bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comorbidity and sorafenib (SOR) therapy in elderly patients with metastatic renal cell carcinoma (mRCC).
Authors: Gernone A. , Pagliarulo A. , Pagliarulo V. 
Published: February 2017

398 Background: SOR is a multikinase inhibitor with activity in mRCC. Older patients (pts) benefit from SOR as reported in the subgroup analysis of the TARGET study populations. We evaluated the efficacy and safety in elderly pts (≥ 70) with comorbidities. Methods: A comprehensive geriatric assessment (CGA) was used in older mRCC pts. From 2007 to 2010, 30 pts (23 males and 7 females) received SOR 400 mg BID continuous dosing. Comorbidities were evaluated using the cumulative illness rating scale for geriatrics (CIRS-G). The total score was 0–4. 10 pts with CIRS-G 1, 12 pts with CIRS-G 2, 8 pts with CIRS-G 3/4. Median age was 76 (70–84), ECOG PS 0–2, 24/30 had undergone prior nephrectomy. The most frequent comorbidities were arrhythmias, hypertension, chronic bronchitis, diabetes mellitus, neurological disease. The endpoints were response rate (RR) evaluated by RECIST criteria and correlations between comorbidities and toxicity. Results: Dose reduction (400–600 mg/die) were required for pts with CIRS-G 3–4. No correlations were found between comorbidities (CIRS-G) and response to SOR. 18 pts (14 pts CIRS-G 1/2, 4 pts CIRSG 3/4) had partial response (PR)with a duration of 24 months (9-30) and 12 pts (8 pts CIRS-G 1-2, 4 pts CIRS-G 3/4) stable disease (SD) for 24 months (7–32). 17/30 pts (12 pts CIRS-G 1/2, 5 pts CIRS-G 5) remain on therapy. Drug related adverse events were mainly grade 1 and 2 and were medically manageable. 4 pts required dose interruption (3 pts CIRS-G 1/2, 1 pt CIRS-G 3/4). Pts with CIRS-G score 3–4 had poorer quality of life but the clinical benefit achieved with SOR therapy was high. Conclusions: Comorbidities in pts with mRCC ≥ 70 years did not result in increased incidence of toxicity on SOR treatment. These data suggest that SOR is effective and safe in elderly pts with an overall clinical benefit rate (PR + DS) particularly high. No significant financial relationships to disclose.
Activity of retreatment with sorafenib for metastatic renal cell carcinoma.
Authors: Nozawa M. , Matsumura N. , Yasuda M. , Okuda Y. , Uemura H. 
Published: February 2017

404 Background: Treatment options for metastatic renal cell carcinoma (mRCC) have increased. Complete remission is, however, rarely seen and patients are treated with multiple sequential therapies. We assessed clinical activity of sorafenib rechallenge after progressing on other therapies. Methods: Patients with mRCC who received a second course of sorafenib therapy after failure of prior sorafenib and other agents were retrospectively identified. RECIST-defined objective response rate and progression-free survival (PFS) and toxicity were analyzed. Results: Fourteen patients with mRCC who were retreated with sorafenib were identified and twelve patients were assessable for this study. 92% were male. Median age at first systemic therapy was 63 years. Prior nephrectomy was performed in 92% of patients. 42% of patients had favorable or intermediate risk, 17% poor, and the rest not available per MSKCC criteria. Eighty-three percent of patients were treated with other agents before initial sorafenib therapy, including 75% interferon-alpha (IFN-alpha), 50% interleukin-2 (IL-2), and 17% sunitinib. First sorafenib therapy began a median of 9.0 months after the diagnosis of mRCC and produced a clinical benefit (PR + SD) rate of 75% and a median PFS of 5.0 months. 67% of patients discontinued initial sorafenib for disease progression and 33% for adverse events. Interval between discontinuation of initial sorafenib and rechallenge was a median of 7.6 months. During the intervening period, 50% of patients were treated with sunitinib, 33% with everolimus, 25% with VEGFR1 vaccine, and others. Clinical benefit rate of 67% and a median PFS of 4.3 months were obtained on sorafenib rechallenge. There was no significant difference in outcome to sorafenib rechallenge based on duration between sorafenib treatments or number or type of intervening treatments. No new severe toxicity was observed during rechallenge. Conclusions: Sorafenib rechallenge has potential to achieve clinical benefits, is well-tolerated, and may be considered after multiple sequential therapies in select mRCC patients. No significant financial relationships to disclose.
Multiphoton microscopy of human prostatic and periprostatic tissue architecture for improving identification of tissue structures: Implication in nerve-sparing radical prostatectomy.
Authors: Grover S. , Mukherjee S. , Sooriakumaran P. , Srivastava A. , Sterling J. , Shevchuk M. , Tewari A. 
Published: February 2017

