tbuckley/cabot-search huggingface dataset:
Is median survival time difference a good measure of effectiveness in the individualized medicine era?
Authors: K. Yoshimura, S. Teramukai, K. Yamazaki, Y. Ohe
Journal: Journal of Clinical Oncology (2011)

e16522 Background: We encountered a discrepancy among survival summary measures in a randomized controlled trial (RCT) report of targeted therapies, for example, erlotinib for pancreatic (NCIC PA.3), bevacizumab for breast (AVADO) and gefitinib for lung cancer (IPASS). The NCIC PA.3 trial is the first to show the significant survival benefit compared to gemcitabine monotherapy, yielding hazard ratio (HR) of 0.82 (log-rank p of 0.038); however, in median, the benefit is only 10 days. It can produce an inconclusive result that makes it difficult to translate evidences to practice. Methods: For a statistical clarification of the discrepancy among the measures, we conducted a model-based study under the scenarios with several trial settings. The simulations corresponded to trials with 400 patients randomly assigned to 2 arms. With considerations for development of an individualized medicine, we additionally defined not only prognostic subgroups but predictive subgroups consisted of sensitive patients, who became long-term survivors only if receiving a targeted therapy. The results are summarized using empirical power under nominal alpha level. Results: The comparison based on HR estimate or log-rank test had favorable performance, that is, the alpha error and the power were always closer to nominal levels. The performance of median survival time comparison strongly depended not only on the hazard around median but also on the existence of prognostic and predictive subgroups. The power of median survival time comparison was always considerably lower than logrank test, especially under the scenarios with prognostic and/or predictive subgroups (Table). Conclusions: The HR estimate and log-rank test can provide a confirmative interpretation of well-conducted RCT results. We should take considerable care in interpreting the difference of median survival time, especially in targeted therapy RCTs. Power of log-rank test Power of median survival time comparison Without subgroups, overall HR of 1.4 92% 82% With predictive but not prognostic subgroups, overall HR of 1.4 94% 60% With prognostic and predictive subgroups, overall HR of 1.3 (attenuated by a prognostic factor) 86% 43%
Stereotactic body radiation therapy in the treatment of unresectable intrahepatic cholangiocarcinoma.
Authors: J. O'Connor, R. Goldstein
Journal: Journal of Clinical Oncology (2011)

335 Background: Unresectable intrahepatic cholangiocarcinoma has a poor prognosis with less than 5% of patients surviving 5 years. We review our experience with stereotactic body radiation therapy (SBRT) in the treatment of unresectable intrahepatic cholangiocarcinoma and evaluate acute toxicity and local control. Methods: From November 2005 until August 2010, 12 patients with unresectable intrahepatic cholangiocarcinoma were treated with SBRT. All patients were evaluated by a liver surgeon and were deemed unresectable prior to radiosurgery. The median tumor size was 4.3 cm (range 1.9–9.3 cm). All tumors were located in the right hepatic lobe. Three patients had received prior radiation therapy and SBRT was given as a boost with a median dose of 24 Gy in three fractions. Nine patients received SBRT as the sole local modality to a median dose of 51 Gy (range 30–55 Gy) in three fractions on consecutive days. Local control was determined by follow-up imaging with MRI. The median follow up is 12 months. Toxicity was assessed using Common Toxicity Criteria (CTC) guidelines version 3.0. Results: Overall, only 3 of 12 (25%) patients experienced acute toxicity. Three patients had abdominal discomfort and one patient had nausea. All toxicities were grade 1. Ten of 12 (83%) patients received chemotherapy. Four patients received chemotherapy before SBRT and five patients received chemotherapy after. One patient received chemotherapy before and after SBRT. Overall local control is 75% for eight patients with follow-up imaging. Two of eight (25%) patients had a complete response. Four of eight (67%) patients had a partial response or stable disease. One patient had a local recurrence 13 months after receiving SBRT (51 Gy in three fractions) and was retreated with SBRT (28 Gy in three fractions) with no acute toxicity. There was no difference in outcome whether SBRT was given before or after chemotherapy. Conclusions: Stereotactic body radiation therapy given sequentially with chemotherapy is well tolerated with few side effects in the treatment of unresectable intrahepatic cholangiocarcinoma and early local control is promising. No significant financial relationships to disclose.
Computer-aided volumetry analysis in assessing pulmonary chemotherapy response in advanced NSCLC comparing with RECIST criteria.
Authors: L. Ding, R. L. Bliss, M. Ingebrand, T. Allen, P. Ives, A. Dudek, R. A. Kratzke
Journal: Journal of Clinical Oncology (2011)

