bluuebunny/crossref_metadata_2025 huggingface dataset:
Renal cell carcinoma (RCC) presenting as cancer of unknown primary (CUP): Diagnosis by molecular tumor profiling (MTP).
Authors: Hainsworth John D. , Spigel David R. , Greco F Anthony
Published: March 2020

e15501

Background: CUP is a heterogeneous clinicopathologic syndrome representing many types of occult clinically undetectable primary neoplasms. With the advent of MTP, the tissue of origin in CUP is frequently identified when used in concert with immunohistochemistry (IHC) and clinical features. Histopathology alone is usually not specific, and diagnostic IHC is often limited. Diagnosis of the RCC subset of CUP has important therapeutic potential given the availability of multiple approved biologic therapies, and the use of MTP may facilitate the correct diagnosis. Methods: 488 CUP patients (pts) seen between 2008 – 2012 had MTP (RT-PCR 92-gene assay, CancerTYPE ID, bioTheranostics, Inc.) of their archived tumor specimens. The clinicopathologic features were reviewed and, where feasible, subsequent additional IHC stains were obtained to support the MTP diagnosis. The response and survival to first-line RCC site-specific therapy were evaluated. Results: RCC was the MTP diagnosis in 22 pts (4.5%), including papillary in 8, clear cell in 7, and unknown subtype in 7. Histology included poorly differentiated carcinoma in 15 and adenocarcinoma in 7 (4 with papillary features, 1 with clear cell features). None had evidence of a primary renal lesion detectable by abdominal computed tomography, and the sites of metastasis most often included retroperitoneal nodes (63%), mediastinal nodes (31%), lung (22%), and bone (18%). Diagnostic RCC IHC stains were performed initially in only 3 tumors (14%), but RCC IHC stains (RCC, PAX 8, others) performed later supported the MTP diagnosis in 7 of 9 tumors where remaining tissue was available. 16 pts received first-line RCC targeted therapies (objective response rate was 18%, median survival of 13.4). Conclusions: RCC is a subset of CUP which can be diagnosed by MTP. RCC is usually not suspected in the absence of clear cell features, and occult RCC appears to commonly be the papillary subtype. RCC IHC may be diagnostic in some CUP tumors, but may be omitted in the initial pathologic evaluation. CUP-RCC pts are important to identify as they may benefit from standard RCC targeted therapies, and respond poorly to empiric chemotherapy.
Graded prognostic assessment index for renal cell carcinoma with brain metastases.
Authors: Garje Rohan , Dahiya Saurabh , Alva Venur Vyshak , Du Lingling , Osei-Boateng Kwabena , Elson Paul , Suh John H. , Chao Samuel T. , Ahluwalia Manmeet Singh
Published: March 2020

e15537

Background: The GPA is a commonly used prognostic index based on RTOG protocols in patients with brain metastases (BM). The purpose of this study was to evaluate the utility of GPA index in a contemporary cohort of renal cell carcinoma with brain metastases (RCCBM) at a larger tertiary care center to predict overall survival. Methods: IRB approval was obtained and the Cleveland Clinic Brain Tumor and Neuro-Oncology Center’s database was used to identify RCCBM patients (pts) treated in the recent era (2000-12). A proportional hazards model was used to assess OS, which was measured from the date of diagnosis of brain metastases to death or last follow-up. Results: 136 RCCBM (100 males), median age 60 years (range 32-79), were evaluated. Pts had a median of 2 (range 1-15) BM; Karnofsky Performance Scale (KPS) was 90-100 in 57%, 70-80 in 38% and <70 in 5%. Extracranial metastasis was present in 93% of pts. OS was 15.0 months (95% C.I. 10.9-17.5). GPA for RCC consists of KPS (90-100, 70-80, <70) and the number of BM present (1, 2-3, >3).GPA was not prognostic for survival (p=.40), and neither GPA coding of KPS nor BM (1, 2-3, >3) was associated with outcome (p=.90 and .26, respectively). In contrast, diagnosis of RCC to BM >5 years, p=.004, brain as an initial site of metastasis, p=.005, normal hemoglobin, p=.01, a single BM, p=.02, controlled primary, p=.02, and age≤65 were found to be independently prognostic for improved OS. Using these factors, an alternative index can be formed. Conclusions: RCCBM specific GPA was notprognostic for OS in this study (p=.40), however a new index was developed based on a revised set of independent prognostic factors that was significant (p<.0001). [Table: see text]
Treatment decision and outcome in mRCC patients with different ECOG performance status.
Authors: Harmenberg Ulrika , Stenmo Kajsa , De Flon Caroline , Wersäll Peter , Sandström Per
Published: March 2020

