tbuckley/cabot-search huggingface dataset:
Medical decision making under uncertainty in adult patients (pts) with multiple primary cancer (MPC)
Authors: E. Gil Deza, L. F. Loviscek, F. Negro, J. C. Calarame, C. Garcia Gerardi, E. L. Morgenfeld, D. Cascallar, S. Carnaval, E. G. Rivarola, F. G. Gercovich
Journal: Journal of Clinical Oncology (2006)

16037 Background: Evidence-based Oncology (EBO) is founded in clinical trials, medical expertise and patient’s quality of life. Pts with MPC are excluded from clinical trials and there is a lack of clinical expertise as regards to these cases. With the aim to analyze the clinical reasoning for treatment recommendation on those pts, we interviewed oncologists in charge (doc’s) at Instituto Oncológico Henry Moore (IOHM) and Universidad del Salvador (USAL). Methods: The medical records of 8,500 pts from IOHM’s database over last eight years (1997–2005) were reviewed in order to measure the incidence and characteristics of MPC pts. A total of 35 oncologists in charge were identified and participated on a survey which had ten points. The 10 items should be ranked in order of importance: 1 = the most important one and 10 = the least one. Results: One hundred and seventy eight MPC pts (2.09%) were detected, and the oncologist in charge was asked to complete the survey. All doc’s completed the survey. The following table shows the rank and the scoring for each item. (See table below) Conclusions: Four domains ( I to IV) in medical decision making for the treatment of MPC pts were identified: I = PS; II = Characteristics of the tumor; III = Morbidity from therapy and IV = Pt preferences. The pt and family preferences were ranked in the last place and it could reflect a paternalistic approach. To our understanding, this is a good model to test clinical skills and biases in medical treatment selection. [Table: see text] No significant financial relationships to disclose.
Somatically mutated immunoglobulin V<sub>H</sub> genes without intraclonal heterogeneity indicate a post germinal center origin of primary intraocular diffuse large B-cell lymphomas
Authors: R. Malumbres, J. Davis, P. Ruiz, I. S. Lossos
Journal: Journal of Clinical Oncology (2007)

8072 Background: Primary intraocular lymphoma (PIOL) is a very rare high grade malignant non-Hodgkin lymphoma, usually of the diffuse large B cell lymphoma (DLBCL) type, which presents in the vitreous, retina and/or the optic nerve. Sixty to 80% of patients with PIOL eventually disseminate to the brain, whereas up to 15% of primary central nervous system lymphoma (PCNSL) patients exhibit ocular involvement. For these reasons, PIOL is regarded as a subtype of PCNSL. Analysis of the immunoglobulin heavy chain (V H ) sequences in PCNSL tumors demonstrated biased overrepresentation of the VH4–34 gene and indicated derivation of these tumors from highly mutated germinal center (GC) B cells with ongoing mutational activity. Whether PIOL tumors are of similar or different origin is presently unknown. Methods: Immunoglobulin V H genes were examined in vitrectomy specimens of 4 PIOL patients, 1 patient with concomitant PCNSL and 1 patient with systemic DLBCL involving the eye. The extracted DNA was amplified by PCR using V H family specific primers, cloned and sequenced. Results: Seven clonal V H rearrangements belonging to the VH4, VH3 and VH1 families were cloned from the analyzed cases. In concordance with previous reports, the lymphomatous eye infiltrate from the PCNSL patient revealed a mutated clonal VH4–34 gene with intraclonal heterogeneity -a manifestation of active ongoing mutational activity. All the PIOL clonal V H rearrangements also exhibited mutated sequences with homology to the germline sequences ranging between 76 to 95%. However, in contrast to PCNSL, 3 out of 4 PIOL cases exhibited no intraclonal heterogeneity while the remaining case demonstrated ongoing somatic mutations in one of the 2 clonal V H rearrangements detected in this tumor. Interestingly, the clinical course of this patient was highly unusual, since he exhibited systemic dissemination during follow-up. Conclusions: Analysis of V H gene sequences from PIOL tumors indicate a post- GC derivation and suggest that they belong to the activated B cell (ABC)-like subtype of DLBCL. This is in contrast to the GC-origin of closely related PCNSL. No significant financial relationships to disclose.
High-dose sequential chemotherapy (HDSC) with peripheral blood progenitor cells (PBPC) support for high-risk breast cancer (BC)
Authors: R. Sabbatini, G. A. Da Prada, G. L. Frassineti, M. Aietta, P. Pedrazzoli, M. Maur, A. Zambelli, N. Giovannini, S. Siena, L. Ponchio, P. F. Conte
Journal: Journal of Clinical Oncology (2007)

