bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eradication of prostatic high grade intraepithelial neoplasia: Hypothesis and clinical proof
Authors: Zweig J. I. 
Published: March 2020

1534 Background: Recently normal prostate tissue has been found to contain a high concentration of retinoid X receptors (RXRs), they are found in the highest concentrations in ectodermal tissue. Loss of these receptors is associated with prostatic intraepithelial neoplasia (PIN), and can be present in patients with a normal PSA. There are 115,000 cases of high grade PIN discovered yearly in the United States.The drug bexarotene used to treat cutaneous T cell lymphoma (CTCL). The compound is not a true retinoid in structure, perusal of the structure reveals two aromatic rings one of which contains a carboxy group which would make one anticipate strong hydrogen bonding when it undergoes binding to the RXRs as if it were a retinoid, resulting in “up regulation” of the tissue with increase in differentiation to normal tissue. Based upon this it was felt that it would be fruitful to try bexarotene in High Grade PIN. Method: The diagnosis was based upon 12 biopsies which were done in conjunction with ultrasound localization of the biopsy site, with careful recording of there anatomical position. The patient was started on bexarotene 225 mg per day. The drug was given as a single dose once daily; this dose is 40% of the dose normally used to treat CTCL. The drug was administered for 30 doses During the period of therapy the patient was on Atorvastin T4 total was within the normal range. Results: Four weeks following the last dose of bexarotene the prostate was rebiopsied with 12 biopsies taken. Six of the biopsies were taken from the putative area, the rest in an enlarging target like pattern. The repeat biopsy was negative for the presence of PIN. 14 months later 12 more biopsies were obtained using the same technique, these repeat biopsies were also found to be negative; ie. 24 negative biopsies over 14 months. It is unlikely that the previously involved area was missed. Conclusion: If a mechanism of action were to be formulated, the induction of and increase in RXRs in normal prostate cells would be reasonable. Cells that undergo the formation of PIN, strong hydrogen bonding and inability of those cells to produce more receptors could result in apoptosis. Undoubtedly further study is required to evaluate the effect of this drug in high grade PIN. No significant financial relationships to disclose.
The histological subtype and grade work as prognostic indicators for platinum-based chemotherapy (CTX) of advanced ovarian carcinoma (AOC)
Authors: Shimizu Y. , Murakami F. , Ogawa N. , Yamada M. , Saskurai S. , Ishiya T. , Katase K. , Hasumi K. , Silverberg S. G. 
Published: March 2020

16015 Background: We previously reported the new histopathologic grading system applicable for all histological types of ovarian carcinoma (Cancer 82:893–901, 1998), which thereafter was reappraised by several investigators. The aim of the present study is to investigate the relationship of the histopathologic type and grade with the effect of CTX for AOC. Methods: Between 1/89 and 12/05, 272 consecutive patients (pts) with pT3 (FIGO stage III or IV) AOC pts received 6 cycles or more of cisplatin (70 mg/m2 for 1 cycle)-based CTX combined with aggressive debulking surgery consisting of hysterectomy, bilateral adnectomy, omentectomy, pelvic to paraaortic lymphadenectomy, with or without more extensive surgery including intestinal resections. Histological types and grade were diagnosed according to the WHO classification system and our system reported method, respectively. Results: Of the eligible 261 pts, response was achieved in 67% (CR: 21.8%, PR: 45.2%) of the pts. Response (CR+PR/total) by histological type was 86% (36+91/148) for serous, 97% (16+13/30) for transitional cell, 67% (5+13/27) for endometrioid, 4% (0+1/29) for mucinous, and 0% (0+0/27) for clear cell, respectively. Response (overall/CR) for chemo-sensitive histological types (serous/transitional cell/endometrioid) by grade (G) was 86%/52% for 21 G1, 90%/31% for 64 G2, and 83%/28% for 118 G3 (CR rate: G3 vs G1 + G2: p=0.02). Response duration (CR/PR) by G was not reached/30 months (mo) for G1, 85 mo/23 mo for G2, 40 mo/16 mo for G3. Response (overall/CR) to 2nd line CTX was 75%/38% for G1, 73%/17% for G2, and 47%/10% for G3. Conclusions: Histological type correlated with platinum-CTX sensitivity. CTX regimens should be designed based on the histological subtypes. New “non-platinum” regimens should be considered for both mucinous and clear cell carcinoma. Histological grade worked as an indicator for CR rate, response duration (thus, progression rate), and response rate to 2nd line CTX. Thus, the grade is considered to be a significant prognostic factor for platinum-sensitive AOC. No significant financial relationships to disclose.
Gestational trophoblastic disease: 25-year experience at the Instituto Nacional de Enfermedades Neoplasicas (INEN)
Authors: Lopez L. Mas , Olivera M. , Casanova L. , Santos C. , Neciosup S. , Gomez H. , Leon J. , Velarde C. , Mariategui J. , Vidaurre T. 
Published: March 2020

