tbuckley/cabot-search huggingface dataset:
Prognostic value of sentinel lymph node involvement in patients with breast cancer
Authors: M. Tobeña, M. Ruiz-Echarri, M. Ortega, E. Prats, E. Millastre, A. Ferrer, P. Razola, J. I. Mayordomo, A. Tres, J. Banzo
Journal: Journal of Clinical Oncology (2008)

22213 Background: Sentinel lymph node is a minimally invasive and accurate staging procedure for patients with invasive breast cancer. Histological SLN involvement with cancer cells requires regional lymph node dissection. Aim: To verify if subgroups of patients with sentinel lymph node involvement in which the risk of histological involvement of additional regional lymph nodes is minimal can be identified and to assess the prognostic value of SLN involvement. Methods: Ninety six consecutive patients with invasive breast cancer and tumour size less than two centimeters by mammography, had lymphoscintigraphy with colloidal 99Tc and radioisotope-guided sentinel lymph node biopsy in the University Hospital of Zaragoza from 1999 to 2005. Pathological assessment included serial sections of the sentinel lymph node with inmunohistochemistry for cytokeratins in selected cases. 39 patients had histological involvement. Results: All patients were females. Median tumour size was 20 mm (range 5–52). Median number of resected sentinel lymph nodes was 2 (range 1–5). With median follow-up of 61 months, 8 relapses have occured (0 in axilla, 2 local relapses, 6 distant metastases). Five relapses occured in 39 patients with SLN involvement (12%) versus 3 in 81 patients without SLN involvement (3%) (p < 0.05). Conclusions: SLN involvement is a significant prognostic factor for relapse in patients with breast cancer and primary tumor size less than two centimeters. No significant financial relationships to disclose.
Significance of neuroendocrine component in mixed adenoneuroendocrine neoplasms.
Authors: Ming-Huang Chen, Ying-Ju Kuo, Yi-Chen Yeh, Pin-I Huang, Chung-Pin Li, Yee Chao
Journal: Journal of Clinical Oncology (2012)

45 Background: Mixed adenoneuroendocrine carcinoma (MANEC) and adenocarcinoma with neuroendocrine differentiation (ADC-NE) are tumors with divergent exocrine and neuroendocrine differentiation. These tumors display variable quantitative extent of the two components. Some studies reported the extent of two components in primary tumor and lymph node are not always the same. The aim of our study is to analyze the neuroendocrine component in primary tumor, angiolymphatic invasion and metastatic lymph nodes. Methods: Tumor histology of 15 patients with MANEC or ADC-NE was evaluated in this study. Neuroendocrine component was confirmed by morphology and immunohistochemistry for synaptophysin and chromogranin A. The extent of neuroendocrine components in primary tumor, angiolymphatic invasion and lymph node were reviewed by two independent pathologists. Results: Fifteen patients with MANEC and ADC-NE tumors were evaluated. Of these, pure neuroendocrine component in angiolymphatic invasion was observed in 9; pure adenocarcinoma component was seen in 4; and both components were seen in 2. The components in lymph node metastases were consistent to angiolymphatic invasion (Table), suggesting the tumor component in angiolymphatic invasion may predict pathology in lymph node metastasis. In high neuroendocrine component group (&gt;50% in primary tumor), 83.3% revealed pure neuroendocrine component in lymph node and 88.9% had angiolymphatic invasion. The pure neuroendocrine component in lymph node and angiolymphatic invasion was higher in high neuroendocrine component group compared to the low neuroendocrine component group, (p=0.012 and p=0.01, respectively). Conclusions: The components of tumor involved in angiolymphatic invasion is consistent with that in lymph node metastasis. High neuroendocrine component predicts the rate percentage of pure neuroendocrine component in lymph node or angiolymphatic invasion. [Table: see text]
Retrospective analysis of first-line chemotherapy in 132 patients with advanced small-bowel adenocarcinoma.
