tbuckley/cabot-search huggingface dataset:
Prognostic factors responsible for outcome in Hodgkin lymphoma: Analysis from a single center in India.
Authors: S. Bansal, S. H. Advani, I. B. Ambulkar, P. Sagar, P. Kanekar
Journal: Journal of Clinical Oncology (2011)

e18554 Background: There is limited data on patients with Hodgkin’s Lymphoma (HL) from India .Our aim was to analyse the outcome of these patients and to identify the risk factors associated with their outcome. Methods: Between May 2004 – Jul 2010 patients diagnosed as HL, and treated upfront with ABVD chemotherapy were included in the study. Limited stage (LS) defined as stage I and stage II non bulky disease and advanced stage (AS) as stage II bulky, Stage III and Stage IV disease. All patients received ABVD 4 to 8 cycles depending on the stage. In cases of relapse or poor response MINE and DHAP chemotherapy was added, followed by ASCT if feasible. Local RT was given to all bulky and residual disease sites. Results: Total 130 patients. Median age 30 yrs (range 5-77 yrs). 91 (70%) males and 39 (30%) females. 61 (47%) had LS disease and 69 (53%) had AS disease. Bulky disease in 38 (29%) and B symptoms in 60 (46%) patients. At the end of therapy 55 (90%) in LS and 48 (70%) in AS were in CR while 5 patients in LS and 19 (27%) patients with AS had progressive or partially responsive disease. One in LS and two in AS died of toxicity. Total 74 (57%) patients received radiation. The projected 5 year OAS and EFS was 91% and 85% for LS and 73% and 57% for AS patients. On univariate , age >45yrs (0.014), Hb <10.5gm/dl (0.028), IPS 4-7 (P<0.000), advanced stage (p=0.001), presence of B symptoms (p=0.026) and on multivariate analysis, age (p=0.05) and advanced stage (p=0.020) were significant predictors of EFS. Bulky disease, extranodal disease and sex of the patient did not have any bearing on the outcome. Conclusions: Our data shows that younger patients do well and advanced stage is a poor prognostic factor. Though ABVD therapy combined with radiation is effective for Limited stage, we need to treat advanced stage patients more aggressively to improve outcome.
Association of a high SCORED value and chronic kidney disease following radical nephrectomy for renal masses
Authors: G. R. Nuss, S. Lucas, G. V. Raj
Journal: Journal of Clinical Oncology (2008)

5117 Background: Radical nephrectomy (RN) represents the definitive surgical intervention for patients with renal masses suspicious for malignancy and a normal contralateral kidney. However, patients with renal masses are at risk for having or developing chronic kidney disease (CKD) stage III (GFR<60 ml/min/1.73m2) which places them at a higher risk for cardiac morbidity and mortality. We examined if a validated predictive model (SCORED) could help stratify the risk of CKD in patients with renal masses. Methods: We identified 293 consecutive patients who underwent RN for a renal mass without evidence of metastatic disease and with a normal contralateral kidney. Using preoperative risk factors, we stratified patients into low (<4) and high (≥4) SCORED values. Glomerular filtration rates (GFR) were estimated by the MDRD equation. Results: In our cohort, RN was performed for renal masses with an average size of 6.9 cm (range 2–24). A higher SCORED value was associated with a higher risk of patients having CKD stage III prior to surgery (38% vs 18% with a lower SCORED value, p <0.004). Furthermore, among patients with a pre-operative GFR ≥ 60 ml/min/1.73m2, a higher SCORED value was associated with a significantly higher risk for developing CKD stage III postoperatively, at a median follow up of 39.0 months (52% and 65% risk of CKD vs 25% and 32% risk of CKD in patients with lower SCORED value at 12 months, and at 24 months respectively, p=0.010). In multivariate analyses including the size of the mass and pre-operative GFR, the SCORED value was associated with development of CKD. Comparative analyses with another cohort of 171 patients undergoing nephron sparing approaches (NSA) revealed that NSAs significantly protected patients from developing CKD stage III post-operatively. Conclusions: Despite a normal contralateral kidney, patients with high SCORED values are at a significant risk of having or developing CKD following RN for renal masses. Nephron-sparing approaches should be used whenever possible. These findings assume greater importance when considering overall survival outcomes of patients with kidney cancer, as CKD stage III is an independent risk factor for cardiovascular morbidity and mortality. No significant financial relationships to disclose.
