions. Results: 68 pts enrolled on study, 22 pts had bone mets at baseline (6 bone only and 16 with bone and soft-tissue mets) (median OS 4.6 mo (95% CI: 3.4-7.7 mo), and median PFS 2.0 mo (95% CI: 1.8-3.9 mo)) of which 15 pts had follow up NaF scans. At baseline, 147 total lesions were analyzed, and the lesion distribution was: spine 29%, ribs 21%, pelvis 18%, skull 11%, femur 6%, scapula 3%, humerus 3%, sternum 3%, sacrum 3%, fibula 1%, and clavicle 0.7%. 5/15 pts had BR (and remained on study 238, 252, 182, 161, and 56 days), 4/15 SD, and 6/15 PD at best response. Sites of PD occurred in bone 10/22, bone and soft-tissue 5/22, and soft-tissue 7/22. The percent difference in number of lesions among responders and non-responders was 43% (p = 0.0039). At baseline, there was no association with PFS or OS and number of lesions (p = 0.84, p = 0.97), SUV (p = 0.83, p = 0.97), or AP (p = 0.97, p = 0.33). Conclusions: Pts with mUC and bone disease have poor overall outcome. Most bone lesions were found in the spine, ribs, and pelvis. Larger studies are needed to assess the correlation of NaF response with clinical outcome in mUC. We have an ongoing study using NaF PET to assess bone mets in mUC treated with cabozantinib/nivolumab/ipilimumab. Clinical trial information: NCT01688999.
Phase II trial of carboplatin and pemetrexed combination in elderly patients with advanced non-squamous non small cell lung cáncer (NS-NSCLC). A Galician Lung Cancer Group Study.
Authors: Mª Carmen Areses Manrique, Natalia Fernández Núñez, Marta Covela Rúa, Ana Alonso Herrero, Maria Jose Villanueva Silva, Francisco J. Afonso Afonso, Gaspar Esquerdo, Begoña Campos Balea, Martin Lázaro Quintela, Jesus Garcia Mata, Sergio Vazquez-Estevez, Urbano Anido Herranz, Joaquin Casal Rubio, Jose Luis Firvida Perez
Journal: Journal of Clinical Oncology (2015)

e19017 Background: The standard treatment for elderly patients in advanced NS-NSCLC is not defined. The aim of this study was to evaluate the efficacy and safety profile of the combination of carboplatin and pemetrexed in this population. Methods: Elegibility criteria included, histologically or citologically confirmed NS-NSCLC clinical stage IIIB vs IV, evaluable disease, no prior cytotoxic chemotherapy, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, an adequate organ function and ³ 70 years old. Patients received carboplatin at an area under the concentration time curve (AUC) of 5 and pemetrexed 500 mg/m2 for four cycles on day 1 every 3 weeks. In non-progressing patients, maintenance therapy with pemetrexed every 3 weeks was optional to continue at the discretion of the investigator, until either disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). The secundary endpoints were the response rate (RR), disease control rate (DCR), overall survival (OS) and the rates of adverse events. Results: A total of thirty-four patients were included in a phase II clinical trial from 6 different centers. The patients demographics were: median age 76 years (range 70-82), 8 female and 26 male; 31 patients adenocarcinoma and 3 large-cell lung carcinoma; tumor EGFR status wild type in all patients. 51% went to manteinance. Among 32 patients evaluated, the RR was 31,3%, disease stabilization 31,3%, disease progression 28,1% and non-evaluable 9,3%. The DCR was 62.5%. In non-manteinance group the PFS was 4.1 months and OS 8.6 months. In the manteinance group instead, the PFS was 9.5 months and OS 11.9 months. Most common attributable adverse events (all grade 3) were fatigue (5) and anemia (2). Each of the toxicities were controllable and there were no treatment-related deaths. Conclusions: These data provided that carboplatin and pemetrexed combination is effective and well tolerated in elderly patients with advanced NS-NSCLC
NEOZOTAC: Efficacy results from a phase III randomized trial with neoadjuvant chemotherapy (TAC) with or without zoledronic acid for patients with HER2-negative large resectable or stage II or III breast cancer (BC)—A Dutch Breast Cancer Trialists’ Group (BOOG) study.