Authors: T. Tsushima, N. Boku, Y. Honma, H. Takahashi, S. Ueda, T. Nishina, H. Kawai, S. Kato, M. Suenaga, F. Tamura
Journal: Journal of Clinical Oncology (2011)

260 Background: No standard care has been established for advanced small-bowel adenocarcinoma (SBA). The aim of this study is to explore a most promising chemotherapy regimen for advanced SBA. Methods: All data were collected from medical records of patients with advanced or recurrent SBA who received chemotherapy between April 1999 and March 2009 at 41 hospitals in Japan. Selection criteria were as follows: 1) histologically proven SBA, excluding ampullary carcinoma, 2) no previous chemotherapy or radiotherapy, 3) ECOG PS 0-2, 4) adequate bone marrow, hepatic and renal functions, 5) no concomitant malignancy. Patients were divided into the five groups by regimens: group A, fluoropyrimidine alone; group B, fluoropyrimidine + cisplatin; group C, fluoropyrimidine + oxaliplatin; group D, fluoropyrimidine + irinotecan; group E, others. Progression-free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier method. Results: Demographics of selected 132 patients were: median age (range), 59 (23-78) years; male/female, 87/45; location of primary tumor, duodenum/jejunum/ileum/unknown, 80/32/17/3; advanced/recurrent disease, 91/41. The numbers of the patients in group A, B, C, D and E were 60, 17, 22, 11 and 22, and objective response rates (ORR) in the patients with target lesions were 20% (9/46), 38% (5/13), 42% (8/19), 25% (2/8), 21% (4/19), respectively. Median PFS and OS were 6.0 and 14.0 months for the whole population, and those in each group are shown in the Table.In comparison with fluoropyrimidine alone (A), oxaliplatin-combined regimens (C) associated with better PFS (HR=0.53 [0.31-0.93], p=0.03) and OS (HR=0.64 [0.33-1.25], p=0.19), while cisplatin-combined regimens (B) did not (HR=1.54 [0.88-2.68], p=0.13 for PFS and HR=1.67 [0.94-2.97], p=0.08 for OS) by univariate analysis. Conclusions: It is suggested that oxaliplatin-combined regimens might be the most promising regimen for advanced SBA. [Table: see text] No significant financial relationships to disclose.
A NSQIP comparison of modern multicenter results for transhiatial versus transthoracic esophagectomy.
Authors: Wesley A. Papenfuss, Moshim Kukar, Steven N. Hochwald, Venkata R. Kakarla, Steven J. Nurkin
Journal: Journal of Clinical Oncology (2013)

68 Background: The surgical approach to esophageal cancer continues to be controversial. A transthoracic approach is often advocated for better oncologic staging and improved survival. A transhiatal approach is often preferred due to a perceived decreased operative morbidity and mortality. Methods: Using the American College of Surgeons-National Surgical Quality Improvement Project (ACS-NSQIP) participant-use file, patients were identified who underwent esophagectomy for cancer at the 240 participating hospitals from 2005-2011. Demographic, clinical, intra-operative variables and 30-day morbidity and mortality were collected. Results: Of the 1108 patients that had esophagectomy, 649 (58.5%) had a transhiatal (TH) resection and 459 (41.4%) had a transthoracic (TT) resection. There were no significant differences in age, gender, comorbid conditions, preoperative chemotherapy or radiation, or ASA class. Operative time was greater in the TT group (360.4 vs. 298.4min, p=0.0001). Thirty day overall mortality (TH=3.4%, TT=4.5%, p=0.3) and mean hospital length of stay(TH=15.25, TT=16.76, p=0.08) were not significantly different. The TH group had a significantly higher superficial wound infection rate (13% vs. 7.4%, p=0.002). The TT group had significantly higher rate of perioperative transfusion (9% vs. 5.1%, p=0.023) and septic shock (12.2% vs. 7.1%, p=0.004). On multivariate analysis, history of congestive heart failure and pneumonia were significant predictors of 30 day mortality. Diabetes, metabolic syndrome and COPD were predictors of morbidity. There were no differences in the rates of pneumonia, need for reintubation, ventilator requirements, or need for reoperation in both groups. Conclusions: In this modern series of patients, utilizing standardized national data collection tools, there was no significant difference in mortality of esophagectomy between transthoracic and transhiatal approaches. However, morbidity rates do vary with an increased rate of substantial morbidity in the transthoracic group including septic shock.