Genomic analysis of prostate cancer.
Authors: Christine M. Barnett, Michael C. Heinrich, Dylan A. Nelson, Jeong Youn Lim, Carol Beadling, Andrea Warrick, Tanaya Neff, George Thomas, Mark Garzotto, Celestia S. Higano, Tomasz M. Beer, David Z. Qian
Journal: Journal of Clinical Oncology (2013)

80 Background: The characterization of actionable mutations is a prerequisite for the development of individualized, targeted therapy. We sought to characterize the prevalence of potentially therapeutically actionable mutations in patients with high risk prostate cancer. Methods: 48 samples of formalin fixed paraffin embedded prostatectomy tissue from a neoadjuvant chemotherapy trial (Garzotto M, Cancer 2010 Apr 1;116(7):1699-708) were analyzed. DNA was extracted from microdissected tumor. Tumor DNA was analyzed for 643 common solid tumor point mutations in 53 genes using mass spectroscopy based sequencing (Sequenom MassArray). Low level mutations were validated using ion chip pH based sequencing (Ion Torrent). In addition, PTEN loss and ERG translocations were examined using immunohistochemistry in associated tissue microarrays. Correlation with relapse during 5 years of follow-up was examined in exploratory analyses of the potential clinical relevance of the genetic alterations examined. Results: Of the 40 tumors evaluable for mutations, 10% had point mutations in potentially actionable cancer genes. Of the 45 tumors evaluable for IHC, 36% had PTEN loss (6% with a heterogenous pattern) and 40% had ERG rearrangement (2% with heterogeneous pattern). Individual mutations were not frequent enough to determine associations with progression. Using Kaplan-Meier analysis with a log-rank test, the 16 patients who had PTEN loss had a significantly shorter median progression free survival, 19 vs. 106 months (p = .01). Conclusions: This study confirms that point mutations in the most common cancer regulatory genes in prostate cancer are rare. However, the PIK3CA/AKT pathway was mutated in 10% of our samples. While point mutations alone did not have a statistically significant effect on relapse, PTEN loss was associated with an increased relapse in high risk prostate cancer treated with chemotherapy followed by surgery. It is yet unclear if the 16 weeks of chemotherapy played a role in selecting for tumors with these biologic features, and this will therefore be the subject of future investigations. [Table: see text]
Lenalidomide (LEN) In Lower-Risk Myelodysplastic Syndromes (MDS) with Karyotypes Other Than Deletion 5q and Refractory to Erythropoiesis-Stimulating Agents (ESAs)
Authors: David Sibon, Giovanna Cannas, Fiorenza Barraco, Thomas Prebet, Norbert Vey, Anne Banos, Caroline Besson, Selim Corm, Michel Blanc, Borhane Slama, Hervé Perrier, Pierre Fenaux, Eric Wattel
Journal: Blood (2010)
Gemcitabine(G) plus cisplatin (C) in advanced carcinoma gallbladder - A large single center experience
Authors: S. Misra, A. Chaturvedi, N. C. Misra
Journal: Journal of Clinical Oncology (2005)

4136 Background: Carcinoma gallbladder (CaGb) is one of the commonest cancers in North India. Patients usually present with locally advanced or metastatic disease where curative surgical resection is not possible. The role of chemotherapy in this situation has not been defined. There exists a need for new effective chemotherapeutic regimens. G has shown some promise in patients with CaGb. We therefore conducted a phase II single institution study of G and C in advanced CaGb patients. Primary end point was response rate (RR) and secondary end points were time to progression (TTP), overall survival and treatment toxicity. Methods: Patients with unresectable or metastatic, cytologically or histologically proven CaGb with ECOG PS ≤ 2, no other malignancy, age ≤ 75 years and serum bilirubin ≤ 2.0 mg/dl received G 1000 mg/m2 on d 1, 8, 15 and C 80 mg/m2 on d 16,17 in divided dose, every 28 days, for a total of 6 courses. Treatment was discontinued for unacceptable toxicity or disease progression. RR was evaluated by abdominal CT scan. Results: From Nov. 1999 to Dec. 2003, 40 patients were included in the study. Patient characteristics: M/F 11/29, median age 55.5 years (range-29–74) median number of cycles 3.5 (range 1- 6). 