tbuckley/cabot-search huggingface dataset:
Bladder and bowel symptoms with intensity-modulated radiation therapy (IMRT) for prostate cancer (PC).
Authors: Neha Vapiwala, Rojymon Jacob, Diane Newman, Alayne Markland, Richard Kennedy, Kathryn Burgio, Tracey Wilson, Thomas Bavaria, Alan J. Wein, Patricia Goode
Journal: Journal of Clinical Oncology (2016)

66 Background: Perioperative behavioral therapy is effective in decreasing urinary incontinence, urgency and frequency after radical prostatectomy (RP). We conducted a pilot study to determine if these symptoms occurred with sufficient frequency and impact on quality of life (QoL) to warrant behavioral therapy prior to and during PC IMRT. Methods: Expanded Prostate Cancer Index Composite Short Form (EPIC-26) is sensitive to health-related (HR) QoL effects of PC therapies. We administered EPIC-26 immediately prior to RT (baseline), and 1, 2, 6, and 12 months (mos) from baseline to PC patients undergoing IMRT at University of Alabama and University of Pennsylvania. Paired Wilcoxon’s test was used to compare rates of bladder and bowel symptoms during IMRT. Results: Of 79 men, 48% were black, with mean: age 64.6+6.9 years; BMI 28.3+5.7; Gleason Score 7.3+1.1 and baseline PSA 11.9+23.6ng/mL; 5% had prior TURP, 30% prior RP, 64% adjuvant hormonal therapy, 8% combination brachytherapy. EPIC domain scores worsened for urinary irritative/obstructive (p&lt;.001), UI (p=0.02), and bowel (p&lt;0.001) symptoms during therapy (at 1 month). Conclusions: Urinary and bowel symptoms were common at baseline and increased slightly during IMRT. Studies of behavioral therapy prior to and during IMRT are warranted. [Table: see text]
A 10-year retrospective review of germ cell tumors not cured with cisplatin-based chemotherapy.
Authors: Elizabeth O'Donnell, Kathryn P. Gray, Michelle S. Hirsch, Praful Ravi, Clair Beard, Christopher Sweeney
Journal: Journal of Clinical Oncology (2013)

325 Background: In 2011, there were about 8260 cases of Germ Cell Tumor (GCT) diagnosed in the US, of those, 350 or 4% will die of their disease. We sought to review our experience with a 10-year cohort of 819 patients treated for GCT at Dana-Farber and synthesize the cumulative findings of those who died from their disease specifically looking for different sub-types of incurable GCTs. Methods: Retrospective review of 819 germ-cell tumors treated in our center between 2000 and 2010 to identify patients not cured with cisplatin-based chemotherapy. Inclusion criteria were men over the age of 18 treated for malignant germ cell tumor between 2000 and 2010 at the Dana-Farber Cancer Institute that died from their disease. The outcomes of interest were smoking history, extent of disease at diagnosis, primary site of disease, histology, presence of lymphovascular invasion, outcomes to first- and second-line therapies, treatment with high dose chemotherapy (HDC), late relapse, brain metastases, and presence or absence of transformed teratoma as cause of death. Results: 38 men were identified. Median age 35. More than half had a smoking history. 3 presented with clinical stage 1 disease, 8 good-risk metastatic disease, 4 intermediate-risk and 22 poor-risk at diagnosis. The majority (28) had testicular primaries, 7 mediastinal, one pituitary, one retroperitoneal and one unknown. 21 of 48 had complete responses to first-line therapy. 4 received HDC for relapsed disease. 10 relapsed after 2 years of disease-free survival. 7 died of transformed teratoma. 63% progressed directly through cisplatin-based chemotherapy and died as a result of non-teratomatous germ cell tumor burden. 18% died from unresectable or transformed teratoma and 26% died after suffering a late relapse of disease. Conclusions: Within the cohort of patient who died from their GCTs there are three distinct biological subtypes – the majority is platinum-refractory germ cell tumor while unresectable/transformed teratoma and late relapse make up the remainder. Understanding the unique biology of these disease states compared with curable disease may provide informative insights into chemotherapy resistance for cancer in general.