e15553

Background: Phase III studies with targeted agents have shown improved survival for mRCC. There is limited outcome data for the whole mRCC patient group. We collect data in a clinical registry at Karolinska for all patients with mRCC in the Greater Stockholm Region since 2007. Here we present the relationship between ECOG performance status and treatment outcome in this population. Methods: Between 2007 and 2012, 273 patients with mRCC were included in the registry. Patients were divided in two groups: Those that were treated with targeted agents and non- treated patients (symptomatically treated). Results: ECOG PS, available for 63%, was lower for patients treated (n=127) compared to patients not treated with systemic therapy (n=46) (median 1 vs. 2. Median OS from diagnosis to death in respective group was 731 day (n=106) and 269 days (n=55). The median OS from date of first metastasis to death was 500 days and 176 days respectively. In the treated group median OS from start of systemic therapy to death was 321 days. There was a difference in median OS from start of systemic therapy to death between patients who received 1 (n=52)(A), 2 (n=32)(B), 3 (n=16)(C) or > 3 lines (n=6)(D) with a median OS of 160.5 days, 395 days, 641 days and 728.5 days respectively. Mean PS at first line treatment was 1.36 for patients who received only one line and ≤ 1 for patients who received several lines. 13/18 patients with ECOG PS 0 at 1st line received >1 line, corresponding numbers for PS 1, 2 and 3 at 1stline were 21/40, 3/14 and 0/4. The average/ medians ECOG PS at time for the last treatment line were 1.36/1 (A), 1.47/1 (B), 1.64/2 (C) and 1.67/2 (D). Median OS from start of systemic treatment to death was dependent on PS at the start of treatment, ECOG 0 (n=18) 622 days, 1 (n=40) 724 days, ECOG2 (n=14) 226 days, ECOG3 (n=4) 44 days. Irrespective of treatment line, patients with PS 0-1 at initiation of any line of therapy had a 55% chance (47/86) of receiving a subsequent line of treatment, while patients with PS 2-3 only had a 19% chance (7/37). Conclusions: Patients with a good performance status, ECOG 0-1 at treatment start, had longer OS and received more lines of treatment. Patients with ECOG PS 3 could in our hands not be treated at all with targeted agents.
Final results from a trial of a combination herbal supplement for biochemically recurrent prostate cancer.
Authors: Dorff Tanya B , Tsao-Wei Denice D , Hawes Debra , Xiong Shigang , Quinn David I. , Gross Mitchell E. , Lieskovsky Gary , Vogelzang Nicholas J. , Groshen Susan G. , Pinski Jacek K.
Published: March 2020

e16020

Background: No standard exists for the treatment of bcrPC. Concern over deleterious effects of androgen deprivation (ADT) and lack of proven survival benefit in this setting makes initiation of ADT inappropriate for some patients. A non-hormonal, non-toxic agent to reduce PSA would be a welcome alternative to observation. We tested Prostate Health Cocktail (PHC), a supplement containing vitamin D & E, saw palmetto, lycopene, green tea and soy extracts, in this population, to see whether it could decrease PSA. Methods: Eligible men had a rising PSA with doubling time between 3 and 36 months, with no evidence of metastases on CT and bone scan. After IRB approval, 40 men were treated with PHC 3 capsules PO daily for 4 week cycles. PSA was repeated after cycle 1, then every 2 cycles thereafter with imaging only as clinically indicated; the primary endpoint was PSA decline. PSA progression was defined as 25% increase above baseline/nadir AND absolute increase of 5 ng/mL or return to baseline. Circulating tumor cells (CTCs) were measured at baseline and after 3 cycles using parylene membrane filters. Results: 60 men screened, 17 failed (28%). Median age was 67 (range 54-84) and baseline PSA 2.8 ng/mL (1.1-84.1). 23% had primary radiation only, 25% had prostatectomy, and 52% had both; 23% had Gleason 8-10. The median # of cycles was 8 (1-13). 15/40 men (37.5%) had a PSA decline (1.1%-55% maximum decrease). 43% stopped therapy for PSA progression, with median time to progression 10.2 months. Circulating tumor cells were detected in 5 of the first 23 subjects; complete CTC data will be presented. There was no significant change in testosterone or DHT during treatment. Toxicities possibly related to PHC included grade 1 or 2 liver enzyme elevations [transient], grade 1 or 2 gastrointestinal symptoms (9), grade 1 weakness/dizziness/pain (5), and grade 1 fatigue (2). 5 men continue on study, 3 lost to f/u, 16 have developed metastases, median time to mets 31.5 months from bcr. Conclusions: PHC induced PSA declines in 37% of patients with bcrPC, and was not associated with changes in serum androgens or significant toxicities. PHC is a potential alternative to observation in select patients with bcrPC. Clinical trial information: NCT00669656.
Critical evaluation of MRI-targeted TRUS-guided transperineal fusion biopsy for detection of prostate cancer.
Authors: Kuru Timur H. , Roethke Matthias , Simpfendoerfer Tobias , Boxler Silvan , Seidenader Jonas , Schlemmer Heinz-Peter , Hohenfellner Markus , Hadaschik Boris
Published: March 2020

e16063

Background: Precise staging of prostate cancer (PC) is essential for individualized treatment decisions. However, the majority of transrectal biopsies are negative for prostate cancer or show imprecise results. Additionally, the rate of upgrading in Gleason scores between biopsy and prostatectomy specimen is around 30-40%. MRI/TRUS fusion has shown encouraging results for detecting clinically significant prostate cancer. Methods: 412 consecutive patients with suspicion of PC were prospectively included in our database. The median age of patients was 65 years (range 42-84). Mean PSA level was 9.56 ng/ml (± 7.9ng/ml, SD). 55% of men had previous TRUS-guided biopsies, 45% underwent primary biopsy. Imaging data and biopsy results were analyzed and a self-designed questionnaire was send to all men regarding further clinical history and adverse effects of the biopsy. Results: In 236 of 412 (57.3%) biopsy samples showed PC. 71.6% of biopsy proven PC were clinically significant (D’Amico criteria). On multiparametric (mp)-MRI, 120 men were reported as highly suspicious for PC and in these tumor detection rate was 83.3% (100/120). In patients without cancer-suspicious MRI-lesions, 31,8% (42/132) men were diagnosed with significant disease (Table 1). Regarding adverse effects, 152 patients (49%) reported hematuria after biopsy. 9 patients (2%) needed temporary catheterization after biopsy due to prostate swelling. In three patients (0.7%) febrile urinary tract infection occurred after biopsy. Major limitation is the limited follow-up of 12-months of biopsy-negative patients. Conclusions: MRI-targeted TRUS-guided transperineal fusion biopsy provides high detection rates of clinically significant tumors. mp-MRI still has its limitations, and therefore systematic biopsies should currently not be omitted. The morbidity of the transperineal saturation approach is reasonable and mainly self-limiting. [Table: see text]
Phase I study of cisplatin (cDDP)/hyperthermia (HT)/lapatinib (Lap) in patients (pts) with recurrent carcinoma of the uterine cervix (rCC) in previously irradiated area (PIA).
Authors: Meerten Esther Van , Westermann A.M. , van Doorn H. C. , Franckena Martine , Kraan Jaco , Wiemer Erik A.C. , Sleijfer Stefan
Published: March 2020