38 patients were evaluable for response. There were 2 CR and 19 PR, for an objective RR of 55.3% (95% CI, 38.3%–71.4%). 7 patients had SD and 10 were NR. All 40 patients were evaluable for toxicity. Main grade 3/4 toxicities included anemia (22.5%), neutropenia (5%), thrombocytopenia (7.5%) and nausea/vomiting (20%). Median TTP for all patients was 24 weeks (95%CI, 20–32 weeks). Median survival time was 32 weeks (95% CI, 18–36 weeks) for the entire population, 44 weeks (95% CI, 32–56) for responders, 32 weeks (95% CI, 20–32) for SD and 12 weeks (95% CI, 4–16) for NR. Patients presenting with jaundice whose jaundice was relieved by biliary stenting had response and survival similar to non-jaundiced patients. Conclusions: G plus C is an effective combination for patients with unresectable or metastatic CaGb and is associated with favorable toxicity profile. This regimen should be evaluated in a phase III trial. No significant financial relationships to disclose.
Prognostic factor for overall survival in the "difficult-to-treat" germ cell tumor patients.
Authors: Terukazu Nakamura, Masakatsu Oishi, Takashi Ueda, Takumi Shiraishi, Hiroyuki Nakanishi, Yoshio Naya, Fumiya Hongo, Koji Okihara, Tsuneharu Miki
Journal: Journal of Clinical Oncology (2015)

402 Background: Our previous observation showed germ cell tumor (GCT) patients who finished at first-, second- or third-line chemotherapy obtained good overall survival. On the other hand, patients with 4th line-or-after chemotherapy showed much poorer outcome. The aim of this study was to investigate the prognostic factor for overall survival in the patients with 4th-line-or-after chemotherapy. Methods: Between August 1998 and December 2013, seventy-four GCT patients had 4th line-or-after chemotherapy at our institution. These patients were defined as ‘difficult-to-treat’ GCT patients in this study. We retrospectively assessed clinical and therapeutic parameters. Median age was 33 y.o.(range;19-55). Nonseminoma was found in 86.5%. Good, intermediate and poor prognosis by IGCCC was 23, 17 and 26 cases, respectively. With regard to IGCCC at salvage, very low, low, intermediate, high and very high was 2, 7, 10, 18 and 6 cases, respectively. Results: Fiver-year overall survival was 55.6%. Choice of 2nd line or 3rd line chemotherapy did not influence overall survival, for example, VeIP (vinblastine, ifosfamide, cisplatin) or VIP (etoposide, ifosfamide, cisplatin) versus other chemotherapy as 2nd line therapy (5-y OS; 55.2% and 56.3%, log-rank, p=0.78). The identical result was observed in paclitaxel-containing therapy such as TIP versus other chemotherapy (paclitaxel, ifosfamide, cisplatin) (5-y OS; 52.8% and 57.1%, log-rank, p=0.90). In the choice of 4th line chemotherapy, gemcitabine-containing regimen was not superior to other chemotherapy (5-y OS; 57.0% and 55.3%, log-rank, p=0.98). Statistical significant parameters were primary site, IGCCC at salvage, required chemotherapy line and serum tumor marker (STM) normalization by univariate analysis. Multivariate analysis showed independent prognostic factor for overall survival was normalization of serum tumor marker during chemotherapy (Hazard Ratio;0.12, 95% Confidence Interval;0.02-0.62, p=0.01). Conclusions: STM normalization is thought to be mandatory for overall survival in the management of ‘difficult-to-treat’ advanced GCT patients.
Primary care nurse practitioners providing survivorship cancer care.