16031 Background: To evaluate the clinical behavior and results of treatment of gestational trophoblastic disease at INEN between 1980 to 2005. Methods: This is a retrospective analysis of patients with gestational trophoblastic disease, clinical characteristics, results of treatment, toxicity, objective response and survival from January 1980 to December 2005. Descriptive statistics and Kaplan-Meier for survival analysis were performed. Results: Since Jan 1980 to Dec 2005. 595 patients were admitted at INEN; Hydatidiform mole 254 (42.7%) choriocarcinoma 201 (33.8%) invasive mole 41(6.8%). FIGO scoring System, high risk (score >6): 247 (41.5%), low risk (score 1–6): 348 (58.5%). Age ranged from 14 to 54 years, with 255 (44%) cases between 20 to 29 years. The sities of metastasis: lung 67.3%, vaginal 17.9%, brain 8.7%, liver 5.1%. The patients with low risks received treatment with Metotrexate 0.4mg/kg x day x 5 days po, reach disease control with a mean course of 6 (1 - 14), complete remission in 66.1% cases and 97% the overall survival rate to 20 years. Patients with high risk received treatment with: MAC 77 patients, MEC 19 patients, EMACO 48 patients and BEP 14 patients and achieved complete remission in 32.5%, 36.8%, 50% and 25% respectively. On the high risk group we detected two groups according to score > 12 and < 12, with diferent probability of survival at 20 years, for the group with score <12, 80% and the group with score >12, 48%. 98 patients were identified with score >12, and the age of these patients ranged from 15 to 51 years, with a mean age of 36.5 years. The blood B- HCG titers of these patients ranged from 198 to 6710,500. Liver and brain metastasis in 26 cases, number metastasis mayor 8 in 78 cases. Conclusions: Gestational trofhoblastic disease is highly curable. Patients of low risk achieved a 97% overall survival rate to 20 years. There are differences in the overall survival rate between patients of high risk with a score < 12 (80%) and score >12 (48%). This group presented with brain and liver metastasis, and it is important to define the best treatment for this group of patients No significant financial relationships to disclose.
The role of intensity modulated radiation therapy for locally advanced hypopharyngeal cancer after resection and ileocolic free flap reconstruction
Authors: Hsieh C. H. , Leu Y. S. , Chang Y. F. , Tai H. C. , Huang M. Z. , Hsiao H. T. , Chang Y. C. , Chen Y. J. 
Published: March 2020

16521 Background: To estimate the toxicity/efficacy of concurrent chemoradiation therapy (CCRT) and with different modalities for locally advanced hypopharyngeal carcinoma post ileocolic free flap reconstruction (ICFR). Methods: Between April 2003 and December 2006, 15 patients had enrolled and a total of 13 patients were treated for locally advanced hypopharyeal cancer after resection and ICFR. The majority in group was stage IVa and all were squamous cell histology. Five were treated with intensity modulated radiation therapy (IMRT)/chemotherapy (CT) and 8 were treated with the conventional radiotherapy (CRT)/CT, both to a median dose of 64.8 Gy. Two to three cycles of CT given concurrent with RT every 3 or 4 weeks of cisplatin, 15 mg/m2 i.v., D1–5, plus 5-FU, 750 mg/m2 continue infusion, D1–5. Two same regiment of CT had applied monthly after CCRT one month latter for all. Results: The mean survival was 33 months (range, 6–42 months). Two-year actuarial overall survival (OS), disease-free (DFS), locoregional progression-free (LRPF) and distant- metastases-free (DMF) rates of all were 74%, 67%, 83%, 83%, respectively. Comparing the IMRT and CRT group, two-year OS, DFS, LRP and DM rates were 67% vs. 62%, 75% vs. 63%, 75% vs. 87%, 100% vs. 75%, respectively. Except OS rate (p = 0.04), others were not statistically significant. In IMRT group, one left side lower neck failure was noted. In CRT group, one over flap and the other over level III of neck recurrent was noted. Speech ability above 70% in IMRT vs. CRT group were 4/5 (80%) vs. 4/8 (50%). Swallowing with solid diet in IMRT vs. CRT group were 3/5 (60%) vs.3/8 (37.5%). Grade III of dermatitis and mucositis for IMRT vs. CRT group were 40% vs. 100% and 20% vs. 87.5%. The median duration of post surgery to start CCRT and of CCRT were 33 days and 54 days. The interval from post-operation to start CCRT and of CCRT longer than median time would influence LRPF rate (p = 0.05). Conclusions: For locally advanced hypopharyngeal carcinoma post ICFR, IMRT results in lower toxicity, better speech, swallowing ability and superior treatment outcomes when compared with the CRT group. Prolong starting CCRT and extend CCRT time influence LRPF rate. No significant financial relationships to disclose.
Paucity of economic analyses of phase III clinical trials conducted by the cooperative oncology groups: A review of the evidence
Authors: Fitzner K. , McKoy J. , Bennett C. L. 
Published: March 2020

