tbuckley/cabot-search huggingface dataset:
MGMT promoter methylation status in metastatic melanoma patients receiving first-line temozolomide plus bevacizumab (SAKK 50/07).
Authors: A. F. Ochsenbein, P. Schraml, D. Mihic, M. Simcock, R. Dummer, O. Michielin, B. Seifert, M. R. Schlaeppi, H. Moch, R. von Moos
Journal: Journal of Clinical Oncology (2010)

8558 Background: The O6-methylguanine-methyltransferase (MGMT) promoter methylation status is a predictive parameter for the response of malignant gliomas to alkylating agents such as temozolomide (Tem). First clinical trials with Tem plus bevacizumab (Bev) therapy in metastatic melanoma (MM) patients are ongoing, yet the predictive value of the MGMT promoter methylation status remains unclear. Methods: We assessed MGMT promoter methylation in primary tumor tissue of 62 MM patients treated with first-line Tem and Bev from the trial SAKK 50/07 by methylation-specific polymerase chain reaction. The MGMT promoter methylation status could be assessed in 42 patients only due to missing paraffin blocks or too less DNA. In addition, the MGMT expression level was analyzed by MGMT immunoreactivity, assessable in 53/62 patients. Analyses used chi-squared test for association and log-rank test for comparison of Kaplan-Meier curves. Results: Eleven of 42 analyzable melanoma tissues (26.2%) revealed a methylated MGMT promoter. Promoter methylation was significantly associated with overall RECIST response CR+PR vs. SD + PD (p < 0.0153). Also, patients with methylated MGMT promoter showed prolonged progression free survival although this was non significant (8.1 vs. 4.0 months; p = 0.1861). Immunohistochemically detected MGMT expression levels were also related to overall disease stabilization CR + PR + SD vs. PD (p = 0.0519). Conclusions: A significant number of melanomas have a methylated MGMT promoter. The MGMT promoter methylation status may also represent a potential predictive marker for Tem plus Bev therapy in MM patients. Larger sample sizes may help to detect significant differences in survival type endpoints. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Essex Pharma, Roche Roche
The efficacy and safety of lenalidomide plus dexamethasone in relapsed or refractory multiple myeloma patients with impaired renal function
Authors: D. M. Weber, A. Spencer, M. Wang, C. Chen, M. Attal, R. Niesvizky, M. Prince, Z. Yu, R. Knight, M. A. Dimopoulos
Journal: Journal of Clinical Oncology (2008)

8542 Background: Renal impairment (RI) is common among patients (pts) presenting with myeloma (MM) and requires aggressive early intervention. Two recently published phase III trials showed significant benefit after treatment with lenalidomide plus dexamethasone (Len/Dex) over Dex alone for pts with refractory or relapsing MM. Methods: In pooled data, 682 pts with serum creatinine (Cr) ≤2.5 mg/dL received treatment at a starting dose of 25 mg/day Len on days 1–21 and 40 mg/day Dex on days 1–4, 9–12, and 17–20days 1–4, every 28-day cycle. We now evaluate efficacy and safety of Len/Dex and Dex alone in the subgroup of pts who had normal (CLcr >80 mL/min), mild (50≤ CLcr <80 mL/min), moderate (30≤ CLcr <50 mL/min), or severe (CLcr <30 mL/min) RI despite Cr ≤2.5mg/dL. Results: Len/Dex significantly improved time-to-progression and response rate compared with Dex for pts with normal to moderately impaired RI (Table; P<0.001); in severe RI TTP was significantly longer with Dex alone, but shorter than for pts without RI or with mild RI. At the starting doses for Len and Dex, the limited number of pts with CrCl < 30 mL/min had a higher percentage of myelosuppression compared with those with CrCl > 30 mL/min (Table). In pts treated with Len/Dex, 78% (42/54) of those with moderate to severe RI had improvement in renal function within 4 months of treatment. Conclusions: Pts with moderate or severe RI respond equally well to treatment with Len/Dex for relapsed or refractory MM. With careful monitoring of adverse events and appropriate dose adjustments, this study showed that a favorable outcome could be achieved with Len/Dex despite renal impairment. Prospective trials will define the activity and tolerability of Len/Dex in patients with RI. Treatment group CLcr < 30 mL/min P 30 ≤ CLcr < 50 mL/min P 50 ≤ CLcr < 80 mL/min P CLcr > 80 mL/min P Len/Dex (n=16) Dex (n=12) Len/Dex (n=42) Dex (n=34) Len/Dex (n=125) Dex (n=132) Len/Dex (n=158) Dex (n=163) Response rate, % ORR 50.0 25.0 0.205 61.9 20.6 0.001 64 19.8 <0.001 63.9 27.0 <0.001 CR 6.3 8.3 21.4 0.0 12.8 2.3 16.5 1.8 VGPR 31.3 0.0 11.9 0.0 21.6 2.3 13.9 4.3 PR 12.5 8.3 26.2 20.6 27.2 15.2 32.9 19.0 Efficacy, months Median TTP 7.9 4.7 0.031 11.4 2.8 <0.001 12.1 4.7 <0.001 11.3 4.7 <0.001 Overall survival 18.6 16.9 0.849 30.4 12.5 0.068 34.7 27.2 0.131 NR 101.2 0.142 Adverse events, % Neutropenia 37.5 8.3 0.184 42.9 5.9 <0.001 39.2 1.5 <0.001 31.0 4.3 <0.001 Thrombocytopenia 37.5 >0.0 0.024 19.0 17.6 1.00 16.0 5.3 0.007 7.0 5.5 0.649 Thrombotic episodes 6.3 8.3 1.00 14.3 2.9 0.122 12.0 6.1 0.126 11.4 1.8 <0.001 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Celgene Celgene Celgene Celgene Celgene
Perioperative management of radical cystectomy patients: A questionnaire survey of the American Urological Association members.
Authors: Hong Truong, Jeffrey Nix, Kamal Smith, Aayush Mittal, Piyush Agarwal
Journal: Journal of Clinical Oncology (2013)

