bluuebunny/crossref_metadata_2025 huggingface dataset:
Sixty-eight consecutive cases of neuroendocrine tumor treated with somatostatin analogues: A 20-year single-center experience.
Authors: Savvoukidis Theodoros , Cameron Silke , Ramadori Giuliano
Published: March 2020

e14707

Background: Neuroendocrine tumours (NET) arise from enterochromaffine and related cells found in epithelial organs throughout the body. Hormone related symptoms in neuroendocrine tumours are well treated with somatostatin analogues. Previous experience has demonstrated some antiproliferative activity of somatostatin analogues in the treatment of NET. Methods: In the last 20 years 68 patients with histologically proven NET were treated: primaries in small bowel (27), pancreas (17), rectum (9), appendix (5), lung (4), unknown (3), extra- adrenal abdominal paragangliomas (2) and stomach (1). The mean age of first diagnosis was 56 years. All of them received somatostatin analogues in long acting depot administration (or combination interferon/somatostatin analogues) for a minimum period of two months and a maximum of 139 months. Somatostatin therapy was started in patients with endocrine-active tumours immediately after the diagnosis and in patients with endocrine-inactive tumours after an observation time of 3 months without therapy if progress was observed. Tumor size was assessed every 3 months after begin of therapy. Results: Best responses were a stable disease in 46 of 68 patients (68%) and a partial remission in 2 (3%). Twenty of 68 patients (29%) showed progress. The responses achieved were in small bowel 20/27; pancreas 14/17; rectum 7/9; appendix 4/5 and lung 3/4. The median duration of response was 34 months. Conclusions: Our results document that treatment with somatostatin analogues prolongs time to progression in NET. Stabilisation of tumour mass itself is a relevant outcome for patients with NET. The benefit of somatostin analogues is indipendent to use of chemotherapy. Because of its efficacy and the good tolerability somatostatin analogues can be considered a first line treatment option.
Neoadjuvant chemotherapy (NACT) with DCF regimen in stage III, squamous cell cancer: Esophagus followed by oesophagectomy—Indian experience.
Authors: Somashekhar S. P. , Rauthan Amit , Zaveri Shabber , Patil Poonam , Holla Soumya
Published: March 2020

e14710

Background: Despite improved surgical techniques and peri-operative care in cancer of the esophagus, the 5 yr OS is 10%. Additional therapy could improve prognosis. At least 10 RCTs comparing NACT to surgery alone have demonstrated a significant increase in median survival of 17 months in the former, compared to 13 months in the latter. We aimed at studying impact of NACT in Indian patients and its impact on surgery and outcome. Methods: The study – Prospective non-randomised study. Between 2007-12, 20 patients were included to analyze the benefit of NACT with DCF (docetaxel 75mg/m2 day 1, cisplatin 75mg/m2 day 1, 5-FU 750mg/m2 per day 1-4) regimen, in stage III Ca. Esophagus, assessed by EUS and PET-CT scan , pre-chemo and post-chemo, in biopsy proven Squamous cell Carcinoma Oesophagus. Prophylactic growth factors were used in all cycles. Results: Post NACT, Partial response of 58.8%, and a complete pathological response of 17.6% were observed with response rage of 76.4%. NACT x 3 cycles used. 4 pt.s had mucositis, but none had grade 3 toxicity, neutropenia in 4 pt.s and febrile neutropenia in only one pt., vomiting and fatige in 5 pt.s . Surgery post NACT was, very easy and there was no significant morbidity, or surgical complication nor any mortality observed due to NACT. On follow-up, two patients died due to systemic recurrence and progression disease progression. Two patients had regional and one patient had , non-regional lymph node disease recurrence. In remaining 16 patients, till to date there is no recurrences and are disease free. All but 2 patients are alive to date. Conclusions: The response rate to NACT (TPF-Regimen) is 76.4%, with maximum benefit in the complete responders. NACT has no adverse impact on the surgical outcome. Surgery is done with acceptable morbidity and very low mortality. Surgical resection post NACT was easy. Impact of this regimen on DFS and OS, have to be ascertained over time.
Comorbidity, characteristics, and survival of gastric cancer patients at a VA medical center.
Authors: Wang Trent P. , Barnes Tanganyika , Gandhi Arpita , Zhong Fengming , Chang Victor Tsu-Shih , Gonzalez Melanie L. , Cheng Lucy , Duque Lourdes , Cogswell Janet , Kasimis Basil
Published: March 2020

e14727

Background: This is to study whether comorbidity indices predict survival in gastric cancer patients (pts). Methods: In an IRB approved protocol, we reviewed the records of pts diagnosed with gastric cancer at a VA Medical Center from 3/1/2000 to 3/31/2011. Comorbidity was assessed with four comorbidity indices, the Charlson Comorbidity Index (CMI), the Kaplan-Feinstein Index (KFI), the Cumulative Illness Rating Scale (CIRS), and VA Comorbidity Scale (VACS). Demographics, stage, histology, grade, weight (wt) loss, hemoglobin (HGB), ALB, Total bilirubin (TBili), creatinine at diagnosis, alcohol or tobacco use, past gastric surgery (pSx), and surgical resection (Sx) were also reviewed. COX survival analysis was performed. Results: There were 49 patients. All were men. 23 (46.9%) pts were Caucasian, 25 (51%) African American and 1 (2%) Hispanic. The median (M) age at diagnosis was 70 years (range 43-90). Median survival was 321 days (4-4221). 17 (35.5%) pts has localized disease (stage I/II), and 31 (64.5 %) advanced disease (stage III/IV). 2 (4%) pts had grade1, 12 (26%) grade 2, 32 (68%) grade 3, and 1 (2.1%) grade 4. M HGB was 12.1 g/dl (range 5.5-16.9), MCV 85.4 fl (59-104), albumin 3.6 g/dl (1.8-4.6), TBili 0.5 mg/dl (0.2-5.1) and creatinine 1 mg/dl (0.7-1.6). M CMI 4.7 (1.1-10.8), CIRS15 5 (0-12), CIRS16 9 (0-19), CIRS17 1.6 (0-2.5), CIRS18 0 ( 0-4), CIRS19 0 (0-1), KFI 3 (0-3), VACS 4 (0-12) Demographic features included alcohol use (51%), M tobacco use 25 PPY (0-80), and M wt loss 9% (0-25) and pSX 5 (10%). 22 pts (47%) has Sx. In univariate survival analysis, only wt loss (p<0.013), stage (p<0.001), grade (p<0.001), Tbil (p<0.003), and Sx (p<0.003) were significant in predicting survival. In multivariate survival analyses, none were significant for predicting survival. Conclusions: Comorbidity did not contribute to the survival of gastric ca pts in this population. More research in a larger sample is needed. Supported by the New Jersey Commission for Cancer Research.
Impact of first-line platinum therapy on survival in patients with platinum-refractory advanced transitional cell carcinoma of the urothelium (TCCU) treated with vinflunine.
Authors: Fougeray Ronan , Choueiri Toni K. , Pons Francesc , Schutz Fabio Augusto Barros , Salhi Yacine , Rosenberg Jonathan E. , Bellmunt Joaquim
Published: March 2020

