tbuckley/cabot-search huggingface dataset:
Analysis of early breast cancer (EBC) cases at IRCH, AIIMS, New Delhi
Authors: V. Raina, M. Bhutani, R. Bedi, A. Sharma, S. Deo, N. K. Shukla, B. K. Mohanti, G. Rath
Journal: Journal of Clinical Oncology (2004)

686 Background: Due to regional differences in environment, lifestyle, social-demographic structure and ethnicity, the presentation and outcome of breast cancer in India may be different from that in developed nations. To gain further insight, we retrospectively reviewed the clinical presentation and outcome of EBC patients and conducted survival analysis based on various features. Methods: During the period 1993 through 1999, 487 women with EBC, treated at our institute, were analyzed. Cox's multivariate regression analysis was used to find prognostic factors significant for overall (OS) and disease-free survival (DFS). Results: The median age at presentation was 47 years (range 23–82), 49.7% were pre-menopausal. When first seen, 96% of the patients had a lump, with 7.8% in clinical stage I, 38.8% stage II a, 47.6% stage II b, and 4.3% stage III. Only 11.3% opted to undergo breast-conserving surgery (BCS) while rest 88.7% had modified radical mastectomy. Adjuvant chemotherapy was administered to 275 women (56.5%), CMF; 250, FEC; 25, and radiotherapy (RT) to 146. Since estrogen receptor status was known for only 173 women (93 positive), most were prescribed tamoxifen 20mg per day for at least 5 years. Ovarian suppression was performed in 62 premenopausal women, by surgery in 34 and RT in 28. At a median follow up of 48 months, 126 (25.9%) patients relapsed (local-regional 19,distant 107) and 94 (19.3%) died. Five year DFS and OS for whole cohort were 73% and 78% respectively; corresponding figures for stage I being 88% and 91%, stage IIA 78% and 82%, and IIB 64% and 72%, respectively. On multivariate analysis, number of lymph nodes involved (4 or more) was the only significant prognostic factor for both DFS and OS (p<0.01), others like age, tumor size and stage being non-significant. Conclusions: Significant differences in EBC presentation in India versus West were noted. The median age at presentation is a decade lower. Due to limited mammography facilities for screening, majority presents with palpable lump, in stage II. The preference for BCS is still very low. The treatment results stage wise are however similar. No significant financial relationships to disclose.
Contents, Vol. 67, 1998
Authors: Lennart Melin, Vappu Viemerö, Christina Krause, Maurizio Fava, Meridith A. Rankin, Jonathan E. Alpert, Andrew A. Nierenberg, John J. Worthington, Christina Hägnebo, Gerhard Andersson, Giovanni A. Fava, Antonella Montanari, Johan Lökk, Lena Hillert, Birgitta Kolmodin Hedman, Barbro F. Dölling, Bengt B. Arnetz
Journal: Psychotherapy and Psychosomatics (1998)
Report card for accelerated FDA approval oncology drugs (1995- 2003): Is it time for a make-up test?
Authors: S. M. Belknap, E. A. Lyons, J. M. McKoy, C. L. Bennett
Journal: Journal of Clinical Oncology (2004)

6002 Background: The FDA adopted accelerated approval in 1992 in order to improve access to new drugs based on studies that evaluated markers likely to predict clinical benefit. Methods: The performance of this program was assessed by reviewing new oncology licensing applications and supplements for new uses approved by the FDA from 1995 to September 2003. Data included: the application filing date for each agent, the date of approval, the types of studies that were assessed during FDA review, and the endpoints used in these studies. Results: Of the 21 oncologic indications which received accelerated FDA approval, subsequent studies that were required for conversion to regular approval were submitted and accepted (n=5) [capecitabine, dexrazoxane, docetaxiel, imitinab mesylate, irinotecan], submitted for regular approval but rejected by the FDA (n=3), or have not been submitted (n=14). Surrogate outcomes included response rate (n=16), symptom improvement (n=1) and reduced time to recurrence (n=1). Fourteen approvals were based on results of phase II clinical trials, while only 5 were based on phase III studies. Fewer than 200 patients were evaluated for efficacy for about 2/3 of the indications. Post-marketing studies identified potentially fatal adverse drug reactions for four of the drugs, three of which were identified within 7 months of initial FDA approval (capecitabine-associated interaction with warfarin, imatinib-associated hemorrhage in GIST, and gemtuzumab-associated VOD). Conclusions: To date, drugs which have received accelerated FDA approval have been frequently evaluated in small, short-term phase II clinical trials, have rarely been converted to regular FDA approval, and can have potentially fatal adverse drug reactions identified in the first year of marketing. No significant financial relationships to disclose.
Near miss or safety incident in patients treated with radiotherapy: What are the contributing factors?
Authors: Greg D. Judy, Prithima Mosaly, Lukasz M. Mazur, Gregg Tracton, Bhishamjit S. Chera
Journal: Journal of Clinical Oncology (2017)

