tbuckley/cabot-search huggingface dataset:
Association of baseline health and gender with small renal mass pathology.
Authors: Wassim Bazzi, Sheila Dejbakhsh, Melanie Bernstein, Jonathan A. Coleman, Paul Russo
Journal: Journal of Clinical Oncology (2014)

515 Background: Previous reports describe that 20% of small renal masses (SRM) are benign and women are twice as likely to have benign pathology. In this study we further explore the association of baseline health and gender with SRM pathology. Methods: After IRB approval, retrospective chart review of patients who have undergone nephrectomy at Memorial Sloan-Kettering Cancer Center from 05/1998 to 10/2012 with final path ≤ 4cm and staged as pT1a if malignant. Tumor size ≤ 4cm was chosen to limit the tumor mass effect on renal function. Patients with solitary kidney, multiple and bilateral tumors, and history of prior renal surgeries were excluded. Collected data included age, gender, race, ASA class for medical co−morbidities which were divided into low (I−II) and high (III−IV), procedure, preoperative serum creatinine, eGFR, and final pathology. eGFR was calculated using the CKD−Epi formula. Preoperative Chronic kidney disease (pCKD) was defined as eGFR &lt; 60 mL/min per 1.73 m2. Malignant pathologies were clear cell renal cell carcinoma (RCC), papillary RCC and chromophobe RCC whereas benign were oncocytoma, angiomyolipoma and other. Logistic regression analysis was performed to determine clinical factors associated with malignant SRM. Results: Our cohort consisted of 1726 patients with mean age 59.7 yrs. 61% (n=1045) were men, 90% (n=1,553) were white, 43% (n=736) had high ASA, 89% (1,540) underwent partial nephrectomy, 30% (n=525) had pCKD, 83% (n=1426) with malignant pathology and mean tumor size 2.5cm. On bivariable analysis patients with malignant SRM had a higher proportion of men (64.3 vs. 42.7%, p&lt;0.001), high ASA class (43.8 vs. 37.3%, p=0.041) and larger tumors (2.6 vs. 2.3, p&lt;0.001). There were no differences in age, race, mean eGFR or proportion with pCKD. On logistic regression analysis by gender factors associated with malignant pathology in women were high ASA class (OR 1.57, 95% CI 1.07−2.32) and tumor size (OR 1.48, 95% CI 1.20−1.81), and in men tumor size only (OR 1.33, 95% CI 1.06−1.67). Conclusions: Our results are in line with previous reports on the association of male gender and larger tumor size with malignant SRM. In addition we do show that among women those with poor health have a higher likelihood for having a malignant SRM.
Hepatitis C as a predictor of treatment outcome in patients with hepatocellular carcinoma treated with the retinoid derivative, TAC-101.
Authors: V. Khanijow, A. O. Kaseb, M. Hassan, V. I. Machicao, H. M. Hassabo, J. L. Abbruzzese
Journal: Journal of Clinical Oncology (2011)

200 Background: Most cases of HCC occur in the setting of cirrhosis secondary to alcohol abuse and hepatitis C, in the United States and Europe. Furthermore, recent data from phase III trials of sorafenib showed better survival in patients with HCV-related HCC. Animal studies suggested that TAC 101 regulates the transcription factor activated protein-1, which is constitutively activated by HCV core protein and contributes to hepatocarcinogenesis in persistent HCV infection. We hypothesized that prognostic impact of HCV-related HCC would be more pronounced in patients treated with TAC 101. Methods: This retrospective analysis included 105 patients treated in 3 clinical trials: TAC-101 (n=27), bevacizumab and erlotinib (n=48), and erlotinib alone (n=30) conducted at The University of Texas M. D. Anderson Cancer Center. Univariate and multivariate Cox regression was performed to estimate the adjusted hazard ratio (HR). Results: HCV was present in 35 (33%) patients. Multivariate survival analyses incorporating age, sex, HBV status, α-fetoprotein level, Child-Pugh classification, CLIP score, and BCLC staging did not identify a significant impact of HCV on OS or PFS. However, in patients who received TAC- 101, the presence of HCV was associated with a significantly reduced risk of disease progression (HR: 0.47, 95% CI:0.24-0.90, p= 0.024). Conclusions: These results indicate a possible beneficial interaction between HCV-related HCC and treatment with the retinoid derivative, TAC-101. HCV infection could be useful as a surrogate biomarker of the therapeutic efficacy of TAC-101. Further research is warranted to study the potential role of TAC 101 in HCV-related HCC patients. No significant financial relationships to disclose.
Association between equivalent uniform dose (EUD) and rates of local progression in liver tumors treated with stereotactic body radiation therapy (SBRT).
Authors: Louis Lu, Yebin Tao, Matthew J Schipper, Daniel Wahl, Matthew H. Stenmark, Theodore Steven Lawrence, Mary Uan-Sian Feng
Journal: Journal of Clinical Oncology (2015)