61 Background: Introperative differentiation of various tissue types would aid the surgeon during dissection in radical prostatectomy. Specifically, it will enhance decision-making with regards wide excision or nerve-sparing. We investigated the value of a novel imaging technology (multiphoton microscopy-MPM) for providing “virtual” histology. Methods: We imaged intraoperative surgical margins and biopsies, as well as radical prostatectomy sections. The imaging was carried out using intrinsic fluorescence and scattering properties of the tissues without any exogenous dye or contrast agent. The corresponding tissues were subjected to hematoxylin and eosin staining for histological confirmation of the structures. Results: High-resolution images of the periprostatic tissue, nerves, prostate capsule, underlying acini, and individual acinar cells were obtained at varying magnifications. There was good correlation between MPM and histology in identification of all anatomic structures. Conclusions: MPM provides microscopy level resolution in fresh human prostatic tissue, without the need for any extrinsic labeling agents or phototoxicity. It shows promise as a real-time intraoperative aid during radical prostatectomy. No significant financial relationships to disclose.
Impact of primary Gleason grade 4 on biochemical recurrence after permanent interstitial brachytherapy in Japanese patients with low- or intermediate-risk prostate cancer.
Authors: Saika T. , Uesugi T. , Edamura K. , Kobuke M. , Nose H. , Ebara S. , Nasu Y. , Katayama N. , Yanai H. , Kumon H. 
Published: February 2017

77 Background: To reveal a predictive factor for biochemical recurrence (BCR) after permanent prostate brachytherapy (PPB) using iodine-125 (125I) seed implantation in patients with localized prostate cancer classified as low or intermediate risk based on the National Comprehensive Cancer Network (NCCN) guidelines. Methods: From January 2004 to December 2009, consecutive 418 Japanese patients with clinically localized prostate cancer classified as low or intermediate risk based on the National Comprehensive Cancer Network (NCCN) guidelines were treated by PPB. The clinical factors including pathological data reviewed by central pathologist and follow-up data were prospectively collected. Kaplan-Meier and Cox regression analyses were used to assess the factors associated with BCR. Results: Median follow-up was 36.0 months. The 2, 3, 4 and 5-year BCR free rates using Phoenix definition were 98.3%, 96.0%, 91.6% and 87.0% respectively. On univariate analysis, primary Gleason grade 4 in biopsy specimen was strong predicting factor (p<0.0001), while Gleason sum, age, initial PSA, initial PSA density, T stage and D90 were insignificant factors. Multivariate analysis indicated that primary Gleason grade 4 was most powerful prognostic factor associated with BCR (hazard ratio=10.101, 95% IC 3.080-33.126, p=0.0001). Conclusions: The primary Gleason grade 4 carried a worse BCR than the primary grade 3 in Gleason score 7 prostate cancer. Therefore, the indication for PPB in patients with Gleason sum 4+3 should deserve careful and thoughtful consideration. No significant financial relationships to disclose.
Update of the HIPRO study: Late toxicity and outcome at seven years.
Authors: Thomson D. , Merrick S. , Swindell R. , Coote J. , Elliott P. A. , Cowan R. , Wylie J. , Logue J. , Livsey J. E. , Choudhury A. 
Published: February 2017

