tbuckley/cabot-search huggingface dataset:
Survival and toxicity with intensity modulated radiation therapy (IMRT) and chemotherapy for esophageal carcinoma, with or without surgery.
Authors: Kristin Kowalchik, Elizabeth Johnson, George P. Kim, C. Daniel Smith, Siyong Kim, Nitesh N. Paryani, Stephen Ko
Journal: Journal of Clinical Oncology (2013)

125 Background: Treatment for locally advanced esophageal carcinoma is radiation and chemotherapy, with or without surgery. Radiation has traditionally been delivered with 3D conformal radiation therapy (3D CRT). This study evaluates late toxicity in patients treated with IMRT as well as early outcomes and acute toxicity. Methods: This is a retrospective review of 32 patients with esophageal carcinoma treated with IMRT at Mayo Clinic Florida from 2008 -2012. Pathology includes squamous cell and adenocarcinomas. Tumor sites include middle and lower thoracic and GE junction. Clinical stages are TX-T3, N0-3, M0-1. All patients received at least one cycle of concurrent chemotherapy. IMRT dose was 50.4 Gy in 28 fractions prescribed to a target volume including the tumor and regional lymphatics. IMRT plans utilized coplaner beams in a 7-9 beam arrangement or volumetric modulated arc therapy. Results: Median follow-up is 8.9 months (range 2.4-23.0) for all patients and 13.1 months (range 2.8-23.0 months) in surviving patients. Median patient age is 69 (range 46-87). Trimodality treatment was completed in 20 patients (62.5%). Surgery was either an open or minimally invasive esophagogastrectomy. The incidence of grade 3 or greater late toxicity at 1 year was 48% in surgery patients and 26% in non-surgery patients. The most common grade 3 or higher toxicity was esophageal strictures in 25%. The incidence of any grade 3 or greater acute toxicity was 65% in the surgery patients and 75% in the non-surgery patients. Overall survival (OS) for all patients at 18 months is 57% (CI 37-86%) and progression-free survival (PFS) is 60% (36-99%). OS and PFS for trimodality therapy at 12 months is 83% (66-100%) and 81% (63-100%) respectively and for bimodality therapy is 34% (12-93%) and 70% (33-100%) respectively. Conclusions: Increased late toxicity occurs in surgery patients, and increased acute toxicity in non-surgery patients. Lower survival in non-surgery patients may be due to early progression, morbidities which preclude surgery or improved survival with surgery. Overall, IMRT is a feasible treatment modality, which may be equally efficacious to 3D CRT for the treatment of esophageal carcinoma.
Randomized phase II study of erlotinib (ERL) in two different schedules with concomitant modified XELOX in the first-line treatment of metastatic colorectal cancer (mCRC): Correlation with serial serum levels of amphiregulin (AMR) and transforming growth factor receptor-alpha (TGFa).
Authors: Anthony T. C. Chan, Stephen Lam Chan, Wing Ming Ho, Wilson Lau, Frankie Mo, Edwin P. Hui, Charles Chan, Annette Poon, Rasalkar Dattatray, S. C. Cesar Wong, Ka Fai To, Ann Dorothy King, Anil Tejbhan Ahuja, Brigette Ma
Journal: Journal of Clinical Oncology (2013)

425 Background: This study evaluated the feasibility of combining XELOX with erlotinib in a 2 different schedules, and the prognostic significance of serum AMR and TGFa in previously untreated mCRC. Methods: Eligible patients (Pt) were randomized to the ‘continuous’ arm (Arm CON) [ERL 100mg daily D1-21, oxaliplatin (Ox) 130mg/m 2 D1, capecitabine (Xe) 825mg/m 2 bd D1-14, q3w], or the ‘intermittent’ arm (Arm INT) [ERL 150mg daily at alternate day on D 1-14, then 150mg daily on D15-21, Ox 130mg/m 2 on D1, Xe 750mg/m 2 bd on D1-14, in a q3w]. Serum levels of AMR, TGFa and CEA were determined serially. KRAS mutation was determined from archived tumors. Results: 60 pts were randomized and there was no difference in the baseline characteristics between the 2 arms. Of the 58 pts evaluated for response, the overall response rates (ORR) were 56.3% (Arm CON) and 66.3% (Arm INT). At a median follow-up of 2.8 yrs, the median overall survival (OS) of pts in Arm CON and Arm INT were 9 m (95% CI: 7.2-18m) and 10.3m (95% CI: 7.2-15.6 m) respectively. KRAS mutation (n = 44 tumors) status did not predict ORR or survival. Gr 3-4 toxicities occurred in 53.3% (Arm CON) and 46.7% (Arm INT) of pts. Multivariate analysis showed that elevated baseline serum TGFa and AMR were independent predictors of inferior PFS and OS, respectively. Post-treatment drop in serum TGFa was associated with shorter OS and PFS, while a drop in serum TGFa and a rise in serum AMR were associated with inferior PFS and OS, respectively. Conclusions: Although there was no statistical difference in the toxicity and efficacy of the 2 arms, the ORR from XELOX and intermittent ERL compared favorably with historic control. KRAS mutation status was not predictive. Serum TGFa and AMR have prognostic significance in this cohort and further prospective studies are warranted. Clinical trial information: NCT01243047.