Frequency, Distribution and Prognostic Value of ABL Kinase Domain (KD) Mutations in Different Subsets of Philadelphia-Positive (Ph+) Patients (Pts) Resistant to Imatinib (IM) by the Gimema Working Party on CML.
Authors: Simona Soverini, Sabrina Colarossi, Alessandra Gnani, Gianantonio Rosti, Fausto Castagnetti, Angela Poerio, Ilaria Iacobucci, Marilina Amabile, Panagiota Giannoulia, Elisabetta Abruzzese, Ester Orlandi, Franca Radaelli, Fabrizio Ciccone, Mario Tiribelli, Clementina Caracciolo, Fabrizio Pane, Giuseppe Saglio, Michele Baccarani, Giovanni Martinelli
Journal: Blood (2005)
Characterization of rectal cancer in patients with Lynch syndrome.
Authors: Zsofia Kinga Stadler, Jinru Shia, Karyn A. Goodman, Andrea Cercek, Neil Howard Segal, Diane Lauren Reidy, Rona D. Yaeger, Garrett Michael Nash, Larissa K. F. Temple, Nancy E. Kemeny, Martin R. Weiser, David Paul Kelsen, Arnold Markowitz, Mark E. Robson, Kenneth Offit, Philip Paty, Jose G. Guillem, Leonard Saltz
Journal: Journal of Clinical Oncology (2013)

350 Background: Lynch syndrome (LS), resulting from a germline mutation in a DNA mismatch repair (MMR) gene, is associated with ~70% lifetime colorectal cancer (CRC) risk. Although LS-associated colon cancer is associated with both favorable prognosis and lack of efficacy to 5-fluorouracil, clinical features of LS-associated rectal cancer (RC) have not been characterized. Methods: Clinical genetics database review (1998–2012) identified all probands with CRC and a deleterious germline mutation in a MMR gene (MLH1, MSH2, MSH6, PMS2) diagnostic of LS. Probands without identifiable mutations or variants of unknown significance were excluded. Clinical history and pedigree was extracted from medical records and Progeny. Results: Of 119 LS patients with CRC, 16 (13.4%) had RC. Mean age at RC diagnosis was 40.6 (range, 23-56) with 31% having synchronous (n=3) or metachronous (n=2) colon cancer. All RC patients met Revised Bethesda and 63% met Amsterdam II criteria. As opposed to LS-associated colon cancer, the majority of RC patients harbored MSH2 mutations (36% colon vs 69% RC, p value 0.01). 11 tumors were analyzed for MSI or defective MMR protein expression by IHC; results were abnormal and thereby concordant with germline test results in all cases. Of 14 RC patients with clinical data, 5 proceeded directly to surgery (4 stage 0/I; 1 stage II). Nine patients received pre-op treatment for clinical stage II/III (n=7) or IV (n=2) disease, with all receiving chemoradiation and five also receiving pre-op FOLFOX. Downstaging of primary tumor occurred in 66.6% (6/9) and of lymph nodes in 77.7% (7/9) of cases. All nine patients underwent R0 resections; however, pCR was not observed in any of the cases. Notably, one patient with clinical T3N+ disease (by MRI and EUS) had upfront surgery identifying pT2N0 disease with prominent tumor infiltrating lymphocytes. Of 14 patients, mean follow-up of 4.3 years (range, 0.3-13.5), none had disease recurrence; however, one was diagnosed with a new primary colon cancer. Conclusions: Although less common than colon cancer,RC is an important component of LS and may be overrepresented in MSH2 mutation carriers. Given high risk of synchronous or metachronous cancers, appropriate surveillance for second malignancies is necessary.
A pilot study of a low-intensity health education intervention on activity and quality-of-life measures for cancer survivors.