e15007

Background: Standard first-line therapy of advanced TCCU is based on cisplatin-based combinations. In patients deemed unfit to receive CISPLATIN, carboplatin-based or non-platinum combinations are considered. A phase III trial comparing vinflunine (VFL) and best supportive care (BSC) with BSC alone for second-line treatment of advanced TCCU patients demonstrated a survival advantage for VFL+BSC. We studied the impact of the first-line platinum therapy on overall survival in second line setting. Methods: Eligible 357 patients of the phase III study were split in the two following subsets: CISPLATIN (Patients with prior CISPLATIN administration) and NO CISPLATIN (patients without prior CISPLATIN administration). Survival was measured from the date of random assignment. Overall Survival (OS) was calculated using Kaplan-Meier method, with log-rank comparisons. Multivariate Analysis of OS was analyzed with the Cox proportional hazards model, including prognostic factors for second-line setting previously identified (Bellmunt, 2010). Updated survival data in 11/2008 cut-off date was used. Results: CISPLATIN group represented 70.3% (n=251) and NO CISPLATIN 29,7% (n= 106). CISPLATIN group had less Liver involvement (25% vs 43%, p=0.0007) and better WHO-PS (>1: 66% vs 76%; p=0.0478). OS was higher in CISPLATIN group for all eligible patients (HR: 0.77; CI 95% 0.61-0.97; p=0.0294), for VFL+BSC arm (HR: 0.78; CI 95% 0.59-1.02; p=0.0693) and for BSC arm (HR: 0.68; CI 95% 0.42-1.08; p=0.0978). Multivariate analysis including prognostic factors (liver involvement, hemoglobin, PS) and prior platinum administration, did not show effect of CDDP on OS. VFL reduced the risk of death by 24% in CDDP-group (HR: 0.76; CI 95% 0.58-0.99; p=0.043) and by 35% in NO CDDP –group (HR: 0.65; CI 95% 0.41-1.04; p=0.0724). Conclusions: Differences in prognostic factors between CISPLATIN and NO CISPLATIN groups may explain the differences in OS in patients who undergo 2nd line therapy. The choice of Cisplatin or no Cisplatin chemotherapy in the first line did not impact subsequent benefit of vinflunine over best supportive care.
The impact of regional anesthesia on bladder cancer outcomes.
Authors: RiChard Jamie , Lipsky Michael , Whalen Michael , Motamedinia Piruz , Finkelstein Julia , Hruby Gregory , DeCastro Guarionex , Curry Saundra , Benson Mitchell C. , McKiernan James M.
Published: March 2020

e15021

Background: Studies in breast and prostate surgery show reduced cancer recurrence after regional (RA) versus general anesthesia (GA). Mechanisms include RAÕs reduced post-operative opioid use and cortisol-mediated immunosuppression. RA may be used alone during transurethral resection of bladder tumors (TURBT) and in combination with GA during radical cystectomy (RC). We assess the impact of RA on short-term bladder urothelial cell carcinoma (UCC) recurrence after TURBT or RC. Methods: From 8/2001 and 6/2006 to 6/2011, 151 patients underwent RC and 488 patients underwent TURBT for bladder UCC, respectively. Those with incomplete resection on TURBT were excluded. Anesthesia included RA or GA for TURBT, and GA alone or GA + RA for RC. Multivariate logistic regression was performed to identify significant predictors of biopsy- or radiography-confirmed UCC recurrence. Results: TURBT. Of 252 patients, 211 received GA and 41 received RA during TURBT. Patient and operative characteristics were similar between groups. Recurrence was 56% at 12 months for GA and RA. Multivariate analysis revealed clinical stage to be the only predictor of UCC recurrence (HR=1.8, p<0.0001). Anesthesia had no affect on 6 or 12 month RFS, DSS or OS (see table). RC. GA was used in 114 patients and 37 patients had GA + RA at RC. There were no between group differences in patient or tumor characteristics. After follow-up of 18 months, 25.9% and 21.6% recurred in GA and GA+RA groups, respectively (p>0.05). There were no differences in RFS, DSS, or OS (see Table). Conclusions: Contrary to other malignancies, our data suggest anesthesia type at TURBT or RC does not affect bladder cancer outcomes. Anesthesia modality should be based on patient comorbidities and procedure type. [Table: see text]
Hypoxia-inducible factor 1α: A screening tool for predicting development of castrate resistant prostate cancer.
Authors: Ranasinghe Weranja Kalana Bodhisiri , Xiao Lin , Kovac Suzana , Chang Mike , Shulkes Arthur , Bolton Damien M , Baldwin Graham , Patel Oneel
Published: March 2020