380 Background: When tumors are near organs at risk such as bowel or heart, this results in partial underdosing relative to prescribed dose. We hypothesized that equivalent uniform dose (EUD) may better capture the biologic effect than other dose metrics. Methods: In this IRB-approved retrospective study, 257 primary and metastatic liver tumors from 168 patients treated with SBRT at the University of Michigan Health System between 2005 and 2014 were identified. Univariate analysis and multivariate Cox regression models were used to correlate patient, tumor, and treatment characteristics with rates of LC. Results: 1 and 2 year LC were 93% and 75% for all. Of the 156 primary liver tumors, 1 and 2 year LC were 94% and 76%, compared to 83% and 61%, for patients with colorectal metastases (CRM). 22 tumors locally progressed in 17 patients of which 9 were CRM, 5 hepatocellular carcinomas (HCC), and 3 other. Tumors that locally progressed received a median prescribed dose of 50 Gy (24 - 60), GTV EUD (a=-10) 49 Gy (23 - 72), and PTV EUD 46 Gy (17 - 69). Median gross tumor volume (GTV) was 21 cc (1-103). Tumors that did not locally progress received a median prescribed dose of 50 Gy (19 - 60), GTV EUD (a=-10) 52 Gy (17 - 86), and PTV EUD 47 Gy (7 - 76). Median GTV was 10 cc (0.2 - 2092). On univariate analysis, CRM (p = 0.005) was correlated with higher progression, while high GTV and PTV EUD (a=-10) (p = 0.01, 0.05) were correlated with lower progression. HCC (p = 0.06) was borderline for low progression. Age, gender, primary or metastatic, prescribed dose, biologically equivalent dose (BED), minimum GTV or PTV dose and GTV did not predict for progression. In a multivariable model including age, gender, histology, prescribed dose, BED, GTV EUD and GTV size, only GTV EUD predicted for LC, HR = 0.947, 95% CI = 0.901 - 0.996, p = 0.036. Every 1 Gy increase in EUD decreased the risk of local failure by 5%. Conclusions: EUD was predictive of local progression even when accounting for histology, size, and dose as measured by prescribed dose and BED. GTV EUD (a=-10) over 47.64 Gy yielded a &gt;95% local control. EUD may be the preferred dose metric in future tumor control studies.
The effect of [-2]proPSA and prostate health index (phi) on the accuracy of the prediction of initial and repeat prostate biopsies compared to tPSA and percent fPSA in young men (age 65 or younger).
Authors: Martin Boegemann, Sébastien Vincendeau, Carsten Stephan, Alain Houlgatte, Laura-Maria Krabbe, Jean-Sebastien Blanchet, Axel Semjonow
Journal: Journal of Clinical Oncology (2014)

171 Background: Prostate-specific antigen (tPSA) based screening reduces mortality. But recent recommendations do not endorse PSA-screening due to possible over-diagnosis and over-treatment and the resulting harm afflicted to patients. Screening studies showed the maximum benefit in young men age 65 or younger. tPSA and percent free PSA (%fPSA) lack specificity in the diagnosis of PCa. [-2]proPSA and the "prostate health index" (phi) improve this diagnostic specifity in a non-age adjusted population. Markers to diagnose clinicaly relevant cancers in young men are needed. Methods: The clinical performance of [-2]proPSA and phi were evaluated in a multicenter study. A total of 1,362 patients (769 age 65 or younger) scheduled for initial or repeated prostate biopsy (668 with, 694 without PCa, each 10 or more core biopsies) were recruited in four different sites based on PSA level 1.6 to 8.0 ng/mL WHO-calibrated (2-10 ng/mL classically calibrated). Serum samples taken prior to digital rectal examination (DRE) were measured for the concentration of tPSA, fPSA and [-2]proPSA with Beckman Coulter immunoassays on Access 2 or DxI800 instruments. Phi was calculated as: [-2]proPSA/fPSA x √tPSA. Results: In univariate analysis [-2]proPSA/fPSA (%[-2]proPSA) and phi were the best predictors of PCa detection in patients at initial biopsy (AUC: 0,72 and 0,73) and repeated biopsy (AUC: 0,74 and 0,74). Analysis of the data for men age 65 and younger (n=593) showed that %[-2]proPSA and phi significantly improved PCa dectection (AUC: 0,72 and 0,73) as compared with tPSA (AUC: 0,53) or %fPSA (AUC: 0,62). In the detection of significant PCa (based on PRIAS criteria) %[-2]proPSA and phi demonstrated the best performance in the whole cohort and in young men (65 and younger) years as well (AUC 0,68 and 0,73). Conclusions: This multicenter study showed that [-2]proPSA and phi have a superior clinical performance in detecting PCa in the PSA range of 2 to 10 ng/mL compared to tPSA and %fPSA at initial and repeat biopsies. This superiority is maintained for the detection of PCa in young men (age 65 or younger).
The introduction of systematic genomic testing for patients with non-small cell lung cancer (NSCLC) at Dana-Farber Cancer Institute (DFCI).
Authors: T. M. Ortiz, V. A. Joshi, S. Heon, M. Butaney, L. Chen, D. M. Jackman, D. J. Kwiatkowski, N. I. Lindeman, P. A. Janne, B. E. Johnson
Journal: Journal of Clinical Oncology (2011)