Authors: Margaret Quinn Rosenzweig, Sara Klein, Mary Connolly, Rose Hoffmann
Journal: Journal of Clinical Oncology (2016)

14 Background: The Oncology Nurse Practitioner Web Education Resource (ONc-PoWER) is an online course developed specifically for nurse practitioners (NPs) in their first year of oncology practice paired with an onsite mentor (physician, nurse practitioner or physician assistant). Based on the Oncology Nursing Society’s Competencies for Entry to Practice, the course consists of 5 interactive modules: 1) the new patient visit 2) presenting a patient with cancer 3) cancer visits across the continuum of care 4) palliative and hospice care 5) self-care and professional development. The purpose of this study was to examine the NPs and mentors experience with the learning activities and to what degree the learning objectives were met. Methods: Dyads of NPs and mentors completed the course over 4-6 months. There are items for course evaluation with Likert scaled responses of 1) did not meet objective 2) somewhat met objective 3) met objective 4) more than met objective 5) exceeded objective expectation. Results: Enrollment is ongoing. Thirty NPs new to practice and 22 oncology mentors have completed evaluations thus far. Responses overall are favorable. Conclusions: The ONcPoWER web enhanced oncology orientation program was favorably evaluated by nurse practitioners new to cancer care and their mentors. This method of electronic orientation could standardize the exposure of essential basic cancer care competencies at entry to oncology nurse practitioner practice and, with some edits to content, for community based primary care nurse practitioners caring for cancer survivors. [Table: see text]
Vanilloid Receptor (TRPV1) Expression on the Neoplastic B-Cell Lymphocytes in Patients with Chronic Lymphocytic Leukaemia.
Authors: Jaroslaw Piszcz, Slawomir Ziarko, Janusz Kloczko, Piotr Radziwon, Eliza Blusiewicz, Edyta Cichocka
Journal: Blood (2006)
The Effect of Imatinib Mesylate on the Signal Transduction Cascade Leading to down Regulation of Telomerase Activity in K562 Cells.
Authors: Rahav Mor, Orit Uziel, Ofer Shpilberg, Judith Lahav, Pia Raanani, Esther Rabizadeh, Meir Lahav, Galit Granot
Journal: Blood (2006)
Role of non-neoplastic renal parenchyma abnormalities in the population with preoperative CKD.
Authors: Maria Carmen Mir, Nicola Pavan, Nachiketh Soodana-Prakash, Raymond R Balise, Vivek Venkatramani, Sam Shabtaie, Varun Channagiri, Alessia Fornoni, David B Thomas, Dipen Parekh
Journal: Journal of Clinical Oncology (2016)

586 Background: Renal cancer is associated with chronic kidney disease. Several studies have shown a 20% rate of preoperative CKD in the population undergoing partial nephrectomy. The non-neoplastic abnormalities (NNA) surrounding a tumor have been suggested as surrogates for long term renal failure. We have endeavored to describe the most relevant features within the above mentioned kidney area in patients with and without preoperative CKD. Methods: We retrospectively reviewed 201 patients who underwent nephrectomy between 2012 and 2014 with available histological assessment of NNA. Additional factors were included in the analysis such as demographic characteristics (age, sex, BMI) and comorbidities (hypertension, diabetes, Charlson comorbidity index). Pathological features were grouped as follows: glomerular (GA), interstitial (IA) or vascular abnormalities (VA). Univariate and multivariate logistic regression analyses were used to determine the associations between NNA and the presence of preoperative CKD stage III. Results: CKD stage III patients were older (68 vs. 56 years, P &lt; .004) and presented a higher rate of DM with end-organ damage (n = 10, 13% vs N = 2 2%). Otherwise, people with and without CKD showed similar demographics. Overall, 56% of patients showed GA, 86% showed IA and 98% of patients presented with VA. In the multivariate analysis adjusted for comorbidities, the most relevant GAs were diabetic glomerulosclerosis (OR 7.32; p = 0.01), segmental sclerosis (OR 4.54; p = 0.0006) and glomerular adhesion (OR 2.80; p = 0.04). In the IA group, interstitial fibrosis (OR 7.36; p &lt; 0.001), tubular atrophy (OR 2.75; p = 0.02) and acute interstitial inflammation (OR 12.47; p = 0.02) were significantly associated with decreased eGFR. Hyperplastic arteriolosclerosis (OR 2.30; p = 0.025) was an independent predictor of baseline eGFR &lt; 60. Conclusions: NNA assessment from surgical specimen is feasible. Patients with baseline CKD present with several abnormalities related to inflammation and healing within the three nephron areas. The further investigation of these abnormalities might have a role in the evaluation of ultimate renal deterioration.