e15117

Background: Currently there is no method to determine which patients starting androgen deprivation therapy (ADT) for prostate cancer (PC) will progress to castrate resistant prostate cancer (CRPC) while the reasons for early metastases and chemoresistance in CRPCs are unknown. We aimed to investigate the potential role of hypoxia inducible factor 1α (HIF1α), a key transcription factor in the cell mediated adaptive response to changes in tissue oxygenation, in predicting the development of CRPC. Methods: 100 prostate tumour samples were divided into Gleason ≤7 (38) and Gleason >7 (62) and stained for HIF1α using immunohistochemistry, blinded to the outcomes. The outcomes of CRPC, metastases and PC specific death were measured and correlated with HIF1α expression. In vitro, the effects of HIF1α on proliferation, survival and migration of PC cells were assessed by cell count and Boyden chamber assays. Results: HIF1α expression in PC was independent of Gleason grade and tumour stage. HIF1α was an independent risk factor for development of CRPC (Hazard Ratio (HR) 10.4), progression to metastases (HR 9.8) and PC specific death (HR 13.4) at median times of 23, 24 and 25 months respectively, from the start of ADT on a multivariate Cox regression analysis (all p<0.05) adjusted for Gleason score, PSA and age. CRPC free survival, metastases free survival and PC specific survival were all significantly decreased in patients with HIF1α on Kaplan Meier analyses. The presence of HIF1α was highly sensitive (all 100%) with excellent negative predictive values (all 100%) for all 3 outcomes, but had poor specificity. HIF1α over-expressing PC3 cells (CRPC) were compared with androgen sensitive LNCaP cells in vitro. PC3 cells were resistant to cytotoxic agents including H2O2 (oxidative stress) and 5-fluorouracil (chemotherapy agent) and had higher rates of migration compared to LNCaP cells. HIF1α knockdown in PC3 cells reversed these effects. Protein translation efficiency in PC3 cells was significantly higher than LNCaP cells. Conclusions: HIF1α is a good screening tool for CRPC. HIF1α expression is likely to contribute to metastases and chemoresistance of CRPCs and is likely upregulated at protein translation in PC cells.
A phase II trial of neoadjuvant metformin in prostatic adenocarcinoma with serum and tissue biomarker evaluation.
Authors: Joshua Anthony Michael , Evren Sevan , Zannella Vanessa E. , Bowes Barbara , Fleshner Neil Eric , Jewett Michael A. S. , Finelli Antonio , Evans Andrew , Koritzinsky Marianne , Sweet Joan , Pollak Michael N.
Published: March 2020

e15118

Background: Metformin is an inhibitor of the complex 1 in the respiratory chain, and is widely used in diabetes due to its effect on reducing insulin resistance. It has also been recently described to have effects via AMPK on inhibiting the mTOR kinase. Significant preclinical and epidemiological studies suggest its role in chemoprevention. These actions provide significant rationale to evaluate its utility in prostate cancer. We conducted a phase II single centre study of neoadjuvant metformin in localised prostate cancer. Methods: Men were required to have histologically confirmed prostate cancer involving at least 20% of at least 1 unfragmented biopsy core. Exclusion criteria included patients who on initial assessment are found to be on treatment with any drug used for the treatment of any form of diabetes, or patients that begin treatment for any form of diabetes during the course of the study. Pts were treated with up to 500mg tid of metformin. Primary objectives were to demonstrate safety and tolerability of neoadjuvant metformin administration in men with prostate cancer and document changes in phospho-AKT signalling indices. Results: 24 patients were enrolled with 22 evaluable; median age was 64 yrs (range, 45-70 yrs). Baseline characteristics included median PSA 6 ng/mL (range, 3.22-36.11ng/mL). Median duration of drug treatment was 41 days (range 18-81). No grade 3 adverse events were reported, all patients underwent subsequent radical prostatectomy with adverse effects related to metformin. Final Gleason scores ranged form 6-8, and final stage ranged from pT2a-pT3b. Significant pre-and post changes were noted in serum IGF1 (p=0.02), fasting glucose (p=0.03), BMI (p<0.01) and waist/hip ratio (p<0.01). There was a trend for a PSA reduction (p=0.08), with 6/22 patients experiencing a PSA fall of greater than 20%. There were no correlations between any metabolic, morphometric or cancer-related serum indices.Tissue results are pending. Conclusions: Neoadjuvant metformin is well tolerated prior to radical prostatectomy. Data to date indicates promising effects on metabolic parameters, tissue results will be presented including proliferation indices and signaling pathway assessments.
Sarcopenia and altered body composition following abiraterone acetate (AA) and corticosteroid (C) treatment in men with castration-refractory prostate cancer (CRPC).
Authors: Mukherji Deborah , Pezaro Carmel Jo , Bianchini Diletta , Tunariu Nina , Mulick Cassidy Amy , Omlin Aurelius Gabriel , Sandhu Shahneen Kaur , Attard Gerhardt , De Bono Johann Sebastian
Published: March 2020