e16504

Background: Pts with rCC in PIA might benefit from cDDP plus HT. Lap inhibits the intracellular tyrosine kinase domain of the epidermal growth factor receptor (EGFR) and HER2. Overexpression of EGFR and HER2 is often seen in pts with CC and might be involved in chemotherapy resistance. Besides, preclinical data suggest a synergistic effect of combining cDDP and Lap. Therefore, this phase I dose-escalation study was performed to determine the maximum tolerated dose (MTD) of Lap added to fixed doses of cDDP and HT. Methods: Pts with rCC in PIA, adequate organ function and ECOG performance status 0-1 were scheduled for 6 weekly administrations of 70 mg/m2cDDP plus locoregional HT. Daily Lap was added on days 1-56, starting at a dose-level of 1000 mg. The MTD was defined as the highest dose where ≤1/6 pts experienced dose-limiting toxicity (DLT). Safety, pharmacodynamics (PhD) and response were assessed. Results: Eight pts were treated. The first 4 pts (2 each at dose 1000 mg and 750 mg) experienced DLT. Of the 4 pts treated at dose level -2 (500 mg), only 1 pt was able to complete the treatment as planned, 2 pts experienced a DLT and 1 pt was not evaluable (NE), because of early progressive disease (PD) (see Table). In the evaluable pts 1 PD, 4 stable diseases and 2 partial responses (PR) were observed. One patient with PR had a resection of the local recurrence. Analysis of the resected specimen showed a pathological complete response (pCR). Enumeration of circulating endothelial cells measured at baseline and during therapy did not show consistent results. The same applied for the PhD on Ki-67, p27Kip1and EGFR in pretreatment and on-therapy skin biopsies. Conclusions: It is not feasible to combine Lap with fixed doses of cDDP and HT in pts with rCC in PIA mainly due to increased cDDP-related toxicity. The observed pCR is intriguing and warrants further investigation of combining HER2-blockade and cDDP/HT. Clinical trial information: NL24464.078.08. [Table: see text]
Expression of mEGFR, pEGFRThr654, and pPKN1Thr774 to predict response to chemoradiation and prognosis in patients with cervical cancer.
Authors: Lang Jin Yi , Huang Jianming , Lai Xin
Published: March 2020

e16531

Background: The aim of this study was to determine the relation between proteins involved in phosphorylation of EGFRThr654 and response to chemoradiation and survival in a well-documented series of cervical cancer patients. Methods: Pre-treatment tissue samples of 90 consecutive FIGO stage IIA-IIIB cervical cancer patients treated with concurrent chemoradiotherapy between January 2007 and December 2009 were collected. Clinicopathologic and follow-up data were collected by a retrospective chart review. Protein expression of membranous EGFR (mEGFR), pEGFRThr654 and pPKN1Thr774 were examined by immunohistochemistry on FFPE tumor specimens. The correlations between protein expression and clinicopathological factors and outcomes were analyzed. Results: mEGFR staining was present in 67.78%, pEGFRThr654 in 91.11%, pPKN1Thr774 in 56.67% of tumors. pEGFRThr654 staining was positively correlated to pPKN1Thr774 (p = 0.04) and to mEGFR staining (p = 0.015). In multivariate analysis, nuclear staining of pEGFRThr654 [hazard ratio(HR)= 4.833; 95%CI=1.959-11.922, P=0.001)] and cytoplasmic staining of pPKN1Thr774 (HR=3.095; 95%CI=1.019-9.406; P=0.046) were prognostic factors for poor overall survival (OS) and also were independent predictors of poor response to (chemo)radiation for progress-free survival (PFS) (HR=2.921, 95%CI=1.360-6.274, P=0.006; HR=2.963, 95% CI=1.187-7.394, P=0.020), and mEGFR staining was an independent prognostic factor for poor PFS (HR=5.934, 95% CI=1.378-25.555, p=0.017). The high expression of pEGFRthr654 is related to poor local control rate (p = 0.000) and to poor short-term efficacy (p = 0.009). Conclusions: mEGFR and pEGFRThr654 immunostaining are frequently observed and independently associated with poor response to therapy and poor PFS and OS in cervical cancer patients primarily treated by concurrent chemoradiotherapy. Our data presents the pEGFRThr654 nuclear translocation as a promising target in Integrated therapies of chemoradiotherapy combined with targeting inhibition of pEGFRThr654 and its nuclear import for cervical cancer.
Oral cavity squamous cell carcinoma in the elderly: A retrospective study in 129 patients over 11 years (2000-2010).
Authors: Gambotti Laetitia , Schwob Emilie , Goudot Patrick , Bertolus Chloë
Published: March 2020