Patterns of systemic chemotherapy in resectable non-small cell lung cancer
Authors: S. Dubey, R. Su, G. Nalbandian, J. Hwang, T. M. Jahan
Journal: Journal of Clinical Oncology (2008)

7590 Background: The International Adjuvant Lung Trial presented in May 2003 was followed by several trials and meta-analyses that demonstrated a clear benefit of adjuvant chemotherapy in stage II and IIIA non-small cell lung cancer (NSCLC) and an uncertain benefit in IB. The goal of this study is to evaluate the impact of clinical trials on patterns of systemic chemotherapy use in patients with resectable NSCLC at the University of California, San Francisco (UCSF). Methods: Data from patients diagnosed with stage I-III NSCLC between 2002–2006 were collected retrospectively. Cases were identified through the cancer registry and included those who were seen at least once at the Thoracic Oncology Program, UCSF. Descriptive statistics were used. The institutional review board approved the study. Results: Final analysis included 172 patients (IB 86, IIA 7, IIB 24, IIIA 50, IIIB 5). Induction chemotherapy (IC) and adjuvant chemotherapy (AC) were administered in 80 (47%) and 45 (26%) patients, respectively. Thirteen patients received both IC and AC. The frequency of chemotherapy administration was highest in IIIA followed by IIIB, IIB, IIA, and IB. A time related trend with AC was seen only in stage IB: 0% (2002), 12.5% (≤6/2003), 12.5% (>6/2003), 30% (2004), 14% (2005), 10% (2006). Of 56 patients who did not receive any chemotherapy, common reasons were: comorbidities (12), IB tumor size <4cm based on negative results of CALGB 9633 study (6), second malignancy (5), patient declined (5). The most common regimens were carboplatin based (IC 66%, AC 53%). Of the 146 patients operated on at UCSF, 36% received chemotherapy in a community center. No major differences in chemotherapy use were noted between patients treated at tertiary care and community centers. Conclusions: Systemic chemotherapy is commonly administered in early surgical NSCLC. At UCSF, AC patterns in stage IB reflected the positive and negative clinical trial results. Neoadjuvant chemotherapy, in our experience, was more commonly administered than adjuvant chemotherapy and may have diminished the impact of adjuvant clinical trial results. This study also suggests that coordinated management between community and tertiary care centers is feasible. No significant financial relationships to disclose.
Patterns of care of locoregional radiation therapy in patients with stage IV rectal cancer: A SEER analysis.
