bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute radiation esophagitis in a phase I dose-escalation trial evaluating helical tomotherapy for inoperable non-small cell lung cancer (NSCLC)
Authors: Cannon G. M. , Jaradat H. A. , Tome W. A. , Khuntia D. , Mehta M. P. , Bentzen S. M. 
Published: March 2020

7694 Background: In an attempt to improve the poor local control in patients with locally advanced and medically inoperable lung cancer we investigated helical tomotherapy as a means to decrease radiation dose to critical normal structures while escalating tumor dose. Methods: Thirty-six patients with Stage I-IV NSCLC requiring definitive radiotherapy and judged not to be surgical candidates due to medical comorbidities or advanced tumor stage were enrolled in this phase I trial. Chemotherapy was given sequentially but not allowed concurrently. Pts were placed in 1 of 4 dose-per-fraction bins, all treated for 25 fractions, with dose per fraction ranging from 2.28 to 3.22 Gy. Bins were calculated to yield normalized total dose (NTD) equivalents in 2 Gy fractions of 60–100 Gy. Dose escalation limiting constraints included esophageal maximum NTD, lung NTD mean, and esophageal effective volume (Veff). Radiotherapy was limited to the primary site and clinically proven or suspicious nodal regions. Elective nodal irradiation (ENI) was not performed. A graded-response logistic regression analysis was performed to identify dosimetric and clinical factors associated with esophagitis. Results: No grade 3 (CTCAE v3.0 and RTOG) acute esophageal toxicities were observed. Only 6 patients (16.7%) required narcotic analgesia (RTOG gr. 2 toxicity). Average mean NTD dose to the esophagus (Dmean)=15.3 Gy. Average volume of the esophagus receiving NTD 55 Gy (V55)=3.65%. Both Dmean and V55 were significantly associated with the grade of esophagitis, with P- values of 0.018 and 0.010, respectively. In this limited series, there was no significant effect of sequential chemotherapy, in agreement with previous studies. Conclusions: 1) Acute esophageal toxicity was minimal despite dose escalation via helical tomotherapy for inoperable NSCLC cancer. 2) The observed significant associations between V55, Dmean, and grade of esophagitis validate improved dose distribution as a strategy to permit radiation dose escalation. Pending acceptable rates of radiation pneumonitis the addition of concurrent chemotherapy is anticipated. Supported by NIH Grant CA-88960. No significant financial relationships to disclose.
Prognostic role of VEGF, EGFR, COX-2, cERB-b2 and ER-alpha in stage 1 non-small cell lung cancers
Authors: Sadasiwan C. , Medendorp S. , Sreedhar R. , Raji A. , Blum M. , DeHoyas A. , Patel J. , Yeldandi A. 
Published: March 2020

7696 Introduction: Five-year survival rates for pathologic stage one NSCLC are between 57–67%. We looked at VEGF, EGFR, COX-2, cERB-b2 and ER-a in relationship to predicting recurrence. Methods: Tumors from 65 consecutive patients with stage I NSCLC were included. After marking representative areas on the slides, tissue microarrays were prepared and stained immunohistochemically using commercially available antibodies. The scoring was done by the pathologist and the principal investigator and is calculated as the product of staining intensity, the percentage of positively stained tumor cells and extent of membrane involvement. Results: 27 (42%) males/38 (58%) females. 75% stage IA/25% stage IB. Median smoking history was 40 pack-years (range 0–160pyr). 77% adenocarcinomas/23% squamous cell carcinomas. 19 (29%) patients had a recurrence of which 14 (74%) recurred locally and 5 (26.%) recurred at distant sites. The most common site of recurrence was the lung. Median time to recurrence was 30 months (range 4–97 mos). Scores for the molecular markers are reported in table 1 . Logistic regression of all the variables on multivariate analysis showed that VEGF scores predicted recurrence (p=0.021, Odds Ratio of 1.021). Scores of >200 for VEGF were even more discriminatory. (p =0.034, Odds Ratio of 7.22). The rate of recurrence in this subgroup of patients was 39.5% as opposed to a rate of 14.8% among those with scores of less than 200. EGFR, COX-2, cERB-B2 and ER alpha were not found to be significant predictors of recurrence. Table 1 . Univariate analysis: Conclusion: VEGF scores predict risk of recurrence in stage I Non Small Cell Lung Cancers. We propose the use of high scores of VEGF, in Stage I Non Small Cell Carcinoma using immunohistochemistry to select those patients who are likely to recur. No significant financial relationships to disclose. [Table: see text]
Impact of pathological staging on survival in patients with epithelial mesothelioma treated with extrapleural pneumonectomy
Authors: Sugarbaker D. , Richards W. G. , Alsup C. A. , Jaklitsch M. T. , Corson J. M. , Godleski J. J. , Chirieac L. R. , Bueno R. , Zellos L. 
Published: March 2020