36 Background: To identify 1) factors that are associated with a near miss or safety incident (NMSI) in patients undergoing radiation therapy; 2) the most common root causes of NMSIs and their relationship with incident severity. Methods: We retrospectively studied NMSIs filed between October 2014 and April 2016. We extracted patient-, treatment-, and disease-specific data from patients with a NMSI (n=200; incident group) and a similar group of control patients (n=200) matched in time, without a NMSI. A root cause was determined for each incident. A univariate analysis was performed to determine which patient-, disease-, and treatment-specific factors were different between the incident and control groups. Next, multivariate logistic regression was used to determine the significant factors contributing to NMSIs. Multivariate logistic regression was used to determine the most common root causes of NMSIs and their relationship with incident severity. A p value of 0.05 was used to test the statistical significance. Results: NMSIs were associated with the following factors: i) head and neck treated sites versus other disease sites (OR 5.2, p=0.01), ii) image-guided intensity modulated radiotherapy (IGIMRT) versus other treatment modalities (OR 3, p=0.009); tumors staged as T2 more frequently had incidents versus other T stages (OR 3.3, p=0.004), and iv) daily imaging versus no imaging or weekly imaging (OR 7, p&lt;0.001). Documentation and scheduling errors were the most common root causes (29%). Communication errors were more likely to affect patients (p&lt;0.0001) and technical treatment delivery errors were most associated with a higher severity score (p=0.005). Conclusions: Several treatment- and disease-specific factors were found to be associated with a NMSI. These factors are similar to what has been previously reported by others. Overall, our results suggest that complexity (e.g., head and neck, IGIMRT, T2, and daily imaging) might be a contributing factor for a NMSI. This promotes an idea of developing a more dedicated and robust QA system for complex cases. Our study highlights the importance of a strong reporting system to support a safety culture and promote continuous learning and improvement efforts.
Clinical characteristics and survival outcome in women with metastatic breast cancer
Authors: J. Wadhwa, G. Kichenadasse, G. S. Chowdhary, T. Seth, V. Raina, S. V. S. Deo, N. K. Shukla, G. K. Rath
Journal: Journal of Clinical Oncology (2004)

811 Background:Breast cancer is the commonest malignancy amongst women in Delhi, India. Most of our patients present with advanced disease. Clinical characteristics and survival outcome of 126 women with metastatic breast cancer (MBC) seen in our center are reported here. Methods: Case records of 126 consecutive patients with MBC diagnosed during December 2001 to October 2003 were analyzed for clinical characteristics and outcome. Results: Thirty six percent of all patients had metastatic disease at the time of initial presentation. 61% of all patients qualified as aggressive and 39% as indolent metastatic disease. Mean age was 50 years ( range, 25 to 82), 62% being post menopausal. Previously described risk factors of early menarche (30 yr) and family history of breast cancer were not significant in our patients (13%, 12%, and 10% respectively). Bone pain was the commonest symptom (25%), while 16% were still asymptomatic when diagnosed with MBC. The predominant sites of metastatic involvement were bones (43%), lymph nodes (14%), lungs (13%), liver (13%), pleural effusion (5%), skin (5%) and brain (1%). Bone and liver lesions when present were most frequently multiple (58% and 45% respectively). Patients were treated as per standard guidelines with chemotherapy, hormonal therapy, palliative radiotherapy and other supportive measures. The median overall survival from the time of diagnosis of breast cancer was 12 months (range, 1 to 312). The median survival since the time of detection of metastases was only 5 months (range, 1 to 74). Conclusions: The unusually high proportion (36%) of patients presenting with metastases at time of initial diagnosis of breast cancer is noteworthy. Therefore, measures to increase awareness regarding breast cancer and strategies for early detection are imperative. No significant financial relationships to disclose.
Malignant haemangiopericytoma: Yangon experience
Authors: S. Mon, A. Pe
Journal: Journal of Clinical Oncology (2004)