81 Background: Dose-escalated radiotherapy for localised prostate cancer improves disease control but at the expense of increased overall treatment time and late toxicity. Given the low alpha-beta ratio for prostate cancer, treatment with hypofractionation should be biologically advantageous. Intensity-modulated radiotherapy (IMRT) allows dose escalation with hypofractionation, while achieving acceptable levels of toxicity. We report our 7 year late toxicity data in patients treated with two such regimens within the Hypofractionated Dose Escalation utilising Intensity-modulated Radiotherapy in Carcinoma of the Prostate (HIPRO) study. Methods: Sixty men, median age 75 years (50-87), with localised adenocarcinoma of prostate (T1-3NOMO) and either Gleason score ≥7 or PSA 20-50ng/L received 57Gy in 19 fractions (n=30) or 60Gy in 20 fractions (n=30) using 5-field inverse-planned IMRT. All patients received neoadjuvant hormone therapy, continuing for up to 6 months after treatment. Late toxicity was assessed at 7 years follow-up using RTOG criteria and LENT/SOMA questionnaire. Results: Forty-four (73%) patients were alive at 7 years. Nine patients (21%) reported RTOG grade 1 bowel or bladder toxicity; there was no grade 2 toxicity or above and no difference between the fractionation schedules. LENT/SOMA questionnaires were returned by 31/44 patients. Mean and median scores were less than one for bowel and urinary symptoms. When compared with pre-treatment, the proportion of patients with significant (maximum LENT/SOMA ≥2) urinary symptoms remained similar (75% vs. 76%), problems with sexual function had decreased (84% vs. 98%) but bowel symptoms increased (62% vs. 25%). At 5 years, overall survival was 83% and 74% and cause-specific survival was 83% and 84% in the 57Gy and 60Gy groups respectively. Conclusions: Dose-escalated hypofractionated IMRT for prostate cancer appears well tolerated with acceptable levels of late toxicity. Studies to assess long term disease control with these regimens are on-going. No significant financial relationships to disclose.
Lower urinary tract morbidity after prostate brachytherapy with cesium-131.
Authors: Smith R. , Beriwal S. , Vargo J. , Benoit R. M. 
Published: February 2017

97 Background: Cesium-131 is a relatively new radioisotope for prostate brachytherapy (PB), with limited long-term data for toxicity profiles. Here we report our 1-year follow up for severity and time to resolution of lower urinary tract toxicity using American Urological Association (AUA) and Expanded Prostatic Cancer Index Composite (EPIC) scoring. Methods: 186 patients with prostate cancer [NCCN risk category: Low (n=79), Intermediate (n=83), and High (n=24)] treated with cesium-131 PB alone (n=128) or combined with external beam radiation therapy (EBRT) + PB (n=58) were followed as part of a longitudinal prospective study. Patients completed AUA and EPIC surveys pre-operatively and at 2 weeks, 4 weeks, 3, 6, 9, and 12 months post-operatively. The mean prostatic volume was 41.3 cm3 (range 14.9 – 89.1) and the mean prostate D90 and V100 were 105.7% and 92.4%, respectively. Outcomes were analyzed using descriptive statistics and student t-tests, with an AUA score increase > 4 and EPIC score decrease > 10 points considered clinically significant. Results: Results are shown in the table below. As expected, there was acute urinary toxicity associated with PB. This is seen in the urinary summary score as well as in every one of the subset scales. These were most significant at the 2 and 4 week marks. The urinary summary score and every subscale improved to within 10 points of baseline by 3 months and stayed there through the 12 months of follow-up. Similar findings were reflected in the AUA scores. Conclusions: For men undergoing PB with cesium-131, results for AUA and EPIC scoring are concordant with no clinically significant differences in lower urinary tract symptoms are observed after 3 months relative to pre-operative values. The largest decreases in symptomatology scoring were witnessed in the irritative/obstructive subset, while the smallest changes relative to pre-operative values were noted in the incontinence subset. [Table: see text] No significant financial relationships to disclose.
Phase III randomized trial of definitive chemoradiotherapy (CRT) with FOLFOX or cisplatin and fluorouracil in esophageal cancer (EC): Final results of the PRODIGE 5/ACCORD 17 trial.
Authors: Conroy Thierry , Galais Marie-Pierre , Raoul Jean Luc , Bouche Olivier , Gourgou-Bourgade Sophie , Douillard Jean-Yves , Etienne Pierre-Luc , Boige Valérie , Martel-Lafay Isabelle , Michel Pierre , Llacer-Moscardo Carmen , Berille Jocelyne , Bedenne Laurent , Adenis Antoine ,   UNICANCER-GI/FFCD PRODIGE Intergroup
Published: February 2017

