tbuckley/cabot-search huggingface dataset:
Finding common ground: Aligning institutional and survivorship steering committee (SSC) goals.
Authors: Andrew Joseph Ward, John Bell, Lindsey Jerkins
Journal: Journal of Clinical Oncology (2017)

80 Background: Developing a Survivorship program goes beyond providing survivorship care plans to patients upon completion of cancer treatment. Programs can take many forms; ranging from very robust with long-term follow-up to minimal, with patients returning to the primary care provider when cancer-specific treatment is complete. To develop our program at an academic medical center with 2900 annual new cancer patients, we chose to enlist a SSC of survivors to help shape our program. Methods: In addition to fulfilling the American College of Surgeons Commission on Cancer Standard 3.3 requirements, we also desire to meet the needs of the patient. Thus, the survivorship program coordinator requested that providers within the Cancer Institute (CI) identify patients to form a SSC. 13 physicians contributed a total of 14 patients as candidates. Each patient was invited to participate and 7 accepted. The initial SSC meeting was held 6 months after initiation of our survivorship program. Results: SSC members represented 5 different primary malignancies and had varying degrees of experience within the treatment continuum. The initial meeting began with an overview of the current services available in the CI. Members were also given the opportunity to share treatment &amp; survivorship experiences. Some of the SSC members utilized patient navigation during CI initial intake; others had experience with CI support groups. Some used ancillary services such as physical therapy, integrative health, financial counselors, and social services; others were not aware these services were available. A list of 4 categories of goals for program development was suggested with a meeting planned again in one year to review progress. Meeting one year later, the group determined progress was made in 3/4 (75%) of the goals. Conclusions: When creating a Survivorship program, patient goals should be considered and aligned with institutional and accreditation goals. One way to ensure that this is accomplished is to enlist front-end input from a SSC that represents a wide variety of treatment experiences and providers. In our experience, this strategy leads to alignment of patient and programmatic goals resulting in increased patient satisfaction and program quality.
Use of inflammatory markers to triage cancer patients requiring nutritional assessment and interventions.
Authors: Stephen John Clarke, Cindy Tan
Journal: Journal of Clinical Oncology (2013)

e17541 Background: Nutritional status impacts on the outcomes of cancer treatment ( http://www.cancer.gov/cancertopics/pdq/supportivecare/nutrition/ HealthProfessional ). Nutrition is a concern of cancer patients. Many centres lack the resources to undertake formal nutritional assessments on cancer patients. Inflammatory markers have been shown to correlate with nutritional status and cancer treatment outcomes. The NLR is the ratio of the neutrophil and lymphocyte counts in a full blood count (FBC). Our aim was to determine if the NLR can be used to identify cancer patients needing nutritional assessment and intervention. Methods: A prospective observational study evaluated sequential new patients attending a cancer centre. All were assessed for nutritional status using the patient generated scored global assessment (PGSGA) tool and categorized as A (well nourished), or B/C (malnourished). A FBC was done in the week prior to treatment. Receiver operation characteristic (ROC) curves were used to determine optimal cut-points for NLR to predict malnutrition. Results: 234 patients were enrolled - 112 had advanced cancer. The median age was 60 years (range 25-83), 108 (46%) were male and 101 (43%) were malnourished at baseline. The mean NLR was higher in malnourished patients (4.1 vs 2.5 – p&lt;0.001), however this was due to differences in advanced cancer patients. The optimal cut point for NLR in all patients to predict malnutrition was 5.0 (4.3 in advanced patients). In advanced patients, an NLR ≥4.3 had a sensitivity and specificity for malnutrition of 42.2% (95% CI 30.1-54.3) and 97.9% (95% CI 88.9-99.9), respectively, producing a positive predictive value of 0.96 (95% CI-0.82-1.00). Thus, NLR while strongly correlated with malnutrition is not sensitive enough alone to be used to identify malnourished cancer patients. However, as &gt;98% of patients with a raised NLR had malnutrition, the NLR could be used to triage patients for nutritional assessment and thereby reduce the workload for clinical dieticians. Conclusions: The NLR is a useful indicator of nutritional status, which when elevated is specific for malnutrition. A low NLR should be reassuring in regard to nutritional status in advanced cancer patients.