e15134

Background: Sarcopenia, or skeletal muscle wasting, is an independent prognostic factor in advanced malignancy (Prado Lancet Onc 2008). Decreased muscle and increased fat are recognized side effects of androgen deprivation therapy. AA is a CYP17 inhibitor administered with corticosteroids (C), approved for treatment of advanced CRPC. AA reduces circulating androgens to ‘super-castrate’ levels; we hypothesized that AA + C would impact body composition. Methods: We retrospectively evaluated 54 CRPC pts treated on a Phase I/II trial. Pts received AA alone followed by combination AA + C on biochemical progression. CT scans at baseline, on AA alone and on AA + C were analyzed. Cross-sectional areas of fat and muscle were measured on 3 consecutive images at L4 using OsiriX 4.0. Muscle area was used to calculate skeletal muscle index (SMI); sarcopenia was defined as SMI <52.4 cm2/m2. Data were analyzed using t-tests and Kaplan-Meier analysis with overall survival (OS) measured from day 1 of AA. Results: Median duration on AA alone was 7.4 months (m; range 1.4-37.5); median duration on concurrent AA + C was 7.4m (range 0.9-46.2). Body composition did not change between two pre-treatment scans (n=29; median 3m apart). On AA alone there was a decrease in total fat (-8.5%, p=0.0001), visceral fat (-9.8%, p=0.0015) and muscle mass (-3.9%, p=0.0023) with a significant decrease in mean body mass index (BMI; -3.4 %, p=0.0118). Conversely AA + C was associated with increased total fat (+15.1%, p<0.0001) and visceral fat (+21.4%, p<0.0001) but no further change in muscle mass. Mean BMI significantly increased on the addition of C, returning to baseline levels (p< 0.0001). Overall, 13 pts (24%) were sarcopenic prior to commencing AA compared to 22 (41%) at the end of treatment. Pts who were sarcopenic at baseline had significantly reduced OS: 26.1m (95%CI 16.6 – 41) vs 46.5m (95%CI 28.6 – 57.5, p=0.0253). Conclusions: Treatment with AA alone resulted in decreased fat and muscle. AA + C increased body fat without further alteration in muscle mass. Changes in BMI did not reflect changes in body composition. Sarcopenia at baseline was a negative prognostic factor in this population.
Assessment of the variability of and effect of hormone therapy on circulating tumor cell numbers and androgen receptor expression in patients with prostate cancer.
Authors: Clarke Noel W , Marley Sarah E , Hughes Andrew M. , Nash Anthony F , Malone Michael D , Growcott Jim W , Hodgson Darren R , Sloane Robert , Moore David J , Ward Tim H , Elliott P. Anthony , Dive Caroline
Published: March 2020

e15141

Background: In prostate cancer (PC) CTC number and character may offer a means of assessing disease load and target engagement. However, capture platforms differ, presenting challenges to enumeration and molecular characterisation. We report the findings of a pilot study assessing the intra- and inter-patient variability of 2 different platforms, and the feasibility of measuring CTC-androgen receptor (AR) expression by immunohistochemistry (IHC) in a single platform. Methods: Following ethical approval, 4 PC cohorts (n = 12, 12, 10, and 6 respectively) were recruited; #1 localised, no hormonal therapy; #2 and #3: castrate-resistant, receiving LHRHa or LHRHa and bicalutamide, respectively; #4: newly diagnosed locally advanced, no hormonal therapy. Blood (2 x 10 mL, 2 visits #1-3; 2 x 10 mL,1 visit #4) was taken and CTCs isolated using either the Cell Search CTC Test (Veridex) or Isolation by Size of Epithelial Cells Technique (ISET) for enumeration, and ISET for AR expression (H-score [(% 1*1+) + (% 2*2+) + (% 3*3+)]). Results: There was no correlation between Veridex and ISET for detection of CTCs (Veridex enumeration:14%, 63%, 53% and 0% of samples in #1 - 4, respectively, vs ISET enumeration: 100% of samples across all cohorts) with the latter platform detecting a significantly higher number of CTCs/4mls from patients in cohort #4 vs #1 (GLS Means 119 vs 46, p=0.0135). For both platforms there was no evidence of a systematic change in the counts at two separate visits 2 weeks apart. AR was detectable in approximately 25-35% CTCs from all cohorts and there were no significant differences in the H-score between the cohorts, although the number of AR-positive cells/4mls was significantly higher in #4 vs #1, and #2 (GLS Means 25 vs 14, 15, p= 0.0197, 0.0398, respectively). Conclusions: Populations of CTCs detected by Veridex and ISET appear stable over short durations (2 weeks) and AR was detected in a proportion of CTCs by ISET using IHC. Further work is required to find alternative methodologies with greater specificity.
Characteristics of stage III and IV M0 prostate cancer (PCa) patients in SEER-Medicare who develop bone metastasis (BM) following diagnosis.
Authors: Hussain Arif , Onukwugha Ebere , Jayasekera Jinani , McNally Diane L. , Seal Brian S. , Mullins C. Daniel
Published: March 2020

e15146

Background: BM is diagnosed in 70-80% of men with metastatic PCa. Less is known about the timing of BM diagnosis following incident non-metastatic PCa and associated patient characteristics. In this study, we determined the incidence and timing of post-diagnosis BM (BMpd) among PCa patients (pts) by incident stage, age, race and year of diagnosis using a large observational dataset. Methods: We analyzed pts aged 66 or older from the linked Surveillance, Epidemiology, and End Results and Medicare (SEER-Medicare) database. Pts with PCa were identified between 2000 and 2007 and were followed until death, Medicare disenrollment, HMO enrollment, or end of the study (December 31, 2009). The cohort included incident stage III and IV(M0) PCa in SEER, and identified BM occurring either within (i.e., +/-) 1 month of the SEER diagnosis month (BM90) or beyond the initial 90-day window (BMgt90) based on the presence of at least one inpatient or one outpatient claim with a diagnosis code of 198.5. We calculated summary and chi-square statistics to examine BMpd, BM90, and BMgt90 by incident stage, age, race and year of PCa diagnosis. Results: Among 9,188 Stage III (72%) and IV(M0) (28%) PCa pts who met inclusion/exclusion criteria, 14.6% (n=1,345) had BMpd: 2.3% (n= 217) had BM90 and 12.3% (n=1,128) had BMgt90. Average age was 72 years and 9% were African American (AA). Incidence of BMpd varied by stage (stage III: 11%; stage IV/M0: 25%; p<0.001) and by age group (66-74 years: 13%; 75-84 years: 19%; >85 years: 22%; p<0.001) but not by race (White: 15%; AA: 16%; Other: 13%; p=0.49). The diagnosis BM90 and BMgt90 varied with stage (stage III: 2% and 9%; stage IV(M0): 4% and 21%; p<0.0001) and age (66-74 years: 2% and 11%; 75-84 years: 3% and 16%; >85 years: 5% and 17%; p<0.001). The incidence of BM decreased over time whether considering BMpd (19% in 2000 to 9% in 2007; p<0.001), BM90 (4% in 2000 to 2% in 2007; p=0.03) or BMgt90 (16% in 2000 to 6% in 2007; p<0.001). Conclusions: BM occurred in only 2% of incident stage III/IV(M0) PCa pts within 1 month of diagnosis, but nearly 15% were diagnosed with BM during a median follow-up of 57 months. Prevalence of BM was highest in stage IV(M0) and older pts.
Cabazitaxel in patients with advanced CRPC after docetaxel failure: Results of expanded program access (EAP) in Spain: Safety and efficacy.
Authors: De Velasco Guillermo , Aparicio Luis Anton , Esteban Emilio , Perez Quionia , Sanchez-Hernandez Alfredo , Pérez-Valderrama Begoña , Batista Norberto , Sepulveda Juan , Castellano Daniel E.
Published: March 2020