Authors: Arnab Basu, Sreyasi Bhattacharya, Kenneth David Miller
Journal: Journal of Clinical Oncology (2016)

221 Background: There is an increasing need for effective targeted health education interventions for cancer survivors related to dietary habits, physical activity and cancer related psychosocial challenges. Methods: We designed an educational program for cancer survivors (n=37 ) presenting for outpatient follow up visits. The program was composed of a 30-60 minute survivorship visit and a series of six 7-10 minute video tutorials shown two at a time either remotely or in person every two months over a six month period about the importance of diet, physical activity and psychosocial aspects of cancer survivorship. Baseline assessments of perceived state of health, physical activity, diet, and the Impact of cancer were made through a series of validated questionnaires, including SF-12, IPAQ, FRDHQ and IOC. Patients were then sent another follow-up survey in approximately 1 year to be filled online; those who could not respond were followed up by phone. Weight and height data were registered during 1 year follow-up visit. Results: 37 Patients initially participated in the study, of these, all 37 either replied/were followed up after a 1 year time period. 87% were women and 70% were African American, 25(66%) of patients had a prior diagnosis of breast carcinoma, 4 (11%) had a prior diagnosis of colorectal Carcinoma. 16 (43%), 13(35%) and 7(18%) of patients had &lt;5 , 5-10 and &gt;10 years since last surgery/chemotherapy. We demonstrated that this type of low intensity intervention is feasible in a medically underserved group of cancer survivors. There was a trend towards an improved Physical Composite Score (25.1 vs 43.1) and Mental Composite Score (54.1 vs 58.1) on the SF-12 questionnaire at the time of follow-up, indicating improved health and functional well being. There were no large noticeable differences in fat related dietary habits. Due to a small sample size, stated differences did not reach the threshold of statistical significance. Conclusions: Our pilot study suggests that a low intensity intervention is feasible and may be associated with improvement in health behaviors in cancer survivors. Larger studies are needed to explore the efficacy of this, and similar interventions.
A single-center experience of small-bowel adenocarcinomas.
Authors: N. A. Khan, W. Conway, J. Fuloria
Journal: Journal of Clinical Oncology (2011)

337 Background: The age-adjusted incidence of small-bowel adenocarcinomas was reported as 1.9 per 100,000 per year (SEER 2003-2007). Even early-stage small bowel tumors are associated with a high risk of recurrence. We performed a retrospective chart review to analyze location, stage at presentation, and recurrence rate of early-stage small-bowel adenocarcinomas at our institution. Methods: Institutional (Ochsner Clinic) tumor registry database was used to identify patients with small-bowel adenocarcinoma from 1983 onward. Medical records were reviewed for pertinent patient information. Results: 44 patients (24 males, 20 females) were identified. 25 (56.8%) patients had a duodenal primary, 8 (18.1%) jejunal, 4 (9.0%) ileal, and 7 (15.9%) patients did not have a documented site of origin. Mean age at presentation was 64 yrs (range 31-84 yrs). The most common presenting symptoms were abdominal pain (40%), melena (25%), and small-bowel obstruction (16%). Histological grade II or III accounted for 64% of all tumors. Almost half of the patients (43.2%) presented with stage IV disease, which was associated with a median survival of 11.5 months. All patients staged as I, II, and III had a curative resection including 33% who underwent a Whipple's surgery. Four patients were not seen in follow-up at our institution and 6 patients died in the postoperative period from various complications. No stage I patient received adjuvant chemotherapy. All available stage II and III patients received adjuvant 5-FU based chemotherapy. The chemotherapy received was as follows: Stage II (two 5-FU, two FOLFOX); Stage III (four 5-FU, one capecitabine/irinotecan, one FOLFOX). The recurrence for each stage is shown in the Table. Conclusions: Although our numbers are small, stage I adenocarcinomas of the small bowel had a significant risk of recurrence. This warrants a multi institutional review of patient data to better quantify the risk of recurrence for this rare tumor and the implications for treatment trials. [Table: see text] No significant financial relationships to disclose.