Overexpression of chemokine receptor cxcr4 in cancer specimens predicts outcome in patients with triple-negative breast cancer
Authors: N. T. Holm, L. Johnson, L. Benjamin, C. Quyen
Journal: Journal of Clinical Oncology (2008)

11064 Background: Triple-negative breast cancers are those that lack ER, PR and HER-2 expression and are known to carry a poor prognosis. Molecular mechanism to account for this is poorly understood. CXCR4 is a chemokine receptor that has been linked to breast cancer invasion and metastasis. We postulate that high CXCR4 overexpression levels in cancer specimens predict a poor outcome in patients with triple negative breast cancers. Methods: 125 patients with triple negative breast cancers were prospectively accrued and analyzed. All had undergone standardized treatment and surveillance protocols. From each specimen, CXCR4 levels were detected using Western blots. Results were quantified against 1 μg of HeLa cells (positive controls). CXCR4 expression was defined as low (<6.6 fold) or high (≥ 6.6 fold). Primary endpoints were cancer recurrence and death. Statistical analysis performed included Kaplan-Meier survival analysis, log-rank test, and Cox proportional hazard model. Results: At a median follow-up of 35 months, patients whose tumors had high CXCR4 overexpression (≥ 6.6 fold) had a significantly higher incidence of cancer recurrence (p= 0.008) and cancer-related death (p= 0.0003) than those in the low CXCR4 group (< 6.6 fold). After adjusting for tumor size and nodal status, the relative risk for cancer recurrence and death in the high CXCR4 group was 2.6-fold (p=0.04; 95% CI: 1.04 to 6.79) and 3.5-fold (p=0.01; 95% CI: 1.24 to 9.97) higher than those in the low CXCR4 group, respectively. Conclusions: High CXCR4 overexpression in cancer specimens predicted a worse outcome in patients who have triple-negative breast cancer. No significant financial relationships to disclose.
A retrospective review of treatment outcomes following definitive chemoradiotherapy or single modality radical radiotherapy among patients with locally advanced esophageal cancer.
Authors: Ben A Fulton, Joanna Gray, Vivienne MacLaren, David McIntosh, Alexander McDonald, Aisling Hennessy, Derek B Grose
Journal: Journal of Clinical Oncology (2015)

196 Background: Definitive chemoradiotherapy (CRT) has been advocated as an alternative to surgical resection for the treatment of locally advanced oesophageal cancer (OC). We have retrospectively reviewed 4 years experience of patients (pts) who underwent contemporary staging and were treated with concurrent chemoradiotherapy (CRT) or single modality radical radiotherapy (RT) with curative intent. Methods: Retrospective analysis permitted identification of consecutive pts who underwent contemporary staging prior to non-surgical treatment for oesophageal carcinoma. The primary outcomes were overall (OS) and disease-free survival (DFS), adjusted for baseline differences in age, tumour staging and histological cell type. All patients were treated with either definitive CRT or single modality RT within a single centre treated between 2009 and 2012. Results: We identified 135 pts in total (median age 69.8 yrs, male=130pts, female=105pts, Adenocarcinoma=85pts, Squamous=150pts). 190 pts received CRT and 45pts were treated with RT. All pts were staged with CT of chest, abdomen and pelvis, 226 pts underwent Endoscopic ultrasound (EUS) and 183 pts had PET-CT. Patients treated with CRT demonstrated longer OS (37 versus 25 months, p=0.02) and DFS (31 versus 16 months, p=0.01) compared to those treated with RT. More advanced tumour stage (stage 3 v stage 1-2) at presentation conferred poorer OS (32 versus 38.2 months) and DFS (11 versus 28 months, p=0.013). We demonstrated an acceptable toxicity profile with only 77 pts (32.8%) and 9 pts (4.2%) experiencing grade III or IV CTC toxicities respectively. Conclusions: This retrospective analysis is in keeping with current treatment paradigms emphasising the importance and safety of concurrent CRT in maximising curative potential for pts undergoing non-surgical treatment of oesophageal cancer. Although retrospective, in comparison to similar retrospective series from our centre, our data suggest improvements in OS and DFS, possibly due to improved patient selection through the use of more effective tumour staging.