e17023

Background: There is no consensus for the management of elderly patients with oral cavity squamous cell carcinomas (OC SCC). Surgeons have to estimate for each patient the benefit or the risk of aggressive treatments in this population. We report the experience of one French university hospital center in the treatment of OC SCC in patients aged > = 70 years. Methods: One hundred and twenty nine patients aged > = 70 years with a primary OC SCC diagnosed between 2000 and 2010 were included retrospectively. Independent risk factors of post-operative complication were identified using a logistic regression. Overall survival (OS) was estimated with Kaplan Meier method. Independent factors of survival were calculated using a Cox model. Results: Mean age was 78 (+/-6), sex ratio was 1.2. Women presented significantly more precancerous lesions (36% vs 21%, p=0.04), less alcohol intoxication (13% vs 59%, p<0.001) and less tobacco consumption (41% vs 81%, p<0.001). Half of the sample was stage T4 of TNM classification. Eighty eight percent of the patients received a curative treatment, including surgery for 101 patients. Among them, the surgical treatment was considered as “standard” (vs “substandard”) for 70%. Thirty percent of the surgical patients presented a post-operative complication. Independent risk factors of complications were T3/T4 stage (OR 4.5 [1.3-15.1]) N+ (vs N0 of TNM classification) (OR 7.3 [2.2-24.0]) and alcohol intoxication (OR 3.6 [1.1-11.4]). The median OS was 13.6 months (43.8 months for T1). There was no significant difference of OS between standard or substandard treatment groups. The independent negative prognostic factors for OS were age > 79 years (HR 1.8 [1.2-2.7]), N+ (HR 1.9 [1.3-2.9]) and ASA score 3/4 (HR 1.8 [1.1-2.9]). Conclusions: In our experience, surgeons probably made the good choice between standard or substandard treatment according to the patient profile but this choice must be oriented by professional guidelines.
Patterns of resource utilization and cost for postmenopausal women with hormone-receptor–positive (HR+), HER2-negative (HER2–) advanced breast cancer (ABC) in Europe.
Authors: Jerusalem Guy Heinrich Maria , Neven Patrick , Marinsek Nina , Zhang Jie , Degun Ravi , Benelli Giancarlo , Saletan Stephen , Andre Fabrice
Published: March 2020

e17520

Background: Healthcare resource utilization varies by disease stage and treatment choice. Notably, chemotherapy (CT) use is associated with extensive healthcare resource utilization and cost. This study reviews the direct and indirect cost implications of CT versus hormonal therapy (HT) in the ABC setting through the first 3 lines of treatment. Methods: A retrospective chart review of postmenopausal women diagnosed with HR+, HER2– ABC in 5 European countries was conducted. Patients must have progressed on at least 1 line of HT and completed at least 1 line of CT in the ABC setting. Patient cohorts based on therapy received in each line were constructed (cohort A: HT 1st-line, CT 2nd-line, and any treatment 3rd-line; cohort B: HT 1st- and 2nd-line with CT 3rd-line; and cohort C: CT 1st-line with any 2nd- and 3rd-line). Costs of care based on resource utilization and country-specific cost were calculated by patient cohort and line of therapy. Working status was also assessed. Results: A total of 355 eligible patient charts between 2008 and 2012 were included in the analysis: cohort A, 218 (61%) patients; cohort B, 26 (7%) patients; and cohort C 111 (31%) patients. Total direct costs over all 3 treatment lines were €14,362 higher for CT versus HT as 1st-line therapy (cohort C vs A) and €10,368 higher for CT versus HT as 2nd-line (cohort A vs B). Monthly direct costs were €2,536 higher for CT versus HT for 1st-line therapy and €1,713 higher for CT versus HT in 2nd-line. Increased costs for CT were due to treatments to manage side effects, use of concomitant targeted therapies, and increased frequency of hospitalizations, healthcare provider visits, and monitoring tests. On switching from HT to CT, there was a doubling of the proportion of patients on sick leaves in both cohorts A and B. Conclusions: These results suggest an increased direct cost of care for CT relative to HT in European postmenopausal women with HR+, HER2– ABC. Furthermore, CT-based therapy appears to be associated with lower productivity of working-age patients, potentially increasing overall indirect costs.
Cancer anorexia-cachexia syndrome in advanced lung cancer: An exploratory analysis of patient-reported outcomes data.
Authors: Nipp Ryan David , Locke Susan C. , Samsa Gregory , Kamal Arif , Abernethy Amy Pickar , LeBlanc Thomas William
Published: March 2020

e17521

Background: The cancer anorexia-cachexia syndrome (CACS) is a debilitating syndrome of involuntary weight loss, anorexia, declining function, muscle catabolism, and inflammation. It affects many patients with cancer, especially those with advanced disease. We aimed to describe the experience of a group of patients with advanced lung cancer who meet published weight-based criteria for CACS. Methods: Tablet computers were used to collect patient-reported outcomes data from 97 patients with advanced non-small cell lung cancer, using the Patient Care Monitor v2.0 and the FACIT family of questionnaires. 25 patients met published weight criteria for CACS (>=5% weight loss in the past 6 months). 51 patients with stable weights were used as a comparison group; those lacking weight data were excluded. Statistical comparisons were made between these groups to explore differences in symptoms, quality of life, and survival. Results: Patients meeting weight criteria for CACS had lower serum albumins (median 3.7 vs. 3.9, p=0.006) and worse performance status by Karnofsky and ECOG (70 vs. 80, p=0.004, and 2 vs. 1, p=0.027). CACS patients had worse FAACT anorexia-cachexia subscale scores (34.5 vs. 38.5, p=0.018) but were not statistically more likely to be prescribed CACS therapies; only 17% of patients in the CACS group were on medication for this (N=4). FACIT fatigue subscale scores were not statistically different between groups, nor was quality of life by FACT-G. Grip strength and 6-minute walk distance were also not statistically different. Patients in the CACS group had a significantly shorter survival (HR 2.066 [95% CI=1.229,3.474], p=0.005). Conclusions: Patients with advanced non-small cell lung cancer who meet standard weight-based criteria for CACS have inferior survival compared to a similar population without weight loss. Though traditional descriptions of CACS presume a general impairment in quality of life, we did not find statistical differences here aside from the anorexia-cachexia subscale score of FAACT. Few patients were prescribed medication to address symptomatic anorexia/cachexia, suggesting it may be an unmet need in patients with advanced lung cancer.
Should adjuvant zoledronic acid be used in early-stage, endocrine-sensitive breast cancer?
Authors: Lamond Nathan William Dana , Skedgel Chris , Rayson Daniel , Younis Tallal
Published: March 2020