Chemotherapy-induced peripheral neuropathy in multiple myeloma patients undergoing maintenance therapy.
Authors: Qiuling Shi, Xin Shelley Wang, James M. Reuben, Evan N. Cohen, Loretta A. Williams, Tito R. Mendoza, Mary L Sailors, Venus M Ilagan, Charles S. Cleeland
Journal: Journal of Clinical Oncology (2013)

9646 Background: After 3-months autologous stem cell transplant (AuSCT), a percentage of multiple myeloma (MM) patients during maintenance therapy continue to experience a complex of symptoms related to peripheral neuropathy. This longitudinal study examined these self-reported neuropathy symptoms and identified circulating inflammatory markers associated with high neuropathy-related symptoms. Methods: MM patients (N=51) rated symptom severity on 0-10 scale via the M. D. Anderson symptom Inventory (MDASI) weekly from 3 to 9 months post AuSCT during maintenance therapy. Patient also rated pain on hand or foot in routine clinic visit. A panel of pro- and anti-inflammatory cytokines, receptors, chemokines was evaluated on serum samples by Luminex. Mixed effect analysis was used to describe the changes on cytokines and symptom outcomes across time. Trajectory analysis identified patients that persistently reported higher or lower symptom severity overtime. Results: During the study period, there was no significant reduction on pain in general or on hand/foot, or change in neuropathic symptoms such as numbness/tingling and muscle weakness. Among a third (33%) of patients who was consistently in high pain (mean 5.5), MIP-1a (p=.001) and MCP-1 (p=.032) showed significant decrease. Approximately 40 % had persistently high numbness/tingling (mean 5.2) across the observation period. Compared to low symptom group patients, this high numbness group had significantly higher IL-6 (p=.019) and TNF-alpha (p=.006). High muscle weakness (mean 3.1) was for 69% of the sample. This group had significantly higher CRP (p=.005) and TNF-alpha (p=.001). Conclusions: This is the first longitudinal study that tracked persistent neuropathy-related symptoms for MM patients post AuSCT. Approximately one third reported painful neuropathy, either from induction therapy or ongoing maintenance therapy. High levels of these neuropathy symptoms were associated with higher levels of specific pro-inflammatory markers. This study provided rationale for examining the effectiveness of anti-inflammation as mechanism driven intervention on peripheral neuropathy in this cohort of MM patients.
Population Genomics of Paramecium Species
Authors: Parul Johri, Sascha Krenek, Georgi K. Marinov, Thomas G. Doak, Thomas U. Berendonk, Michael Lynch
Journal: Molecular Biology and Evolution (2017)

Population-genomic analyses are essential to understanding factors shaping genomic variation and lineage-specific sequence constraints. The dearth of such analyses for unicellular eukaryotes prompted us to assess genomic variation in Paramecium, one of the most well-studied ciliate genera. The Paramecium aurelia complex consists of ∼15 morphologically indistinguishable species that diverged subsequent to two rounds of whole-genome duplications (WGDs, as long as 320 MYA) and possess extremely streamlined genomes. We examine patterns of both nuclear and mitochondrial polymorphism, by sequencing whole genomes of 10–13 worldwide isolates of each of three species belonging to the P. aurelia complex: P. tetraurelia, P. biaurelia, P. sexaurelia, as well as two outgroup species that do not share the WGDs: P. caudatum and P. multimicronucleatum. An apparent absence of global geographic population structure suggests continuous or recent dispersal of Paramecium over long distances. Intergenic regions are highly constrained relative to coding sequences, especially in P. caudatum and P. multimicronucleatum that have shorter intergenic distances. Sequence diversity and divergence are reduced up to ∼100–150 bp both upstream and downstream of genes, suggesting strong constraints imposed by the presence of densely packed regulatory modules. In addition, comparison of sequence variation at non-synonymous and synonymous sites suggests similar recent selective pressures on paralogs within and orthologs across the deeply diverging species. This study presents the first genome-wide population-genomic analysis in ciliates and provides a valuable resource for future studies in evolutionary and functional genetics in Paramecium.