11026 Background: Recent reports suggest that intensified adjuvant chemotherapy with stem cell support improve disease free (DFS) and overall survival (OS) in subgroups of patients with high risk BC. We retrospectively analyzed the efficacy, safety and feasibility of a program of HDSC with PBPC support (according to the Milan protocol, ASCO 2001) in patients with BC at high risk of recurrence Methods: Between February 1995 and January 2001, 201 non-consecutive patients with more than 3 positive axillary nodes at surgery, median age 46 (range 27–62), has been evaluated. Median number of involved nodes was 15 (range 3–48), 38% and 49% pts had ER and PgR negative tumors, respectively. Fourty-sevent percent of pts had tumors with a high proliferative activity. HDSC consisted of sequential administration of cyclosphosphamide 7 g/m 2 (day 0) plus filgrastim 5 μg/kg s.c. daily and stem cell collection, methotrexate 8 g/m 2 plus vincristine 2 mg/m 2 (day +16), and two consecutive courses of epidoxorubicin 120 mg/m 2 (days +23 and + 38) plus filgrastim 5 μg/kg s.c. daily. Myeloablative therapy (day +58) consisted of thiotepa 600 mg/m 2 and melphalan 160 mg/m 2 plus PBPCs and filgrastim 5 μg/kg s.c. daily. Results: Three pts discontinued the program permanently because of toxicity. A median of 9,35x10 6 /kg (range 3.35–35.62) CD34+ cells was infused. Engraftment for neutrophils (&gt; 500/μl) and platelets (&gt; 20.000/μl) was observed a median of 9 days (range 7–17) and 10 days (range 7–18) after PBPC infusion, respectively. No treatment-related deaths were recorded. After a median follow-up of 79 months, 108 (54%) pts are disease- free. Ninety-three patients experienced disease recurrence [9/93 (10%) pts had loco regional disease recurrence and 84/93 (90%) pts distant recurrence], of whom 58/93 (63%) have died. Five-year DFS and OS from the start of treatment are 55% and 71%, respectively. No poor marrow function, myelodysplastic syndrome or secondary tumors were observed. In 2-sided log-rank tests, hormone-receptor status and the number of tumor-positive axillary lymph nodes were significant prognostic factors for DFS. Conclusions: Our results confirm that HDSC is a safe procedure and is associated with favorable outcome in patients with high-risk BC. No significant financial relationships to disclose.
Prognostic value of preoperative surgical morbidity risk-stratification using morphometric data obtained from routine abdominal CT scans in the setting of pancreatic cancer resection.
Authors: Shawna Grimm, Tiffani Dawn Shelton, Charles David Goldman, Jan Franko
Journal: Journal of Clinical Oncology (2013)