10593 Background: Assessing of therapeutic tumor response in clinical trial by Response Evaluation Criteria in Solid Tumors (RECIST) was suggested to carry high variability. Computer-aided volumetry analysis for pulmonary nodules has demonstrated better sensitivity and reproducibility than RECIST criteria, however mostly on phantom nodules. There are no studies testing volumetry analysis on disease response in a clinical trial. Methods: We identified 28 patients with valid pulmonary lesions from a phase II clinical trial using new chemotherapy regimen in patients with stage IIIB/IV Non-small cell lung cancer. Up to five largest pulmonary lesions on pre-treatment CT and CT after 2 cycles of chemotherapy were analyzed using computer-aided volumetry software (LMS-lung/track, Median Technologies, Valbonne, France). Disease response on pulmonary lesions from volumetry analysis and from RECIST were compared. Progression free survival was correlated to the disease response analyzed by volumetry software and RECIST. Results: Total of 91 pulmonary lesions were analyzed on 56 CT scans. The patients with disease progression, stable disease or partial response determined by volumetry were 6 (21.43%), 13 (46.43%) and 9 (32.14%) respectively. The pulmonary progression, stable disease and partial response by RECIST were 1 (3.57%), 23 (82.14%) and 4 (14.29%). The difference was statistically significant by Bhapkar’s test of marginal homogeneity (p-value 0.0046). Among stable disease categorized by RECIST, 5 cases were determined to be progressive disease by volumetry, 7 cases were diverged into partial response category. From Wald Test of Cox regression model, the volumetry analysis is better at predicting progression-free survival (p-value 0.3650 for RECIST, p-value 0.0688 for volumetry). Conclusions: Volumetry analysis may identify disease progression or response earlier than RECIST criteria. It also predicts PFS better compare to RECIST.
Moderators of acupuncture effectiveness in breast cancer survivors: Randomized clinical trial (RCT).
Authors: Oxana Palesh, Nadia Haddad, Rosa Schnyer, Eric Neri, M. Melissa Packer, Jamie M. Zeitzer, Rachel Manber
Journal: Journal of Clinical Oncology (2016)

162 Background: The popularity of acupuncture among cancer patients highlights the need for studying its effectiveness for mitigating side effects of cancer treatments. Insomnia is prevalent among cancer patients and is associated with fatigue and reduced quality of life (QOL). It is also closely linked with depression, sleep apnea, and circadian disruption. Using data form an RCT of acupuncture for insomnia among breast cancer survivors, we examined depression, apnea and circadian factors as moderators of acupuncture effectiveness. Methods: 68 breast cancer survivors (54 years, SD = 9) experiencing insomnia symptoms were randomized to receive 12 sessions of acupuncture (N = 34) or sham (N = 34; using placebo needles). Measures included the Insomnia Severity Index, Brief Fatigue Inventory, and FACT—G, obtained at baseline, mid-treatment (3 weeks), end of treatment (6 weeks), and follow-up (10 weeks). Results: Although acupuncture produced significant improvements from baseline to follow-up in insomnia symptoms, fatigue, and QOL, these improvements did not differ from sham. Compared to sham, the acupuncture produced significantly greater improvements in: 1) insomnia severity (p = 0.03) and QOL (p = 0.02) among those with greater tendency for morning chronotype; 2) fatigue (p = 0.01) among those with lower apnea risk; and 3) QOL (p &lt; 0.001) among those with lower depression scores at baseline. Conclusions: These findings suggest that acupuncture might be more effective among certain subgroups of patients. Moderators of insomnia, fatigue, and QOL include morningness tendency, lower risk for sleep apnea and lower depression scores, respectively. Our findings on depression are in line with prior research that has found that patients with less severe depression may have a greater capacity for acupuncture response perhaps due to higher availability of serotonin. Additional research is needed to test whether acupuncture is a viable treatment option for subgroups of cancer survivors with insomnia. Clinical trial information: NCT01162018.
Software-assisted Computed Tomography Quantification of Airway Remodeling in the Normal Aging Process
Authors: Sébastien Bommart, Hélène Kovacsik, Isabelle Vachier, Nicolas Molinari, Arnaud Bourdin
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

