tbuckley/cabot-search huggingface dataset:
Hematologic toxicity and dose intensity in older patients with colorectal cancer receiving systemic chemotherapy
Authors: M. Shayne, E. Culakova, D. C. Dale, M. S. Poniewierski, D. A. Wolff, J. Crawford, G. H. Lyman
Journal: Journal of Clinical Oncology (2008)

4052 Background: While the risk of colorectal cancer (CRC) as well as comorbidities increase with age, systemic chemotherapy has become a mainstay of treatment across age groups. Trends in chemotherapy dosing, toxicity, and supportive care for patients with CRC from a nationwide study were examined. Methods: Patients with CRC (N=521), including 255 ≥ 65 years of age, were prospectively registered at 115 US community oncology practices. Primary outcomes included anemia (hemoglobin <10g/dL), thrombocytopenia (platelets <75x109/L), febrile neutropenia (FN; fever/infection and absolute neutrophil count (ANC) nadir <1x109/L) or severe neutropenia (SN; ANC <5x109/L), and both planned and actual relative dose intensity (RDI) compared to standard regimens. Differences among patients age 18–64 (50.5%) and age ≥ 65 (49.5%) were compared. Results: No significant differences in disease stage or type of chemotherapy regimen were reported between older and younger patients. Older patients in this study, however, were more likely to have comorbid conditions (p=0.048) and significantly poorer ECOG performance status (p=0.0004) than younger patients. CRC patients ≥ 65 years of age compared with patients <65 experienced significantly higher rates of neutropenic complications: 12.1% vs. 5.9% (p=0.015), anemia: 22.9% vs. 14.9% (p=0.023), and thrombocytopenia: 6.3% vs. 1.6% (p=0.007), respectively. Actual RDI <85% over four cycles was observed in 42.2% of patients with half of reductions in RDI planned from the start of chemotherapy. Although older patients with CRC were less likely to have body surface area >2 m2 than younger patients (p=0.002), no difference in average actual or planned RDI or colony-stimulating factor (CSF) use between older and younger patients was observed. Prophylactic CSF was administered in <10% in both older and younger patients. Conclusions: Older patients with CRC experienced higher rates of chemotherapy-related hematologic toxicity compared with younger patients. While CSFs have been shown to reduce the risk of SN in CRC, this study demonstrates that most patients with nonmetastatic disease do not receive CSF prophylaxis but rather undergo substantial reductions in chemotherapy dose intensity potentially compromising curative treatment. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen Amgen Amgen
The relationship between tumour necrosis, circulating IL-6 concentrations, and inflammatory responses in patients undergoing curative resection for colorectal cancer.
Authors: Graeme JK Guthrie, Campbell SD Roxburgh, Colin H Richards, Paul G. Horgan, Donald C. Mcmillan
Journal: Journal of Clinical Oncology (2013)

404 Background: Cancer-associated inflammation, in the form of systemic and local inflammation, and tumour necrosis are known to have prognostic value in colorectal cancer (CRC). In addition, recent work has reported a direct relationship between the systemic inflammatory response and loss of skeletal muscle in patients with CRC. However, the inter-relationships between these inflammatory responses, tumour necrosis, metabolic upset and circulating biochemical mediators are unclear in CRC. Interleukin-6 and its downstream signalling cascades have been implicated in both cancer-associated inflammation and cancer-associated muscle wasting. The aim of the present study was to examine whether circulating IL-6 concentrations may link tumour necrosis, local and systemic inflammatory responses, and metabolic upset in patients undergoing curative resection for colorectal cancer. Methods: The study included 118 patients undergoing surgery for CRC between 2004 and 2009. Data were collected from pre-operative blood tests. Routine pathology specimens were scored for Klintrup criteria and tumour necrosis. Results: Tumour necrosis was associated with increased T-stage (p&lt;0.01), reduced inflammatory cell infiltrate (p&lt;0.05), increased IL-6 (p&lt;0.001), IL-10 (p&lt;0.01), and VEGF (p&lt;0.001) and with markers of the systemic inflammatory response: mGPS (p&lt;0.001), anaemia (p&lt;0.05); increased white cell (p&lt;0.001), neutrophil (p&lt;0.05) and platelet (p&lt;0.001) counts. Circulating IL-6 was associated with increased IL-10 (p&lt;0.01), VEGF (p&lt;0.001), increased mGPS (p&lt;0.001), increased white cell (p&lt;0.01) and platelet (p&lt;0.01) counts and low skeletal muscle index (p&lt;0.01). On Spearman rank correlation there were significant associations between circulating concentrations of IL-6 and IL-10 (r s = 0.39, p&lt;0.001) and CRP (r= 0.42, p&lt;0.001). Conclusions: Interleukin-6 appears to be associated with systemic inflammation, tumour necrosis, and sarcopenia in colorectal cancer. However, the lack of an association between IL-6 and the local inflammatory response suggests a more complex relationship with the tumour inflammatory cell infiltrate.
A phase II study of dasatinib in patients with transplant and nontransplant-related unresectable/metastatic cutaneous squamous cell carcinoma.
Authors: T. Olencki, S. Peters, P. Hoang, C. Taylor, M. A. Villalona-Calero, K. L. Kendra
Journal: Journal of Clinical Oncology (2010)