6119 Background: As a rare vascular tumor with varying malignant potential, management of malignant haemangiopericytoma is still a challenging area in clinical practice. Materials and methods: Retrospective study of clinical outcome of total 12 patients with malignant haemangiopericytoma treated during 1984 to 2002 at Medical Oncology Unit, Military hospital, Yangon, Myanmar. Results: Age range from 3 yrs to 71 yrs (mean 32.8 yrs). 7 patients (58.3%) with localized disease and 5 patients (41.6%) with metastasis in lungs reported as initial presentation. Primary tumors involved extremities in 4(33.33%), head and neck in 3 (25%), retroperitoneal region in 2(16.6%), liver 1(8.3%), uterus 1(8.3%) and trunk 1(8.3%). Histology reports showed varying mitotic activity from 1–2 mitosis/HPF in 25%(3), 3–5 mitosis/HPF in 33.33%(4) and > 5 mitosis/HPF in 41.6%(5). Radical resection or possible debulking of primary tumor was done in 9(75%) and biopsy only done in 3 patients. One underwent removal of metastasis lung nodules. Postoperative radiotherapy was given to one patient (8.3%). All patients received systemic chemotherapy using doxorubincin containing regime or Cisplatin and Etoposide combination. Disease stabilization was achieved in 3 out of 5 with metastasis lesions. Median survival time was 19 months (95%CI 10.41,27.59) for those with pulmonary metastasis. Among 7 with localized disease, one died of progressive recurrent lesion and the other died due to cardiac cause during follow up period (range from 23 to 113 months). No recurrence in the rest 5 pts for mean follow up of 64.7 months. Conclusion: Chemotherapy shows disease stabilization and improved quality of life in metastasis disease in this study. Multimodality treatment approach is important in management of malignant haemangiopericytoma. Sharing of international institutions experiences is needed for further more understanding of disease nature and better management. No significant financial relationships to disclose.
Applying a mitotic index to circulating tumor cells and its prognostic significance: A cytological approach to patient stratification.
Authors: Daniel L Adams, Stuart S Martin, Saranya Chumsri, Monica Charpentier, R. Katherine Alpaugh, Massimo Cristofanilli, Cha-Mei Tang, Christian C. Haudenschild
Journal: Journal of Clinical Oncology (2015)

11029 Background: It has been well documented that enumeration of Circulating Tumor Cells (CTCs) isolated from the peripheral blood of breast cancer patients can be used as a prognostic indicator of survival. Typically, CTC identification relies on immunohistochemical stains used in an absent/present method (i.e. CK+/CD45-). However, the methodology for identification of CTCs is highly subjective, and histological cytology remains the standard identifier of cancer cells. We expand upon our work regarding the cytological criteria of CTCs, Adams et al, Cytometry 2015, to determine if pathological grading criteria can be applied to CTCs. We report the assessment for overall survival of late stage breast cancer in relation to CTC number and presence of active mitosis. Methods: A prospective pilot study of 30 single blinded Stage III/IV breast patient samples were provided by Fox Chase Cancer Center and University of Maryland Baltimore. 7.5mL whole blood was diluted in pre-fixation solution and filtered by CellSieve microfiltration. Cells were fixed, permeabilized, and stained with DAPI, an antibody cocktail against CK 8/18/19, EpCAM, and CD45. CTCs were enumerated and identified as described by Adams et al. Cytometry 2015. CTCs were further subtyped by 1) number of pathologically definable CTCs (PDCTCs) and 2) presence of mitotic events, identified by standard visual cues (e.g. prophase, anaphase, etc.). Kaplan-Meier plots and Hazard ratios were determined at 24 months. Results: PDCTCs were found in 87% (26 of 30) of patient samples tested. Of the 14 patients who had ≥ 5 CTCs/7.5mL, 36% (5 of 14) survived 24 months. Of the 16 patients who had < 5 CTCs/7.5mL, 81% (13 of 16) survived 24 months. By contrast, 12 of the 30 patients who had ≥ 1 CTC with a mitotic event, 17% (2 of 12) survived 24 months. Of the 18 patients who had no mitotic CTCs, 89% (16 of 18) survived 24 months. Conclusions: Stratification of breast cancer patients based on number of CTCs is a prognostic indicator of patient survival. Our data suggests that prognostic value is increased by subtyping CTCs based on their mitotic index as assessed by overall survival over a 24 month period.
Tissue Engineering of the Urethra: A Systematic Review and Meta-analysis of Preclinical and Clinical Studies
Authors: Luuk R.M. Versteegden, Paul K.J.D. de Jonge, Joanna IntHout, Toin H. van Kuppevelt, Egbert Oosterwijk, Wout F.J. Feitz, Rob B.M. de Vries, Willeke F. Daamen
Journal: European Urology (2017)
Cetuximab combined with either gemcitabine (G) followed by docetaxel (D) or carboplatin/gemcitabine (CP/G) in chemotherapy-naive patients (pts) with advanced non-small cell lung cancer (NSCLC): Safety profile from the ongoing phase II/III GemTax IV trial
Authors: M. Serke, L. R. Pilz, S. Cicenas, C. Eschbach, J. Fischer, C. Kortsik, C. Schumann, M. Steins, C. Manegold
Journal: Journal of Clinical Oncology (2009)