Authors: Ayoub Charehbili, Saskia van de Ven, Gerrit-Jan Liefers, Vincent T. H. B. M. Smit, Hein Putter, Joan Barbara Heijns, Laurens van Warmerdam, Lonneke Kessels, Wouter Dercksen, Manon J. Pepels, Eduard Maartense, Hanneke W. M. Van Laarhoven, Birgit Vriens, Martin N. Wasser, Neveen A.T. Hamdy, Elma Meershoek – Klein Kranenbarg, Elise van Leeuwen-Stok, Cornelis J. H. Van De Velde, Judith R. Kroep, J. W. R. Nortier
Journal: Journal of Clinical Oncology (2013)

1028 Background: The role of bisphosphonates when added to the neoadjuvant treatment of BC in enhancing the efficacy of therapy is still unknown. Methods: NEOZOTAC is a national, multicenter, randomized study comparing the efficacy of TAC (docetaxel, Adriamycin and cyclophosphamide i.v.) CT followed by G-CSF on day 2 with or without ZA 4 mg i.v. ,q 3 weeks in patients (pts) with stage II/III, measurable, HER2-negative BC and absence of prior bisphosphonate usage. The primary endpoint is the pathologic complete response (pCR) rate in the resection specimen and positive lymph nodes. 228 pts are needed to show an improvement of the pCR rates from 17% to 34% in the experimental arm using a 5% significance level based on the two-sided Fisher’s exact test with a power of 80%. Randomization was done by using the Pocock’s minimisation technique stratified by cT, cN and estrogen receptor status. pCR rate was analyzed using the Cochran-Mantel-Haenszel test, adjusting for the stratification factors. Analysis was based on intent-to-treat. An unplanned subgroup analysis of postmenopausal women (PMW; FSH &gt;20 and estradiol &lt;110) and baseline vitamin D levels was performed. Results: From July 2010 to April 2012, 250 patients from 25 participating sites were randomized. Pathologic response data of 228 patients are currently available. pCR rate did not differ between the two study arms (17% vs 16%, p = 0.81). However, a trend in benefit in favor of ZA was observed in PMW (18% vs 11%, OR 1.90, 95% C.I. 0.52 – 6.88). Patients with severe vitamin D insufficiency (&lt;25 nmol/L) seemed to respond worse to CT numerically (6% vs. 18%). At ASCO pCR and clinical response data of all patients will be reported. Conclusions: Previously, we have shown that adding ZA to neoadjuvant CT is safe with good compliance.In this study, treatment with ZA did not result in a pCR benefit in the total study population. However our findings suggest that addition of ZA to neoadjuvant CT might be effective for enhancing response in PMW with BC. Clinical trial information: NCT01099436.
Spiritual care provided by oncology physicians and nurses to advanced cancer patients.
Authors: Zachary Epstein-Peterson, Adam Sullivan, Andrea C. Phelps, Michael J. Balboni, Tyler J. Vanderweele, Tracy A. Balboni
Journal: Journal of Clinical Oncology (2012)

9116 Background: For many patients facing a diagnosis of advanced cancer, religion and/or spirituality (R/S) play an important role in coping with illness. Data suggest that cancer patients receiving spiritual care (SC) have better quality of life and receive less futile, aggressive interventions at the end of life. National palliative care guidelines include SC as a key component of end-of-life care. However, current SC practices and the role clinicians should play in SC provision remain unclear. Methods: The Religion and Spirituality in Cancer Care (RSCC) study is a survey-based, cross-sectional study of oncology physicians and nurses and advanced cancer patients from five Boston-area institutions. The survey elicited respondents’ R/S beliefs/practices, their views on the appropriateness of SC in the advanced cancer care setting, and their experiences in giving or receiving SC (e.g., spiritual history, referrals to chaplains). In total, 68 patients, 204 physicians, and 114 nurses responded (response rates: patients = 73%; clinicians = 63%). Multivariable analyses (MVAs) were performed to determine predictors (e.g., clinician demographics, R/S, spiritual care training) of SC provision by clinicians. Results: All respondents reported a low frequency of SC provision, with only 9% of patients receiving SC from physicians, 20% from nurses, and physicians reporting performing SC during only 8% of interactions, nurses during 12% of interactions. In MVAs, prior training in spiritual care was significantly associated with SC provision (OR physicians 5.89, CI 2.14-16.22; OR nurses 10.42, CI 1.30-89.19), as was the provider identifying as being spiritual (OR 3.85 physicians CI, 2.12-6.98; OR 2.92 nurses CI, 1.15-7.42). Conclusions: These data highlight the current inadequacies of SC provision by clinicians, despite national palliative care guidelines, and underscore the central role of SC training for doctors and nurses, as this was the strongest predictor of SC provision. Given the important role that SC has in end-of-life care and the paucity of data guiding its provision, we hope this research will advance the understanding of how to integrate SC into end-of-life care, and ultimately improve patient outcomes at the end-of-life.