17052 Background: Cancer care is expensive, accounting for $72 billion in direct medical costs. New oncology drugs are frequently costly, and can be > $100,000 per patient. Hence, assessments of the costs and cost-effectiveness of cancer pharmaceuticals alongside phase III clinical trials conducted by the NCI-sponsored cooperative oncology groups represents an important opportunity to generate relevant economic data. Methods: Review of published cost and cost-effectiveness analyses for cancer drugs conducted alongside phase III clinical trials conducted by the NCI-sponsored cooperative clinical trial groups. Results: See Table . Conclusions: Despite increasing concerns over the high costs of cancer pharmaceuticals and the need to evaluate the costs and cost-effectiveness of these agents, NCI sponsored phase III clinical trials rarely include economic assessments. Future phase III clinical trials with expensive new cancer agents conducted by cooperative clinical trials groups should include prospective economic assessments. [Table: see text] No significant financial relationships to disclose.
The number of residual metastatic lymph nodes following neoadjuvant chemotherapy predicts disease-free survival in patients with stage III NSCLC
Authors: Kim S. , Cho B. , Moon J. , Choi H. , Shin S. , Sohn J. , Kim J. 
Published: March 2020

18024 Background: The prognosis of patients with stage III non-small cell lung cancer (NSCLC) who achieved pathological complete response or downstaging following neoadjuvant chemotherapy is better than those with residual metastatic lymph node (LN). However, the prognostic significance of the number of residual metastatic LNs remains unclear. Methods: From January 2001 to January 2006, 42 consecutive patients with stage IIIAN2 (22 patients) and IIIB without pleural effusion (20 patients) were treated with neoadjuvant chemotherapy. Thirty four of 42 patients were pathologically staged by mediastinoscopy. Neoadjuvant chemotherapy consisted of 3 cycles of platinum based doublet (21 patients with gemcitabine, 15 with paclitaxel, and 6 with docetaxel). Results: After neoadjuvant chemotherapy, pathological complete response and downstaging was achieved in one patient and 24 patients, respectively. No pathological LN metastasis was present in 9 patients (21.4%), and LN metastasis was present in 33 patients (78.6%). With a median follow up of 23 months, the 2-year disease free survival (DFS) rate of patients without residual LN metastasis was statistically better than that of patients with residual LN metastasis (46% and 18% in patients with residual LN, p=0.03). Among 33 patients with residual LN metastasis, age (p=0.01), pathological downstaging (p=0.09) and number of residual metastatic LNs (median 14 months in LN =4 vs median 5 months in LN =5; p=0.01) were significant predictors of DFS in univariate analysis. In multivariate analysis, number of residual metastatic LNs was an independent predictor of DFS among patients with residual LN metastasis, irrespective of pathological downstaging. Conclusions: The number of residual metastatic lymph nodes following neoadjuvant chemotharpy is an independent predictor of DFS in patients with stage III NSCLC. No significant financial relationships to disclose.
Distinctive characteristics of non-small cell lung cancer in younger patients: A national cancer database (NCDB) analysis of patients under 40 years old (1998–2003)
Authors: Velcheti V. , Goodgame B. , Morgensztern D. , Gao F. , Baggstrom M. , Govindan R. 
Published: March 2020