e19026 Background: Dasatinib, an oral protein tyrosine kinase inhibitor with specificity for multiple kinase families such as BCR-ABL, c- src, c-KIT, PDGFbeta receptor, and EPHA2. Antitumor efficacy has been demonstrated in rhabsomyosarcoma, squamous cell of the head and neck (HNSC), and non-small cell lung cancer (NSCLC). Dasatinib inhibits src activity and downstream signaling in 2 related cancers HNSC and NSCLC. Transgenic mouse models suggest c-src plays an important role in squamous cell skin cancer promotion and progression. This mechanism of action and similarity between squamous cell of the skin and HNSC and NSCLC make this an attractive agent in the treatment of squamous cell of the skin. Methods: Patients with squamous cell cancer with at least 50% of the tumor biopsy compatible with squamous cell histology or basalosquamous cell (squamous differentiation) are eligible if ≤ 1 prior chemotherapy treatment. Prior topical therapy, radiation, or 1 prior therapy with a monoclonal antibody is permitted. Normal organ and marrow function is required. Patients must not be receiving inhibitors/inducers of CYP3A4. Following consent, eligible patients will receive dasatinib (70 mg po BID) continuously with reductions based on toxicity. The initial dose of 100 mg po BID was reduced due to intolerance. Photographs and/or radiographic evaluation will occur every 2 cycles. Pretreatment biopsy is required. The primary objective: to determine the objective response rate (CR + PR). Secondary objectives: to determine of progression-free survival, assessment of pretreatment presence of total EphA2 and total and active Src and FAK, and assessment of COX-2. A one stage trial design is used with 35 evaluable patients. Results: Three patients have been treated at the 100 mg dose and 2 at the 70 mg dose. Conclusions: Enrollment is ongoing. Supported by N01-CM-62207. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Genentech, Novartis Genentech, GlaxoSmithKline, Pfizer, Synta
Molecular profiling of non-urothelial bladder cancer: Adenocarcinoma and squamous cell carcinoma.
Authors: Daniel M. Geynisman, David Arguello, Sandeep K. Reddy, Zoran Gatalica
Journal: Journal of Clinical Oncology (2016)