Automated quantitative analysis of AKT/mTOR pathway in patients treated with nanoparticle albumin-bound paclitaxel (ABI-007, Abraxane) and (sirolimus)Rapamycin
Authors: M. M. Abu-Khalaf NULL, C. Moeder NULL, S. Gettinger NULL, D. Rimm NULL, L. Harris NULL
Journal: Journal of Clinical Oncology (2008)

14670 Background: pp70S6K inhibition and pAkt up-regulation has been reported with mTOR inhibitors. We evaluated changes in these targets following rapamycin (R) therapy by Automated Quantitative Analysis (AQUA), a novel technology that uses molecular methods to define subcellular compartments, and then quantifies the amount of protein expressed within the compartment by co-localization, permitting preservation of tissue morphology while quantifying protein expression in paraffin-embedded tissue. Methods: Cohorts of 3–6 patients (pts) with advanced solid tumors were enrolled and treated. Escalating oral dose of R (5–40 mg) was administered on days -7, 2, 9 and 16 and intravenous fixed dose of Abraxane (100 mg/m2)on days -14, 1, 8, and 15 of a 28 day cycle. Tumor tissue was collected by core biopsies from consenting pts for measurement of pre and post day -7 R therapy of p70S6K, pp 70S6K, Akt, pAkt by AQUA. Primary antibodies used to define tumor compartment included mouse monoclonal Cytokeratin AE1/AE3 (M3515, Dako Corporation, Carpinteria, CA) or wide-spectrum screening rabbit anti-cow cytokeratin antibody (Dako Z0622) each at 1:100. Target antibodies were incubated overnight at 4ºC and included Akt ((2H10): cat#2967, mouse mAb, used 1:700), pAkt (736E11-Ser473) used at 1:100), and p706SK (49D7) used at 1:200 and pp70S6K (1A5- Thr389) used at 1:100. Results: To date 16 pts with have been treated in 4 cohorts as follows; Cohort 1 (5/100, n = 3), Cohort 2 (10/100, n = 6), Cohort 3 (20/100, n = 3), Cohort 4 (40/100, n =4). To date, pre and post therapy tissue sample was collectied in 4 patients (1 lung/cohort 1, 1 sarcoma/cohort 1, 1 melanoma/cohort 3, and 1 endometrial/cohort 4). We found a decrease in the pp70S6K and pAkt in post therapy samples from baseline in 4 patients, and a decrease in the p70S6K in 3 of 4 patients. Pre and post therapy Akt analysis is available on 2 of the 4 patients (cohort 3 and 4), and showed an increase from baseline in both. Conclusions: Consistent with prior reports, we found a decrease in the pp70S6K post rapamycin therapy. Although we found an increase in total Akt in the 2 patients, there was a decrease in pAkt in 4 patients. AQUA analysis of molecular targets of AKT/mTOR pathway is feasible. The MTD has not yet been reached and enrollment continues, and additional samples will be collected. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Abraxis Oncology, HistoRx HistoRx Abraxis Oncology Abraxis Oncology
Effect of neoadjuvant dose-painted IMRT to 56 Gy for locally advanced esophageal cancer on outcomes.