Correlation of chemotherapy delivery and survival outcomes of follicular lymphoma in the immunchemotherapy era.
Authors: Kitsada Wudhikarn, Anna M Button, Brian J. Smith, Thomas Matthew Habermann, Carrie A. Thompson, James Robert Cerhan, Brian K. Link
Journal: Journal of Clinical Oncology (2013)

8563 Background: Optimal initial treatment of follicular lymphoma (FL) is unknown. Rituximab as monotherapy (R) or as a component of immunochemotherapy (R+Chemo) is established as effective and it is now reasonable to re-examine the role of chemotherapy dosing. We explored clinical features, systemic treatment and chemotherapy delivery with comparative effectiveness of delivered dose intensity (DDI) on outcomes. Methods: We reviewed the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource database along with medical records on newly diagnosed grade I-IIIa FL who received systemic therapy from 2002 to 2009. Presenting clinicopathologic factors, outcomes and systemic therapy details including doses of chemotherapy were collected. The event-free (EFS) and overall survival (OS) effects of systemic therapy and chemotherapy DDI were analyzed with multivariate Cox regression. Confounding effects of FLIPI, grade, stage, and age were considered in the analysis. Results: From 2002 to 2009, 631 newly diagnosed FL were enrolled. Median follow up duration was 52.7 months. We identified 322 grade I-IIIa FL treated with systemic therapy including 93 R and 229 R+Chemo. Age and stage were similarly distributed between the R and R+Chemo groups; however, patients in the R group had lower grade (p&lt;0.01) and FLIPI (p=0.03). Multivariate analysis showed no significant differences in EFS (HR=1.24, p=0.28) or OS (HR=0.55, p=0.13) for R compared to R+Chemo. Among R-CVP or R-CHOP treated FL, DDI data were collected for 73 doxorubicin (dox) and 137 cyclophosphamide (cyc) patients. Eighty-five percent of patients received 90% or more pre-planned DDI. After controlling for confounding factors, higher cycDDI was associated with improved EFS (HR 0.55, P=0.04) and OS (HR 0.74, P=0.03). No significant OS or EFS effects of doxDDI were observed. Conclusions: Addition of chemotherapy to rituximab was not associated with a detectable difference in survival outcomes in grade I-IIIa FL at a median follow-up of 52.7 months. Among R+Chemo treated FL, chemotherapy was delivered completely in most patients and more completed delivery of cyclophosphamide was associated with improved EFS and OS.
PI3K pathway as a major determinant of resistance to HER2-targeted therapy in advanced gastric cancer.