7517 Background: Systematic genomic testing to identify potential predictive biomarkers to select targeted therapy is emerging for NSCLC. DFCI introduced systematic testing for mutations in BRAF, HER2, PIK3CA and EML4-ALK translocations in addition to routine characterization of EGFR and KRAS in July 2009 as part of a prospective study. One and a half years have passed, thus we report our initial experience. Methods: Providers consented patients with advanced non-squamous NSCLC. Pathology specimens were dissected and analyzed by PCR-Sanger sequencing for mutations in selected exons of EGFR, KRAS, BRAF, PIK3CA and HER2. ALK rearrangements were detected with fluorescence in-situ hybridization. Results: Between 7/1/2009 and 4/12/2010, 226 consecutive patients were tested. The median age was 62 years. 134 (59%) were female, 195 (86%) had adenocarcinoma, 174 (77%) were former/current smokers and 182 (81%) had stage IIIB/IV disease. Five patients had two different specimens tested; three of these had repeat analyses due to test failure, one patient had two sites tested and another had two synchronous tumors tested. Of the 231 specimens, 25 (11%) either failed analysis or were inconclusive. The most frequent reason for inconclusive results was less than 50% tumor in the specimen (15/25). Of the remaining 206 specimens (204 pts), all underwent mutation testing for BRAF, HER2 and PIK3CA; 197/204 for EGFR, 187/204 for KRAS and 116/204 for ALK rearrangements. Mutations were identified in 110/204 (54%) patients (EGFR: 30; KRAS: 52; BRAF: 9; HER2: 9; ALK: 8; PIK3CA: 5) of whom three had concurrent mutations, all involving PIK3CA. The median time to complete testing for this initial phase was 30 days. From 7/1/2009 to 6/15/2010, 31 of 61 (51%) patients with EGFR, HER2, BRAF or EML4-ALK alterations were treated with molecularly targeted therapy based on their genetic alteration. Compared to 67% of patients with EGFR mutations, 9.6% patients with KRAS mutations received erlotinib. Conclusions: Large scale testing for alterations in EGFR, KRAS, BRAF, PIK3CA, HER2 and EML4-ALK is feasible and has an impact on treatment at our center. Updated results will be presented in June 2011.
Dramatic increase in number of cancer cases and the use of definitive treatment in the extreme (≥ age 85) elderly.
Authors: J. E. Gross, D. J. Becker, L. B. Harrison, G. C. Smith, R. D. Ennis
Journal: Journal of Clinical Oncology (2011)