Post-progression treatment with APC8015F may have prolonged survival of subjects in the control arm of sipuleucel-T phase III studies.
Authors: L. G. Gomella, C. Nabhan, J. B. Whitmore, M. W. Frohlich, D. J. George
Journal: Journal of Clinical Oncology (2011)

4534 Background: Sipuleucel-T is an autologous cellular immunotherapy approved by the FDA for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer. Methods: After disease progression, subjects in the control arms of 3 randomized controlled trials (RCT) of sipuleucel-T were offered 3 infusions of APC8015F, an autologous immunotherapy made from cells cryopreserved at the time of control generation. Results: 165/249 (66.3%) of the control group received APC8015F. Median time from randomization to first APC8015F infusion was 5.2 months (range 1.8 to 33.1), and from objective disease progression to first infusion was 2.2 months (range 0.5 to 14.6). 145 subjects (87.9%) received all 3 infusions. APC8015F-treated subjects had improved post-progression survival relative to untreated controls (HR = 0.52 [95% CI: 0.37, 0.73]; unadjusted Cox regression; P = 0.0001, log rank test), with median survival times of 20.0 and 9.8 months, respectively. APC8015F-treated subjects had more favorable prognostic features than untreated controls. To account for these differences, a Cox regression model was fit using backward selection, and included the following independent predictors of post-progression survival: lactate dehydrogenase, alkaline phosphatase, ECOG status, age, number of bone metastases, and hemoglobin. In addition, the model included post-randomization salvage treatment and docetaxel use as time dependent covariates. This analysis revealed a positive docetaxel effect (HR = 0.86 [95% CI: 0.60, 1.22]; P = 0.40), and a positive APCF8015F treatment effect (HR = 0.78 [95% CI: 0.54, 1.11]; P = 0.17). In subjects who received at least one infusion of APC8015F, the cumulative product lot release characteristics of CD54 upregulation and total nucleated cell counts were correlated with survival after salvage treatment (p=0.03 and p=0.04, respectively). Conclusions: Post-progression treatment with APC8015F may have extended survival of subjects, potentially reducing the magnitude of survival difference observed between sipuleucel-T and controls in RCT.
Molecular Characterization of Relapsed Core-Binding Factor (CBF) Acute Myeloid Leukemia (AML)
Authors: Mridul Agrawal, Andrea Corbacioglu, Nikolaus Jahn, Lars Bullinger, Maria-Veronica Teleanu, Verena I. Gaidzik, Daniela Weber, Gudrun Göhring, Michael Luebbert, Walter Fiedler, Peter Brossart, Thomas Kindler, Markus Radsak, Mark Ringhoffer, Katharina S. Götze, Richard Greil, Felicitas Thol, Michael Heuser, Arnold Ganser, Richard F. Schlenk, Hartmut Döhner, Peter Paschka, Konstanze Döhner
Journal: Blood (2015)
Induction of primary systemic therapy by weekly paclitaxel: Predictive value of hormone receptors, HER-2, topoisomerase II- alpha, and other biological markers in relation to pathological complete response
Authors: S. Takao, M. Miyashita, N. Kohno, K. Wakita, M. Konishi, I. Kokufu, H. Yoshimura, Y. Kasahara, S. Kohno, T. Ienaga
Journal: Journal of Clinical Oncology (2009)

e11525 Background: Randomized phase II study of epirubicin(E) plus cyclophosphamide (C) vs. weekly paclitaxel (P) as primary systemic therapy (PST) in stage II and III breast cancer(BC) have shown that there was no significant difference in the pathological complete response (pCR) rate between the EC and P groups (#568 ASCO 2008). The aim of this study is to evaluate the predictive value of hormone receptors, HER2, topoisomerase IIα(TOP II) and other biological markers in the EC and P groups as PST. Methods: Tissue samples were obtained before PST from pts who were randomized to either Arm A (EC: E 75 