8048 Background: The EGFR-targeting antibody cetuximab is undergoing broad clinical investigation in NSCLC. Our randomized trial assesses the safety of cetuximab combined with 2 different chemotherapy (CT) regimens in pts with advanced NSCLC. Phase II results are reported. Methods: Pts with histologically confirmed stage IIIB or IV NSCLC, WHO PS 0–2, and no prior CT received cetuximab 400 mg/m 2 loading dose followed by 250 mg/m 2 weekly either combined with G 1000 mg/m 2 days 1 + 8 for 2 cycles (3qw) followed by D 75 mg/m 2 day 1 for 2 cycles (q3w) (arm A) or CP AUC5 day 1 and G 1200 mg/m 2 days 1 + 8 for 4 cycles (q3w) (arm B). Maintenance cetuximab was administered until disease progression or unacceptable toxicity. Results: 229 pts evaluable for safety received 1810 infusions of cetuximab combined with CT and 1216 infusions of maintenance cetuximab. 35 pts in arm A received 1–26 cycles (median 4) of maintenance cetuximab and 6 pts received ≥10 cycles; 50 pts in arm B received 1–22 cycles (median 3) and 7 pts ≥10 cycles. Grade 1 or 2 skin reactions related to study medication occurred in 84% of pts in arm A and 77% in arm B. In general, toxicity was more common in pts receiving CP (leukopenia and neutropenia 10%; pneumonia and fever 10%). In arm B, thrombopenia developed in 14% of pts and allergic reactions in 8%. Toxicities requiring clinical intervention are shown below. Updated results will be presented for 320 pts. Conclusions: Cetuximab does not significantly increase CT toxicity in the induction phase and is well tolerated in the maintenance phase. Notably, ∼75% of pts developed skin rash (grade 3/4 in ∼5% of pts). [Table: see text] [Table: see text]
Phase I study combining UCN-01 with irinotecan in resistant solid tumor malignancies
Authors: P. M. Fracasso, M. A. Rudek, M. J. Naughton, J. Picus, J. S. Rader, R. C. Chen, C. L. Fears, S. A. Goodner, J. Dancey, H. L. McLeod
Journal: Journal of Clinical Oncology (2004)