Pilot investigation of variants in DNA repair pathways and association with response to platinum-based chemotherapy in bladder cancer.
Authors: Ryan P. Kopp, Kelly Lynn Stratton, Ilana Rebecca Garcia-Grossman, Emily C. Zabor, Irina Ostrovnaya, Tinu Thomas, Gloria Gerber, Shaheen Riaoh Alanee, Kasmintan A. Schrader, Peter H. O'Donnell, Dean F. Bajorin, Vijai Joseph, Kenneth Offit
Journal: Journal of Clinical Oncology (2014)

343 Background: Germline single-nucleotide variations (SNVs) in DNA repair genes may have a role in response to platinum-based chemotherapy in bladder cancer (BC). As a pilot project we created a discovery cohort using an extreme phenotype model of BC response to neoadjuvant chemotherapy; we identified candidate SNVs in DNA repair genes via whole exome sequencing, and sought to replicate these findings in a validation cohort. Methods: We sequenced exomes of a discovery cohort with ≥ cT2 BC and neoadjuvant chemotherapy [6 complete responders (CR, pT0N0 and 1 year disease free interval) vs. 9 non-responders]. We identified SNVs within 377 DNA repair pathway genes. We filtered for SNVs with high impact effects, and moderate impact missense variants. The discovery phase resulted in 16 candidate SNVs which we genotyped (matrix-assisted laser desorption/ionization-time of flight) within a validation cohort of 303 BC patients treated with platinum-based neoadjuvant or first-line chemotherapy. Primary outcome was pathologic (neoadjuvant) or radiographic (first-line) CR, with secondary outcome CR+partial response (PR; RECIST criteria or pathologic downstaging). We used additive genetic model and logistic regression to analyze association between individual SNVs and both CR and CR+PR. Multivariate models included MSK risk score for CR or chemotherapy (cis- vs carboplatin) for CR+PR. Results: We included 303 patients (186 neoadjuvant, 117 first-line; 272 cisplatin, 31 carboplatin), median age 64, including 67 (22%) CR and 153 (50%) CR+PR. Genotyping was adequate for analysis in 14 of 16 SNVs—none were associated with CR. SNVs associated with CR+PR were rs2072454 (EGFR, p=0.031 unadjusted, p=0.035 adjusted for chemotherapy) and rs1805321 (PMS2, p=0.014 unadjusted, p=0.019 adjusted for chemotherapy). Findings were not significant after adjusting for multiple comparisons. Conclusions: Using an extreme phenotype model we identified SNVs in genes of the DNA repair pathway that may have an association with platinum-based chemotherapy response in BC. A larger validation study is required to increase power and reduce the impact of multiple testing prior to confirming significance.
Pathogeneses of noninflammatory locally advanced breast cancer.