mg/m 2 and C 600 mg/m 2 every 3 W for 4 cycles) or Arm B (weekly P: P 80 mg/m 2 weekly for 12 w). Pts received PST for 12 w, then underwent surgery. All pts received a crossover regimen as adjuvant chemotherapy.The pretreatment expression of estrogen receptor (ER), progesterone receptor(PgR), HER2, P53, Ki67, P21 and CD31 were analized by immunohistochemical staining. The status of TOP II gene was evaluated by FISH. Results: One-hundred- sixty pts (Arm A: n=82, Arm B: n=78 ) were estimable. The pCR rates were 13.4% in Arm A and 17.9% in Arm B(p=0.43). In both arms, pCR rate was significantly higher for pts whose tumors did not express ER nor PgR(ER/PgR-) compared with the receptor positive(ER/PgR+) pts. Pts with HER2 positive tumors tend to have higher pCR rate in Arm B compared with Arm A (32.2% vs. 12.5%;p=0.11). The pCR rate for pts with HER2 negative BC were not different in both Arms(A:14.0% vs. B:8.5%). Pts with triple negative (TN) (ER/PgR, HER2-) BC achieved almost same pCR in both Arms (A:25.0% vs. B:23.1%). However, the pCR rate for pts with nonTN BC was significantly higher in ArmB compared to Arm A (16.9% vs. 8.6%, p&lt;0.001). The deletion and amplification of TOP II gene were not predictive of higher pCR rate to ArmA than to Arm B. The pretreatment expression of P53, Ki67, P21 and CD31 was unlikely to predict the higher response of any Arm. Conclusions: Althogh valuable predictive factor of pCR were not detected between EC and weekly P group, the efficacy of weekly P therapy as PST were equal to EC therapy regardless of HR,HER2 and TOP II gene status. Therefore, induction of PST by weekly P therapy seems to be promising. No significant financial relationships to disclose.
Mediastinal lymph nodes staging by <sup>18</sup>F-FDG PET/CT for early-stage non-small cell lung cancer: A multicenter study.
Authors: X. Li, H. Zhang, L. Xing, L. Zhang, W. Xu, G. R. Yang, J. Yu
Journal: Journal of Clinical Oncology (2011)

e17523 Background: Accurate staging of mediastinal lymph nodes is a critical factor determining operability and stereotactic body radiation therapy (SBRT) in patients with non-small cell lung cancer (NSCLC). This multicenter study is to evaluate the accuracy of 18F-FDG PET/CT to detect mediastinal lymph nodes (MLN) metastases for T1-2 NSCLC. Methods: The data of patients with T1-2 NSCLC who received preoperative CT staging, FDG PET/CT staging and radical surgery were retrospectively reviewed in three centers between Oct. 2004 and Jan. 2009. The MLN metastasis was confirmed histopathologically after thoracotomy and lymph node dissection. The sensitivity, specificity, accuracy, PPV and NPV were calculated and compared for PET and CT. Clinical and pathological factors were analyzed for the correlation with MLN metastases. Results: Eighty-six patients were enrolled. The sensitivity, specificity, accuracy, PPV and NPV for MLN metastasis on CT were 49%, 93%, 89%, 59% and 92% respectively, with 80%, 90%, 90%, 62% and 93% on PET. (P=0.023, 0.07, 0.87, 0.89, 0.17). There were 50 patients with clinical T1-2N0 NSCLC. In these patients, the NPV for MLN metastasis with FDG PET were 82% (41 of 50). It was showed that FDG uptake of primary tumor (P=0.006) and T stage (P=0.007) were correlated with lymph node involvement. Only 1 patients were found MLN metastasis in 26 patients with primary tumor FDG PET SUV<6.67, whereas 8 patients had MLN metastases in 24 patients with SUV>6.67, P<0.01. There were 6 and 3 patients found MLN metastasis in T1 (n=44) and T2 (n=6) NSCLC, respectively. Conclusions: FDG PET/CT improves the sensitivity of N staging in T1-2 NSCLC. However, the NPV was less than 90% in clinical N0 patients, suggesting that improvement of accurate N staging is warranted by incorporating PET with other minimal invasive approaches, including EBUS and EUS.