e17599 Background: Patient frailty is imparative to surgical planning, post-operative morbidity and mortality, and ultimately the ability to undergo adjuvant therapy in cancer treatment. Sarcopenia has been correlated with long term survival in the setting of pancreatic resection for cancer. However, it has not been evaluated in the early post-operative setting. Here, we evaluate the prognostic value of morphometric parameters measured on abdominal CT scans in fifty patients undergoing pancreatic resections and comparing with postoperative complications. Methods: Post-operative complications of fifty patients who underwent pancreatic resection for suspected neoplasm were graded via Clavien Dindo classification and then correlated with standardized morphometric measurements from CT scans. Results: Thirty-two men and 18 women (age 63±13 years) underwent pancreatic resection for cancer. Total psoas muscle area (2555±791 vs 1821±805,p=0.008), L4-alba distance (113±29 vs 119±27,p=0.597), rectus muscle (10.1±2.5 vs 7.8±4.5,p=0.016) and SQ fat thickness (20±11 vs 29±10,p=0.024). Logistic regression modeling including age, gender, and total psoas area predicted complication occurance (pseudo R2=0.350, p=0.008) and their number (pseudo R2=0.191,p=0.002), but not grade 3 and higher complications (pseudo R2=0.68,p=0.451) or pancreatic leak (pseudo R2=0.020,p=0.873). Similar results were obtained when age and gender variables were combined with rectus muscle thickness (pseudo R2=0.422), L4-alba distance (pseudo R2=0.377), and SQ fat thickness (pseudo R2=0.392). In each case, &gt; Grade 3 complications and pancreatic leak was not predicted with morphometric data, age and gender. Conclusions: There are significant age and gender-related differences in morphometric data obtained from abdominal CT scans. Prognostic models provide statistically significant prediction of complication occurrence, but explain only up to 42% of variability in complication occurrence. Moreover, clinically important complications (grade 3 and higher) and pancreatic leak was not predicted with this model based on our limited dataset.
Diagnostic and Prognostic Role of Fecal Calprotectin As a Biomarker for Gastrointestinal Graft Versus Host Disease: A Systematic Review of Literature
Authors: Abdul Rafae, Mustafa Nadeem Malik, Ali Younas Khan, Anum Qureshi, Muhammad Abu Zar, Ceren Durer, Seren Durer, Ahmad Kamal, Insija Ilyas Selene, Jemin Aby Jose, Muhammad Jahanzeb Khalil, Hafiz Muhammad Fazeel, Muhammad Usman, Awais Ijaz, Faiz Anwer
Journal: Blood (2018)
Cutaneous Ulcerations in Anti-MDA5 Dermatomyositis
Authors: Alexandra Charrow, Ruth Ann Vleugels
Journal: New England Journal of Medicine (2019)

A 48-year-old man presented with painful hand ulcerations and progressively worsening shortness of breath. Chest CT revealed organizing pneumonia, and antibody testing confirmed the diagnosis of anti-MDA5 dermatomyositis.
Phase II trial of gemcitabine (G) with pazopanib (P) or gemcitabine with docetaxel (T) in advanced soft tissue sarcoma (STS).
Authors: Neeta Somaiah, Brian Andrew Van Tine, Elizabeth Goodwin Hill, Mohammed M. Milhem, Scott Schuetze, Christian Frederick Meyer, Daniel Y. Reuben, Anthony D. Elias, William L. Read, Sant P. Chawla, Amy E. Wahlquist, Elizabeth Garrett-Mayer, Andrew S. Kraft
Journal: Journal of Clinical Oncology (2019)