3139 Background UCN-01, 7-hydroxystaurosporine, is a cell cycle modulator that abrogates the G2 checkpoint induced by DNA damaging agents, such as irinotecan, leading cells to apoptosis. We performed a Phase I study combining UCN-01 with irinotecan to define the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) in resistant solid tumor malignancies and evaluate pharmacokinetics (PK) and pharmacodynamics (PD) of the combination. Methods Patients were treated with irinotecan on days 1, 8, 15, 22 followed by UCN-01 on days 2 and 23 every 42 days. Dose escalation proceeded as follows: Blood samples were collected for pharmacokinetics of irinotecan, SN-38, SN-38 glucuronide and aminopentanocarboxylic acid (APC), and total and unbound UCN-01. Polymorphonuclear cells and normal rectal tissue were collected for cell cycle profiling and phosphorylation of Chk1, Cdc25c, and Cdc2. Results Eleven patients with resistant solid tumor malignancies were treated. In dose level 3, a grade 3 ANC with a >14 day treatment delay was dose-limiting. We are presently expanding this level to 6 patients. In cycle 1, dose level 3, a grade 3 malaise/fatigue occurred. No grade 4 toxicity occurred. PK analyses demonstrated the area under the curve (AUC) of irinotecan, SN-38, SN-38G, and APC was not influenced by UCN-01 administration through dose level 3. In the first two dose levels, there was no significant increase in the AUC of UCN-01. PD samples were collected and analyses will be performed at completion of patient enrollment. Response data on 11 patients reveal 6 with stable disease (range 5–26 weeks) and 5 with progressive disease. Conclusions The combination therapy of UCN-01 and irinotecan at dose level 3 is well-tolerated. At this time, there is no evidence of a PK interaction between these agents. Patient accrual continues at dose level 3. No significant financial relationships to disclose.
Hospital costs in relation to body-mass index in 1·1 million women in England: a prospective cohort study
Authors: Seamus Kent, Jane Green, Gillian Reeves, Valerie Beral, Alastair Gray, Susan A Jebb, Benjamin J Cairns, Borislava Mihaylova, Hayley Abbiss, Simon Abbott, Rupert Alison, Miranda Armstrong, Krys Baker, Angela Balkwill, Isobel Barnes, Valerie Beral, Judith Black, Roger Blanks, Kathryn Bradbury, Anna Brown, Benjamin Cairns, Dexter Canoy, Andrew Chadwick, Dave Ewart, Sarah Ewart, Lee Fletcher, Sarah Floud, Toral Gathani, Laura Gerrard, Adrian Goodill, Jane Green, Lynden Guiver, Alicia Heath, Darren Hogg, Michal Hozak, Isobel Lingard, Sau Wan Kan, Nicky Langston, Kath Moser, Kirstin Pirie, Alison Price, Gillian Reeves, Keith Shaw, Emma Sherman, Rachel Simpson, Helena Strange, Sian Sweetland, Sarah Tipper, Ruth Travis, Lyndsey Trickett, Anthony Webster, Clare Wotton, Lucy Wright, Owen Yang, Heather Young, Emily Banks, Valerie Beral, Lucy Carpenter, Carol Dezateux, Jane Green, Julietta Patnick, Richard Peto, Cathie Sudlow
Journal: The Lancet Public Health (2017)

Excess weight is associated with poor health and increased health-care costs. However, a detailed understanding of the effects of excess weight on total hospital costs and costs for different health conditions is needed.
Nomogram for prediction of prognosis in patients treated for oral cavity squamous cell carcinoma.
Authors: Pablo H. Montero, Changhong Yu, Purvi D. Patel, Frank L. Palmer, Ian Ganly, Jatin P. Shah, Michael W. Kattan, Snehal G. Patel
Journal: Journal of Clinical Oncology (2012)

5562 Background: TNM staging is an effective tool for prognostic prediction in patients with oral cavity cancer, but it disregards variables such as the anatomic subsite, medical comorbidity, lifestyle, etc. A nomogram has the ability to take into account many factors predictive of outcome for an individual patient, beyond the traditional TNM. We have developed a nomogram to accurately predict overall mortality (OM) and disease specific mortality (DSM) in individual patients treated for oral cancer. Methods: Demographic, host, and tumor characteristics of 1,617 oral cancer patients treated with surgery and adjuvant treatment between 1985 and 2009 were available from a preexisting database. Recurrent disease was recorded in 509 patients, 328 died of cancer-related causes and 542 died of other causes. The median follow-up was 42 months (range 1-300 months). Cox proportional hazards regression model was used for OM and competing risk regression was used for DSM. Death from other causes was treated as competing risk for DSM. Missing values in the predictors were multiply imputed before analysis. Variables analyzed as prognosis predictors included age, gender, race, alcohol/tobacco use, anatomic subsite, comorbidity, tumor size/thickness, bone/deep muscle invasion, nodal status/level, grade, vascular/perineural invasion, margin status and adjuvant therapy. Step-down method was used to select the statistically most powerful predictors for inclusion in the final nomogram for each outcome. Results: Age, severe comorbidity, subsite, tumor size, bone/deep muscle invasion, margin status, vascular and perineural invasion, nodal status and level, and adjuvant therapy were the variables with highest predictive value for OM. The most influential predictors of DSM were gender, tumor size, nodal status and location, subsite, margin status, grade and vascular invasion. Nomograms were generated for prediction of OM and DSM. The nomograms were internally validated with correction for over-fitting; bias-corrected concordance index for OM was 75% and DSM 76%. Conclusions: We have developed nomograms that can accurately estimate OM and DSM based on tumor and host characteristics of an individual patient treated for oral cancer.