e15149

Background: Cabazitaxel is the new chemotherapy standard as second line in castrate resistant prostate cancer (CPRC) [Tropic Trial, Lancet 2010]. The aim of this study was to analyze the baseline characteristics and outcomes in a different cohort of patients (pts) from six hospitals in Spain within to EAP. Methods: We report a cohort of 65 pts including in EAP trial, who have progressed on or after docetaxel-based chemotherapy. Cabazitaxel was administered a standard dose of 25 mg/m2 IV q3wks. All pts had proven histology confirmation of prostate adenocarcinoma and progressive disease (radiologic and/or rising PSA) at the beginning of the treatment. Results: We collected data of 65 pts between 3-2011 to 12-2012. Median age was 63 years (range 45-83) and ECOG 0-1-2 in 26%-58%-16% respectively. Median basal PSA was 864 and Gleason grade was 7. Seventy-eight percent had bone metastases, 33% ganglionar metastases and 14% visceral metastases. Previous therapy was: hormonal, median 2 lines and chemotherapy was median of 1.6 lines. Thirty percent (20 pts) had received ketoconazole. Median of previous docetaxel dose was 1029 mg/m2(50-3750). Seventy percent of pts received G-CSF as primary prophylaxis in any cycle, 24% (16pts) had grade >3 neutropenia and 6 pts (9%) had febrile neutropenia. Other toxicities were: g3 anemia 3pts (4,6%), g3 asthenia 5pts (7,7%), g3 diarrhea 1 pt (1,5%). No toxic death was reported. The PSA response rate to cabazitaxel was 64% (31pts) and the median of cabazitaxel cycles administered was 6 at last follow-up. Median progression free survival was 4.4 months (2.7-6.1). Conclusions: These results confirm the efficacy and safety of cabazitaxel in this setting. Similar baselines parameters to Tropic trial were observed. This data reflex that Cabazitaxel in CRPC pts after docetaxel failure require the use of G-CSF in daily clinical practice.
Factorial phase II randomized trial of continuous (C) or intermittent (I) docetaxel (D) with or without estramustine (E) as first-line treatment for castration-resistant prostate cancer (CRPC): Preliminary results of HOPLITE trial.
Authors: Caffo Orazio , Lo Re Giovanni , Sava Teodoro , Buti Sebastiano , Sacco Cosimo , Basso Umberto , Zustovich Fable , Martini Thomas , Perin Alessandra , Veccia Antonello , Russo Lucianna , Facchini Gaetano , Barile Carmen , Gernone Angela , Pappagallo Giovanni L. , Galligioni Enzo
Published: March 2020

e15160

Background: Pts who receive first line for CRPC are usually treated with 8-10 consecutive courses of D. The pts quality of life (QL) may be worsened and an I administration could limit this effect. E is an old drug showing a synergistic action with D. This study is aimed to compare QL of C and I D and whether E added to D improved its activity, in a 2 × 2 factorial design. Methods: CRPC pts were randomized to: C D 70 mg/m2 IV q 3 wks for 8 courses alone (arm A) or with E 280 mg/TID PO for 5 days starting 1 day prior to D (arm B), or the same treatments given with a 3-month rest period after the first 4 courses (arm C and D, respectively). The primary end points were QL (EORTC QLQ C30 and BPI) of A+B vs C+D and 1-y PFS (according to PCWG2) of A+C vs B+D. Results: 148 CRPC pts were enrolled from 11/06 to 10/10 with 128 pts evaluable at this time. The median age was 69 (range 42-81) and the median baseline PSA was 55.6 (range 0.33-4212). The major hematological toxicities were: anemia G3 (3 pts), neutropenia G3 (4 pts) – G4 (5 pts), febrile neutropenia (5 pts). Comparing C and I, QL outcomes were not statistically different in terms of general QL items. Comparing D and DE, 1-y PFS was superimposable (10% and 13.5%, respectively). The 2-y overall survival was not different between I and C arms 42.5% and 53.7% respectively) and between D and DE arms (42.8% and 53.5% respectively). Conclusions: These preliminary results suggest that I treatment did not produce a QL advantage compared to C treatment, while the addition of E to D did not improve 1-y PFS of CRPC pts.
Outcome research: Ambulatory intraperitoneal chemotherapy in stage IIIC ovarian cancer.
Authors: Garcia Gerardi Carlos , Vidaurreta Javier , Gil Deza Ernesto , Kohen Nelson , Levit Claudio , Morgenfeld Eduardo L. , Alessandria Sebastian , Rivarola Edgardo G. J. , Gercovich Felipe G.
Published: March 2020