18035 Background: Non-small cell lung cancer (NSCLC) is disease of the elderly and is rare in younger adults. NSCLC in younger patients may be biologically different and have a different presentation and natural history. Methods: We identified in the National Cancer Data Base (NCDB), all patients diagnosed with NSCLC from 1998 to 2003. NCDB is a cancer database maintained by the American College of Surgeons. The NCDB data is obtained from the cancer programs participating in the Commission on Cancer NCDB annual call for data. Data on gender, race, stage and histology were obtained from the NCDB. The characteristics of patients with NSCLC from 16–39 years of age were compared to the entire group. Results: In the NCDB, 551248 patients with NSCLC diagnosed from 1998- 2003 were identified. Of these 4093 were in the age group 16–39. We compared the characteristics of NSCLC in younger group to the entire cohort (Table). Younger patients were more likely to be women, 52% vs 42% (p<0.001), and more likely to present with distant disease (stage 3 & 4) 75% vs 61% (p<0.001). Adenocarcinoma was more common in younger patients, 48% respectively, vs. 38%. Squamous cell carcinoma was far less common in younger patients, 12% vs 28% (p<0.001). Conclusions: Patients with NSCLC who are < 40 years old at diagnosis are more likely to be women and have adenocarcinoma histology. Younger patients present with advanced stage more often than those who are older than 40 years at diagnosis. Table: Characteristics of younger patients with NSCLC [Table: see text] No significant financial relationships to disclose.
Retrospective review of DPACE therapy for aggressive, refractory multiple myeloma (MM)
Authors: Gerrie A. S. , Xu W. , Fung S. , Stewart A. K. , Reece D. , Trudel S. , Mikhael J. , Chen C. I. 
Published: March 2020

18500 Background: Oral dexamethasone ± thalidomide with a 4-day infusion of cisplatin, doxorubicin, cyclophosphamide, and etoposide (DPACE) is an effective induction therapy prior to transplant in patients (pts) with MM. Limited experience also suggests DPACE may reduce disease burden as a salvage regimen for aggressive, refractory MM. Methods: We performed a retrospective review from 1999- 2005 of all MM pts who received DPACE ± thalidomide as a salvage regimen at our center. Results: A total of 39 pts received DPACE at a median 23 mos from diagnosis (range, 10–84). Median age was 53 years (34–70), 51% stage 3 at diagnosis. Plasma cell leukemia had developed in 12 pts and leptomeningeal disease in 4 pts at time of DPACE. Ten of 24 pts (42%) with cytogenetics had del 13q. Pts were heavily pretreated (median 3 prior regimens; prior autotransplant [ASCT] 38%; thalidomide 64%; and bortezomib 10%). Pts received 1–4 cycles as tolerated for refractory (83%) or relapsed (17%) disease. Thalidomide was used in 41% of cycles. Hematologic toxicity was common (grade 3–4 neutropenia 92% and thrombocytopenia 72%). Although G-CSF was used in 71% of cycles, febrile neutropenia was common (53%) and 26% required hospitalization. Overall RR was 36% (14 pts: PR 12, VGPR 2). An additional 8% achieved MR, 23% SD. PD occurred in 15% and 18% died on therapy (4 progressive MM; 2 neutropenic sepsis, 1 GI bleed). No prior ASCT (p=0.04) and <4 prior regimens (p=0.04) predicted for response to DPACE. Eleven pts proceeded to ASCT and one pt to a clinical trial with lenalidomide with a median OS from DPACE of 24.7 mos (95% CI, 11.2–63.6). Those who did not bridge to transplant or trial (n=27) had a short median PFS of 3.0 months (95% CI, 1.2–5.5) and OS of 6.7 mos (95% CI, 1.8–9.7). OS for all 39 pts was 8.7 mos (95% CI, 6.4–12.4). Conclusion: DPACE may be effective salvage therapy for heavily pretreated MM pts. Although the RR of 36% in this poor prognosis cohort is reasonable, the PFS is short and suggests that the best role for this regimen is in bridging to more definitive therapy such as transplantation. [Table: see text]
Low-dose dexamethasone and thalidomide with higher frequency zoledronic acid (dtZ) for newly diagnosed multiple myeloma
Authors: Teoh G. , Tan D. , Chuah C. , Hwang W. , Yiu R. , Kuperan P. , Tien S. , Lee L. , Ang A. , Kam G. 
Published: March 2020

