tbuckley/cabot-search huggingface dataset:
Impact of body mass index on quality of surgery and survival outcomes in patients undergoing radical cystectomy for bladder cancer: A Cooperative Group Report
Authors: G. V. Raj, D. Cohen, H. B. Grossman, H. Herr, S. M. Donat
Journal: Journal of Clinical Oncology (2005)

4696 Background: Quality of surgery as reflected by node count/density, surgical margin and local recurrence rates, and pathologic variables (pathologic stage and nodal status) have been shown to impact survival in bladder cancer. Population studies report an increased risk of cancer related death as body mass index (BMI) increases. We evaluated the Southwest Oncology Group 8710 database of 307 patients prospectively randomized between neoadjuvant chemotherapy with radical cystectomy (RC) versus RC alone, to determine whether BMI significantly impacted the quality of surgery, pathologic stage, or survival outcomes. Methods: Of 278 patients with available BMI data, surgical and pathologic data, 55% (n=152) received neoadjuvant chemotherapy. Median follow-up time was 8.4 years. BMI was examined as a continuous and categorical variable, using WHO classifications of normal (BMI<25), overweight (25–29.9) and obese (≥30). Clinical and pathologic variables were tested in univariate and multivariate analyses. Results: BMI distribution was similar between the two study arms with 103 having a normal BMI, 109 overweight, and 66 obese. BMI did not impact the quality of surgery with comparable negative surgical margin rates, total node counts/density, and proportion of patients with >10 nodes harvested between the three BMI categories (p>0.05). Although the pathologic organ-confined and node positive rate was similar between the BMI groups in the 2 arms, there was a significant association between a higher BMI (>25) and the likelihood of achieving pathologic P0 status (40% vs 27%) at RC (p=0.05). This was especially true among those receiving neoadjuvant chemotherapy (59% v 39% P0 rate, p=0.029), but did not translate to a lower local recurrence rate or better overall survival in those with a higher BMI. In multivariate analyses, only local recurrence, pathologic stage >T2, node count >10, and neoadjuvant chemotherapy, were significantly associated with better overall survival (p<0.05). Conclusions: High quality surgery (RC) with or without chemotherapy can be achieved in patients with higher BMI with similar survival outcomes compared to normal weight patients. No significant financial relationships to disclose.
Updated survival results of the randomized phase II study comparing cisplatin/capecitabine (CX) with epirubicin plus CX (ECX) in advanced gastric cancer (AGC).
Authors: T. Lim, J. Yun, J. Lee, S. Park, J. Park, Y. Park, H. Lim, W. Kang
Journal: Journal of Clinical Oncology (2011)

46 Background: We previously reported results of a randomized study showing that CX is equally active to ECX in terms of progression-free survival (PFS) (Yun et al. Eur J Cancer. 2010). Here we report updated overall survival (OS) results with an additional 12 months' follow-up. Methods: Ninety-one chemotherapy-naïve patients with histologically-confirmed, measurable AGC were randomized to receive CX (cisplatin 75 mg/m 2 iv on day 1 and capecitabine 1,000 mg/m 2 bid po on days 1-14, n=45) or ECX (epirubicin 50 mg/m 2 plus CX, n=44) every 3 weeks. After CX or ECX had failed, second-line chemotherapy (SLC) was recommended for all patients if their performance status was preserved. Results: Treatment duration was similar for both arms (4.4 for CX v 4.2 months for ECX). There was no relevant difference in the occurrence of overall grade 3 or 4 toxicities between the CX and ECX arms (80% v 78%, respectively; p=0.516). However, none in the CX and 12% in the ECX arm discontinued treatment because of toxicity. There were no significant differences in therapeutic efficacy between CX and ECX with respect to the response rate (38% v 37%, respectively), PFS (6.4 v 6.5 months), as well as OS (12.7 v 13.8 months; p=0.51). After failure, 60% of patients (26 CX and 28 ECX patients) received SLC. However, OS was not differed whether a patient was treated with SLC or not (13.1 v 11.2 months; p=0.94). Conclusions: The present analysis confirms previous findings that both CX and ECX appear to be comparatively active as first-line chemotherapy for AGC. Furthermore, the role of SLC in AGC warrants further evaluation. No significant financial relationships to disclose.
Correlating radiologic response criteria with pathologic tumor viability in HCC patients undergoing localized radiation followed by surgical resection.
Authors: Ik Jae Lee
Journal: Journal of Clinical Oncology (2013)