e15507

Background: Intraperitoneal chemotherapy in stage III ovarian cancer is indicated following the results of the GOG 172 study but the ambulatory application of the scheme in 24 hours continuous infusion is not feasible. Following expert recommendations (Walker, ASCO 2009 Educational Book), we evaluated the feasibility of administrating a modified GOG 172 regime in an ambulatory form. Methods: Between September 2009 and October 2010, ten patients diagnosed with stage IIIC ovarian cancer and optimal cytoreduction received the following treatment in ambulatory form: IV paclitaxel (135mg/m2/3hrs Day 1), followed by IP cisplatin (60-75mg/m2 Day 2), plus IP paclitaxel (60mg/m2 Day 8). Cycles were administered every 21 days, up to a maximum of six cycles. The tolerance for this treatment was evaluated according to the CTC for Adverse Event 3.0. Results: Population Characteristics: Mean age (47 years; range 26-64). PS (0: 4 pt; 1: 6 pt). Pathology (Papillary: 7 Pts; Mucinous, Endometroid and Poorly Differentiated: 1 pt each). N-positives: 4 pt; N-negatives: 6 pt. Intestinal resection: 1pt. In all cases, treatment was applied according to the specified parameters. Total number of cycles administered: 37 (mean cycles per pt 3 range 2-6). The average time of treatment application was 3 hours per day (9 hours total). Toxicity (G3-4): Leukopenia (2 pts). Toxicity (G1-2): Alopecia (10 pts), Anemia (9 pts), Myalgia (8 pts), Neurologic (7 pts), Fatigue (6 pts), Nausea and vomiting (6pt), Renal (2 pts), Allergy (1 pt), Pain at Catheter site (1 pt). With an average follow up time of 16 months (Range: 9-26), none of the patients have died. Three patients have progressed after the Intraperitoneal chemotherapy, while seven are alive without evidence of disease after the treatment. Conclusions: 1) The modified GOG 172 scheme can be safely applied in an ambulatory form. 2) The time required for applying the treatment is similar to that of other frequently used treatments (BEP, paclitaxel – trastuzumab, R-CHOP, b-FOL). 3) Patient tolerance was very good. 4) With an average follow-up of 16 months, all 10 patients are alive and 7 of them remain free of disease.
Hospital readmission after surgical cytoreduction for epithelial ovarian carcinoma: An assessment of risk.
Authors: Clark Rachel Marie , Growdon Whitfield Board , Wiechert Andrew , del Carmen Marcela G , Goodman Annekathryn , Boruta David M. , Bradford Leslie , Garrett Leslie A. , Schorge John O.
Published: March 2020

e15545

Background: Hospital readmissions are common, possibly avoidable, and may be used as a metric for assessing an institution’s quality of care. We performed a retrospective analysis to determine risk factors associated with readmission after ovarian cancer cytoreduction surgery. Methods: We identified all patients with stage II-IV ovarian cancer who underwent cytoreduction at our institution between 2003-2011. A retrospective chart review was performed and clinical variables extracted. Utilizing linear and logistic regression these variables were correlated with risk of readmission. Results: A total of 463 patients were included in the analysis. Average age was 62 years. Median length of stay was 8.6 days (range 2-55). Optimal cytoreduction (<1.0cm residual disease) was obtained in 368 patients (81%) and 233 patients (50%) underwent bowel resection or radical upper abdominal procedure (splenectomy, liver resection, diaphragmatic surgery). Perioperative complications were observed in 148 patients (32%). A large proportion of our cohort was discharged to rehabilitation facilities (12%) or with a visiting nurse (38%). Of the entire cohort, 55 (12%) were readmitted within 30 days. Readmission was significantly associated with increased length of stay (OR 1.05, 95% 1.01 – 1.1) and perioperative complications (OR 3.5, 95% 2.0 – 6.3). Radical surgery was associated with an increased length of stay (p <0.001) but not with readmission (p = 0.8). Multivariate logistic regression revealed that complications were the only independent factor associated with readmission (OR 3.2, 95% 1.7- 6.0). Further multivariate analysis revealed that reoperation was associated with the greatest risk (OR 8.4, 95% 3.3 -21.1) of readmission. Conclusions: Readmission after ovarian cancer cytoreduction affected 12% of our population. While perioperative complications and increased length of stay were associated with an increased risk of readmission, multivariate analyses suggested that perioperative complications, specifically reoperation, placed the patient at the greatest risk. Comorbidities, radical surgery and the use of ancillary/rehabilitation services had no significant effects on the risk of readmission.
Growth in head and neck cancer clinical research in the NCRN and NCRI: Expanding opportunities for patients across the United Kingdom.
Authors: Seymour Matthew T. , Moser Rachel , Cooper Matthew , Fisher Sheila , Poole Karen , Nutting Christopher
Published: March 2020

e16007

Background: The National Institute for Health Research Cancer Research Network (NCRN) was established in 2001 to benefit patients by improving the coordination, integration and speed of cancer research. Networks were established in England (NCRN), Scotland, Wales and Northern Ireland, supporting recruitment to a national portfolio across the NHS. In a decade recruitment to cancer studies has increased five fold in England to 20% of new incident cases. Head and Neck cancers affect basic functions including breathing and eating; particularly devastating for patients. The NCRI Head and Neck Cancer Clinical Studies Group is one of 23 Groups funded by NCRI members with a UK wide remit to develop a national portfolio of clinical studies. All CSGs include patients and carers as members resulting in active patient involvement in trial design, patient information and strategic direction of the portfolio. Methods: The last decade has seen unprecedented growth in the Head and Neck portfolio, which now includes 43 studies from only three studies in 2003/4. By 2010/11, 95% of UK Cancer Local Research Networks (37 networks) were recruiting to Head and Neck studies from only 2 networks in 2001/2, expanding trial access for patients and developing Head and Neck research expertise in new sites and with new investigators. Results: Numbers of patients participating in Head and Neck studies has grown exponentially. Since 2006/7 UK patient recruitment has risen 15-fold from 126 to 1890, representing almost 25% new incident cases of Head and Neck cancer. Conclusions: Rapid portfolio growth and associated network activity has expanded opportunities for patients with Head and Neck cancer; providing access to new therapeutic agents and treatment modalities, including NIHR CRN-adopted commercial trials and studies in a surgical setting. Participation in studies demonstrating the effectiveness of Intensity Modulated Radiotherapy in reducing xerostomia (including PARSPORT), has supported integration of this technique into cancer service.
Hürthle cell neoplasm of thyroid gland: An institutional experience.
Authors: Agrawal Ritesh , Chand Gyan , Mishra Anjali , Agarwal Gaurav , Agarwal Amit , Verma Ashok Kumar , Mishra Saroj Kanta
Published: March 2020