e17564

Background: Adjuvant zoledronic acid (ZA) appears to improve disease-free survival (DFS) in women with endocrine-sensitive breast cancer and low estrogen levels (LEL) including post-menopausal women, and pre-menopausal women treated with LHRH agonists. ZA, however, is also associated with potential adverse events and incremental drug acquisition costs. An overall assessment of the long-term clinical and economic impacts of adjuvant ZA may therefore help guide the decision to adopt this novel therapeutic option. We examined the incremental quality-adjusted life-years (QALY) and costs per QALY associated with adjuvant endocrine treatment plus ZA relative to endocrine treatment without ZA in women with endocrine-sensitive breast cancer and LEL. Methods: A generic state-transition model was developed to compute cumulative costs, from a Canadian perspective, and QALY associated with and without adjuvant ZA (4 mg IV qM*3→ q3M*8 → q6M*5) over a 25-year horizon for women with endocrine-sensitive breast cancer and LEL. Costs, utilities, DFS and adverse events were derived from relevant clinical trials, the literature and local resources. One-way and probabilistic sensitivity analyses were conducted for key model parameters. Results: Adjuvant ZA was associated with incremental QALY gains of 0.80 and 0.52 and resultant CU estimates of $3,571 and $7,683 per QALY gained in pre- and post-menopausal women, respectively. CU estimates were robust across reasonable uncertainty ranges in all parameters. Conclusions: Adjuvant ZA appears to be associated with long-term QALY gains in women with endocrine-sensitive breast cancer and LEL as well as CU estimates that are well below commonly accepted North American thresholds. The favourable long-term clinical and economic impacts observed in this study further support the use of adjuvant ZA in this setting.
The experience in the management of 15 patients with chronic myeloid leukemia (CML) in a community clinic in Puerto Rico.
Authors: Castro Justiniano
Published: March 2020

e18015

Background: CML is a malignant clonal disorder of the hematopoietic stem cells that results in an increased myeloid cells but also erythroid and platelets in the peripheral blood and marked myeloid hyperplasia in the bone marrow. The management of this condition in a rural community clinic is a challenge due to the complexity in the routine monitor of these patients with molecular studies. In addition, data from Hispanic population treated with imatinib in USA is limited. Methods: A total of 15 patient with CML followed in a private clinic form June 2001 to January 2012 were included in the analysis for the study. Results: The patients included 10 males and 5 females. Median age was 51 years. All patients received imatinib 400mg. There were 4 patients with initial WBC > 50,000/mm3. All patients were in chronic phase with less 1% of blasts, except for one that had 7%. Twelve patients had a low Harford score, 2 with moderate and 1 high risk. Conclusions: Our data suggest that imatinib is highly effective in this population of patients. The CCR at 6 months was 80% and the MMR at 12 months was 80% compared with the data from the IRIS (CCR at 6 months, 74.7%) and DASISON (MMR at 12 months, 28%) trials. This group of patients demonstrates high CHR, CCR and MMR in comparison of what is reported in the literature. The study also present a group of Hispanic patients were the information about imatinib response is limited. The possibly that certain ethnic group has a different pattern of response as compared with Caucasian is intriguing. Lastly, it is evident that adequate care could be offer event in rural community clinics. [Table: see text]
Does presence of chronic obstructive pulmonary disease (COPD) influence clinical behavior in patients with early-stage non-small cell lung cancer (ESNSCLC)?
Authors: Yamamoto Satomi , Kawaguchi Tomoya , Tamura Taro , Asami Kazuhiro , Okishio Kyoichi , Atagi Shinji , Yoon Hyungeun , Matsumura Akihide , Shimizu Shigeki , Kitaichi Masanori , Takada Minoru , Hirata Kazuto
Published: March 2020

e18530

Background: CDPD and lung cancer sometimes occurs simultaneously. COPD has been recognized as an inflammatory disease and may potentially affect biology of the accompanying tumor. It is not fully understood whether presence of CDPD influences clinical characteristics, pathological findings and/or clinical outcomes in patients with ESNSCLC. Methods: Retrospective and consecutive data were collected from the medical records of patients who underwent surgical resections at Kinki-chuo Chest Medical Center, Japan, between January 2009 and December 2010. CDPD status was classified as absence of COPD, stage I and II COPD based on the criteria of Global Initiative for Chronic Obstructive Lung Disease (GOLD). Histology, vascular / lymphatic invasion and the status of epidermal growth factor receptor (EGFR) were determined using the surgical materials. Results: A total of 319 cases was included with median age of 67 (range, 36 - 89). There were 81 cases of relapse and 40 cases of death during the median follow up of 28 months (11 days to 49 months). In the subgroup of non-COPD, stage I and II COPD, the median age, the number of case in gender (male/female), performance status (PS, 0/1), histology (squamous cell carcinoma [SQ] /non SQ), smoking status (never/ever), and EGFR status (wild type/mutant) were 67, 72, 72 (p<0.001) and 105/110, 48/12, 38/6 (p<0.001) and 170/40, 53/7, 27/14 (p=0.029) and 31/184, 12/48, 14/28 (p<0.001) and 89/122, 7/53, 2/39 (p=0.002) and 47/37, 21/3, 9/3 (p=0.013), respectively. No significant difference was observed in disease-free survival (DFS, log-rank p=0.411) and overall survival (OS, log-rank p=0.127) between the patients with and without COPD. In multivariate analysis adjusted for age, gender, PS, histology, smoking status, pathological stage, vascular / lymphatic invasion and EGFR status, presence of COPD did not affect DFS (HR=1.457, p = 0.279) nor OS (HR=0.993, p = 0.990).Conclusions: Although COPD was significantly associated with the elderly, male gender, presence of symptoms, SQ histology, ever smoking, and wild type EGFR, it did not add values of prognostic factors in patients with ESNSCLC.
Capecitabine-gemcitabine in thymic epithelial tumors.
Authors: Palmieri Giovannella , Buonerba Carlo , Di Lorenzo Giuseppe , Federico Piera , Nappi Lucia , Rescigno Pasquale , Calabrese Filomena , Ottaviano Margaret , De Placido Sabino , Damiano Vincenzo
Published: March 2020