11008 Background: P is a multi-tyrosine kinase inhibitor with efficacy in many sarcoma subtypes. We designed a trial to assess the benefit of adding P to G as an alternative regimen to the commonly used combination of G+T in pts with STS (NCT01593748). Methods: We performed an open-label, randomized phase 2 trial enrolling pts with advanced non-adipocytic STS who had received prior anthracycline based therapy. Pts were assigned (1:1 stratified randomization based on leiomyosarcoma and prior pelvic radiation) to receive G 1000 mg/m 2 on days 1 and 8 with P 800 mg daily or G 900 mg/m2 on days 1 and 8 and T 100 mg/m2 on day 8, repeated q 3 wks. The primary objectives were estimating median PFS and rate of grade ≥3 adverse events (AEs). Secondary objectives included estimating the hazard ratio (HR) and response rates. Cross-over was allowed for RECIST progression. Sample size of 90 was derived based on the precision of 95% confidence intervals (CI) for reporting toxicity and PFS in each arm. Results: A total of 90 pts enrolled; 45 on each arm. Pt characteristics and results are detailed in Table. Median PFS was 4.1 months for each arm (p= 0.3, based on stratified log-rank test). The clinical benefit rate (PR+SD) was 29% for each arm (p&gt;0.99, based on Fisher’s exact test). The rate of related grade ≥3 AEs were 20.6% with G+T and 19.9% with G+P. Related grade ≥3 AEs (%) occurring in ≥10% of pts (G+T; G+P): anemia (36, 20), fatigue (29; 13), low platelets (56; 51), low neutrophils (20; 49), AST increase (2; 13) and hypertension (2; 20). Conclusions: This study demonstrates comparable efficacy between G+P and G+T, suggesting that G+P can be considered for second-line therapy in advanced non-adipocytic STS. Pt Characteristics and Results. Clinical trial information: NCT01593748. [Table: see text]
Extended intersphincteric resection with quadrant resection of external sphincter after neoadjuvant mid-course chemoradiotherapy in the very low rectal cancer.
Authors: Nahmgun Oh, Sanghwa Ko, Hyunsung Kim
Journal: Journal of Clinical Oncology (2012)

e14181 Background: To evaluate the results of extended intersphincteric resection of T3 rectal cancer situated below 4cm from the anal verge, comparing the results of simple intersphincteric resection of T2 rectal cancer after mid-course chemoradiotherapy. Methods: Between 2000 Between 2000 and 2006, 67 patients with rectal cancer below 4cm from anal verge, underwent abdomino-intersphincteric resection reconstructed by inversion proctoplasty with a colonic J-pouch and diverting ileostomy. All patients received a total irradiation dose of 30 Gy with conventional fractions for 3 weeks. Capecitabine was administered 1000mg/m2 twice a day on 21 days during radiotherapy, followed curative surgery in a week without resting period. After preoperative radio-chemotherapy, patients with overt T2 lesion were 27 cases (40.3%) and received intersphincteric resection (Group I: simple intersphincteric resection), and patients with borderline cases or T3 lesion were 40 cases (59.7%) and received intersphincteric resection with quadrant resection of upper external sphincter and primary repair of the external sphincter as inversion proctoplasty (Group II: extended intersphincteric resection). Results: The mean patients age was 61.2 years. The mean location of cancer was at 3.2cm from anal verge (2-4cm). Anastomotic leakage was confirmed in 11 patients (16.4%). There was no postoperative mortality. The grade I, II of continence by Kirwan classification was 81.5%, 80.0% in Group I and II. Under 3 times stool frequency per day was 51.9%, 62.5% in Group I and II. Two patients (3.0%) experienced locoregional recurrence of pelvic cavity. 5-year overall survival rate was 83.6%. Conclusions: Simple and extended intersphincteric resection is seemed to be a safe and functionally acceptable procedure. And, neoadjuvant mid-course chemoradiotherapy using oral capecitabine 2,000 mg/m2/day on 21 days during 2 Gy radiation of each 15 weekdays is seemed to be a tolerable and effective modality, in patients with very low rectal cancer.
Outcome analysis of locally advanced adenocarcinoma/adenosquamous carcinoma and squamous cell carcinoma of cervix after definitive radiotherapy.
Authors: Jenny Ling-Yu Chen, Chao-Yuan Huang, Sung Hsin Kuo, Jason C. Cheng
Journal: Journal of Clinical Oncology (2013)