Authors: R. Shridhar, M. D. Chuong, S. E. Hoffe, M. Biagioli, K. Almhanna, J. Weber, S. Kucera, S. Vignesh, J. S. Barthel, K. Meredith
Journal: Journal of Clinical Oncology (2011)

144 Background: Standard of care chemoradiation doses of 50.4 Gy for locally advanced (T3, T4, and/or node positive) esophageal cancer is associated with a pathologic complete response (pCR) rate of 40% at our institution. We evaluated whether pCR would be increased with 4D CT planning scans, intensity-modulated radiation therapy (IMRT) delivery with motion management, and dose painting to 56 Gy in 28 fractions. Methods: This retrospective review of 9 patients who have undergone esophagogastrectomy (7 adenocarcinoma, 2 squamous cell) evaluates our initial experience with neoadjuvant dose painted IMRT to 56 Gy. Pre-treatment workup included PET scan, chest and abdomen CT scans, endoscopic ultrasound (EUS), and EUS-guided fiducial marker placement. Fiducial markers were placed superior and inferior to the gross endoscopic tumor volume to facilitate analysis of tumor motion with 4D CT simulation. Internal target volumes (ITVs) of gross disease were generated to account for motion. Once the GITV was generated, a clinical target volume (CTV) encompassing a 3-4 cm superior margin and 3-4 cm distal margin was contoured. Two planning target volumes (PTVs) were created for dose painting: PTV 50.4 and PTV 56 Gy in 28 fractions. IMRT was utilized for all patients with either a weight belt or with compensators. Concurrent cisplatin and continuous infusion 5-FU were delivered with radiotherapy and patients were restaged 3-6 weeks after completion for response evaluation. Results: Treatment was well tolerated without any grade 3 acute morbidity. Surgical complications were not increased in this group overall. However, there was 1 patient with a chyle leak and radiation pneumonitis, but her case was complicated by having a remote history of radiotherapy. Six of the 9 treated patients were found to have a pCR (4 adenocarcinoma, 2 squamous cell). Two had a near CR with &lt; 5 mm of residual disease. One additional patient with an initial bulky T4N1 tumor had 9 mm of viable tumor. Conclusions: With motion management, dose painted IMRT to 56 Gy is feasible and may be associated with improved rates of pathologic complete or near complete response. No significant financial relationships to disclose.
The effect of prostate brachytherapy technique on quality of life outcomes: 5-year outcomes of a prospective cohort study.
Authors: James Austin Talcott, Jack A. Clark, Judith Manola, Irving D. Kaplan, Anthony L. Zietman, Anthony Victor D'Amico
Journal: Journal of Clinical Oncology (2014)

166 Background: Brachytherapy (BT) is widely used to treat clinically localized prostate cancer, but techniques vary and may affect patient outcomes. Methods: We prospectively studied three Boston-area patient cohorts who received different BT techniques: MRI guided, target volume avoids transition zone (MRBT) and two cohorts using standard imaging and planning techniques (USBT 1 and USBT 2 ). We surveyed patients pretreatment and at intervals after, using the validated PCSI scales for urinary incontinence (incont), obstruction/irritation (obstir) bowel problems, sexual dysfunction and the effect of incont on their lives (incontQOL). Based on early results showing increased acute urinary toxicity, USBT 2 providers adopted an element of USBT 1 technique. We report final 5-year follow-up. Results: Of 286 eligible patients, 73 MRBT patients and 190 USBT patients (99 USBT 1 and 91 USBT 2 patients) completed at least 3-month surveys. Patient differed by age (median: MRBT 65.3 years vs. USBT 68.3 p=0.005, USBT 2 65.3 vs. USBT 1 68.3 p=0.004) and education (MRBT 8%≤high school vs. USBT 23%, p&lt;0.001) but other demographic and clinical variables were similar. MRBT patients had more pretreatment obstir symptoms and better sexual function pretreatment. USBT 2 patients had greater increases in acute (3-month) obstir (28.8 vs. 20.0, p=0.01) and incont (12.2 vs. 7.1, p=0.01) than USBT 1 but not bowel or sexual dysfunction, and all outcomes were similar at 5 years. Changing USBT 2 technique eliminated the acute urinary differences. Compared to MRBT, USBT patients had greater increases in acute urinary morbidity (obstir 28.8 vs. 20.0, p=0.01; incont 9.6 vs. 2.2, p=0.002; incontQOL 10.2 vs. 2.4, p=0.0002) and long-term incontinence (incont 7.5 vs. 3.3, p=0.05; incontQOL 5.6 vs. 1.2, p=0.01). Other outcomes did not differ. Conclusions: QOL outcomes vary by BT technique. Measuring QOL may provide useful information for patients choosing treatment and providers assessing their technique. Clinical trial information: NCT00681694.