316 Background: Radical cystectomy (RC) is the standard treatment for patients with muscle invasive bladder cancer. RC is associated with more post-op complications and longer length of stay (LOS) after surgery than other urologic procedures. There is little information about peri-op pathways in the urologic literature. This study investigates practice patterns of urologists in the United States on peri-op management of bladder cancer patients undergoing RC. Methods: All AUA members were invited via email to an online survey from April to August 2012. The 31-items questionnaire of multiple choice and open-ended questions related to training, practice, and peri-op protocols. Results: A total of 375 urologists participated in the survey, 28.9% have oncology fellowship training, 46.4% training in robotic RC, and 30.1% perform robotics or laparoscopy. Of participants, 41.6% follow a clinical pathway however most utilize experience/training rather than an evidence-based protocol. Even with current evidence for enhanced recovery after surgery (ERAS) only 39.5% of respondents perform pre-op nutritional assessment. Most require a prolonged fast, no carbohydrate loading, and give all patients bowel prep pre-op. Most administer antibiotic prophylaxis before incision and continued 24 hrs, however only ~1/3 administer thromboprophylaxis pre-op, 15% give neither pre or post-op. Of respondents only 5% initiate a diet on post-op day (POD) 1 or before. 38.6% routinely send patients to ICU after surgery. Epidural, narcotics, or NSAIDs are commonly used for pain control, narcotics being the most common. Overall first flatus is reported on POD3 to 4, first bowel movement on POD4 to 5. Most patients are discharged on POD6 to 7. Urologists with oncology fellowship stated shorter LOS compared to those without (POD6.19 vs 6.64). Those doing open RC stated longer LOS compared to those doing robotic or laparoscopic RC (POD6.54 vs 6.03). Conclusions: ERAS studies have shown objective parameters that can improve peri-op outcomes. However, this survey shows significant individual differences in peri-op management of bladder cancer with the majority of urologists using personal experience as their primary guide.
Does adjuvant treatment affect survival in patients with positive lymph nodes at radical prostatectomy?
Authors: Catherine R. Harris, Clint Cary, Janet E. Cowan, Matthew R. Cooperberg, Peter Carroll
Journal: Journal of Clinical Oncology (2014)