217 Background: Various radiologic response criteria have been developed for solid tumors. This study attempts to identify the optimal criteria for hepatocellular carcinoma (HCC) after localized treatment including radiotherapy. Methods: We reviewed 40 consecutive HCC patients who underwent surgical resection after radiotherapy of curative intent between 2000 and 2011. Radiation was delivered concurrently with intraarterial 5-fluorouracil/cisplatin (36), concurrently with capecitabine (2), and after receiving transarterial chemoembolization (2). For radiotherapy, 45 Gy in 25 fractions (32) or 50 Gy in 20 fractions (8) was delivered. Images from pre-RT and pre-resection CT were compared to determine treatment response according to Response Evaluation Criteria in Solid Tumors (RECIST), the World Health Organization (WHO) criteria, modified RECIST (mRECIST), and European Association for the Study of the Liver (EASL) criteria. Findings from pathologic reports including extent of tumor necrosis were correlated with degree of response from each set of criteria. Results: Intermodal agreement among criteria was highest between RECIST and WHO (p&lt;0.0001) and between mRECIST and EASL (p&lt;0.0001). All criteria showed strong correlation with reduction in α-fetoprotein (p=0.001 for EASL and mRECIST, 0.026 for RECIST, and 0.043 for WHO). Percent of viable tumor by EASL was most strongly correlated with percent of pathologic viable tumor (p&lt;0.0001), followed by RECIST, mRECIST, and WHO (p = 0.011, 0.013, and 0.013). Resection was carried out after 2 complete (5%), 36 partial (90%), and 2 stable (5%) responses according to EASL criteria. Three year disease-free (DFS) and overall survival (OS) were 29 and 61 months. Complete necrosis showed trends toward improved DFS (p=0.136) and OS (p=0.088). Multiplicity was independent prognostic factor for both DFS and OS (p=0.005 and 0.001). Conclusions: EASL criteria showed strongest correlation with pathologic tumor viability after localized treatment for HCC. Prospective clinical trial is warranted.
A meta-analysis of patient outcomes with subcentimeter disease after chemotherapy for metastatic nonseminomatous germ cell tumor (NSGCT).
Authors: Elizabeth O'Donnell, Kathryn P. Gray, Praful Ravi, Christopher Sweeney
Journal: Journal of Clinical Oncology (2013)

324 Background: Around a quarter of men with metastatic nonseminatous germ cell tumor (NSGCT) have a residual mass, typically in the retroperitoneum, after chemotherapy. While post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) is accepted to be the best way to manage large retroperitoneal masses, the treatment of small residual masses (≤1cm) is controversial. Both PC-RPLND and surveillance produce good outcomes for men in this situation, and we sought to review our experience of surveillance and synthesize the cumulative findings in the form of a meta-analysis. Methods: We searched PubMed and abstracts from ASCO and AUA to identify relevant, English language studies. Inclusion criteria was the presence of a subcentimeter post-chemotherapy retroperitoneal mass. The Dana-Farber Cancer Institute cohort was constructed from a database of men undergoing cisplatin-based chemotherapy for metastatic NSGCT. The outcomes of interest were the proportion with necrosis, teratoma or active cancer on histology at PC-RPLND, and the total number of relapses, retroperitoneal (RP)-only relapses and overall survival in men undergoing surveillance. Results: A total of 47 men formed our surveillance cohort and three relapsed with a median follow-up of 5.4 years and median time to relapse of 12.7 months. All three were alive at a median of 4.2 years after relapse with salvage therapy. On meta-analysis, the pooled estimates of necrosis, teratoma and active cancer in the 588 men who underwent PC-RPLND were 71%, 24% and 4% respectively. Of the combined 455 men who underwent surveillance, the pooled estimate of relapse rate was 5%, with an RP-only relapse rate of 3%. Overall, of the 15 men who suffered an RP-only relapse on surveillance, two died of disease. Conclusions: Surveillance is an alternative strategy for managing men with minimal residual RP disease after chemotherapy and avoids an RPLND in about 95% of men who are cured with chemotherapy alone.
Correlations between functional Interleukin-1 and changes in fatigue and quality of life in children and adolescents with cancer.
Authors: Emiliana de Omena Bomfim, Elen Anatriello, Michelle Darezzo Rodrigues Nunes, Jordana Carvalhes Moraes, Michel Marcossi Cintra, Luis Carlos Lopes-Junior, Michele Miyauti, Lucila Castanheira Nascimento, Regina Aparecida Garcia de Lima, Milena Floria-Santos
Journal: Journal of Clinical Oncology (2015)