Patient-reported symptom frequency and distress after open and minimally invasive esophagectomy.
Authors: Debora Goldman, Inderpal S. Sarkaria, Nabil P. Rizk, Rachel Grosser, Amanda Ghanie, Valerie W. Rusch, Manjit S. Bains, Jack E. Burkhalter, David Randolph Jones, Camelia S. Sima
Journal: Journal of Clinical Oncology (2015)

e17724 Background: We sought to describe and compare longitudinal treatment-related symptom frequency (Sym-F) and distress (Sym-D) after open esophagectomy (OE) or minimally invasive esophagectomy (MIE). Methods: Sequential patients undergoing OE or MIE for esophageal cancer were enrolled in a prospective, 2-arm, nonrandomized clinical trial. Treatment-related Sym-F and Sym-D were assessed using the 27-item patient self-reported Memorial Symptom Assessment Scale-Short Form (MSAS-SF) at before surgery (BL), at the first postop visit (POV), and at 4, 8, and 12 mo postop. Total Sym-F count (0–27) and total Sym-D score (0–108) were recorded at each time point and compared between and within cohorts across time. Results: Between 2012 and 2014, 138 patients (83 OE, 55 MIE) were enrolled, with no significant differences between groups at BL. For both groups, total Sym-F and Sym-D increased between BL and POV (p≤0.001) but recovered to BL levels within 4 mo for MIE and 8 mo for OE. Compared with the OE group, the MIE group had significantly lower Sym-F and Sym-D at POV, with no differences later (Table). The MIE group had fewer symptoms of reflux (p=0.024) and lack of appetite (p=0.033) at POV and decreased fullness at 8 mo (p=0.007). Internal consistency of MSAS was 0.80-0.91 (standardized Cronbach’s Alpha) for each of the 5 time points. Conclusions: Patient self-reported global symptom frequency and distress are improved in the short-term with MIE, compared with OE, with improvements persisting to 8 mo after surgery. Clinical trial information: NCT01558648.Symptom frequency and distress score following OE or MIE. OE MIE P N Median (IQR) N Median (IQR) Symptoms reported (range, 0–27) BL 83 5.0 (1.0-10.0) 55 4.0 (2.0-8.0) 0.76 Postop 78 10.0 (7.0-13.0) 53 8.0 (4.0-10.0) 0.004 4 mo 62 7.5 (4.0-12.0) 45 4.0 (2.0-11.0) 0.60 8 mo 40 6.5 (3.0-11.5) 29 5.0 (3.0-7.0) 0.072 12 mo 27 7 (2.0-13.0) 23 3.0 (2.0-9.0) 0.16 Total distress score (range, 0–108) BL 70 6.4 (3.2-12.0) 46 4.8 (3.2-10.4) 0.40 Postop 77 13.6 (8.0-21.6) 52 9.6 (5.6-16.0) 0.005 4 mo 60 10.4 (5.2-16.8) 37 8.8 (4.0-13.6) 0.44 8 mo 37 10.4 (3.2-15.2) 25 6.4 (4.0-8.8) 0.063 12 mo 30 8 (3.2-13.6) 24 4.8 (1.6-12.8) 0.293
High-volume esophageal endoscopic submucosal dissection centers: a cut above the rest?