423 Background: Adenocarcinoma (ADA) and squamous cell carcinoma (SCC) are rare and often aggressive histologic subtypes of bladder cancer. For advanced disease, no clear standard therapies exist and NCCN guidelines suggest only fluorouracil, cisplatin, paclitaxel and ifosfamide as possible options. Thus, novel therapies based on underlying tumor biology are needed. The purpose of this study was to identify potential therapeutic options for these histologic subtypes, utilizing multiplatform tumor profiling. Methods: 49 ADA and 24 SCC specimenswere tested via a multiplatform profiling service (Caris Life Sciences, Phoenix, AZ) consisting of gene sequencing (Sanger or next generation sequencing [NGS]), gene amplification (CISH or FISH), and protein expression (immunohistochemistry [IHC]). 52% of cases were from metastatic sites. Results: Both ADA and SCC exhibited high rates of TP53 aberrations (82.4% and 72.7%, respectively). Sequencing revealed mutations in BRCA2 (14.3%), SMAD4 (12.5%), PTEN (11.8%), KRAS (8.7%), NRAS (5.6%), and KIT (5.3%) in ADA. In addition, PIK3CA (21.4%), HRAS (18.2%), BRCA1 (16.7%), BRCA2 (16.7%), and FBXW7 (9.1%) mutations were detected in SCC. Amplification in EGFR (27.3%) and ERBB2/HER2 (16.7%) were found in ACA. Meanwhile, only one ERBB2 (6.3%) amplification was found in SCC using ISH. MET was not amplified in either ACA or SCC. For both ACA and SCC, EGFR had the highest level of protein expression (100% and 85.7%, respectively). Of note, PD-1 (44.4% in both) and PD-L1 (11.1% and 22.2% in ACA and SCC, respectively) were expressed in both subtypes. Although differential rates of somatic alterations, amplification, and protein expression were found between ADA and SCC, only TLE3 was significant (19.2% versus 60.0%, respectively, p = 0.0154). Conclusions: Differential results in gene alteration, amplification, and protein expression imply the potential utility of tumor profiling in guiding therapeutic decision-making in ADA and SCC of the bladder. PIK3CA/AKT/mTOR pathway aberrations are similar to what has been reported in urothelial bladder cancer. Targeting the PD-1/PD-L1 axis may be a therapeutic option. Further studies are warranted in both diseases.
Overcoming the Negative Impact of Age Using Fludarabine-Based Conditioning Regimens for HLA-Identical Sibling HSCT in Patients with Severe Aplastic Anemia (SAA): A Study from the EBMT-SAA Working Party.
Authors: Sebastien Maury, Paolo Anderlini, Romaine Viollier, Rosi Onetto, Frederique Garban, Didier Blaise, Catherine Cordonnier, Judith Marsh, Andrea Bacigalupo, Jakob Passweg
Journal: Blood (2006)
Management of premenopausal women with neoadjuvant endocrine therapy: A single institution experience.
Authors: G. Nagaraj, J. Pacheco, M. J. Ellis, J. A. Margenthaler, C. X. Ma
Journal: Journal of Clinical Oncology (2011)

e11014 Background: In postmenopausal women with hormone receptor positive (HR+) breast cancer, neoadjuvant endocrine therapy (ET) provides effective down staging of tumor for improved surgical outcome and offers an important advantage of assessing tumor endocrine responsiveness for individualized therapy in the adjuvant setting. While approximately 60% of breast cancer in premenopausal is HR+, the role of neoadjuvant ET in this population is not defined. Methods: Retrospective review of our institution’s database from year 2003 to 2010 identified a total of 12 premenopausal women with 14 different tumors (2 patients with bilateral tumors) treated with neoadjuvant ET. The average age was 46 years. Most of the patients were referred to medical oncologist by surgeons to improve operability. The predominant reason to choose ET was based on tumor being estrogen receptor rich and low grade with 10 out of 14 tumors being grade 1. Most patients were treated with combination of gonadotropin releasing hormone agonist with either an aromatase inhibitor or tamoxifen. The average duration of ET was 4.25 months with 5 patients undergoing oophorectomy during the course. 2 patients also received chemotherapy (CT), 1of whom was switched to endocrine therapy after CT and the other switched from ET to CT after 1 month. Results: Out of the 13 remaining patients on ET prior to surgery, all were noted to have some clinical response. 3 had non-palpable tumors and 6 had at least a partial clinical response (PR) (with >30% decrease in size). With regards to radiologic response, 10 patients had quantifiable data available before and after therapy, of which a PR was noted in 3 tumors and 6 had at least stable to less than a partial response. In terms of surgical outcomes, 12/13 patients had negative margins at surgery. Breast conservation surgery (BCS) was performed on 3, simple mastectomy with negative margins in 7 and remaining 3 patients underwent modified radical mastectomy. Conclusions: As with all therapeutic intervention, we identified responders and non-responders to ET emphasizing the heterogeneity of breast cancers. In addition to improving surgical outcomes in general, this approach helps identify the highly endocrine sensitive tumors.
A novel risk score for prediction of hypersensitivity reactions in cancer patients receiving carboplatin: Retrospective observational analysis.
Authors: Orawan Suppramote, Prapatsara Pongpunpisand, Kanlaya Ladkam, Somkiat Rujirawat
Journal: Journal of Clinical Oncology (2016)