e19540 Background: The population 85 years of age or older is the fastest growing age demographic in the US. This growing population, with an increased susceptibility to cancer, could lead to a rapid growth in the number of cancer patients of advanced age. We evaluated the degree to which this is occurring for all cancers and for each specific malignancy. We also examined the use of the definitive treatments of radiotherapy and surgery in this population. Methods: Using the Surveillance Epidemiology and End Results (SEER) database we investigated the annual number of cases and rates of cancer diagnosis and treatment (radiotherapy, surgery) in individuals ≥85 years of age. We reviewed all cancer data collectively and individual cancers separately for the years 1997-2007. Linear regression was used. Results: The total number of cancer cases diagnosed in the US in people >85 years old increased 81% (p < 0.009) during the period 1997-2007. Use of radiotherapy in this population increased 82% (p<.009) over the same time period. The use of surgery increased, but only by 11% (p<.009). Although the number of cases increased significantly, the incidence rate of cancer diagnoses/100,000 decreased by 86% (p<.009) over the same years. The rates of radiotherapy treatment and surgery/100,000 decreased by 86% (p<.009), and 20% (p<.009) respectively. When individual cancers were analyzed, all increased in number of cases except for breast and bowel cancers. The rates decreased for breast cancer, increased for skin, prostate and lung cancer and remained stable for the others. Conclusions: There has been a marked increase in the number of people ≥85 years of age who have been diagnosed with cancer and treated, especially with radiotherapy, over the last ten years, despite an overall decline in the rate of cancer in this population. This is a major public health issue, with implications for health care costs and needed support services to treat this population. In addition, the majority of clinical trials that guide treatment decisions do not include patients of this age. There is an urgent need for clinical trials designed for this patient population.
Multidisciplinary care and management of very low-risk prostate cancer.
Authors: Ayal A. Aizer, Jonathan J. Paly, Anthony L. Zietman, Paul Linh Nguyen, Clair Beard, Sandhya K. Rao, Irving D. Kaplan, Andrzej Niemierko, Michelle S. Hirsch, Chin-Lee Wu, Aria F. Olumi, M. Dror Michaelson, Anthony Victor D'Amico, Jason Alexander Efstathiou
Journal: Journal of Clinical Oncology (2013)

55 Background: The National Comprehensive Cancer Network (NCCN) recommends active surveillance (AS) as the primary management option for patients with very low-risk prostate cancer (VLRPC) and an expected survival of &lt;20 years. Factors associated with selection of AS are therefore of clinical importance. We hypothesized that care at a multidisciplinary clinic (MC), where multiple physicians simultaneously review each case, will be associated with increased rates of AS in men with VLRPC, including those with limited life expectancy. Methods: Of 630 patients with low-risk prostate cancer managed at one of three tertiary care centers in Boston, MA in 2009, 274 (43.5%) had VLRPC. Patients were either seen by one or more individual providers in sequential visits (N=178) or at an MC (N=96), in which concurrent consultation with two or more of the following specialties was obtained: urology, medical oncology, and radiation oncology. Results: Patients seen at an MC were more likely to select AS than those seen by individual providers (64% vs 30%, p&lt;.001), an association which remained significant on multivariable logistic regression (OR=4.16, p&lt;.001), see Table. When the analysis was limited to patients with an expected survival of &lt;20 years based on the 2007 Social Security Life Table, this association remained highly significant (OR=5.19, p&lt;.001). Conclusions: Multidisciplinary care is strongly associated with selection of AS, adherence to NCCN guidelines, and minimization of over-treatment in patients with VLRPC. [Table: see text]
Positron emission tomography during preoperative combined modality therapy for rectal cancer may predict ultimate pathologic response: A prospective analysis
Authors: D. B. Chessin, T. Akhurst, H. Yeung, J. Shia, E. Riedel, P. B. Paty, L. Saltz, B. D. Minsky, S. Larson, J. G. Guillem
Journal: Journal of Clinical Oncology (2005)

3612 Introduction: Early knowledge of rectal cancer response to preoperative combined modality therapy (CMT) may provide an opportunity to identify patients with minimal response and who may benefit from alternative treatment regimens. We prospectively evaluated the novel concept of assessing rectal cancer response with fluorodeoxyglucose positron emission tomography (PET) early after the commencement of preoperative CMT. Methods: 21 prospectively accrued patients with locally advanced rectal cancer (ERUS T3–4/N1) received preoperative CMT (5040 cGy with 5-FU-based chemotherapy). Patients were imaged with a PET scan prior to and 10–12 days after (early PET) commencement of CMT. PET scans were interpreted by two Nuclear Medicine physicians using four specific parameters [(SUVmax, SUVaverage, total lesion glycolysis (TLG), and visual response score (VRS)]. Percent pathologic response was quantified using whole mount sections. Pathologic complete response (pCR) was defined as no viable tumor cells on pathologic analysis. Statistical analysis was performed using the Spearman rank correlation coefficient and Wilcoxon rank sum test. Results: Pathologic response rates ranged from 60–100%. PET identified a response in 20 of 21 pathologic responders (95%). The association of PET parameters with pathologic response is tabulated. Conclusion: FDG-PET imaging 10–12 days after commencement of preoperative CMT may predict ultimate extent of pathologic response. In so far as increased response is associated with improved long-term outcome, early PET may allow identification of patients who may benefit from a change in chemotherapeutic regimen. No significant financial relationships to disclose.
Factors associated with acute toxicity during chemoradiation therapy for rectal cancer.
Authors: Pooja Monpara, Scott Rice, Talha Shaikh, Jeffrey M. Farma, Elin R. Sigurdson, Crystal Shereen Denlinger, Efrat Dotan, Joshua E. Meyer
Journal: Journal of Clinical Oncology (2016)