95 Background: Several studies have explored the hypothesis of involvement of the immune system in the cancer-related fatigue (CRF) and quality of life in adults with cancer via release of cytokines. However, how the immune system may produce these outcomes remains a largely unanswered question. Furthermore, research on fatigue in children and adolescents with cancer has included primarily self-reports of this symptom, with scarce although increasing data exploring biologic variables related to this symptom. Methods: To comprehensively examine the influence of cytokines in the fatigue and health related quality of life (HRQOL) in children and adolescents with cancer, we investigated the plasma levels of pro and anti-inflamatory cytokines and its correlation with fatigue and HRQOL in children and adolescents with cancer. Plasma levels of 6 cytokines were measured via flow cytometry. Results: The final sample consisted of 33 hospitalized children and adolescents aged between 8 and 18 years. We found a correlation between general fatigue and IL-1β (r = –0.361, p = 0.039) and correlation with quality of life was noted with IL-1β (r = –0.382, p = 0.028). The results of this research indicate that there may be a relationship between cytokines and fatigue, and HRQOL in children and adolescents with cancer. When analyzed the correlation between fatigue and some confounding variables found the link between general fatigue and neutrophils (r = –0.360, p = 0.040). This correlation is a novel found in this population under cancer condition, implicating a possible interleukin-hematological pathway for CRF in oncology. Conclusions: Our study confirms the potential role of cytokines in developing cancer-related symptoms, thus supporting the utility of the neuroimmunological approach to the discovery of biomarkers linked to the clusters of cancer-related symptoms.
Does prostate brachytherapy that avoids the central zone prevent long-term urinary incontinence? Five-year results of a multi-institutional comparative cohort study.
Authors: J. A. Talcott, A. L. Zietman, I. D. Kaplan, J. A. Clark, A. V. D'Amico
Journal: Journal of Clinical Oncology (2011)

4665 Background: To evaluate a prostate brachytherapy technique (XBT) designed to reduce urinary dysfunction by avoiding central prostate radiation, we prospectively compared outcomes of XBT patients to 2 standard technique (SBT) groups. Methods: We surveyed newly diagnosed, untreated patients with clinically localized prostate cancer before brachytherapy to gather clinical and quality of life information, with follow-up 1, 3, 12, 24, 36, 48 and 60 months after treatment. XBT treatment was at Brigham and Women's Hospital, SBT at Beth Israel-Deaconess or Metrowest Hospitals or at Massachusetts General Hospital. Results: As of December 2010, 263 enrolled patients with at least 3-month follow-up, including 73 XBT patients and 190 SBT patients, 99 at 1 site and 91 at the other, and 167 (63%) had completed 5-year follow-up. Tthe treatment groups were similar before treatment. For all patients, urinary obstruction/irritation was increased for 24 months but rose less and resolved earlier for XBT patients. One SBT group reported greater urinary dysfunction, but the problem resolved after a technique change. At 60 months after SBT, but not XBT, urinary incontinence appeared to rise (P=0.09). Sexual dysfunction rose for 36 months for all groups but not thereafter. Conclusions: Sharply reduced periurethral radiation suppresses post-treatment increases in urinary obstruction/irritation and may prevent long-term urinary incontinence, although definitive results may require longer follow-up. Declining sexual dysfunction appears to halt after 36 months.
Correlation of <i>BRAF</i> and <i>NRAS</i> mutation status with tumor characteristics and treatment outcomes in melanoma patients with brain metastasis.
Authors: Eugene Jon Koay, Amanda Dawn Bucheit, John Andrew Jakob, Eric D. Hyun, Stephen H Settle, Paul D. Brown, Michael A. Davies, Erik P. Sulman
Journal: Journal of Clinical Oncology (2012)