18506 Background: Although dexamethasone (Dex), thalidomide (Thal) and zoledronic acid (Zol) have frequently been combined for the treatment of multiple myeloma (MM), the ideal dosing schedule is unknown. We previously reported that lower doses of Dex and Thal can be effectively combined with high-frequency dosing of Zol (Haematologica 2005). Methods: This “dtZ” regimen - which comprises weekly Dex 20 mg OM for 4 days, Thal 50 mg ON, and 3-weekly Zol 4 mg - resulted in an impressive response rate (RR) of 61.6% and near complete remission (nCR)/complete remission (CR) rate of 7.7% in 26 patients with relapsed/refractory MM. Results: In this present study, we treated 22 newly diagnosed MM patients with “dtZ” and report an even more impressive RR of 100.0% and nCR/CR rate of 20–35%. The median time to response was 1.8 months and median time to maximum response was 2.2 months. The median time to progression (TTP) has not been achieved yet. As expected, low-dose Dex/Thal resulted in lower (18.1%) grade 3 or 4 toxicities. These were all infections; which lead to further dose-reduction of Dex. There were no thromboembolic events, despite the fact that aspirin was not routinely given. Of particular interest, 3- weekly Zol was not associated with any significant decrease in renal function, and none of our patients developed osteonecrosis of the jaw (ONJ). In fact, at the time of writing of this abstract, more than 1,000 doses of Zol had been administered in a 3-weekly fashion to these as well as other patients, and only 1 patient developed ONJ. This patient who had already received greater than 20 doses of Zol healed uneventfully after receiving appropriate outpatient dental treatment, and subsequently received another 8 doses of Zol with no recurrence of ONJ. Conclusion: In conclusion, the Zol-based “dtZ” regimen is potentially a highly-effective and safe frontline regimen for MM. Using Zol every 3 weeks with lower doses of Dex and Thal does not appear to increase the rate or severity of nephrotoxicity or ONJ. Although we do not know exactly why every patient responded to “dtZ”, we speculate that this could be due to a critical balance that has been achieved between the anti-MM, anti-osteoclastic and immunostimulatory effects of the individual drugs of the combination. No significant financial relationships to disclose.
First efficacy assessment of a phase II study with cyclophosphamide, vincristine, liposomal doxorubicin, and prednisone plus rituximab, administered every two weeks (R-COMP-14) as primary treatment for NHL
Authors: Herrero J. , Gómez-Codina J. , Provencio M. , Rueda A. , Llanos M. , Lobo F. , Vicente D. , Sabín P. , García-Arroyo F. , Iglesias C. 
Published: March 2020

18519 Background: R-CHOP is the standard treatment for CD20+ aggressive B-cell non-Hodgkin lymphoma (DLBCL). Dose dense regimens have shown better outcome and acceptable tolerability compared to standard. Liposomal doxorubicin has demonstrated significant less cardiotoxicity and acute toxicity when compared with standard doxorubicin. The aim of the study is to assess the efficacy and safety of the R- COMP-14 (Myocet™-modified CHOP) in newly diagnosed aggressive DLBCL. Pegfilgrastim was used to provide prophylactic bone marrow support. Methods: Patients (Pts) with stages III, IV or I, II (IPI = 1) were included in this single arm, multicentric, 2-step (Simon design) phase II trial. Treatment: eight biweekly cycles of liposomal doxorubicin 50 mg/m2, cyclophosphamide 750mg/m2, vincristine 1.4 mg/m2 (max. 2mg), rituximab 375 mg/m2 and prednisone 100 mg/d d1–5. Pegfilgrastim was administered on day 2 at standard dose. Interim analysis shows: Twenty-six out of 28 Pts were evaluable for efficacy. Median age: 51 y (28 - 64). Ann Arbor stage: I-II (IPI = 1) 42%, III 29%, IV 29%. Extranodal involvement: 50%. Median basal LVEF was 66% (range 44 - 80). Results: The overall response rate was 84% (CR 64% and PR 20%). Three (12%) Pts had PD and 1 (4%) SD. Median n° cycles was 8 (2-8); the median relative dose intensity per week was 93.5%. Only 4.8% of cycles were delayed and 4.2% of the cycles were administered with dose reduction due to related adverse events. Grade 3–4 neutropenia and thrombocytopenia were observed in 4.0% and 0.6% of cycles respectively. Febrile neutropenia experienced in 3.3% of cycles. Non-hematological G3–4 toxicities per cycles were hepatic (1.7%), emesis (1.2%) and G3 neurotoxicity, asthenia and infection (0.6% each). No other relevant toxicities were observed. Median LVEF after completion of treatment was 63% (range 52 - 76), there was no cardiac clinical event related to the treatment, nor irreversible toxicities. Conclusions: This Interim analysis confirmed the efficacy and safety of the dose-dense regimen in order to continue with the second step of the study. R-COMP-14 treatment with pegfilgrastim bone marrow support warrants further exploration. No significant financial relationships to disclose.