734 Background: Acute toxicity may be a factor interfering with receipt of chemoradiation (CRT) therapy for rectal cancer. The purpose of this study was to identify clinical and treatment factors associated with increased acute toxicity in patients receiving CRT therapy for rectal cancer. Methods: We identified patients with rectal adenocarcinoma treated with CRT between 2006-2014 at an NCI-designated cancer center. Patients with metastatic disease or missing treatment information were excluded. Acute toxicity information including weight loss, pain, fatigue, constipation, diarrhea, anorexia, and performance status was extracted from weekly on treatment visit notes. Multivariable logistic regression was used to assess predictors of grade 3+ toxicity using covariates significant on univariable analysis. Results: A total of 148 patients were included with a median age of 59 (range 29-99). The majority of patients were male (55%) and received 5-FU based chemotherapy (82%). During CRT, 35 (24%) patients experienced at least one grade 3+ toxicity: 13 (9%) patients experienced grade 3+ fatigue, 1 (1%) experienced grade 3+ constipation, 11 (7%) experienced grade 3+ diarrhea, 14 (10%) experienced grade 3+ pain, and 11 (7%) experienced grade 3+ anorexia. Eight (5.4%) patients had an ECOG performance status &gt; 3 and 28 (19%) patients had weight loss &gt; 5 lbs during CRT. On multivariable analysis, increased distance from the anal verge (OR 0.78 95% CI 0.636-0.998) was associated with a decreased risk for grade 3+ pain and age &gt; 75 was associated with an increased risk of grade 3+ anorexia (OR 6.07 95% CI 1.067-34.56). Clinical T4 disease was associated with an increased risk of weight loss &gt; 5 lbs (OR 0.17 95% CI 0.100-0.446). On multivariable analysis, there were no factors associated with grade 3+ fatigue, diarrhea, or constipation. There were no factors associated with a decline in performance status to &gt; 3 while on treatment. Conclusions: Our results suggest that rectal cancer patients who are older, have more advanced disease, or with low lying tumors may be at an increased risk for treatment-related toxicity. Identifying predictors of toxicity may allow for tailored interventions to minimize toxicity for these patients.
Palliative biliary stents and clinical outcomes.
Authors: L. J. Howie, K. W. Mitchell, S. M. Dy, I. S. Browner
Journal: Journal of Clinical Oncology (2011)

e19728 Background: Malignant biliary obstruction can be associated with with pruritis, jaundice, nausea and anorexia. For patients with unresectable tumors, hyperbilirubinemia may exclude patients from hepatically excreted chemotherapy. Biliary stent procedures are used to relieve obstructive jaundice and associated symptoms but can be associated with complications. We conducted a retrospective cohort study to evaluate outcomes of biliary stent placement in patients with unresectable cancer and to describe patient characteristics that might predict poor outcomes. Methods: Patients with unresectable malignancies who underwent initial biliary stent placement at a comprehensive cancer center from 2008 to 2010 were identified using billing data. Characteristics including age, type of tumor, and pre-procedure serum bilirubin were collected. Results: 36 patients underwent biliary stent placement, 23 of whom met selection criteria (exclusions: 5 initial stent placed elsewhere, 8 placed for acute infection). Primary malignances were pancreatic (8), colon (5), melanoma (2), esophageal (2) and one case each of gastroesophageal junction, hepatocellular, gallbladder, gastric, ovarian and lung. Average age was 61 with 47.8% of patients >=65. Thirty day mortality was high with 42% 30 day mortality including 4 deaths during the admission for stent placement (3 with post-procedure sepsis and one patient with a bleed). Baseline bilirubin for patients with mortality within 30 days was 16.1 compared to baseline bilirubin of 9.0 in patients who lived >30 days post-procedure. Thirty percent of those who died within 30 days were >=65 while 61.5% of those who lived >30 days were in this age group. Twenty-six percent of patients went on to receive chemotherapy. Conclusions: Biliary stent placement is associated with significant mortality both related to advanced disease and procedure related complications. Serum bilirubin >10 at time of initial stent placement may be associated with increased 30 day mortality, but older age does not appear to be associated. This merits further evaluation with a larger cohort to identify patients with characteristics associated with increased risk for poor outcomes as well as those who might receive additional therapy.