LBA4003 Background: CRT is one of the best treatment options for localized EC. As new combinations are required to improve safety and survival, we launched a randomized phase II study to assess the complete response (CR) rate of CRT with FOLFOX versus 5FU/cisplatin in 97 pts with localized EC (Conroy 2010). The trial having met its objectives, it has been pursued as a phase III trial. Stratified randomization was performed centrally in a 1:1 ratio according to histological type, pretreatment weight loss in the prior 6 months (<10% vs ≥10%), ECOG PS (0 vs 1 vs 2), and center. Methods: Pts with technically unresectable cancer or those with surgical contraindications or who refused to undergo surgery were eligible. Eligibility criteria also included age >18 years (y), PS ≤ 2, previously untreated adenocarcinoma or squamous cell EC (any T, N0 or N1, M0 or M1a). The radiation dose was 50 Gy (2Gy/fr) 5 d/wk for 5 wks in both arms. In Arm A, pts received 6 bimonthly cycles (cy): oxaliplatin 85 mg/m2 d1 and leucovorin 200 mg/m2 followed by 5-FU 400 mg/m2 bolus d1 then 1,600 mg/m2 46h continuous infusion (ci) ; the first 3 cy were delivered during RT, the 3 other after. In Arm B, pts received 4 cy: cisplatin 75 mg/m2 d1 followed by 5FU 1,000 mg/m2/d ci d1-4, the first 2 cy during RT and 2 other after. The primary endpoint was PFS. Main secondary endpoints were OS, grade 3-4 toxicities, and quality of life. A total of 266 pts would provide 90% power to detect a 20% 3y-PFS difference (α=0.05). Results: 267 pts were enrolled between 10/2004 and 08/2011. Treatment cohorts were well balanced: male 81%; median age 61 y; PS 0 53%, squamous cell 85.8%, stage III 52%, IVA 6.0% and IVB 3.0%. Full treatment was delivered to 67.9% and 72.2% of pts in arms A/B, respectively. 7 toxic deaths occurred in each arm. Grade 3/4 toxicities per pt (%) in arms A/B were neutropenia 30.6/31.3, febrile neutropenia 5.3/7.0, anemia 5.4/11.0, asthenia 17.6/10.2, respectively. The median FU time was 25.3 mos. 3y-PFS was 18.2/17.4 % (HR=1.07; 95%CI =0.80-1.43) and median OS was 20.2 /17.5 m (HR=1.06; 95%CI =0.77-1.46). Conclusions: CRT with FOLFOX does not improve PFS compared to cisplatin and 5-FU and has similar toxicities.
Efficacy of RAD001/carboplatin in triple-negative metastatic breast cancer: A phase II study.
Authors: Singh Jasmeet Chadha , Volm Matthew , Novik Yelena , Speyer James L. , Adams Sylvia , Omene Coral Oghenerukevwe , Meyers Marleen Iva , Smith Julia Anne , Schneider Robert , Formenti Silvia , Goldberg Judith D. , Li Xiaochun , Davis Samantha , Beardslee Brian , Tiersten Amy 
Published: February 2017

108 Background: Triple-negative breast cancer cells are unable to repair double stranded DNA breaks and have sensitivity to platinum agents. Rapamycin acts synergistically with platinum agents to induce apoptosis and inhibit proliferation in breast cancer cell lines. RAD001 (oral mTOR inhibitor) and Carboplatin combination may have activity in triple-negative breast cancer. Methods: The primary objective is to estimate clinical benefit (complete remission (CR) + partial remission (PR) + stable disease (SD) lasting >6 months) and toxicity of the combination in triple negative metastatic breast cancer patients who have had 0-3 prior chemotherapy regimens. This design has > 80% power to test the null hypothesis i.e. clinical benefit rate is ≤ 10% vs. alternative hypothesis that clinical benefit rate is ≥ 30%. Prior carboplatin is allowed. Women with treated brain metastasis are eligible. Originally, carboplatin AUC 6 was to be administered every 3 weeks along with daily 5mg of RAD001 with a 3 patient run-in and then 10 mg daily. Due to a surprising amount of thrombocytopenia, the dose of carboplatin was first amended to AUC 5 and most recently to AUC 4 with 5 mg of RAD001 (no escalation to 10 mg). Results: 23 out of 25 patients have been recruited. Median age is 59. Thus far, there have been 1 CR, 5 PR’s, 8 SD's and 6 PD’s. One SD was achieved in a patient progressing on single agent carboplatin at study entry. Median duration of response is 13 weeks (range: 6-74 weeks). 5 patients had grade 3/4 thrombocytopenia and 4 patients had grade 3 neutropenia (no febrile neutropenia). 13 patients had treatment held and/or dose reductions secondary to hematological toxicity. Since dosing amendment for carboplatin to AUC 4 the regimen has been well tolerated (only 1 patient with grade 3 neutropenia and thrombocytopenia). 1 patient had grade 3 dehydration. The estimated clinical benefit rate is 45% (95% C.I.: 23%, 67%). Median time to progression or death is 85 days from start of treatment. Conclusions: Our study has met the primary end point of demonstrating clinical benefit in triple-negative metastatic breast cancer. Dose-limiting thrombocytopenia was an unexpected side effect requiring protocol amendment. Patient accrual continues at the amended dosing.
Cetuximab in combination with irinotecan as second-line treatment in patients with platinum-resistant gastroesophageal cancer (GEC).
Authors: Schoennemann Katrine Rahbek , Yilmaz Mette K. N. , Bjerregaard Jon Kroll , Jensen Helle Anita , Nielsen Kirsten Marie , Vestermark Lene Weber , Pfeiffer Per 
Published: February 2017