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Pathologic complete response rates after neoadjuvant treatment in rectal cancer: An analysis of the NCDB.
Authors: Patrick D. Lorimer, Russell C. Kirks, Danielle Boselli, Anthony Joseph Crimaldi, Joshua S. Hill, Jonathan C. Salo
Journal: Journal of Clinical Oncology (2016)

713 Background: Pathologic complete response (pCR) of rectal cancer following neoadjuvant therapy is associated with decreased local recurrence and increased overall survival. The present study utilizes a large national dataset to identify predictors of pCR in rectal cancer. Methods: The NCDB was queried for patients with non-metastatic rectal cancer (2004-2011) who underwent neoadjuvant therapy (regional radiation dose 4500 cGy, boost dose 540 cGy) followed by surgical resection. Generalized linear mixed models were used to analyze the probability of pCR by hospital volume with adjustments for demographic, socioeconomic, staging, and tumor characteristics. Hospitals were separated into groups based on the number of resections performed per year &lt;2, 2-5, and 5+. To account for clustering of cases at individual hospitals, a random effect was used at the hospital level and covariates were included as fixed effects. Results: 7,859 patients met inclusion criteria from 951 participating hospitals. Generalized linear mixed models demonstrated that the odds of achieving pCR was independently associated with more recent diagnosis, female gender, private insurance, smaller tumor size, lower grade, lower clinical T-classification, increasing interval between the end of radiation and surgery, and treatment at higher volume institutions (Table). Conclusions: The incidence of pCR was associated with favorable tumor factors (size, grade, T classification), demographics (insurance status) as well as treatment factors (time between radiation and surgery and institutional volume). With the data available, it is not clear what is driving the higher rates of pCR at high volume institutions. Research specifically targeted at understanding processes which are associated with pCR in high volume institutions is needed so that similar results can be achieved across the spectrum of facilities caring for patients in this population. [Table: see text]
Impact of hepatic function and tumor extent on survival in patients with unresectable hepatocellular carcinoma treated with liver-directed therapies.
Authors: Marisa E. Hill, Sanjib Basu, Bulent Arslan
Journal: Journal of Clinical Oncology (2016)

358 Background: Transarterial chemoembolization (TACE) has demonstrated survival advantage over best supportive care in patients with unresectable hepatocellular carcinoma (HCC), and non-randomized data suggests that survival in HCC treated with yttrium-90 radioembolization ( 90 Y) is similar to that achieved with TACE. Eighty to 90% of patients with HCC have underlying cirrhosis, so survival analyses of liver-directed treatments (LDT) should take into account both tumor extent and liver function. Methods: We conducted a retrospective study to evaluate the effect of tumor extent and liver function on the survival of patients treated with TACE and/or 90 Y for HCC. Patients with unresectable HCC treated at Rush University Medical Center between 2002 and 2014 were analyzed. Liver function parameters prior to first treatment were recorded for each patient, and survival measured from time of first treatment to death or last follow up was calculated. Statistical inference for overall survival was performed using Kaplan-Meier method, log-rank test, and Cox proportional hazards regression model. Results: The difference in overall survival between patients with unilobar disease and with bilobar disease (n=35 and 23, median survival of 19.4 and 12.8 months, respectively) was not found to be significant (p=0.838). However, the difference in overall survival among patients with Child Pugh A (n=22, median not reached), B (n=30, median= 11.4 months) and C (n=6, median=3.8 months) cirrhosis was strongly significant (p &lt; 0.001). In a multivariate Cox proportional hazards analysis, the association of Child class (coded on an integer scale) with overall survival, adjusted by the extent of the disease, continued to be strongly significant (HR=1.93, p &lt; 0.001). Conclusions: Liver function may be just as important a determinant of survival in patients undergoing liver directed treatments for HCC as is extent of disease. Larger, prospective studies are needed to confirm this hypothesis.
Methylation ESR1 as a potential factor of resistence to HER2/neu therapy in patients with breast cancer.
Authors: Joaquina Martínez-Galán, Cynthia S. González Rivas, Julia Ruiz Vozmediano, Lucia Portellano, Juan Ramón Delgado
Journal: Journal of Clinical Oncology (2013)