157 Background: Men who are found to have positive LN at the time of RP are at risk for worse prognosis and outcomes. Our purpose is to determine whether RT after RP has a greater survival benefit than ADT alone or surgery alone in these men. Methods: This study cohort consisted of men who had RP at the University of California, San Francisco. Men with positive pelvic LN were stratified by type of adjuvant therapy: ADT, RT with or without ADT, or RP only. T-test and chi-square were used to compare clinical and pathologic characteristics. Biochemical recurrence-free, metastatic recurrence-free, and disease-specific survival were assessed with the Kaplan-Meier method, log-rank test, and Cox proportional hazards regression. Biochemical recurrence was defined as two consecutive prostate-specific antigen values &gt;=0.2ng/mL. Results: Of the 1,600 men had pelvic LN dissection at time of RP, 105 had positive LN. Mean age was 61 (SD 7). Median number of LN dissected was 14 (IQR 10-21) for pN1 patients versus nine (5 to 15) for pN0, p&lt;0.01. Median percentage of positive LN was 11% (IQR 7-17). Men with positive LN had higher clinical risk and worse pathologic grade, positive margin rates, and T-stage compared to men without positive LN, all p&lt;0.01. Recurrence-free survival was 55% for pN1 versus 81% for pN1 at 5 years, log-rank p&lt;0.01. Following positive LN dissection at RP, 29 men received ADT monotherapy, 43 men received RT (+/- ADT), and 33 had not yet undergone treatment after RP during a median follow up of 28 months (IQR 6 to 70). Rates of seminal vesicle invasion by treatment group were 52% for ADT, 65% for RT (+/- ADT), and 35% for RP only, p=0.03. Men who underwent ADT alone, RT (+/- ADT), and RP only had few outcome events to date and similar rates of MFS (97% versus 93% versus 92%, p=0.76) and DSS (96% vs. 100% vs. 100%, p=0.32) at 3 years. Cox regression adjusted for surgical CAPRA score also showed that MFS and DSS did not differ between ADT alone, RT (+/- ADT), and RP only groups. Conclusions: Men with positive LN at the time of RP have aggressive clinical and pathologic features. Nevertheless, metastatic recurrence-free and prostate cancer-specific survival rates 3 years after surgery remain good. Although no additional survival benefit to post-RP RT was seen in this cohort of men with limited follow up, further follow up is ongoing.
Age at diagnosis and treatment for prostate cancer (PC) in two distinct integrated health care systems.
Authors: Deanna S. Cross, Rezwan Islam, Crystal Jacobson, Mark A. Ritter, C. Daniel Mullins, Anitha Nallu, Arif Hussain
Journal: Journal of Clinical Oncology (2013)

240 Background: An older age at diagnosis may affect the stage at which PC is diagnosed as well as the treatment decisions made by the providers and/or the patients. Here we compare two geographically and ethnically distinct PC cohorts to determine whether age affects treatment decisions. Methods: Populations- Marshfield Clinic (MC): individuals were included in the cohort if they were diagnosed with PC between January, 2005 and December, 2010 and enrolled in a population based biorepository. Veterans Affairs (VA):– cohort included individuals diagnosed with PC between January, 2010 and December, 2010 within the Baltimore VA Medical Center (BVAMC). Retrospective chart review using electronic abstraction from the EMR was performed at each site. Statistical analysis was performed using the chi-square test for categorical variables or Fisher's exact test if the cell size was under 5. Results: Compared to the MC population, the VA population had a younger median age at diagnosis (63 vs. 68), more African American men (63% vs. 0.5%) and exhibited higher median PSA at diagnosis (7.92 vs 5.78 ng/dL). Seventy nine percent of VA and 87% of MCpatientswere stage 1 or 2 at diagnosis (p=0.03). Stage was not associated with older age (age &gt;/= 75) in either population. Individuals in the VA system were more likely to receive radiation (48% vs. 16%) and less likely to receive surgery than the MC population (18% vs. 59%). There were also several similarities in treatment decisions amongst these different populations. For instance, individuals with an older age (&gt;/= 75 vs. other age categories) at diagnosis were more likely to receive non-aggressive treatments such as hormonal therapy or no treatment (&gt;67% vs. &lt;15% p=0.0001). Because the stage at diagnosis may affect treatment decisions, we also investigated treatments for stage 2 disease; in this category, individuals &gt;/= 75 were still more likely to receive less aggressive treatment at both MC and BVAMC (&gt;29% versus &lt;3.4%, p=0.0001). Conclusions: This initial analysis suggests that individuals with an older age at diagnosis are more likely to receive non-aggressive treatment even when the stage of disease is the same as that of a younger individual across two distinct patient populations.
Relapse in breast cancer: How much mode of breast cancer detection matters? Results from an Italian national cancer institute.
Authors: A. Crispo, G. D'Aiuto, M. Grimaldi, M. Rinaldo, M. Barba, I. Capasso, G. Botti, G. Caolo, K. Tsapakina, M. D'Aiuto, A. Amore, M. Di Bonito, M. De Laurentiis, G. Frasci, M. Montella
Journal: Journal of Clinical Oncology (2011)