e16503 Background: To compare tumor characteristics, treatment response, failure patterns, and clinical outcome of patients with cervix locally advanced adenocarcinoma (AC)/adenosquamous carcinoma (ASC) and squamous cell carcinoma (SCC). Methods: Medical records for 36 patients with stage IIB–IVA histologically proven cervix AC/ASC and 199 patients with SCC who received definitive radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) between 1995 and 2009 were retrospectively reviewed. The clinicopathologic features, radiation dose, treatment response, recurrent pattern, metastases pattern, and survival outcome between histologic groups were evaluated. Results: Compared with the SCC subgroup of patients, patients with AC/ASC were significantly younger (mean age, 56 vs. 62 years, p=0.007), more of them without clinical symptoms were diagnosed by abnormal Papanicolaou smear findings (16.7% vs. 5.5%, p = 0.019), and less responded to treatment (complete response, 72.2% vs. 86.9%, p = 0.024). After a median follow-up of 59.3 months, patients with AC/ASC had worse 5-year recurrence-free survival (RFS) (33.7% vs. 58.7%, p = 0.046), worse 5-year distant metastasis-free survival (40.2% vs. 70.3%, p = 0.002), and trends toward worse 5-year local recurrence-free survival (62.4% vs. 75.7%, p = 0.127) and worse 5-year overall survival (OS) (40.1% vs. 58.0%, p = 0.062) than those with SCC. In univariate analysis, early FIGO stage and complete treatment response were found to be significantly associated with both RFS and OS. Histology of non-AC/ASC and Point A biologically equivalent doses in 2-Gy fractions &gt;85Gy were significantly associated with better RFS, and CCRT was significantly associated with better OS. In multivariate analysis, complete treatment response remained significant factor for predicting better RFS, and early FIGO stage, CCRT and complete treatment response remained significant factors for predicting better OS. Conclusions: Cervix AC/ASC may behave more aggressively than does SCC. For this subgroup of cervical cancer, more comprehensively effective treatment is warranted.
Association of telomere length with clinical outcomes in patients with colorectal carcinoma.
Authors: Mahadi Ali Baig, Titto A Augustine, Amartej Merla, Gil Atzmon, Temuri Budagov, Sanjay Goel, Radhashree Maitra
Journal: Journal of Clinical Oncology (2013)

e14540 Background: Telomeres (T) consist of thousands of copies of TTAGGG tandem repeats capping the ends of the chromosome. T along with enzyme telomerase provides protection against any threats to the genome that might arise as a consequence of “end replication problem”. Studies have linked short TL with premalignant and malignant stages of CRC carcinogenesis. However, the relation of TL to the clinical outcomes has not been conclusively determined. In this study we evaluated the association of TL with clinical outcomes in a cohort of 75 CRC patients. Methods: Tumor DNA was isolated from formalin fixed paraffin embedded specimens. TL was measured by using a qRT-PCR method that provided the relative T copy number, compared to reference copy number of the housekeeping gene, β-Globin, which resulted in a T/S ratio. One T/S ratio unit is equivalent to a mean TL of 4,270 base pairs (BP). Results: From 75 patients, 118 tissue samples were identified (66 primary, 52 metastases, 29 matched pairs). Age at diagnosis (&gt;/&lt; median) had a statistically significant difference in TL (mean BP 4700 vs. 4374; p=0.05) with shorter TL in the advanced age. Females had longer TL compared to men (mean BP 4722 vs. 3669 respectively; p=0.04). Stage at diagnosis (localized Vs Metastatic) had a statistically significant difference in TL (mean BP 4047 vs. 5704; p=0.03). Shorter TL was associated with shorter progression free survival (PFS) for patients treated with cetuximab/panitumumab (3963 vs 5295 p=0.022). Patients treated with cetuximab/panitumumab who had Shorter TL were also found to have significantly decreased Overall Survival (OS) (101.1 Months vs 153.02 Months p&lt;0.0001). We failed to find a difference in the TL between primary and metastatic sites in the 29 patients with paired samples. There was no difference of TL seen with size of the tumor. Furthermore there was no difference in TL between various metastatic sites. Conclusions: TL is a potential biomarker predictive of clinical outcome (OS &amp; PFS) for patients treated with cetuximab/panitumumab. Tumor TL reduces with advancing age and appears to be sex dependent. Further studies to validate TL’s predictive role in patient outcomes are underway.
Bevacizumab plus temsirolimus as second-line treatment for advanced hepatocellular carcinoma (HCC).
Authors: Leonidas Chelis, Savas Deftereos, Nikolaos Xenidis, Kiriakos Amarantidis, Eleni Kyrillos Hamalidou, Prokopios Dimopoulos, Prodromos Michailidis, Evagelos Christakidis, Kostantinos Mimidis, Dimitra Pitsiava, Anastasios Karayiannakis, Stylianos Kakolyris
Journal: Journal of Clinical Oncology (2012)