Authors: Jennifer K. Logan, Thomas A. DiPetrillo, Kara Lynne Leonard
Journal: Journal of Clinical Oncology (2013)

477 Background: Per the 2012 NCCN guidelines, pelvic radiation therapy (RT) is one of the preferred treatment regimens for patients with metastatic rectal cancer (MRC). This study aims to analyze patterns of care and outcomes data for the use of neoadjuvant/adjuvant pelvic RT in patients with MRC using the SEER database. Methods: Patients with stage IV rectal or rectosigmoid cancer were identified in the SEER database (1973-2009). Patients were stratified according to their primary site of disease (rectum vs. rectosigmoid), T-, and N-stage. Treatment regimens (+/- surgical resection, +/-RT, or a combination of both) were recorded. Fischer's exact test was used to compare RT rates based on stratified factors. 2-yr survival rates were compared among treatment groups. Results: A total of 6,873 patients with stage IV rectal CA and 3,417 patients with rectosigmoid CA were identified. In total, 20.5% of rectal CA patients received surgery alone while 38.7% received RT alone or RT + surgery. Within the rectosigmoid group, 51.4% of patients received surgery alone and 15.1% of patients received either RT alone or RT + surgery. The use of RT differed significantly between those with Tis-2 and T3-4 disease (p &lt; 0.001) and between those with N0 vs. N1-2 disease (p &lt; 0.001). 2-yr and 5-yr survival differed significantly between treatment groups with the highest survival rates among those receiving surgery and RT. Detailed data is provided in the table below. Conclusions: The primary treatments for patients with MRC include surgery +/- RT. RT is used more commonly in patient with primary rectal (as opposed to rectosigmoid) tumors, N0, or Tis-T2 disease. Treatment with combination surgery and RT is associated with prolonged survival. [Table: see text]
Impact of pelvic lymphadenectomy during primary cytoreductive surgery on survival in epithelial ovarian cancer: A prospective study.
Authors: K. Pushpalatha, K. S. Kumar, L. Kumar, P. K. Julka, S. Mathur
Journal: Journal of Clinical Oncology (2011)

e15563 Background: To evaluate the impact of pelvic lymphadenectomy during primary cytoreductive surgery on survival in epithelial ovarian cancer (EOC). Methods: Between October 2008 and July 2010, 26 patients of EOC, FIGO stage IC-IV underwent primary cytoreductive surgery followed by six cycles of chemotherapy with paclitaxel and carboplatin. 13 patients (study group) underwent pelvic lymphadenectomy and 13 patients (control group) did not. Results: Patient characteristics were similar in both groups with respect to median age (49 yrs vs 50 yrs, p=0.3), menopausal status (53.8% vs 69.2%, p=0.4), mean Hb [G/dl] (10.7 vs 10.8, p=0.8) and mean albumin (G/dl; 3.7 vs 3.7, p= 0.9). However patients in control group had more advanced disease, FIGO stage III-IV, 84.6% vs 38.5%, p=0.04. Intraoperative data was not significantly different in study vs control groups; operating time (126 mins vs 132 mins, p=0.2), mean blood loss (815.4 mL vs 1,000mL, p=0.06), mean blood transfusion (1,300 mL vs 1,800 mL, p=0.09). Postoperative complications included sepsis (7.6% vs 23.07%, p=0.5), vesico-vaginal fistula (7.6% vs 0%, p=1.0), subacute intestinal obstruction (0% vs 7.6%, p=1.0), haemorrhage (0% vs 15.3 %, p=0.4), admissions in ICU (7.6% vs 23.07%, p=0.5),seizures (7.6% vs 0%, p=1.0), urinary tract infection (15.3% vs 7.6%; p=1.0) in study and control groups respectively. Postoperatively, 3 patients died in control group compared to one in study group (7.6% vs 23.07%, p=0.5). Optimal debulking rate (residual disease ≤ 1 cm) was higher in the study group; 84.6% vs 23.08%, p=0.005. The median progression free survival is 13 months (range 7.8 to 24.1 months) vs 12.1 months (range 6.1 to 26.7 months ) and the median overall survival is 13.3 months (range 8.2 to 28.6 months) vs 16.1 months (range 7.2 to 28.6 months) in the study and control group respectively. Conclusions: In this pilot study, we did not observe significant difference between progression free survival and overall survival in patients who underwent lymphadenectomy compared to control group.
Statistical analysis of episensitization using transition probability functions and PFS2 for “ROCKET”, a two stage phase II study of RRx-001, a multi-epigenetic agent, investigating resensitization to irinotecan in colorectal cancer.