Authors: Vinay Chandrasekhara
Journal: Endoscopy (2017)

Endoscopic submucosal dissection (ESD) was first developed in Asia for en bloc resection of early gastric cancer [1]. The procedure was slow to disseminate for various reasons, including lack of training and expertise, higher risk of adverse events, and smaller percentage of patients with early gastric cancer who would be suitable candidates for ESD in Western populations [2]. As endoscopists became more comfortable with the procedure and devices, ESD started to be used for en bloc resection of superficial lesions throughout the colon and esophagus. The esophagus is an interesting frontier for ESD because there is a much larger Western population with early neoplastic lesions, and endoscopists are more accustomed to the idea of wide-area endoscopic resection and intramural endoscopy within the esophagus.
Shorter or standard chemoradiotherapy in elderly glioblastomamultiforme (GBM) patients.
Authors: Sonia Brugnara, Lucianna Russo, Dante Amelio, Michele Nagliati, Diego Trevisan, Francesca Maines, Chiara Trentin, Maurizio Amichetti, Franco Chioffi, Enzo Galligioni
Journal: Journal of Clinical Oncology (2014)

e13003 Background: The optimal treatment in elderly GBM patients is still debated. Previous studies with shorter RT course (40Gy/15F.) have shown no statistically significant difference in OS compared to standard treatment (60Gy/30F). Nowadays the role of combined RT and Temozolomide (TMZ) is being investigated in a large ongoing study (NCIC-CTG CE.6/EORTC 26062). Methods: In this study we retrospectively evaluated the outcome of elderly (> 65 years) glioblastoma patients consecutively treated in our Center between 2005 and 2012 with RT (40 Gy/15 F.) plus concomitant and adjuvant TMZ (“short Stupp”) Group 1, or with RT ( 60 Gy/30 F) plus concomitant and adjuvant TMZ (Classical Stupp’s Protocol) Group 2. Median age of the 18 pts was 71y (range 65-78), with KPS >50% in 14/18 (77.7%) and < 50% in 3/18 (16%), (1 not recorded). Nine pts were males and 9 females. Eight out of 18 pts (44%) had received radical surgery, 6 (33%) subtotal, and for 4 (22%) only biopsy. All patients were treated with post-operative radiotherapy: 60Gy/30 F in 9 pts (50%) and 40Gy/15 F in the remaining 9 (50%). TMZ was added concomitantly to RT for 5 weeks in Group 2 (60Gy /30) and for 3 weeks in Group 1 (40 Gy/15). TMZ was continued for al least 6 months after RT in non progressing pts. Results: In Group 1 adjuvant TMZ was administered in 3 out of 9 pts only (33%), median 3 cycles, range 1-5. Severe haematological toxicity was observed after concomitant treatment in 2 patients (Plts G4, Neutroph. G4), whereas 1 pt presented a tromboembolic event (G4), impaired liver enzymes in 1 patient (Hep G2). Neurological toxicity G2, due to RT, occurred in 2 patients and skin toxicity only in 1 pt. In Group 2 adjuvant TMZ was administred in 7/9 pts (77%), median cycles were 6 (range 0-24); haematological toxicity was mild (Plts G4 in 1 and G1 in 3 pts, Neutroph G2 in 1 pt) , whereas neurological toxicity (G1)after RT was higher, occurring in 6/9 pts (66%). Median PFS was 4, 8 (mos) in Group 1, and 10.2 (mos) in Group 2, while median OS was 11 and 13.5 mos respectively, 1 patient is still alive. Conclusions: Waiting for the results of the large randomised study, we found that both treatments are feasible in clinical practice in elderly GMB patients, with manageable toxicity.
MAGNIFY: A randomized, phase 3b trial in patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) investigating lenalidomide plus rituximab (R<sup>2</sup>) induction followed by maintenance R<sup>2</sup> followed by lenalidomide versus R<sup>2</sup> induction followed by rituximab (R) maintenance.