e12012 Background: The reasons for variation in breast cancer survival are multifactorial. In patients diagnosed with early breast cancer, evidence has emerged relatively to more favorable outcomes associated with disease detection in a screening context. Methods: To investigate whether mode of breast cancer detection may affect patient important outcomes following breast conservative therapy (BCT). We analyzed data on 448 patients with early breast cancer treated at the National Cancer Institute of Naples between January 2004 and June 2006. Breast cancers were categorized into mammography- and self-detected (MG and S-D) cases. The actuarial survival rates were calculated using the Kaplan–Meier method, and statistical significance differences between rates were evaluated by the log-rank test. Cox proportional hazard model was used for multivariate analysis including tumor characteristics, use of systemic therapy, and age to assess risk factors for local and distant metastasis free survival (LRFS, and DMFS respectively), and overall survival rates (OS). Results: The median follow up duration was 61,2 months (range 4-83). The 5-year DFS and OS for MG and S-D breast cancer cases were 89.7% and 73.1% (p = 0.001) and 93.5%.vs. 82.1 (p = 0.007), respectively. On multivariate analysis, mode of breast cancer was a significant predictor of DFS, with hazard ratio (HR) for MG detected cases being 2.11 (95% CI 1.04-4.86). In the same group, a suggestion for a predictor role on OS was given (HR 2.6, 95% CI 0.92-7.57). Conclusions: Following BCT, mammographic detected early breast cancer cases showed a significant advantage in terms of DFS and a non significant improvement in OS. mode of breast cancer detection might further add to the decision process leading to individualized patient management.
Somatic mutation detection from liquid biopsy-derived cellular aggregates formed by magnetic 3D bioprinting.
Authors: Hubert Tseng, Cristian Ionescu-Zanetti, Jeff Jensen, Jacob A Gage, William L Haisler, Pujan K Desai, Angela Liao, Reynolds Brobey, Mehdi Dehghani, Glauco R Souza, Robert J. Amato
Journal: Journal of Clinical Oncology (2016)

291 Background: A challenge in the analysis of circulating tumor cells (CTC) is their scarcity, and the inability to expand them for further analysis. To overcome this obstacle, we used magnetic 3D bioprinting to form CTC spheroids that could grow. The principle of magnetic 3D bioprinting is the magnetization of cells with nanoparticles and their subsequent printing into spheroids. For this project, CTCs can be aggregated into close contact to interact and grow in culture. In this study, we demonstrated the ability to aggregate CTCs and perform next generation sequencing (NGS) to detect somatic mutations from renal and prostate cancers. Methods: Blood samples from prostate and kidney cancer patients were enriched for CTCs (Isoflux, Fluxion), from a starting blood volume of 7.5-14 mL. CTCs were isolated immunomagnetically for EpCAM+ EGFR+ cells, then enumerated for CK+ CD45-. The cells were then removed of microbeads, then magnetized by incubation with NanoShuttle (NS, Nano3D), a magnetic nanoparticle assembly, and printed into spheroids in 384-well plates. After 4 d of growth, the cells were lysed and DNA was amplified by whole genome amplificaiton (WGA) with the NGS kit (Fluxion) and quantified via qPCR. Targeted libraries were sequenced using the PGM (ThermoFisher) sequencing instrument; data was analyzed using a customized variant calling/filtering pipeline based on standard Ion Reporter alignment tools and VarSeq for variant filtering and functional interpretation. Results: CTCs were successfully aggregated using magnetic 3D bioprinting, and grew over 4 d. We then demonstrated the detection of somatic variants within a majority of the samples, for both prostate and renal cancers. Using the commercial Oncomine, we found a median of 5 COSMIC variants (32 total) per sample using cell cultures. Conclusions: We successfully developed methods to aggregate CTCs with magnetic 3D bioprinting, expanded them, and then detected somatic mutations using NGS.
Multiple cases of squamous cell carcinoma of the tongue and oral cavity in patients treated with long-term pegylated liposomal doxorubicin (PLD) for ovarian cancer.
Authors: T. L. Cannon, F. Muggia, D. Hirsch, E. A. Andreopoulou, A. R. Kerr, M. D. DeLacure
Journal: Journal of Clinical Oncology (2011)