Authors: Nacer Abrouk, Tony R. Reid, George A. Fisher, Corey Allan Carter, Paul M. Thambi, Bryan Oronsky, Gary Fanger, Scott Caroen, Christopher Parker, Meaghan Stirn, Jan Scicinski
Journal: Journal of Clinical Oncology (2016)

TPS775 Background: The development of resistance to chemotherapies in cancer leads to disease progression resulting in impaired survival. RRx-001, a ROS-mediated DNMT and HDAC inhibitor, may resensitize patients to previously effective, now refractory therapies, improving survival. A randomized two-stage Phase 2 trial of RRx-001 vs regorafenib (ROCKET) is underway to assess the impact of resensitization to irinotecan on overall survival in irinotecan refractory tumors. Transition Probability Functions (TPF) using Markov Chains have previously been used in clinical trials and provide a powerful tool for resensitization analysis. Methods: Patients with metastatic colorectal cancer who previously responded, then progressed on irinotecan-based therapies, with or without bevacizumab, cetuximab or panitumumab and an ECOG PS 0-1 are randomized to receive RRx-001 1x/week or regorafenib until progression or unacceptable toxicity in Stage 1. Patients then advance to Stage 2 to receive irinotecan-based therapies. This trial is designed to detect an increase in median OS of 3 mo., corresponding to a 33% reduction in risk of death. The primary endpoint, overall survival (OS), employs a two-sided log-rank test to compare treatment groups. The hazard ratio and its 95% CI are derived from the Cox proportional hazards model. Kaplan-Meier survival curve estimates are graphically depicted by treatment group. Secondary endpoints include PFS, PFS2 and Transition Probability Functions to address the resensitization hypothesis, KRAS or p53 status dependence. The analysis of PFS2, defined as time to progression (or death) from randomization to progression in Stage 2 (post Irinotecan therapy) is a key secondary endpoint and its analysis uses the standard two-sided log-rank test. TPF estimates will be derived from the Markov Chain transition probability matrix. The study should provide compelling evidence in support of the ability to return to previously beneficial chemotherapy treatment. Recruitment is ongoing. Clinical trial information: NCT02096354.
Effect of renal function on continuation of S-1 adjuvant chemotherapy in gastric cancer patients.
Authors: Katsuya Makihara, Sayaka Azuma, Hiroyuki Ueno, Izumi Nakata, Kazuyoshi Yamamoto, Kazuhiro Nishikawa, Motohiro Hirao, Kazumasa Fujitani, Toshimasa Tsujinaka
Journal: Journal of Clinical Oncology (2015)

90 Background: The results of ACTS-GC study showed that postoperative adjuvant chemotherapy with S-1 is the standard treatment for patients with stage II and stage III gastric cancer (GC) in Japan. In addition, completion of 12 months of S-1 treatment and a high relative performance (RP) value were reported to be related to improved survival. The plasma 5-fluorouracil concentration in patients receiving S-1 treatment is known to be significantly higher in patients with 50 ≤ Ccr &lt; 80 mL/ min than in those with Ccr ≥ 80 mL/ min. The aim of this study was to investigate the association of the dose of S-1 based on renal function and compliance with S-1 treatment. Methods: This study is retrospective cohort study, included GC patients who were administered S-1 adjuvant chemotherapy at the Osaka National Hospital in Japan between August 2006 and August 2013. Cohort A comprised patients with Ccr ≥ 80 mL/min, those with 50 ≤ Ccr &lt; 80 mL/min and dose reduction by one level, and those with Ccr &lt; 50 mL/min and dose reduction by two levels. Cohort B included patients with Ccr &lt; 50mL and dose reduction by one level. We compared the completion rate of 12 months of S-1 treatment and the RP value between cohorts A and B. Results: In total, 103 patients were included in this study: cohort A included 53 patients, and cohort B included 50 patients. The completion rate of 12 months of S-1 treatment was significantly higher in cohort A at 83% than in cohort B at 56% (OR: 3.8 [95% CI: 1.6–9.9], p = 0.003). The median RP value was significantly higher in cohort A at 93.8% than in cohort B at 74% (p = 0.007). In the subgroup analysis, no difference was found in the completion rate among patients with S-1 dose &lt; 65 mg/m². Conclusions: Renal function was found to be an important factor for compliance with S-1 treatment as adjuvant chemotherapy for GC. The results of the present study suggest the need for dose reduction by one level in patients with Ccr &lt; 80 mL/min.