Authors: David Jacob Andorsky, Paula J. Franson, Jorge L Mouro, Jiahui Li, Kenneth A. Foon, Jeff Porter Sharman
Journal: Journal of Clinical Oncology (2015)

TPS8606 Background: Combination of the immunomodulatory agent lenalidomide (Revlimid) with rituximab (R2) is a promising therapeutic option for patients with R/R NHL. As frontline therapy, R2 provided a 90% overall response rate (ORR) in patients with follicular lymphoma (FL), marginal zone lymphoma (MZL) and small lymphocytic lymphoma (Fowler, Lancet Oncol, 2014) and 89% ORR in MCL patients (Ruan, ASH, 2014). In phase 2 trials of R2, patients with R/R MZL, FL, and MCL achieved ORRs of 80% (55% complete response [CR]), 73% (36% CR), and 57% (36% CR), respectively (Raderer, EHA, 2014; Leonard, ASCO, 2012; Wang, Lancet Oncol, 2012). These trials support further investigation of R2 therapy in R/R NHL. Methods: The efficacy and safety of 12 cycles of combination R2 for induction with randomization to R2 (Arm A) vs R (Arm B) maintenance will be compared in R/R FL, MCL, or MZL patients as part of the phase 3b MAGNIFY trial. Approximately 500 patients will be randomized 1:1 to 28-day (d) treatment cycles (C). Both patient groups will receive R2 induction with lenalidomide (20 mg/d on d 1-21; 12 C) + R (375 mg/m2 on d 1, 8, 15, 22 in C1; d1 of C 3, 5, 7, 9, 11). Patients in Arm A will receive R2 maintenance with lenalidomide (10 mg/d on d 1-21; C 13-30) + R (375 mg/m2 on d1 of every other C from 13 to 29), followed by lenalidomide (10 mg/d on d 1-21) until progression. Following 12 cycles of induction with R2, patients in Arm B will receive maintenance R (375 mg/m2 on d1 of every other C from 13 to 29). Eligibility criteria include R/R FL grades 1-3b, transformed FL, MZL, or MCL; previous systemic therapy; ≥ 1 measurable lesion; and adequate bone marrow, liver, and renal function. Progression-free survival is the primary endpoint. Secondary endpoints include rate of CR/CR unconfirmed (CRu), overall survival, ORR, duration of response, duration of CR/CRu, and safety. An exploratory endpoint, health-related quality of life will be measured using the FACT-Lym questionnaire. The MAGNIFY trial is currently enrolling; 38 patients have been enrolled as of January 30, 2015 (NCT01996865). Clinical trial information: NCT01996865.
Dynamic sentinel lymph node biopsy in patients with invasive squamous cell carcinoma of the penis: A prospective study of the outcome of 500 inguinal basins assessed in a single institution.
Authors: Wayne Lam, Hussain M Alnajjar, Susannah La-Touche, Matthew Perry, Catherine M Corbishley, James Pilcher, Sue Heenan, Nicholas Watkin
Journal: Journal of Clinical Oncology (2012)

4640 Background: Dynamic sentinel node biopsy (DSNB) in combination with ultrasound scan (USS) has been the technique of choice at our centre since 2004 for the assessment of non palpable inguinal lymph nodes in patients with squamous cell carcinoma of the penis (SCCp). Sensitivity/false-negative rates may vary depending on whether results are reported per patient or per node basin and with and without USS. The purpose of this study was to determine the long-term outcome of DSNB and ultrasound-guided fine needle aspiration cytology (FNAC) in our cohort of newly diagnosed patients and to analyse any variation in sensitivity of the procedure. Methods: A prospective cohort study over 6 years (2004 to 2010). Inclusion criteria: New diagnosis SCCp, T1G2 or greater definitive histology, non-palpable nodes in inguinal basin. Exclusion: patient with persistent/untreated local disease. Sensitivity of the procedure was calculated, per node basin, per patient, DSNB alone, USS/DSNB combined. Minimum follow up 12 months. Results: 500 inguinal basins in 264 patients underwent USS+/-FNAC and DSNB. 70 (14%) positive inguinal basins in 57(22%) patients were identified. 9 (2%) inguinal basins had no tracer uptake. 2 inguinal basins were confirmed false negative at 8 and 12 months. 2 inguinal basins had positive USS+FNAC and negative DSNB. Overall sensitivity of the technique is reported in the table. Conclusions: DSNB in combination with USS has excellent performance characteristics to stage patients with clinically node-negative penile cancer with a 3% false negative rate. USS improves performance by 4% over DSNB alone. There is no difference in performance of the combined technique if it is reported per node basin or per patient. [Table: see text]
Phase II study of rituximab plus high-dose ara-C (HDAC)-containing chemotherapy (CTX) followed by ASCT in untreated mantle cell lymphoma (MCL): Japan Clinical Oncology Group study (JCOG0406).