Influence of baseline inflammatory markers on the response to first line chemotherapy and overall survival in advanced NSCLC
Authors: G. Kasymjanova, N. MacDonald, J. S. Agulnik, C. Pepe, H. Kreisman, V. Cohen, R. Sharma, B. Gagnon, D. Small
Journal: Journal of Clinical Oncology (2008)

8102 Background: An elevated baseline C-reactive protein (CRP) is a significant marker presaging shortened patient survival in non small lung cancer (NSCLC) and other tumors. The reason for this association is not clear. Methods: Newly diagnosed NSCLC pts with 3B/4 disease had CRP and WBC measured prior to 1st treatment between February 2005 and September 2007. Response evaluated by chest CT following two cycles of CTX and categorized as progression (PD) and free from progression (FFP). Pts were assigned a prognostic index (PI) score of 0 if CRP ≤10mg/L and WBC ≤ 11x109/L, 1 if one of the markers was elevated, or 2 if both were elevated. We investigated the association between PI and response to 2 cycles of CTX, as well as survival. Results: 121 pts were enrolled and assigned a Prognostic Index (PI) score: 41 patients PI of 0, 54 pts PI of 1 and 26 pts PI of 2. There was no difference in age, sex, PS and stage distribution. 82 patients had FFP and 39 had a PD following 2 cycles of therapy. There was significantly higher prevalence of progression among pts with PI of 2, and FFP among the PI of 0, p=0.002 Regression analysis showed that PI (p<0.003) was the only significant predictor of response among the variables such as age, sex, ECOG PS, stage and PI. Median survival was 19.5 mo for PI 0, 8.4 mo for PI 1 and 6.1 mo for PI 2 (P<0.001). There was no interaction between CRP and WBC. The PI was significant predictive factor of survival along with PS, and stage (p=0.001). Conclusions: The presence of an inflammatory state expressed by high levels of CRP and WBC correlates significantly with both 1st line chemotherapy response and survival. CRP and WBC should be considered in stratification decisions in clinical trials. Studies to combat inflammation at onset of chemotherapy also have merit. PI Freedom from progression Total No progression Progression 0 34 (83%) 7 (17%) 41 (100%) 1 37 (69%) 17 (31%) 54 (100%) 2 11 (42%) 15 (58%) 26 (100%) Total 82 (68%) 39 (32%) 121 (100%) No significant financial relationships to disclose.
Chronic kidney disease and the risk of incident renal and urothelial cancer in a population-based cohort of 1.2 million adults.
Authors: William Thomas Lowrance, Natalia Udaltsova, Juan Ordoñez, Paul Russo, Alan S. Go
Journal: Journal of Clinical Oncology (2012)

351 Background: Prior studies have observed an increased risk of cancer in patients with end stage renal disease, but whether less severe chronic kidney disease influences the risk of cancer is uncertain. Methods: Among 1,190,538 adults at least 40 years of age and no prior dialysis, renal transplant or known cancer who received care within Kaiser Permanente Northern California, we examined the independent association between estimated glomerular filtration rate (eGFR) and the risk of cancer, overall and by type, between 2000 and 2008. Incident cancers were identified from a comprehensive regional cancer registry and potential confounders were ascertained using validated algorithms based on health plan electronic medical records. The impact of time-varying eGFR on incident cancer risk was examined using multivariable extended Cox regression, after excluding any cancers detected during the first two years of follow-up and any eGFR values within 3 months before a cancer diagnosis to reduce potential biases. Results: During 6,000,420 person-years of follow-up, 76,809 incident cancer diagnoses were identified among 72,875 patients (38,744 M, 34,131 F). After adjustment for possible confounding factors, the risk of renal cancer increased with lower eGFR (ml/min/1.73 m 2 ): the adjusted hazard ratio [HR] for renal cancer was 1.35 (95% CI: 1.18–1.55) for eGFR 45–59, HR 1.65 (1.37 to 1.97) for eGFR 30–44, and HR 2.09 (1.62 to 2.70) for eGFR &lt;30. There was a similar association between eGFR and urothelial cancer. However, there was not a significant multivariable association between eGFR and prostate, colorectal, lung, breast, or any cancer. Conclusions: We observed a graded, independent increased risk of renal and urothelial cancer risk with lower eGFR in a large, population-based cohort. However, lower eGFR was not significantly associated with other major cancer types. Additional research is needed to understand potential contributing mechanisms between reduced renal function and renal or urothelial malignancies, as well as whether differential cancer screening strategies are effective in patients with chronic kidney disease.