Contemporary utilization of non-surgical management for stage I renal masses.
Authors: Benjamin T. Ristau, Elizabeth Handorf, Matthew Schaff, Simon P. Kim, Mohammed Haseebuddin, Nikhil Waingankar, Miki Haifler, David Cahn, Richard Evan Greenberg, Rosalia Viterbo, David Y. T. Chen, Alexander Kutikov, Robert G. Uzzo, Marc C. Smaldone
Journal: Journal of Clinical Oncology (2016)

564 Background: While active surveillance has gained traction as a primary treatment strategy for small renal masses in patients with significant competing risks, population level trends of non-surgical management (NSM) remain poorly characterized. Using a large national cancer registry, our objective was to assess temporal trends in utilization of NSM for stage I renal cell carcinoma (RCC). Methods: The National Cancer Database (NCDB) was queried for all patients with stage I RCC from 2003-2012. Patients were categorized as surgical intervention (partial [PN] or radical nephrectomy [RN]) or NSM, and patients undergoing ablative techniques were excluded from analyses. Temporal trends were assessed using Cochran-Armitage tests. Adjusting for patient, clinical, and tumor characteristics, multivariable logistic models were used to examine the association between clinicopathologic characteristics and receipt of NSM. Results: Of 176,975 patients identified, 89% underwent surgical intervention (PN 35.5%, RN 53.5%) and 11% underwent NSM respectively (Stage Ia: 13.1%, Stage Ib: 6.3%). From 2003-2012, utilization of NSM (6.1 vs. 13.1, p &lt; 0.001) and PN (24.4 vs. 47.3%, p &lt; 0.001) significantly increased, while performance of RN significantly declined (69.5 vs. 39.6, p &lt; 0.001). Following adjustment, increased age (51-60 years: OR 1.70 [CI 1.6-1.8]; 61-70 years: OR 2.61 [CI 2.4-2.8]; 71+ years: OR 6.37 [CI 5.7-7.1]), African American race (OR 1.11 [CI 1.03-1.2]), Charlson score 2+ (OR 1.34 [CI 1.2-1.4]), and insurance status (uninsured: OR 1.71 [CI 1.5-2.0]; Medicaid: OR 1.92 [CI 1.7-2.1]; Medicare: OR 1.39 [CI 1.3-1.5]) were associated with receipt of NSM, while patients with tumors &gt; 4cm (OR 0.42 [CI 0.40-0.45]) were less likely to undergo NSM. Conclusions: In hospitals reporting to the NCDB, utilization of NSM as a primary treatment strategy for stage I RCC has doubled from 2003-2012, most notably for tumors ≤ 4cm (Stage Ia). In absence of validated algorithms differentiating between active surveillance, watchful waiting, and those who lost access to care, racial and insurance disparities should be interpreted cautiously.
Rate of implementation of universal testing for Lynch Syndrome in a county hospital system.