Authors: Michinori Ogura, Kensei Tobinai, Taro Shibata, Kiyoshi Ando, Mitsutoshi Kurosawa, Hiroshi Gomyo, Naokuni Uike, Norifumi Tsukamoto, Noriko Fukuhara, Tatsu Shimoyama, Masafumi Taniwaki, Kisato Nosaka, Yoshihiro Matsuno, Tomomitsu Hotta, Kunihiro Tsukasaki, Yasuo Morishima, Kazuhito Yamamoto
Journal: Journal of Clinical Oncology (2015)

8565 Background: Although HDAC-containing CTX with rituximab (R) followed by high-dose CTX (HDC) with autologous stem cell transplantation (ASCT) has been recommended in younger untreated MCL patients (pts), no standard regimen has been established. Methods: Eligibility criteria included untreated MCL; stage II bulky, III or IV; and aged 20 to 65. In R-High-CHOP, doses of CPA and DXR were 1,500 and 75 mg/m2, respectively. Pts received 1 cycle of R-High–CHOP followed by 3 cycles of CHASER {CPA 1,200 mg/m2 on day (d)3, Ara-C 2 g/m2 on d4-5, ETP 100 mg/m2 on d3-5, R on d1 and d15} every 3 weeks. Peripheral blood stem cells (PBSCs) with > = 2 x 106 cells/kg were harvested during CHASER. ASCT was performed to pts in CR or PR after R-High-CHOP/CHASER. HDC of LEED consisted of L-PAM 130 mg/m2 on d1, CPA 60 mg/kg on d-4 to d-3, ETP 500 mg/m2on d-4 to d-2. The primary endpoint was 2 yr-PFS. The planned sample size was 45 pts, which provided at least 90% power with the expected 2 yr-PFS of 50%, threshold of 30%, and a one-sided α of 10%. Results: From June 2008 to June 2012, 45 pts with a median age of 59 (38-65) yrs were enrolled. The numbers of pts with low-, intermediate- and high-risk group by the simplified MCL International Prognostic Index (MIPI) was 28, 15 and 2. 40 and 35 pts completed induction CTX and HDC. A median number of harvested PBSCs was 3.8 (0.4 to 38.4) x 106/kg in treated 43 pts. Among 36 pts with successfully harvested PBSCs, 35 pts completed HDC. At a median follow-up period of 46 (1-71) months among censored pts, 2-yr PFS was 77% (95% CI; 62-87), which met the primary endpoint. 5-yr PFS was 52% (95% CI; 34-68) and 5-yr OS was 71% (95% CI; 51-84). Overall response rate and %CR after induction CTX were 96% and 82%. Most common G4 toxicities were hematologic: %G4 neutropenia and thrombocytopenia were 80% and 0% in R-High-CHOP, 91% and 89% in CHASER, and 94% and 77% in LEED. 4 pts developed secondary malignancies; AML, prostate cancer, DLBCL, and ATL. Conclusions: In younger pts with untreated MCL, R-High-CHOP/CHASER/LEED with ASCT demonstrated high efficacy with durable PFS and OS and acceptable toxicity profiles, and is considered to be a standard treatment option. Clinical trial information: 000001220.