e282 Background: Hypersentitivity reactions (HSRs) from carboplatin are high incidence and most severity in Chulabhorn hospital. These reactions are associated with several causes including patient factors and experience in drug used. A reliable and valid tool for evaluated risk of HSRs before started carboplatin infusion should lead to prevent or decrease severity of the reactions. We innovated risk score to screen patient at high risk of HSRs. Methods: From October 2013 to September 2014, all cancer patients who received carboplatin in Chulabhorn hospital were included. A retrospective study design to developed risk scoring system for prediction of patients at high risk of carboplatin hypersensitivity called “Hypersensitivity risk score”. The hypersensitivity risk score was calculated for all patients receiving carboplatin and data for carboplatin hypersensitivity were obtained from medical records. Expected and observed HSRs were analyzed by using receiver operating characteristic (ROC) curve. Results: Seventy-three cancer patients received carboplatin and five (7%) patients had HSRs. Our scoring algorithm based on cancer type, number of carboplatin retreatment, duration between each retreatment, and number of carboplatin infusions prior to first reaction. All significant predictors were weighted into points and categorized to risk group which ranged from 0 to 8 . The ROC analysis for hypersensitivity risk score indicated good predictive accuracy with an area under the curve of 0.96 (95 %CI: 0.91-1.00). Data showed high sensitivity (80%) and specificity (94.85%) for a risk score cut-off of 4. The hypersensitivity risk score clearly differentiated the low (0-1), intermediate (2-3) and intermediate-high (4-5) and high (6-8) risk patients. Conclusions: The hypersensitivity risk score is a simple scoring system with high predictive value and differentiates low versus high risk patients. This score should be used for screen high risk of hypersensitivity reactions in patients receiving carboplatin.
Prognostic value of positron emission tomography (PET) in patients (pts) with metastatic or locally advanced cervical cancer (CC): A monoinstitutional experience.
Authors: V. Murgia, E. Bagatin, O. Caffo, A. Caldara, E. Magri, V. Vanoni, B. Zeni, S. Brugnara, M. C. di Pasquale, A. Ferro, M. Frisinghelli, B. Soini, F. Valduga, A. Veccia, M. Camerani, S. Tateo, L. Tomio, E. Galligioni
Journal: Journal of Clinical Oncology (2011)

e15591 Background: The prognosis of CC is related to both primary tumor stage, size, and histologic grade and to the lymph nodes status. Recently, the use of PET in CC staging is increasing. Furthermore, it has been hypothesized that some PET parameters such as tumor uptake of fluorine-18-labeled fluorodeoxyglucose (18FDG) measured as maximum standardized uptake value (SUVmax) and tumor volume may be associated with aggressive biological characteristics of cancer cells, in patients with CC. The present report is aimed to evaluate the prognostic role of PET in CC patients treated with chemotherapy (CT) alone or concurrent chemo/radiotherapy (CT/RT). Methods: Between January 2007 and November 2010, a consecutive series of 24 pts with CC was treated with CT or CT/RT. All pts underwent a baseline 18FDG PET (Siemens Biograph 64 True Point). PET scan was performed at 1 hour after injection of 4 MBq/Kg of 18FDG. For each assessment we evaluated SUVmax, while metabolic tumor volume (cervix and lymph node) was measured by an automated contouring program with a fixed threshold of SUV max = 2.5. For each pt we also recorded traditional prognostic factors (histology, tumor grade, smoking status, age, and stage). Progression Free Survival (PFS) and Overall Survival (OS) were calculated by Kaplan-Meier methods. Results: Major pts characteristics were: median age 54 yrs (range 33-77); median PS 0 (range 0-2); smokers 17 and no smokers 7; FIGO stage: Ib2 in 2 pts, IIa in 1, IIb 4, IIIb in 7, IVa in 4, IVb in 6; squamous histotype 21 pts and adenocarcinoma 3. No statistically significant relationship was found between PET parameters and traditional prognostic factors, excepting for stage with earlier stages (I-III) having a lower tumor volume compared to patients with IV stage (58.77 vs 136.5 mm3 p = 0.031). Similarly, PFS and OS were not influenced by PET parameters. Conclusions: From our preliminary data, PET parameters are not able to distinguish pts with different prognosis. Anyway, PET may increase our ability of tumor measuring. Larger samples are need to definitively assess the prognostic value of PET in CC.
Inappropriate lumpectomy in early breast cancer: Experience from a Tertiary Care Centre in India.
Authors: Veda Padma Priya Selvakumar, Rajeev Kumar
Journal: Journal of Clinical Oncology (2015)