e16023

Background: Hürthle cell carcinoma is a relatively rare thyroid malignancy. Aim of this study was to analyze clinical behavior and outcome of patients with Hürthle cell carcinoma managed at a tertiary care academic medical institution in northern India over last two decades. Methods: This retrospective study was conducted at the Department of Endocrine Surgery, SGPGIMS, Lucknow, India. Hospital records of 27 patients with FNAC proven Hürthle cell neoplasm operated between January 1991 and December 2011 were reviewed. Demographic data, clinical presentations, FNAC reports, surgical procedure undertaken, histology reports and follow up data were reviewed. Statistical analysis was done using SPSS software version 15.0 by Kruskal-Wallis and Mann-Whitney tests. p-value <0.05 was considered siginificant. Results: Among 2,066 thyroid surgeries (796 for differentiated thyroid carcinoma) performed during the study period, 27 patients had FNAC of Hürthle cell neoplasm. Histology revealed Hürthle cell adenoma (HCA) (n=10), Hürthle cell carcinoma (HCC) (n=09), and others (n=8). Sensitivity of FNAC to diagnose Hürthle cell lesions (HCA or HCC)) is 70.37%. Among histology proven Hürthle cell lesions, mean size of nodules was 6.10 + 3.27 cm (range 2.50- 13 cm); for HCA it was 4.84 + 3.32 cm (range 2.60- 13.00 cm) and for HCC, it was 7.50 + 2.75 cm (range 2.50- 10 cm). There was no significant difference in age, sex and size of nodules for development of malignancy (p-value 0.967, 0.105, 0.100 respectively). Cervical lymph node metastases were present in 44.45% and distant metastases in 22.22% of HCC. Three patients had local recurrence; one expired of distant metastases, two had repeated surgeries with control of disease. The overall mortality was 22.22% among Hürthle cell carcinomas. Conclusions: The diagnosis of Hürthle cell neoplasm on FNAC should be interpreted with caution by the treating surgeon who should corroborate with other features such as age, duration and progress of the goiter, lymph node status etc. so as to clinically ascertain possibility of malignancy to plan appropriate surgical procedure. Regular follow-up is essential to pick up recurrence at the earliest and to treat it surgically since these tumors don’t pick radioiodine.
Paclitaxel (P) and cisplatin (C) concurrent with radiotherapy (RT) for larynx preservation (LP) in advanced resectable laryngeal (L) and hypopharyngeal (HP) squamous cell carcinoma (SCC): Final results of a prospective phase II trial.
Authors: Nicolau Ulisses Ribaldo , Oliveira Thiago Bueno , Carvalho Andre Lopes , Santana Rosane O , Valadares Adriana D , Salvajoli Joao Victor , Chinen Ludmilla T.D. , Araujo Bertha Catherine B. , Martins Sandro José , Castro Junior Dalvaro Oliveira , Kowalski Luiz Paulo , Feher Olavo
Published: March 2020

e16046

Background: Since the results of the RTOG 9111 trial, cisplatin based chemoradiation (CRT) has been the standard of care for LP in advanced laryngeal SCC. Recently, the role of taxanes in managing head and neck SCC has been studied. In 2002 we reported the interim results of a phase II clinical study designed to test the efficacy of P and C concurrent with RT for organ preservation in advanced L and HP SCC. Here we report the long term survival and LP rates. Methods: Eligible patients had untreated advanced L and HP SCC, stage T3N0 or higher and suitable for radical total laryngectomy. Treatment consisted of weekly P (30 mg/m2) and C (20 mg/m2) concurrent to RT up to 7040 cGy in 180 cGy/day fractions. Response evaluation was performed at 5040 cGy and at 4 weeks after completing RT. Salvage surgery was planned for patients not responding at 5040 cGy, residual tumor at the end of RT or at the time of local recurrence. Neck dissection was planned for clinically positive neck (cN1-3). Results: Between 06/1999 and 10/2001, 48 patients were enrolled in a single institution (35 L; 13 HP), 40 male and 8 female with a 58-year median age (39-74). The majority had T3 (64%) N1-3 (52%) disease and 38% needed tracheostomy prior to treatment. Grade (G) 3 and 4 mucositis was noted in 27% of patients, G 3-4 odynophagia in 50%, G 3-4 radiodermatitis in 35% and G 3-4 leucopenia in 13%, with no treatment related death. Two patients needed salvage surgery, one after 5040 cGy and one after 7040 cGy. The complete response rate to treatment was 95%. At a median follow up of 66 months the LP rate at 2 and 5 years were 88% and 54%, respectively. Recurrence free survival (RFS) was 51% at 2 and 47% at 5 years and overall survival (OS) was 81% and 52% at 2 and 5 years, respectively. Conclusions: The finding of similar LP rate and survival compared to the recent reports of high dose cisplatin CRT and neoadjuvant 3 drug CT followed by CRT in an advanced disease population suggests a role for platinum plus taxane as a radiosensitizer regimen in this scenario with acceptable toxicity, but further evaluation in a direct comparative trial with the standard regimen is needed.
Stereotactic radiosurgery for patients with recurrent head and neck carcinoma: Five years’ observation report.
Authors: Kawaguchi Koji
Published: March 2020

e16049

Background: The aim of this study is to examine the effect of stereotactic radiosurgery (SRS) in the treatment of advanced, recurrent lesions for head and neck carcinoma both with and without lymph node involvement. Methods: Between April 2006 and July 2007, 22 patients (mean age 67 years) with advanced, recurrent head and neck carcinoma were treated with SRS by CyberKnife-II. All of the patients excepted one had biopsy confirmed disease prior to SRS. Patients included 3 rT2, 8 rT3, and 9 rT4; 8 of the patients had lymph node metastases. Marginal SRS doses were 20-42 Gy delivered in two to five fractions. Starting one month after SRS, all patients received S-1 oral chemotherapy for one year. Results: At an overall median follow-up of 64 months (range, 4-69 months), for the 14 locally recurrent patients without lymph node metastases, 9 patients (64.3%) had a complete response (CR), 1 patient (7.1%) had a partial response (PR), 1 patient (7.1%) had stable disease (SD), and 3 patients (21.4%) had progressive disease (PD). For the 8 patients with lymph node metastases, 1 patient with a single retropharyngeal (12.5%) had CR; the remaining 7 patients (87.5%) all progressed. Nine patients have died from their cancer. The overall 5-year survival for the patients with and without lymph node metastases was 12.5% and 78.6%, respectively. Conclusions: These results show the benefit of stereotactic radiosurgery salvage treatment for advanced, recurrent lesions, without lymph node metastases in previously irradiated head and neck cancer.
Examining variation in mammography and breast cancer treatment quality.
Authors: Dupuy Danielle , Orsi Jennifer M. , Rauscher Garth , Murphy Anne Marie , Weldon Christine B. , Trosman Julia R. , Robinson Patricia A. , Marcus Elizabeth A.
Published: March 2020