101 Background: Inspired by the promising results seen in patients (pts) with chemo-resistant metastatic colorectal cancer we evaluated a biweekly schedule of cetuximab (cet) and irinotecan (iri) (Cetiri) (Pfeiffer et al. Ann Oncol 2008) in platinum resistant GEC. Methods: We treated and evaluated 111 consecutive pts with histological verified GEC adenocarcinoma and documented failure to first-line platinum-based treatment. Pts received cet 500 mg/m2 and iri 180 mg/m2 day 1 every 2nd week until progression or unacceptable toxicity. Toxicity was evaluated according to NCI-CTCAE v. 3.0. Response rate (RR) was evaluated according to RECIST v. 1.0 every 8th week. Clinical parameters and blood samples at baseline were analyzed in order to find prognostic and predictive values for prolonged overall survival (OS). Results: Pts were included from December 2007 to August 2010. Median age was 61 years (range 33-80). Performance status (PS) was 0-1 in 95 % of the pts. Thirty-six (46%) pts had more than two organs involved. Median number of courses was 8 (1-46). RR was 14% (2 CR, 13 PR) and 63% had stable disease for at least 2 months. Median PFS and OS were 3.2 months (CI 2-4) and 5.6 months (CI: 5-7) respectively. Seventy six (68%) pts had treatment induced skin toxicity, rash. In a univariate analysis PS 0-1, normal baseline haematology and skin rash was associated with significantly increased survival. These parameters retained significance in a multivariate analysis. One patient had a curative resection after end of treatment and four pts are still alive. Conclusions: Biweekly Cetiri is a convenient and well-tolerated second-line (SL) regimen in pts with GEC adenocarcinoma. Good performance status, normal baseline and development of skin rash indicate increased survival. Based on our findings biweekly Cetiri can be recommended as SL treatment to GEC pts in a good PS. Further studies into the role of rash are warranted.
Survival analysis of adjuvant chemotherapy with S-1 plus cisplatin for stage III gastric cancer.
Authors: Takahari Daisuke , Hamaguchi Tetsuya , Yoshimura Kenichi , Katai Hitoshi , Ito Seiji , Fuse Nozomu , Kinoshita Taira , Yasui Hirofumi , Terashima Masanori , Gotoh Masahiro 
Published: February 2017

107 Background: The efficacy of S-1 for stage II-III gastric cancer has been shown. However, the survival of stage III remains unsatisfactory (the 3-year recurrence free survival rates in stage IIIA and IIIB receiving S-1 were 68.0% and 49.8%, respectively). We already reported the feasibility of S-1 plus cisplatin as adjuvant chemotherapy for Stage III gastric cancer after curative resection (ASCO-GI 2009, Cancer Chemother Pharmacol 2011). Here we evaluate the recurrence and survival as secondary endpoints. Methods: Japanese patients with stage III gastric cancer who underwent D2 gastrectomy were enrolled. Treatment consisted of 3 cycles of S-1 (40 mg/m2 po) twice daily on days 1-21 and CDDP (60 mg/m2 iv) on day 8 and S-1 monotherapy was given on days 1-28 every 6 weeks until 1 year post surgery. Results: From August 2007 to September 2009, 63 patients were accrued. 35 patients were stage IIIA, the rest 28 patients were IIIB. After a median follow-up 2.9 years, 15 patients experienced recurrence, and 12 patients died. The 3-year recurrence free survival rate was 76.4% (95%CI:63.0-85.4%, IIIA 88.8%, IIIB 60.1%). The 3-year overall survival rate was 78.5% (95%CI:63.4-87.9%, IIIA 85.0%, IIIB 71.9%). The site of recurrence was mainly peritoneum (n=10), liver (n=3), and lymph node (n=3). Conclusions: Our results indicated that adjuvant therapy with S-1 plus 3 cycles of cisplatin may reduce recurrence and improve survival of stage III gastric cancer. This treatment should be considered as an experimental arm comparing with S-1 monotherapy for the next postoperative adjuvant phase III trial.