e18536

Background: Thymic epithelial tumors (TET) are a rare disease. Once loco-regional treatments have failed, platinum-based chemotherapy is employed to prolong survival and palliate symptoms. In November 2005, we started prospective multi-center trial to test capecitabine-gemcitabine in pretreated TET. Mature results are awaited. We here retrospectively review all patients with TET treated at our Institution with this schedule. Methods: Patients with pathologically confirmed TET receiving at least one cycle of capecitabine-gemcitabine were included in this analysis. Descriptive statistics and frequency counts were used to summarize characteristics of the study population. Median numbers were presented with interquartile ranges. Results: Twenty-three patients were included in this single-center analysis. Six patients had a thymic carcinoma, while three, eight, two and four patients had a B1, B2, B2/B3 and B3 TET, respectively. Median age was 52 years (47-58).Eleven patients were female. Gemcitabine was delivered at the dose of 800-1,000 mg/m2 by 30-minute infusion on days 1 and 8 every 3 weeks along with oral capecitabine at the dose of 500-650 mg/m2 twice daily on days 1 to 14. Fourteen patients had an ECOG performance status of 0, one of 2, the remaining of 1. Seven patients had an IV a tumor, while the remaining had a IVb tumor. All patients, except for three for whom capecitabine-gemcitabine was the first line of therapy, had received a platinum-based regimen. Only one patient was primary refractory, while a complete response was obtained in 2 patients, a partial response in four patients, and the remaining had stable disease. Median PFS was 7 months (range, 4-9). Median survival was 12 months (6-20). Treatment was well tolerated. Twelve patients showed grade 3/4 toxicity, of whom two patients showed severe anemia, six severe neutropenia, four severe thrombocytopenia, two severe diarrhea and one severe fatigue. Conclusions: In this retrospective analysis, gemcitabine-capecitabine was confirmed to have a high activity in TET. Mature results from the ongoing multicenter trial are awaited.
Did the 2004 World Health Organization (WHO) histologic classification result in better prognostic categories for resected thymomas as compared to 1999 WHO classification scheme?
Authors: Yonan Yousif , Zander Dani , Varlotto John M. , Toth Jennifer , Reed Michael , Gilbert Christopher , Flickinger John Charles , Recht Abram , Belani Chandra Prakash , DeCamp Malcolm M.
Published: March 2020

e18552

Background: The classification of thymic epithelial neoplasms is subject of controversy. The purpose of our investigation is to see whether the 2004 histologic classification results in better prognostic categories than that of the 1999 classification. Methods: The SEER 18 database was used to investigate incidence and overall survival/cause-specific survival (OS/CSS) of resected thymomas during 2000-2009. Incidence was examined by frequency and trend analyses. Patients diagnosed with first primary localized thymoma/thymic carcinoma were selected in two time periods (2000-2003: N=201; 2005-2009: N = 497). The median follow up is 79 months and 27 months respectively. OS/CSS in two patients group were analyzed by Kaplan-Meier estimation, log-rank tests, and multivariate proportional hazards modeling. Results: The proportion of six histology categories (A, AB, B1-B3,C) did not change significantly during the two time periods. Compared to patients diagnosed in 2000-2003, OS was not significantly different in patients diagnosed in 2005-2009 in the log rank tests or multivariate analysis after accounting for treatment, tumor factors, and patient characteristics (OS, HR=0.737, p=0.1580; CSS, HR=0.731, p=0.3711). Histology as 6 categories is a significant predictor for OS in the multivariate analysis in 2005-2009, but not in 2000-2003. However, the predictive role of histology is similar in both time periods in the multivariate analysis of CSS. Complete resection, classification C, and tumor stage are significantly linked to OS and CSS. Conclusions: Patients diagnosed after 2004 did not have better survival outcomes than earlier patients. The WHO classification of 2004 may be a better predictor of OS than that of 1999 as shown by the wide-spectrum of pathologists reporting to SEER.
Clinical value of PET/CT's SUV max at baseline, early follow-up, and end of treatment reevaluation as a prognostic factor in small cell lung cancer patients with extended disease.
Authors: Ponce Aix Santiago , Manneh Kopp Ray , Sepulveda Juan Manuel , Núñez Juan A. , Iglesias Lara , Pascual Tomas , Parrilla Lucia , Ruiz Solis Sebastian
Published: March 2020

e18558

Background: Patients with Small Cell Lung Cancer (SCLC) have been staged by the two-stage system. This system defines limited disease (LD) when is confined to ipsilateral hemithorax that can be encompassed within tolerable radiation field; extended disease (ED) is defined as the disease extending outside the hemithorax. The IASLC recommended that TNM staging should be used in SCLC including clinical trials. However these systems have shown poor correlation between clinical findings and the pathological results. Objectives: Evaluate prognostic factors as age, ECOG and PET CT’s SUV max at base line, early follow up and end of treatment reevaluation; and their correlation with Overall survival (OS) and Progression free survival (PFS). Methods: Prospectively were recruited patients with histologically confirmed SCLC and ED and were evaluated with basal PET CT, early follow up (PET CT after 2 cycles of Platinum based chemotherapy) and end of treatment assessment with a PET CT after 6 cycles. Comprehensive database including clinical data were collected as age, ECOG, site of metastases, type of treatment and outcome. 23 patients were recruited from January 2010 to June 2012 and the follow up made until January 15th 2013. The Cox correlation test was used. Results: Median age 66,5 years (range 52-80) the OS was 7,9 months (CI 95% 6.7-9.1) and the PFS was 5,3 months (CI 95% 4,5-6,2). The baseline ECOG was an independent prognostic factor for OS (p= <0,0001) and PSF (p= 0,008). Age was not prognostic in our data. SUV max at baseline was an independent prognostic factor for OS (p= 0,001) and PFS (p= 0,009). For early follow up were evaluated 14 patients and for end of treatment reevaluation were assessed 9 patients. Differences between SUV max at baseline and early follow up or with end of treatment reevaluation were not predictive for PFS or OS. Conclusions: In our study the ECOG and basal PET CT SUV max are independent prognosis factors with consistent correlation with OS and PFS. The early follow up and end of treatment reevaluation with PET CT did not predict outcome in our patients. Further studies should be considered to test the value of follow up with PET CT.
Cytoplasmic ERß expression to predict efficacy and survival of EGFR-TKI in EGFR-mutant NSCLC.
Authors: Wang Zhijie , Wang Jie , Wang Xiaodong , Shen Zhirong , Ding Xiaosheng , Bai Hua , Duan Jianchun , An Tongtong , Wang Yuyan , Zhuo Minglei , Wang Shuhang , Wu Meina
Published: March 2020