e16531

Background: In Chicago, Illinois, black women are 62% more likely to die from breast cancer (ca) than white women, a disparity exceeding that of the US (41%) and New York City (27%). Geographically disparate rates may suggest health system drivers of the disparity. The Chicago Breast Cancer Quality Consortium was established in 2008 to examine the quality of screening and breast cancer care to answer the question of whether variations in quality contribute to the known disparity while identify opportunities for quality improvement interventions. Methods: Mammography (mammo) screening data was collected from each site. Treatment (tx) data for each woman with a primary breast ca diagnosis who received her first course of tx at that site was collected. Measures, methods and benchmarks were developed using existing guidelines and approved by expert advisory groups. Analysis was performed to determine if sites could demonstrate they met benchmarks. Results: CY2009 aggregate screening and tx data was collected from 52 and 21 sites respectively. Only 61% (32) of sites could demonstrate that they met >50% of the screening mammo benchmarks, while 76% (16) of sites could demonstrate they met >50% of tx benchmarks. Conclusions: A lower proportion of sites could show they meet quality mammo benchmarks as compared to tx benchmarks. There was room for improvement in both. Further site-specific inquiry is underway to determine if results are reflective of data collection issues or actual quality issues. [Table: see text] [Table: see text]
Perceptions concerning clinical trials in oncology patients.
Authors: Lee Dana , Chao Ju-Hsien , Stevens Sandy , Kloecker Goetz H.
Published: March 2020

e16533

Background: Accrual to clinical trials among adult cancer patients is persistently low. Patient preference plays an important role in enrollment. To identify the reasons why patients decline study participation, it is important, to evaluate the perceptions of newly diagnosed oncology patients about clinical trials. Methods: Patients were given a ten-question survey reflective of their attitudes regarding clinical trials as a treatment option at their initial visit. The self-directed questionnaire was scored on an ordinate scale from strongly agree (1) to strongly disagree (5). Results: Ninety-two new patients were surveyed in the cancer - specific multispecialty clinics in an academic cancer center. The patients expected information relating to eligible clinical trials and privacy protection by university sponsored studies as they strongly concurred with “I expect my doctor to inform me about clinical trials that I am eligible for” (mean score 2.15, p=0.001) followed by “all possible measures to protect my privacy are likely to be taken in a clinical trial that is sponsored by a university” (2.36, p=0.36). The strongest disagreement was “If enrolled in a clinical trial, I am comfortable being assigned by a method such as ‘flipping a coin’ or ‘throwing a dice’” (3.73, p=0.001) and “I would be willing to participate in a clinical trial as a first line treatment option” (3.50, p=0.001). Industry sponsored trials, phase 1 trials, second line treatment trials, privacy concerns and investigator initiated trials and time commitment and altruistic reasons did not significantly deviate from the mean preference (2.5) by a one sample T-test analysis. Conclusions: Patients consider the option of clinical trials as important in their treatment, and expect to be informed by their oncologist about clinical trials. Newly diagnosed cancer patients perceive randomization and first line trials negatively. Since randomized data provides new standards for care and hope for improved treatment, patients and their families must be educated about their importance.
Cost-effectiveness of robot-assisted lobectomy compared with VATS lobectomy for early-stage lung cancer in the National Health Insurance Program of Korea.
Authors: Lee Hyun-Sung , Jang Hee-Jin , Park Seong Yong , Joo Jungnam , Zo Jae Ill
Published: March 2020

e16534

Background: Robotic surgery has proven to be one of the most effective cutting-edge technologies for successful minimally invasive surgery. This study aimed to evaluate the cost-effectiveness of robot-assisted lobectomy (RAL) for the treatment of early stage lung cancer with video-assisted thoracic surgery (VATS) lobectomy. Methods: From February 2009 to April 2011, one hundred twenty patients underwent RAL for clinical stage I or II non-small cell lung cancer. The consecutive 100 patients who underwent RAL were compared with 100 patients who underwent VATS lobectomy during the similar period under intent-to-treat analysis. Clinicopathologic characteristics and surgical outcomes were analyzed. Adverse events were defined as operative morbidities, mortality and conversion to open thoracotomy. The adverse events were adjusted by NCI-CTCAE 3.0 grade. Incremental cost-effective ratio (ICER) was defined as difference of total cost divided by difference of adjusted adverse events. Results: Tumor size was slightly larger in RAL group with 3.2cm in mean size of tumor. RAL needed longer operation time than VATS group. However, the console time during operation was similar with operation time in VATS lobectomy. The median length of postoperative stay was significantly shorter after robotic surgery than VATS. Operative morbidities developed in 9 patients in RAL and 21 in VATS (p=0.028). Conversions to thoracotomy were happened in 2 cases in RAL and 7 cases in VATS (p=0.170). The total hospital costs were higher in RAL than those in VATS ($14,186 vs. $11,509, p<0.001). ICER between RAL and VATS was $16,111 (80% CI; $9,190~$33,860) and NNT (numbers needed to treat) was 6.01. If six patients are treated by RAL, one case of adverse operative events could be diminished and its additional cost is $16,111. Conclusions: Robot-assisted lobectomy for early stage lung cancer is safe as well as feasible, and it results in a satisfying postoperative outcome compared with those after VATS lobectomy. Despite higher total costs, RAL is highly cost-effective to treat early stage lung cancer in National Health Insurance Program of Korea.