Authors: P. B. Dahi, C. A. Axiotis, K. Dhiran, J. Weedon, M. El-Tamer, A. S. Braverman
Journal: Journal of Clinical Oncology (2011)

e11004 Background: Locally advanced breast cancers are staged as T3 if larger than 5 cm, or T4 if they involve the overlying skin or underlying chest wall. The purpose of this paper is to evaluate any differences in pathologic attributes of T3 and T4 lesions. Methods: All patients with locally advanced breast cancer without evidence of distant metastasis that presented to the KCHC, Breast Clinic from 1982 to 2010, were examined to determine whether their BC’s involved ≥50% of their breast volumes, defined by gross replacement of at least one hemisphere. Core needle biopsy or post-mastectomy specimens from tumors involving a known per cent of breast volume were evaluated for: 1) pathological grades and lympho-vascular invasion (LVI); 2) hormone receptor (ER/PR) expression >0; 3) epidermoid growth factor 2 (her2) overexpression (3+), determined by immunohistochemical staining or fluorescent in situ hybridization. Results: The data base included 98 patients with T3N1 and 120 patients with T4a-c disease. The tumor mass involved more than 50% of the breast in 23/98 (24%) of T3 lesions and 65/120(54%) T4 lesions (p<0.001). One and 23% of T3 and T4a-c patients respectively presented with total replacement of the breast (p<0.001). The table lists the pathologic attributes of the T3 and T4a-c tumors for which the tests were conducted. There were no significant differences between any of the pathologic attributes of the T3 and T4a-c groups. Conclusions: These data are consistent with the hypothesis that erosion of the overlying skin or underlying chest wall in breast cancer may be simply due to neglect and delay, rather than an inherent biologic aggressiveness. P calculated by Fisher’s exact test (2-sided). T3 % T4a-c % P Grade 3 51/82 62 51/84 61 =0.874 ER>0 36/63 57 38/67 57 =1.000 PR>0 29/63 46 31/67 46 =1.000 ER/PR>0 27/63 43 33/67 49 HER2+ 25/58 42 21/60 35 =0.455 Triple neg 13/59 22 17/60 28 LVI 6/20 30 11/29 38 =0.761
A phase II study of complete neoadjuvant therapy in rectal cancer (CONTRE): The Brown University Oncology Group.
Authors: Kimberly Perez, Victor Pricolo, Matthew Vrees, Thomas A. DiPetrillo, Nicholas Oldenberg, Adam Klipfel, Steven Schechter, Timothy J. Kinsella, Leslie Roth, Thomas Cataldo, Nishit Shah, Adam J. Olszewski, Debora Isdale, Howard Safran, William M. Sikov
Journal: Journal of Clinical Oncology (2013)

335 Background: While preoperative chemoradiation followed by surgery is the standard approach for patients (pts) with newly diagnosed clinical stage II-III rectal cancer, many are unable to tolerate postoperative adjuvant chemotherapy which may compromise disease-free and overall survival. CONTRE is a multicenter phase II study designed to determine the feasibility of administering all chemotherapy prior to surgery and to assess its impact on pathologic complete response (pCR) and complete (R0) resection Methods: Pts with T3-4 and/or N1-2 rectal cancer, staged by endorectal ultrasound (ERUS) and pelvic MRI, receive modified (m) FOLFOX6 every 2 weeks x 8 cycles, followed by repeat MRI and proctoscopy to assess response. Pts then receive 50.4 Gy IMRT with 5-FU 225 mg/m 2 /day or capecitabine 825mg/m 2 BID, 5 days per week during radiation, followed by surgery 4-8 weeks later. Results: Thus far, we have enrolled 36 of a planned 39 pts (median age 58, range 30-79; T2-1, T3-30, T4-2; N1-20, N2-7). 28 of the first 30 (93%) completed 8 cycles of mFOLFOX6. 26 pts have completed chemoradiation while 2 chose to proceed directly to surgery. All patients opted to receive capecitabine during radiation. Grade 3/4 toxicities during chemotherapy and chemoradiation have included diarrhea (16%) and neutropenia (12%), with grade 3 renal and cardiac toxicities reported in one patient each. A clinical complete response after chemotherapy alone was achieved in 3 of 29 (10%). Of the first 21 pts undergoing surgery, pCR has been achieved in 6 (29%) and R0 resections in 100%. Thus far, all pts have been able to undergo sphincter-sparing resections. Study accrual will be completed by the meeting. Conclusions: A larger proportion of stage II-III rectal cancer pts are able to complete mFOLFOX6 (&gt;90% in our cohort) when administered prior to chemoradiation and surgery. Complete neoadjuvant treatment may represent a well-tolerated alternative to the current standard treatment sequence and a platform for the evaluation of novel therapeutics such as targeted agents during preoperative therapy. Funded in part by LIFEcycle, Inc. Clinical trial information: NCT01363843.