e19067

Background: Estrogen receptor pathway has been reported to be interacted with epidermal growth factor receptor (EGFR) signal pathway. This study focused on the impact of intracellular ERβ localization (cytoplasmic or nuclear) on efficacy of EGFR-TKI. Methods: Tumor tissue specimens from 149 stage IV NSCLC patients treated with EGFR-TKI were analyzed using immunohistochemistry (IHC) for ER expression (ERα or β) and their associations with clinicopathological variables and clinical outcomes. Significance of cyto-ERβ expression was further examined in NSCLC cell lines. Results: The expression of ERα and ERβ was detected in 15% and 28.9% of the patients, respectively. Cyto-ERβ positive cases showed shortened PFS compared with negative ones (3.1 months vs. 7.3 months, p=0.061). In the EGFR-mutant subgroup, differences of PFS were enlarged with significant statistics (4.7 months vs. 10.9 months, p=0.042). COX’s proportional hazard model showed that female, EGFR mutation and c-ERβ status were independent predictors for PFS. PC-9 cells present ERβ in cytoplasma and nucleus. Estrodial (E2) induced PC-9 cells moderately resistant to erlotinib with a 3-fold increase of IC50, and the resistance can be reversed by ER blocker (fulvestrant) or siRNA directed to ESR2. The E2 function was accomplished by nongenomic activation (MAPK phosphorylation) caused by E2 via cyto-ERβ. Combination treatment with erlotinib and fulvestrant turned out to be far more effective than either treatment alone in PC-9 cells. Conclusions: Cyto-ERβ expression may predict relatively poor efficacy to EGFR-TKI compared with non- cyto-ERβ expression in NSCLC patients harboring EGFR mutation.
Use of the 92-gene assay to identify tumor type and direct predictive biomarker testing in limited tissue specimens.
Authors: Operana Theresa N. , Schroeder Brock , Erlander Mark G. , Schnabel Catherine A.
Published: March 2020

e19072

Background: Limited tissue availability from biopsies can limit comprehensive diagnostic testing and individualized care. The 92-gene assay is a gene expression-based cancer classifier that requires a minimal number of tumor cells (~300) and may improve the efficiency of tissue usage as a molecular complement to IHC in cases with limited diagnostic material. In this study, the reporting rate and utility of molecular classification in limited tissue cytology specimens, as well as the frequency of directed predictive biomarker testing were examined. Methods: Four hundred thirty eight FFPE cytopathology cases (ie, fine needle aspirates, pleural effusions, ascites) with indeterminate diagnosis where the 92-gene assay (CancerTYPE ID, bioTheranostics Inc.) was used in clinical care were included in the analysis. The 92-gene assay reporting rate and tissue availability to perform downstream biomarker testing were analyzed. Results: The 92-gene assay provided a molecular diagnosis in 86% (n=378) of cytopathology specimens submitted for diagnostic testing. Twenty-four distinct tumor types were predicted including: 9% lung (n=41), 8% urinary bladder (n=34), 8% pancreaticobiliary (n=34), 8% ovary (n=34), 7% gastroesophageal (n=32), 5% intestine (n=20), and 1% melanoma (n=5). In 66 patients with molecular diagnoses where reflex biomarker testing was applicable (lung, CRC, melanoma), 33% of cases had additional predictive biomarker testing performed, and 2 or more biomarker tests were performed on 15% of cases. The most common tests ordered were EGFR mutations (n=16), KRAS mutations (n=8), BRAF mutation (n=8), and ALK rearrangement (n=5). Conclusions: These findings demonstrate the suitability and high reporting rate of the 92-gene assay in limited tissue cytologic specimens and successful predictive biomarker testing in appropriate cases. With the growing number of molecularly-targeted therapies requiring predictive biomarker testing, use of the 92-gene assay may have increased utility in indeterminate cancer cases where limited tissue specimens are the only option for diagnosis and treatment planning.
Metronomic weekly paclitaxel in metastatic or recurrent non-small cell lung cancers.
Authors: Tandon Nidhi , Noronha Vanita , Prabhash Kumar
Published: March 2020