77 Background: In India the incidence of breast cancer has shown an increasing trend over the past few decades and the majority of patients present with early breast cancer in the cities. A disturbing trend in the present setting is that a substantial proportion of patients are referred for the management of early breast cancer after inappropriate excision as diagnostic procedure in the primary care setup. Methods: The medical records of all patients who underwent surgery for early breast cancer post-lumpectomy status from September 2010 to December 2014 were reviewed retrospectively. The patterns of incision for lumpectomy, the margins of excision, the T stage, pre-operative imaging, the type of surgery and adjuvant therapy, the lapses in lumpectomy and various challenges it poses for further management and how it was combated were scrutinized in detail. Results: About one hundred and fifteen women were found eligible for the study. The mean age of onset was 47.33 years [Range 28-78]. The ratio of Left : Right were 57 : 58. The Margins and T status were known only in seventeen patients. Imaging ruled out any residual disease in breast in twenty eight patients. Twenty-seven patients underwent breast conservation with reconstruction, 82 underwent modified radical mastectomy and six of them underwent only axillary dissection. Only 41 patients had no residual primary disease on final histopathological evaluation. All patients underwent adjuvant therapy based on the approximate T staging. 12 patients were lost to follow up at one month.103 patients are alive and 101 disease free at an average follow up of 13.6 months. Conclusions: In early breast cancer, inappropriate lumpectomy for diagnostic purpose alters the course of surgical and adjuvant management. Hence it should be discouraged and not advocated as standard of care.
Graded Repression of PU.1 Expression by GATA Factors Influence Hematopoietic Progenitor Cell Fate
Authors: Stella T. Chou, Charles Bailey, Yu Yao, Zan Huang, Kim Nichols, John Crispino, Ross Hardison, Gerd Blobel, Chris Vakoc, Mitchell J. Weiss
Journal: Blood (2008)
Obturator canal lymph node metastasis from rectal carcinoid tumor.
Authors: Yi-Zarn Wang, Michael Anthony Hall
Journal: Journal of Clinical Oncology (2012)

440 Background: The optimal treatment option for rectal carcinoid tumor remains unsettled. Trans-anal excision has been accepted for small tumors (&lt; 1-2 cm in size) without lymph node involvement. Larger tumors, and those with lymph node metastasis, however, are usually treated via low anterior resection (LAR) with total mesorectal excision (TME). Midgut carcinoid tumors have been found to have the tendency to obstruct lymphatic flow and create a detour in lymphatic passage. We hypothesize that rectal carcinoid may have similar potential to develop alternative lymphatic pathways outside of the mesorectal envelope, thus escaping surgical removal with traditional TME. Methods: A retrospective chart review of rectal carcinoid patients who underwent radical LAR with TME between 2006 and 2011 was conducted to determine if any extra-mesorectal metastasis had occurred. Results: 19 patients who underwent LAR with TME for rectal carcinoid were identified. 14 patients had radio-guided surgery (RGS). 12 of which, were injected with TC-99 intra-operatively and 2 had a preoperative injection of In-111 for octreotide scan. 6 of the 19 patients (31.5%) were found to have obturator canal lymph node metastasis, confirmed by final pathologic review. 5 of these 6 patients had the nodal metastasis to the right obturator canal. Of note, 4 of the 6 patients complained of debilitating foot and medial thigh pain on the affected side, with complete symptom resolution after surgical excision. Conclusions: Up to 31.5% of rectal carcinoid patients can have extra-mesorectal lymph node metastasis that could easily be missed by the traditional TME. Preoperative octreotide scanning with In-111 injection or intra-operative Tc-99 peri-tumor injection, with concomitant RGS can easily identify and remove such metastasis. Symptomatic improvement can be accomplished with its removal. The effect of such extra-mesorectal metastasis on patients’ long term or disease free survival is yet to be determined.