8584 Background: The management of melanoma has evolved rapidly with the identification of activating mutations in the majority of patients (pts). We reviewed characteristics and outcomes of molecularly characterized melanoma pts with brain metastasis (BM) to help design and interpret future clinical trials. Methods: We reviewed clinical and pathologic features of melanoma pts with known BRAF and NRAS mutation status and BM. Pt demographics, intra- (IC) and extra-cranial (EC) tumor characteristics, and IC/EC disease treatments were correlated to BM treatment outcomes (local and distant brain control [LC, DC]) and overall survival (OS). Univariate and multivariate analyses were performed to identify significant associations between mutation status and outcome. Results: We identified 296 pts with melanoma BM and known BRAF/NRAS mutation status diagnosed from 2005 to 2011. Mutation prevalence was BRAF 57%, NRAS 17%, and wild-type for both genes (WT) 26%. The initial treatments given for BM were surgery/radiosurgery (SRS) 60%, surgery/SRS + whole brain radiation (WBRT) 7%, WBRT alone 19%, systemic therapy alone 9%, and no treatment 5%. Mutation status was not significantly associated with sex, performance status, EC disease status, number of brain lesions, or BM treatment. Pts with mutations were younger (p&lt;0.0001) and more likely to have symptomatic BM (p=0.0003) than WT pts. In univariate analysis, BM treatment strategy (p&lt;0.001) and mutation status predicted for poor LC, with 6 month LC rates of 70% for any mutation and 88% for WT (HR=1.86, p=0.048). Compared to systemic agents alone, use of radiation (SRS or WBRT) improved LC for pts with a mutation (HR 0.23, p=0.0006). Subsequent multivariate analysis identified mutation status and radiation treatment as independent predictors of LC (HR 2.5 and 0.25, respectively). Mutation status did not predict for DC or OS. Conclusions: The presence of BRAF and NRAS mutations predicts worse LC following conventional treatments for melanoma BM. Radiation may improve LC in pts with a mutation. This data suggest a role for combining radiation with targeted therapies in melanoma pts with activating BRAF or NRAS mutations in the treatment of BM.
Conflict of interest in economic analyses of targeted therapies in oncology.
Authors: A. D. Nearchou, A. Valachis, N. P. Polyzos, D. Mauri, P. A. Lind
Journal: Journal of Clinical Oncology (2011)

6120 Background: A potential financial relationship between investigators and pharmaceutical manufacturers has been associated with an increased likelihood of reporting favorable conclusions about a sponsor’s proprietary agent in pharmacoeconomic studies. The purpose of this study is to investigate whether there is an association between conflict of interest and outcome in economic analyses of new targeted therapies in oncology. Methods: We searched Pubmed (last update 1/2011) for economic analyses of targeted therapies (including monoclonal antibodies, tyrosine-kinase inhibitors, mTOR inhibitors) in oncology. Two investigators independently extracted information from each of the included studies. The trials were qualitatively rated regarding the cost assessment as favorable, neutral or unfavorable, based on pre-specified criteria. Results: Overall, 75 eligible studies were identified. Economic analyses which were funded by pharmaceutical companies were more likely to report favorable qualitative cost estimates (27/31 [87%] vs. 21/44 [48%], p-value = 0.001). The presence of author affiliated with manufacturer was not associated with study outcome. Furthermore, if only studies including a conflict of interest statement were included (61 out of 75), studies that reported any conflict of interest with manufacturers (author affiliation and/or funding and/or other conflict of interest) were more likely to report favorable results of targeted therapies compared to studies without conflict of interest (31/40 [78%] vs. 9/21 [43%], p-value = 0.007). Sponsorship from other non-profit sources had no significant impact on study outcome. Conclusions: Our study reveals a potential threat for industry-related bias in economic analyses of targeted therapies in oncology in favor of analyses with conflict of interests between authors and manufacturers. A more balanced funding of pharmacoeconomic analyses from other sources may limit the skepticism about the role of pharmaceutical companies on cost analyses.
Utility of routine endoscopy in the follow-up of resected gastric carcinoma.
Authors: M. Satolli, W. Evangelista, C. Mecca, R. Napoletano, A. Giacobino, A. Novarino, F. Brusa, J. Fiore, L. Pomba, M. Garino, G. Fronda, L. Ciuffreda
Journal: Journal of Clinical Oncology (2011)