e19095

Background: Metastatic non small cell lung cancer (NSCLC) has a median survival of 4 months in absence of therapy. We present our experience with metronomic weekly paclitaxel in patients with metastatic or recurrent NSCLC and those with poor performance status. Methods: This is a retrospective analysis of prospectively collected data of patients with metastatic or recurrent NSCLC without significant neuropathy who were heavily pretreated or platinum ineligible from Feb 2010 to Oct 2012 at our centre. Patients were treated with paclitaxel at 80 mg/m2 over 1 hour weekly and underwent regular follow up. Chemotherapy was discontinued on disease progression or intolerable side -effects or patients choice. Patients who received at least 4 cycles of chemotherapy were included in the analysis. Toxicity was graded according to CTCAEv4.03. Statistics were calculated using SPSSv18.0. The progression-free survival was calculated from date of start of paclitaxel till date of symptomatic deterioration, radiological progression or start of next line of therapy or death due to any cause. Overall survival was calculated from date of start of paclitaxel to the date of death due to any cause. Results: Of the 100 patients studied (median age = 57 y, range 29–77 y), 74% were males, 51% were smokers, 45% had comorbidities, 35% had PS>2 and 74% had adenocarcinoma. About 53% received >2 prior lines of chemotherapy. Patients received a mean of 16.9 cycles of paclitaxel (range 4-72) after which it was withheld in 63% due to PD (53% radiological, 10% clinical) and in 12% due to toxicity. The response rates were 37% (CR-3% and PR-34%) while 35% had SD. 9% required dose reduction while 32% had delay in dose administration. G.3 adverse events observed were 12%-anaemia, 10%-neutropenia, 2%-febrile neutropenia, 15%- sensory neuropathy and 4%-motor neuropathy. The median OS was 12 months while median PFS was 5 months. Conclusions: Weekly paclitaxel is a promising and well tolerated therapy for advanced NSCLC.
Non-invasive and quantitative analysis for EGFR T790M mutation in the patients with advanced non-small cell lung cancer received EGFR-TKI therapy.
Authors: Chen Rui , An Tongtong , Wang Jie , Bai Hua , Wang Zhijie , Zhao Jun , Wu Meina , Zhuo Minglei , Duan Jianchun , Wang Yuyan , Wang Shuhang
Published: March 2020

e19101

Background: Approximately 50% of advanced non-small cell lung cancer (A-NSCLC) patients with EGFR sensitive mutation who develop acquired resistance to EGFR-TKIs reportedly have a secondary EGFR T790M mutation. Establishing a dynamical, quantitative and noninvasive detection system of EGFR T790M mutation in process of disease therapy for NSCLC is critical to personalized targeted therapy. Methods: 135 A-NSCLC patients with EGFR mutation who received EGFR-TKIs and presented acquired resistance (PFS≥6 months) were included into this study. All patients provided the plasma samples for molecular analysis when disease progressed. 109 patients of them had matched TKI-naive plasma. T790M mutation was measured qualitatively and quantitatively by ARMS and Digital PCR (DggPCR), respectively. Association of T790M mutation with clinical charateristics were evaluated. Results: DgPCR was more sensitive than ARMs to detect T790M mutation in plasma [pre-treatment 29.4% (32/109) VS 5.5% (6/109); post-treatment: 43.0% (58/135) VS 25.2% (34/135)]. 32 patients with pre-treatment T790M mutation predicted shorter PFS and OS compared with 77 T790 M negative patients (PFS, F 12.7 VS 9.2 months, P=0.004, GOS, F 27.0 VS 18.8 months, P=0.002). Patients with or without post-treatment T790M mutation have no significantly different PFS and OS. However, quantified the ratio of copy number of mutant T790M to wild-type by DgPCR, patients were divided into high-frequency groups (≥5%), low-frequency group (0%-5%) and wild-group (0%) according to the number of positive signals observed from DgPCR results. 12 patients in high-frequency group showed shorter PFS and OS compared with wild group and low-frequency group (PFS 9.5 VS 11.9 months, P=0.033, G9.5 VS 13.6 months, P=0.028, GOS, F 18.5 VS 21.2 months, P=0.044, 18.5 VS 28.8 months, P=0.001). Conclusions: Non-invisive and quantitative detection of T790m mutation by digital PCR is feasible in clinical practice. High contents of T790M when disease progression after EGFR-TKIs therapy predicted poor prognosis.
Awareness about EGFR testing and use of TKIs in advanced lung cancer: A questionnaire-based survey of medical oncologists from India.
Authors: Parikh Purvish M.
Published: March 2020

e19116

Background: EGFR is an important driver mutation in lung cancer. The pattern of usage of EGFR mutation testing is not well defined in the Indian population. Methods: A total of 70 medical oncologists from India were interviewed to identify current practices in the management of advanced lung cancer. They were in clinical practice for 2 to 35 (median 9) years. Their affiliation included medical college (21), regional cancer center (6), corporate hospitals (29) and private practice (14). Their collective experience in conducting international clinical trials in lung cancer was significant (range 0 to 35 trials). Results: The number of new patients with lung cancer seen by them in a month was a median of 8 (range 1 to 20). EGFR testing on the lung cancer tissue was recommended in a median of 60 % (range 10 to 100 %) of paients and was actually carried out in a median of 30 % (range 0 to 90 %). Tissue samples were inadequate for EGFR testing in 30 % of cases (range 2 to 95 %). Method of EGFR testing used included IHC by 06, molecular by 52 and both by 12 of the oncologists. The time to obtain a report was 10 days (range 5 to 21 days). EGFR testing showed mutation/ overexpression in approximately 25 % of cases (range 0 to 70 %. In a large national tertiary cancer center with inhouse laboratory that did testing by PCR and sequencing, EGFR mutations were seen in 30 % of 481 samples. The EGFR mutations considered clinically important included del 19 by 56, L858R by 41 and T790M by 31 of the responding oncologists. The first line therapy used in EGFR mutation positive Lung cancer patients was platinum doublet chemotherapy by 7, gefitinib by 55 and erlotinib by 8 oncologists. The side effects of TKIs considered important were diarrhea by 64, mucositis by 47, rash by all 70, paronychea by 50, nausea vomiting by 52, fatigue by 51 and myelosuppression by 6. The common methods of managing these side effects included dose reduction by 22, drug interruption by 50, symptomatic treatment by 49 and counseling by 22. Conclusions: The awareness about EGFR mutation and use of TKIs among medical oncologist is increasing in India. However availability of sufficient tissue for molecular testing remains a problem.