<i>HER2, EGFR, PIK3CA</i> mutations in HER2+ metastatic breast cancer (MBC) patients (pts) treated with trastuzumab (T): Incidence and correlation with response
Authors: S. Gori, V. Ludovini, M. Colozza, L. Pistola, F. R. Tofanetti, A. Flacco, J. Foglietta, E. Minenza, L. Stocchi, V. De Angelis, L. Crinò
Journal: Journal of Clinical Oncology (2008)

1031 Background: Resistence mechanisms to T are still undefined. EGFR, pMAPK, pAKT and PTEN status by IHC were not correlated with response to T in our previously series of 45 HER2+ MBC pts. No data are reported about incidence of HER2, EGFR and PIK3CA genes mutations and their correlations with response to T. in HER2+ MBC pts. Methods: From 4/1999 to 3/2006, 133 consecutive pts were treated with T. Tumor tissues for this analysis were available from 41 pts. Genomic DNA was isolated from paraffin-embedded tumor specimens, amplified for HER2 (exons 19, 20, 21 and 22, encoding the kinase domain), EGFR (exons 18, 19, 20 and 21) and PIK3CA (exons 9 and 20, encoding a part of elical and kinase domains, respectively) genes by nested polymerase chain reaction and sequenced in both sense and antisense directions. Results: We found mutations of HER2 in 3 pts (7.3%), of EGFR in 6 pts (14.6 %) and PIK3CA in 5 pts (12.2%) with HER2+ tumors (Table); correlations with response to T are reported (Table). The same HER2 mutation in exon 20 was identified in 2 pts with pAKT+ tumor (IHC) and no response to T. PIK3CA mutations were associated with pAKT+ status only in 2 pts. In all 5 tumors with PIK3CA mutations, a PTEN+ status (IHC) was observed, consistent with the speculation that PIK3CA mutations and loss of PTEN expression are mutually exclusive. A pt presented 2 mutations: 1 in ex 20 of HER2 (P780_H781insC) and 1 in ex 20 of PIK3CA (L1026P). CNS metastases developed in 9/13 (69.2%) pts with mutations of these genes, but only in 12/28 (42.8%) pts without mutations. Conclusions: In our series of HER2+ MBC pts the incidence of HER2, EGFR and PIK3CA mutations is relatively low and therefore any correlation with response to T is difficult. An intriguing observation is the higher incidence of CNS metastases reported in the 13 pts with these mutations. If confirmed in larger studies, these data could help to identify HER2+ pts with a higher risk of brain metastases. Gene Exon Mutation analysis Mutation code Response to T. CNS metastases HER2 20 insertion P780_H781insC PD YES 20 insertion P780_H781insC SD YES 21 missense S856P CR YES EGFR 18 missense T710I CR NO 20 missense L815P PD NO 20 missense S784F CR YES 20 missense V765M PR YES 21 missense E872K; CR YES 21 missense E866K PR YES H835P PIK3CA 9 missense D549N PR YES 20 missense H1048Y PD YES 20 missense A987V PR NO 20 missense M1004I; PR NO 20 missense H1048Y SD YES L1026P No significant financial relationships to disclose.