Authors: Ashish Sharma, Johanna Chan, Tony Trang, Milena Gould Suarez
Journal: Journal of Clinical Oncology (2016)

533 Background: Lynch Syndrome (LS) is the most common cause of inherited colorectal cancer (CRC). Universal testing is recommended as a cost effective strategy for screening for LS in all patients with CRC diagnosed &lt; 70 years of age. This has shown to be beneficial in clinical decision making and cancer surveillance of both the patient and at risk relatives. According to a study in 2012, 71% of NCI institutions were performing universal testing versus 15%-36% of programs in the community. The aim of our study was to determine the outcomes of Universal Testing for LS in CRC in a County Hospital System. Methods: IRB-approved retrospective chart review of all patients diagnosed with colorectal cancer from cancer registry at Harris County Hospital District from March 2010 to Dec 2013. Patients between 18-70 yr were included. We collected data on patient characteristics, universal testing [immunohistochemistry (IHC) at our institution], and LS diagnosis (confirmed with germline testing for mismatch repair gene) in our patient cohort diagnosed with CRC. Descriptive statistics were performed using t-test for continuous variables. Results: Overall, 430 patients had CRC diagnosis in our study period, and 54 years was median age of diagnosis. IHC was performed in 359/430 (83.4%) CRC cases. IHC was positive in overall 26/430 (6%) cases of CRC. LS was confirmed in 9/430 (2%) CRC cases. IHC was more often positive with CRC diagnosed in patients younger than 50 years than in patients 50 years or older (7.91% vs 3.09%; p = 0.04). Conclusions: Universal testing for screening of LS amongst patients with CRC can result in significant rates of detection. In this study we have shown that this is possible in a largely safety-net setting.
A phase II study of BAY 43–9006 in patients with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) and nasopharyngeal cancer (NPC)
Authors: L. L. Siu, E. Winquist, M. Agulnik, S. F. Chin, G. R. Pond, R. Cheiken, P. Francis, O. Petrenciuc, E. Chen
Journal: Journal of Clinical Oncology (2005)

5566 Background: Bay 43–9006, a novel bi-aryl urea, is a potent inhibitor of kinases of Raf-1 (C-Raf) and B-Raf which are critical members of the RAS/RAF/MEK/ERK signalling pathway. In addition, Bay 43–9006 inhibits other pro-angiogenic protein tyrosine kinases, including VEGFR-2/3 and PDGFR-β. Overexpression of these signal transduction and angiogenic markers has been associated with poor prognosis in epithelial malignancies. We conducted a phase II study to examine the efficacy of Bay 43–9006 in advanced HNSCC and NPC. Methods: Patients (pts) with advanced HNSCC and NPC with measurable disease, no more than one prior chemotherapy regimen for recurrent and/or metastatic disease, performance status (PS) ECOG 0–2, and adequate organ functions were eligible. Bay 43–9006 was administered orally at 400 mg BID on a continuous basis, in 28-day cycles. Responses were evaluated every 8 weeks according to RECIST criteria. Results: Seventeen patients have been enrolled to date (9m/8f). Median age was 59 years (range 46 - 77); 82% had PS 0 or 1 and 18% PS 2; 65% HNSCC and 35% NPC; 11 pts had received prior chemotherapy, 3 had received prior erlotinib and 16 had received prior radiation therapy. All pts were evaluable for toxicity and 10 for response assessment to date. Six pts (60%) (4 HNSCC and 2 NPC) had stable disease ranging from 3 to 6 cycles, and 4 pts (40%) had progressive disease. A total of 36 cycles had been administered (median number/patient: 2; range 1–6). No grade 4 toxicity was seen. Main haematological toxicity was grade 3 lymphopenia in 5 (29%) pts. Common grade 3 non-hematological toxicity included hyponatremia in 4 (24%), dyspnea in 3 (18%), and non-specific pain in 3 (18%) pts. Grade 1/2 non-hematolgical toxicity included fatigue in 15 (88%), hypertension in 6 (35%), hand-foot syndrome in 6 (35%) and skin rash in 3 (18%) pts respectively. One pt died of intracranial tumoral hemorrhage, deemed to be unlikely related to treatment. Conclusions: Bay 43–9006 was well tolerated. Although no objective response was seen to date in this group of heavily pretreated patients, over half of the evaluable patients had achieved tumor stabilization. Further trial accrual is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer
Identification of the activating cytotoxicity receptor NKG2D as a senescence marker in zero-hour kidney biopsies is indicative for clinical outcome
Authors: Julia Günther, Thomas Resch, Hubert Hackl, Arne Sattler, Susanne Ebner, Paul Viktor Ritschl, Matthias Biebl, Robert Öllinger, Stefan Schneeberger, Gerald Brandacher, Hubert Schwelberger, Bettina Zelger, Diana Stauch, Andreas Pascher, Johann Pratschke, Katja Kotsch
Journal: Kidney International (2017)