e14567 Background: The mTOR pathway has a central role in HCC not only in the tumor growth but also in the insulin driven hepatocarcinogenesis and is reported activated in 40-50% of HCC patients. Temsirolimus is an mTOR inhibitor with proven efficacy in renal cell carcinoma. The angiogenesis inhibitor bevacizumab has shown promising activity in HCC. Sorafenib represents the only drug with proven efficacy in HCC but currently there is no standard 2nd line treatment for patients who progress on sorafenib. Therefore, we performed a phase II study to determine the activity of a bevacizumab plus temsirolimus combination in second-line HCC. Methods: Patients who had progressed on sorafenib were eligible. Other eligibility criteria included ECOG PS 0-2 and Child- Pugh score A. The combination consisted of bevacizumab 10 mg/Kg plus temsirolimus 25 mg (total dose) given i.v. biweekly. After the enrolment of the 1/3 of the preplanned 40 patients (n=13) an interim analysis had to be performed to evaluate biologic activity. Biologic activity was defined either as a partial response by RECIST criteria or a &gt; 50% decline in AFP in at least 2 of 13 patients. An expanded panel of possible biomarkers of response including VEGF, HGF, FGFb, TSP-1 and others, were measured at baseline. Results: The median age of the first 13 patients was 67 years (53-79 years) . The patients performace status was 0 (n=3), 1 (n=4) and 2 (n=6) and 11 of 13 patients had extrahepatic disease. Four patients had radiographic partial responses and five patients had &gt; 50% reduction in AFP. Seven patients (53,8%) showed bioactivity. It is of note that two of them experiencing durable and long lasting partial remissions of 20 and 16 months respectively are still on treatment. One patient developed reversible posterior leycoencephalopathy syndrome (Grade 4 ) and one grade 4 hypertension. Grade 3 non-hematologic toxicities included hyperglycemia (n=3), hyperlipidemia (n=2), diarrhea (n=2) and infection (n=2). Conclusions: The combination of bevacizumab plus temsirolimus is well tolerated with encouraging activity. The study's preplanned criteria for activity have been met and the study continues accrual.
Dynamic FET PET Imaging of a “Butterfly” IDH-Wildtype Anaplastic Astrocytoma
Authors: Norbert Galldiks, Anna Brunn, Gereon R. Fink, Karl-Josef Langen
Journal: Clinical Nuclear Medicine (2019)

A variety of neoplastic and nonneoplastic conditions involve the corpus callosum, which may result in a "butterfly" appearance on conventional MRI. Typically, that pattern shows a bilateral and heterogeneous contrast enhancement of the lesion, occasionally with central nonenhancing areas indicating intralesional necrosis. In contrast, anaplastic gliomas may show only minimal or even a lack of contrast enhancement on MRI. We here report neuroimaging findings in a 69-year-old man with a "butterfly" pattern on dynamic FET [O-(2-[F]-fluoroethyl)-L-tyrosine] PET and the diagnosis of an anaplastic astrocytoma (WHO grade III; IDH-1/-2 wildtype, no 1p/19q co-deletion) but without typical MRI contrast enhancement.