24 Background: Estrogen receptor (ER)-positive breast cancers are considered prognostically more favorable than ER-negative tumors and are often responsive to anti-estrogen therapy. Whereas tumors overexpressing HER2 are endocrine resistant and they require the blockage of the HER2 pathway in addition to estrogen deprivation. To evaluate epigenetics differences in tumor-related genes to ESR1 and HER2/neu status in primary breast cancer is the objective of this study. Methods: We quantified methylation levels of promoter of ERS1 which are to confer growth adventage to cells in 107 women with breast cancer. Real Time QMS-PCR SYBR green (methylation-specific PCR) was used to analyze the hypermethylation. Tumours were classified as phenotype basal, luminal A, Luminal B, and phenotype HER2+. Results: Presence of methylated ESR1 in serum of breast cancer patients was associated with ER-negative phenotype (p=0.0179). Of the available cases, 60 pts (56%) were Luminal A, 10 pts (9.3%) Luminal B, 13 pts (12%) Basal like, and 9 pts (8.4%) HER2+. We observed that methylated ERS1 was preferably associated with phenotype Basal Like and worse interval progression free and survival global though p &gt; 0.05 and the amplification HER2+ was correlation with significant more frequent methylation gene (p&lt;0.05). Thet hypermethylation of normal ERS1 and 14-3-3σ combined differentiated between breast cancer patients and healthy controls (p = 0.0001) with a sensitivity of 81% (95% CI: 72–88%) and specificity of 88% (95% CI: 78–94%). Conclusions: This study identifies the presence of variations in global levels of methylation promoters genes in healthy controls and breast cancer with different phenotype classes and shows that these differences have clinical significance. These showed that frequent methylation had a strong association with molecular phenotype of breast cancer and perhaps in the future can explain therapy resistance related to RE and HER2/neu status and this may be of significance in the assessment of targeted therapy resistance related to ER and HER2/neu status in breast cancer patients.
TGFβ1 gene polymorphisms with the risk of radiation pneumonitis in non-small cell lung cancer in different ethnic study.
Authors: X. Niu, S. Lu, H. Li, Y. Liu, Z. Chen, D. Zhou, M. Kan, Z. Li, Y. Yu, C. LV
Journal: Journal of Clinical Oncology (2011)

10606 Background: To investigate whether non–small-cell lung cancer (NSCLC) patients in Chinese with risk of radiation pneumonitis (RP) (grade≥3) by radiotherapy display reliable single nucleotide polymorphisms (SNPs) marker(s) located in transforming growth factor 1 (TGFβ1) gene. Methods: DNA was isolated from blood samples obtained from NSCLC patients (n=167) treated with deﬁnitive radiotherapy alone (n=125) or concurrent chemoradiation (n=42). Eight SNPs of the TGFβ1 gene (rs1800469, rs1800471, rs1982073, rs4803455, rs11466345, rs12983047, rs10417924, and rs10980942) were genotyped by direct DNA sequencing method. Kaplan-Meier cumulative probability was used to assess the risk of grade≥3 RP and Cox proportional hazards analysis to evaluate the effect of TGFβ1 genotypes on such risk. Results: There were 125 men and 42 women in the study with median age of 58 years. 53 (31.7%) patients developed grade 2 RP, 46 (27.5%) developed grade≥3 RP, respectively, based on CTCAEv3.0. SNP rs1982073 with RP risk in Caucasians was failed to validate to associate with the risk of grade≥3 RP in Chinese NSCLC patients. Multivariate analysis found AG/GG genotypes of novel TGFβ1 rs11466345 to be associated with a statistically signiﬁcantly higher risk of RP grades≥3 (HR=2.295; 95% CI, 1.101 to 4.783; P=0.027), compared with the AA genotype, after adjustment for age, smoking status, and dosimetric parameters. Conclusions: Our results showed that AG/GG genotypes of novel TGFβ1 rs11466345 were associated with higher risk of RP in Chinese NSCLC patients treated with radiotherapy. Further studies are warranted to confirm these findings in different ethnic populations.
The quality of chemotherapy and surgery in reporting of metastatic colorectal cancer
Authors: R. C. Martin, V. Abdomerovic, K. M. McMasters
Journal: Journal of Clinical Oncology (2005)