5557 Background: Long-term maintenance therapy with PLD has been explored as a treatment for relapsed ovarian cancer (Andreopoulou et al. Ann Oncol 2007; 18:716-21). Our institution has monitored a cohort of patients on this therapy for side effects and secondary malignancies. Methods: We report on four patients receiving long-term PLD for advanced stage ovarian cancer who developed malignant and/or pre-malignant lesions of the tongue and/or oral cavity. Results: All four patients had received maintenance therapy with PLD for periods of at least three years. Three patients were diagnosed with squamous cell carcinoma (SCC) of the tongue and/or oral cavity, and one with sublingual mucosa high-grade dysplasia. Noteworthy was a patient with three separate SCCs of the oral cavity. Three of the four patients had deleterious BRCA mutations. None of the patients were former smokers. Immunohistochemical staining for p16 was negative in all of the SCC specimens. Conclusions: Secondary cancer of the oral cavity followed long-term PLD treatment of patients with recurrent ovarian cancer. These findings have implications on surveillance and preventative measures for this population. Patients with secondary oral SCC/dysplasia. Diagnosis Duration of treatment with PLD (months) Cumulative dose of PLD (mg/m2) Age at ovarian cancer diagnosis Age at oral cancer diagnosis HPV status Outcome T1N0M0 SCC of the tongue 96 1,800 65 76 - Died of cardiogenic shock. Sublingual dysplasia 132 2,320 55 67 - Alive; no evidence of malignancy at this time. T2N0 SCC of the tongue 32 2116 67 71 - Alive; no evidence of either malignancy at this time. Multi-focal oral SCC with three separate T1N0 lesions: left retromolar, anterior hard palate, and right buccal mucosa 80 3000 43 52 - Partial response to chemotherapy for oral SCC refractory to XRT. No evidence of ovarian cancer recurrence.
Harvesting lymph nodes in gastric cancer surgery: A prospective randomized controlled study.
Authors: Toru Aoyama, Hirohito Fujikawa, Junya Shirai, Kameda Yoichi, Haruhiko Cho, Tsutomu Hayashi, Yasushi Rino, Shinichi Hasegawa, Takashi Oshima, Munetaka Masuda, Mari Saito Oba, Satoshi Morita, Takaki Yoshikawa
Journal: Journal of Clinical Oncology (2014)

28 Background: Harvesting lymph node (LN) after gastrectomy is essential for accurate staging. Conventional method (CONV) to retrieve LN immediately after surgery is accepted in Japan but its efficacy and quality highly depends on the case and examiners. Another method is to retrieve LN stained by methylene blue dye (MBD), by which the physicians may easily pick up blue LN. This trial evaluated the efficiency and quality of both methods in randomized fashion. Methods: Key eligible criteria are as follows. (i) Histologically proven adenocarcinoma of the stomach, (ii) Clinical stage I-III, (iii) R0 resection is planned by gastrectomy with D1+ or D2 lymphadenectomy. Examiners for harvesting LN are qualified based on the experience. After curative surgery, LNs are harvested from the specimen immediately after surgery in the CONV group and from the specimens who had been fixed with 10% buffered formalin with methylene blue for 48 hours in the MBD group. The primary endpoint is the ratio of the pathological number of the harvested LNs per time (minutes) as an efficacy measure. The secondary endpoint is the pathological number of harvested LNs as a quality measure. The sample size was determined to be 60 considering the primary measurement as 40 LNs / 30 minutes in CONV and 40 LNs / 22.5 minutes in MBD with two-sided alpha error of 5% and statistical power of 80%. Results: Between August 2012 and December 2012, 60 patients were assigned to CONV (n=29) and MBD (n=31). Total/subtotal gastrectomy was 12/17 in CONV and 12/19 in MBD, respectively. D1+/D2 was 17/12 in CONV and 15/16 in MBD, respectively. Baseline demographics were well balanced between the both. The number of pathological harvesting LNs (median, range) was 32 (11-57) in CONV and 41 (17-79) in MBD (P=0.005). The time per case for harvesting LN (median, range) was 33 (15-58) minutes in CONV and 25 (13-102) minutes in MBD (p=0.743). The ratio of the number of the harvested LNs per time (median, range) was 1.12 (0.42-2.07) in CONV and 1.42 (0.50-3.07) in MBD (p=0.01). Conclusions: When harvesting LN in gastric cancer surgery, methylene blue dye-assisted technique is superior in the efficacy and quality as compared with conventional method. Clinical trial information: UMIN000008624.