Authors: Hyo Song Kim, Xianglan Zhang, Kyu Hyun Park, Ji Soo Park, Ki Hyang Kim, Hyun Cheol Chung, Sun Young Rha
Journal: Journal of Clinical Oncology (2013)

4089 Background: Despite the improvement of survival with trastuzumab treatment, it is still unclear why majority of patients are initially nonresponsive or eventually become resistant to HER2-based therapy. To evaluate resistant mechanism and stimulate the development of rational drug, we investigated the role of phosphoinisitide 3-kinase (PI3K) pathway activation. Methods: With tumor tissues from HER2-overexpressing advanced gastric cancer, PIK3CA mutation status (by pyrosequencing of exon 9 and 20) and phosphatase and tensin homolog (PTEN) expression levels (using immunohistochemical analysis) were evaluated for the therapeutic response to HER2-based therapy. Results: Forty nine patients received trastuzuamb (n=39) or lapatinib (n=10) in combination with chemotherapy regimen. The age at diagnosis was 61 years and all the cases were HER2 positive and/or amplified. PTEN-loss was found in 67% (n=33) and all the patients showed PIK3CA wild-type tumors. Twenty nine patients (59%) responded to HER2-based therapy (complete and partial response), without significant difference between PTEN-loss and normal tumors (61% vs 62%). Among the patients with responsive disease, time to best response was not different but duration of response was shorter for the PTEN deficient patients (155 vs 244 days, P=0.016). In addition, PTEN-deficient patients have significantly shorter progression-free survival (median 160 vs 286 days, P=0.018), which implying the functional role of PTEN for the acquired resistance to HER2-based therapy. Conclusions: This data suggests PTEN as an important predictor for the early progression and acquired resistance to HER2-based therapy. Activated PI3K pathway may provide a biomarker to identify patients who may need additional or alternative therapies.
Randomized phase III trial of carboplatin/paclitaxel alone (CP) or in combination with bevacizumab followed by bevacizumab (CPB) and secondary cytoreduction surgery in platinum-sensitive recurrent ovarian cancer: GOG0213, an NRG Oncology/GOG Study—Analysis of patient reported outcomes (PRO) on chemotherapy randomization.
Authors: Karen Basen-Engquist, Helen Q Huang, Thomas J Herzog, Deborah Kay Armstrong, Paul Sabbatini, Joan L. Walker, Byoung Gie Kim, Keiichi Fujiwara, Krishnansu Sujata Tewari, David M. O'Malley, Robert L. Coleman
Journal: Journal of Clinical Oncology (2015)

5525 Purpose: GOG 213 is a bifactorial, phase III, randomized trial studying the efficacy and tolerability of the incorporation of B and secondary cytoreduction in women with platinum sensitive recurrent EOC. The primary endpoint was OS. Here we report intervention related PROs. Methods: PRO’s were assessed using the ovarian Functional Assessment of Cancer Therapy-Trial Outcome Index (FACT-O TOI, QoL endpoint for chemotherapy objective), treatment side effects related to B (TSE-B), physical function (PF) subscale of the Rand SF-36 (QoL endpoint for surgical randomization), and treatment side-effects related to surgery (TSE-Surg). Assessment time points were baseline, prior to cycles 1, 3 and cycle 6, 6 mo. after cycle 1, and 12 mo. after cycle 1. QoL scores were compared using a linear mixed model adjusting for baseline score, age, and assignment to secondary surgery. Mixed effects mixed distribution model evaluated treatment differences in physical functioning on the RAND SF-36. Results: Patients randomized to CT (n = 298 (88%)) or CTB (n = 302 (90%)) were evaluable for QoL. Treatment compliance was 93% at baseline, 88% at cycle 3, 83% at cycle 6, 82% at 6 months and 78% at 12 months. More CTB patients completed PRO assessments (P = 0.037). FACT-O TOI scores at baseline were similar. Subscales of FACT-O showed no differences in TSE-Bev, except pre-cycle 3 physical well-being, which was negatively impacted by treatment (p = 0.028). CPB patients had significantly worse physical functioning (P = 0.0156): treatment difference of 3.4 points (95% CI: 0.05-6.7, p = 0.048) at cycle 3 and 6.8 points (95%CI: 3.0-10.6, p = 0.0004) at cycle 6. Conclusion: Treatment with CPB was not associated with a significant difference in health-related QoL measured by the FACT-O TOI. While receiving CPB, patients may experience lower physical functioning with recovery to baseline during maintenance B. Clinical trial information: NCT00565851.