4093 Background: Despite a declining incidence in many developed countries, gastric cancer remains the second most common cause of cancer-related deaths globally. Follow-up with routine endoscopy after resection of gastric carcinoma is frequently performed without definitive evidence of its impact in survival rate. Methods: To evaluate the usefulness of routine endoscopy for the follow-up of patients with history of surgically resected gastric carcinoma, we conducted a retrospective study of patients with gastric carcinoma diagnosed between 1993 and 2009, in whom routine endoscopy was performed yearly after surgical resection with curative intention. Clinical data including site of recurrence, treatment and outcome were recorded. Results: Four hundred and sixtyseven patients with the diagnosis of gastric cancer within the study period were found and radically resected. Only three hundred and seventy patients reached the 5-year follow-up period. One thousand four hundred and sixty eight endoscopies were performed in total. The average number of endoscopies per patient was 3.96, and mean time between endoscopies was 11.7 months. Of the 370 resected cases with a five-year follow-up period, 129 (34.9%) developed a recurrence: 12 locoregional, 59 peritoneal, 45 metastatic disease, 13 local and peritoneal. Routine endoscopy was able to detect asymptomatic isolated locoregional recurrence only in 2 (1.55%) patients. Only in three (3/129 = 2.3%) patients the recurrence was resectable and the patients lived respectively 41, 49 and 107 months after recurrence. Ten out of the 12 locoregional recurrences were symptomatic (83.3%), and were not detected by routine endoscopies. These patients were unresectable with a median survival of 9.78 months (CI 2-20 months). Conclusions: In our experience, routine endoscopy has limited usefulness for the detection of resectable asymptomatic gastric cancer recurrences. The majority of recurrences are not detected by routine endoscopy, but present with symptoms that require further investigation. Randomized cost-efficiency studies are needed to confirm these findings.
Phagocytosis of Co-Developing Neutrophil Progenitors by Dendritic Cells in Culture with Granulocyte-Colony Stimulating-Factor and Tumor Necrosis Factor-α: Induction of T Regulatory Cells by Co-Developing Dendritic Cells.
Authors: Yoshinobu Saito, Makoto Hirokawa, Kunie Saito, Yong-Mei Guo, Miwa Hebiguchi, Yoshinari Kawabata, Atsushi Komatsuda, Naoto Takahashi, Junsuke Yamashita, Ken-ichi Sawada
Journal: Blood (2006)
Does phase I radiotherapy dose of 30.6Gy in 17 fractions provide adequate microscopic nodal disease control in squamous cell carcinoma of the anus?
Authors: Yolanda Sydney Augustin, Diana M. Tait, Maria Hawkins
Journal: Journal of Clinical Oncology (2012)

588 Background: Definitive chemoradiation has been established as the standard of care for patients with squamous cell carcinoma of the anus. The ACT II study recommends 30.6Gy in 17 fractions for Phase I to the lower pelvis with a superior border 2 cm above the inferior aspect of the sacro-illiac joints, then a Phase II boost of 19.8Gy in 11 fractions to the tumor and involved nodes. Our goal was to retrospectively evaluate patterns of failure in the volumes that received microscopic dose 30.6Gy. Methods: Between January 2002 and December 2008, 106 patients with non-metastatic squamous cell carcinoma of the anus were treated with definitive chemoradiation. 81 (76.45%) of these patients received Phase I dose of 30.6Gy.The tumor stage was Tx or T1 in 18 % , T2 in 36% , T3 in 29%, and T4 in 12% of patients. The nodal stage was N0 in 57%, N1 in 13%, N2 in 14% and N3 in 11% of patients. The median radiotherapy dose was 50.4 Gy (range 50.4Gy -60 Gy). Concurrent chemotherapy was given with 5-fluorouracil (5-FU) and cisplatin in 12%, 5-FU and mitomycin C in 34%, capecitabine and mitomycin C in 38% and other regimens in 8% of patients. The median follow-up interval was 43 months (range 3.2 - 112.9 months). Results: A total of 21 patients (19.8%) experienced persistent or progressive disease during follow up. Out of this total, 16 patients received 30.6Gy in Phase I. Of these, 5 patients (4.7%) had persistent disease at the end of chemo-radiation, 4 patients (3.7%) relapsed in the anal region, 2 patients (2.4%) relapsed in the 30.6Gy area and 5 patients (6.2%) developed metastases. 8 patients with local recurrence/persistent disease underwent salvage surgery. Estimated 3 year rates for locoregional control and overall survival were 78% and 82% respectively. Conclusions: The majority of locoregional failures involve the anus and mesorectum, while nodal recurrence occurs rarely supporting the use of 30.6Gy for microscopic nodal disease control. This makes the case for dose escalation of primary tumours in Phase II. Placing the superior border of the radiotherapy field at 2 cm above inferior sacroiliac joints for phase I could potentially spare bone marrow and small bowel toxicity with minimal risk of nodal relapse.