3600 Background: Despite reports from numerous surgical and systemic clinical studies for patients with metastatic colorectal cancer (MCC) to the liver, there is limited ability to directly compare these results. As a result, patients with liver metastases often receive conflicting management recommendations. Therefore, the aim of this study was to evaluate the reporting of prognostic factors in clinical studies of MCC and define parameters for uniform study reporting. Methods: Randomized clinical trials (RCT) and retrospective series (RP) of over 75 patients from 1980 to 2001 in MCC were reviewed to identify 10 critical prognostic elements of overall survival reported in both types of journals. Chi square was utilized to evaluate differences between factors. Results: Overall, there were 201 articles (91 RCT and 109 RP)with 63,589 patients analyzed. Results from systemic and surgical clinical studies were evaluated for the number of prognostic factors reported. A review of 201 reports found 0 (0%) reporting all prognostic factors and further evaluation of both RCT and RP demonstrated no significant difference in reporting criteria met (table). Factors found significantly greater in surgical trials were disease free interval, # hepatic metastases, and a lymph node postive primary compared to systemic trials with performance status and complication rates (p<0.001). Conclusions: The reporting of results in MCC in chemotherapy trials and surgical reports is limited to general outcomes with paucity of prognostic factors, which hinders any ability to compare to results across treatments. A mandatory reporting criteria of all metastatic colorectal trials is needed to better facilitate the interpretation and comparison of data from systemic therapy and surgical studies, and ultimately improve the therapeutic decision-making process for patients. No significant financial relationships to disclose.
Selective organ preservation with neoadjuvant chemotherapy in the treatment of muscle invasive transitional cell carcinoma (TCC) of the bladder.
Authors: Shaista Hafeez, Robert Anthony Huddart
Journal: Journal of Clinical Oncology (2013)

310 Background: Radiotherapy has been previously associated with high treatment failure for those with muscle invasive bladder cancer. Evidence suggests modern organ sparing approaches may have favourable outcome in appropriately selected patients. We investigate whether response to neo-adjuvant chemotherapy can guide selection for bladder preservation and identify those patients likely to have greater success with radical radiotherapy treatment. Methods: Retrospective analysis of 94 patients with T2-T4aN0M0 bladder TCC treated between January 2000 and June 2011. Patients received platinum based chemotherapy following transuretheral resection of bladder tumour, with repeat cystoscopy (+biopsy) performed to guide subsequent management. Poor responders were advised to proceed with surgery. We report on the outcome of 79 individuals who received radiotherapy. Results: 56 (60%) patients achieved complete response following chemotherapy (72% with stage T2). 15 (16%) patients achieved partial pathological response. 12 patients had radiological assessment of partial response made. 11 patients had poor response. All patients achieving complete response, 22 with partial response and 1 with poor response proceeded to radical radiotherapy. Median time to disease progression following radiotherapy was 17months (range 8-91). 5 patients developed invasive recurrence, 17 developed superficial recurrence, 4 developed local nodal disease and 7 developed metastasises. After median follow-up of 36 months (range 6-114), 50 patients were alive with no disease, 24 had died (14 from metastatic bladder cancer and 10 from other causes). 5 patients were alive with active disease (4 with localized and 1 with metastatic disease). 13 required cystectomy (9 for superficial disease, 3 for invasive recurrence, and 1 for treatment related toxicity). Of those alive and disease free 84% had an intact bladder. 82% had an intact bladder at last follow-up or death. Conclusions: Neoadjuvant chemotherapy followed by radical radiotherapy allows bladder preservation in over 80% of selected patients with survival rates comparable to contemporary surgical series.
Treatment of Progression of Myeloproliferative Disorders(MPD) to MDS/AML by Azacytidine (AZA) : A Preliminary Report on 17 Patients (pts)
Authors: Sylvain Thépot, Raphael Itzykson, Emmanuel Raffoux, Murielle Roussel, Caroline Dartigeas, Francois Dreyfus, Christian Recher, Sylvain Pilorge, Bruno Cassinat, Blandine Beve, Rose-Marie Mbida, Jean-Jacques Kiladjian, Lionel Ades, Pierre Fenaux
Journal: Blood (2008)