7706 Objective: There is no universally accepted staging system in malignant pleural mesothelioma (MPM). A seventeen-year single institution experience of surgically treating a large epithelial MPM cohort with extrapleural pneumonectomy (EPP) gives insight to the applications and limitations of BWH/ DFCI and AJCC staging systems. Methods: We retrospectivly reviewed 526 consecutive patients with epithelial MPM who were surgically explored at our institution since 1988 with intent to perform EPP. Pathologic diagnoses of mesothelioma were confirmed and clinicopathologic data were recorded. Kaplan-Meyer survival from diagnosis was calculated. Those who underwent EPP were staged using BWH / DFCI (J Thorac Cardiov Surg 117:5463;1999) and AJCC (6th Edition) criteria. Operative deaths were included in the analysis and patients received varied adjuvant regimens. Results: Of 526 patients explored for potential EPP, 53 (10%) underwent alternative pleurectomy and 55 (11%) were unresectable. The remaining 418 (79%) underwent EPP. Of these, 307 (73%) were male. Median age at diagnosis was 57.9 years (17–78). Operative mortality was 5%. Median follow-up was 16 months and 23% of observations were censored. Overall median, 1-yr, 3-yr and 5-yr survival was: 18.9 mo., 68.8%, 26.3%, and 13.9%. The table below presents Kaplan-Meyer survival by stage. Conclusions: 1) Both pathological staging systems stratify survival in this cohort, although each system is limited in that a majority of patients are classified as stage 3. 2) BWH / DFCI criteria identify more stage 1–2 patients with favorable prognosis, 164 (39%) vs 46 (11%). 3) AJCC criteria classify more patients to stage 4, 76 (18%) vs 4 (1%), but appear to identify some patients with relatively favorable prognosis. 4) Selected criteria from both systems might be combined to optimally stratify patients with epithelial MPM undergoing EPP. No significant financial relationships to disclose. [Table: see text]
Open-label study of pemetrexed alone for chemonaive patients and pre-treated patients with malignant pleural mesothelioma: Outcomes of the International Expanded Access Program (EAP)
Authors: Taylor P. , von Pawel J. , Castagneto B. , Dark G. , Marangolo M. , van Klaveren R. , van Meerbeeck J. , Adachi S. , Blatter J. 
Published: March 2020

7709 Background: In a previous phase II study of chemonaive malignant pleural mesothelioma (MPM) patients (pts), single-agent pemetrexed (P) resulted in a 14.1% response rate (RR) and median survival of 10.7 mos (95% CI 7.7–14.5) (Scagliotti 2003). Likewise, the P arm in a phase III study of pre-treated MPM pts yielded an 18.7% RR (40.7% with stable disease, SD) and median survival of 8.4 mos (95% CI 6.2–10.5) (Jassem 2006). The EAP provided 3311 MPM pts with access to P alone, P plus cisplatin, or P plus carboplatin in 13 countries. In this abstract we report on the safety and efficacy data of those MPM pts treated with P alone. Methods: Eligible pts had histologic or cytologic diagnosis of MPM and were either chemonaïve or previously treated with =1 line(s) of chemotherapy. Pts pre-treated with P were allowed if they had experienced clinical benefit from the prior P. Treatment consisted of P (500 mg/m2) once (day 1) every 21 days with standard pre-medication of vitamin B12, folic acid, and dexamethasone. Investigator-determined response (RR) and survival data (with censoring) were recorded at the end of study participation. Myelosuppression data (CTC) were also collected. Results: 812 MPM pts (319 chemonaïve; 493 pre-treated) received =1 dose of P and were evaluated for safety, and 643 pts (247 chemonaïve; 396 pre-treated) were evaluated for efficacy (RR and survival). In chemonaïve pts with MPM, the median age was 69 yrs (range: 39–87 yrs), 78.1% were male, and 71.6% had a KPS ≥80 (of the 93% who had PS evaluated). In pre-treated pts with MPM, the median age was 63 yrs (range: 31–85 yrs), 75.9% were male, and 74.5% had a KPS ≥80 (of the 95% who had PS evaluated). Both groups received a median of 4 cycles (chemonaive group range 1–18; pretreated group range 1–23). See the table for efficacy and safety data. Conclusions: Results of the EAP confirm earlier phase II and phase III studies. No significant financial relationships to disclose. [Table: see text]
Effect of the combination of pegylated liposomal doxorubicin and bortezomib on time to progression (TTP) and overall survival of patients with relapsed/refractory multiple myeloma compared with bortezomib alone
Authors: Harousseau J. L. , Nagler A. , Sonneveld P. , Bladé J. , Hajek R. , Spencer A. , Robak T. , Xiu L. , Zhuang S. H. , Orlowski R. Z. 
Published: March 2020

8002 Background: Proteasome inhibition with bortezomib is a standard of care for patients with relapsed/refractory multiple myeloma (MM). Recently, we reported the results of an interim analysis for the DOXIL-MMY-3001 study, a large multi-national, phase III, randomized study of patients with previously treated MM demonstrating that the combination of pegylated liposomal doxorubicin (PLD) and bortezomib resulted in a 45% risk reduction of experiencing disease progression over bortezomib alone (Orlowski et al, 2006 ASH Meeting, Abstract #404). The improvement in TTP was associated with an overall survival (OS) trend favoring the combination therapy (P=0.113; hazard ratio[HR], 1.48, 95% Confidence Interval [CI], 0.91 to 2.41). We now present an updated survival analysis with a median follow up of 11 months. Methods: 646 patients at 123 centers in 18 countries received either intravenous bortezomib, 1.3 mg/m2, on days 1, 4, 8, and 11 of every 21-day cycle, or the same bortezomib regimen with PLD, 30 mg/m2, on day 4. Results: As previously reported, median TTP was improved from 6.5 months for bortezomib alone to 9.3 months for the PLD+bortezomib combination (P=0.000004; HR, 1.82; 95% CI, 1.41 to 2.35). The complete+partial response rate was 43% for bortezomib and 48% for PLD+bortezomib (P=0.251). Median duration of response was increased from 7.0 months (95% CI, 5.9 to 8.3) to 10.2 months (95% CI, 10.2 to 12.9) with combination therapy (p=0.0008). Updated OS analysis showed PLD+bortezomib significantly improved OS (p<0.05; HR, 1.41, 95% CI, 1.002 to1.97). Both groups received a median of 5 cycles of treatment. The safety profile of the combination was consistent with the known toxicities of the two agents. Grade 3/4 adverse events were more frequent in the combination group primarily due to increase in myelosuppression and GI toxicities. Conclusions: PLD with bortezomib is superior to bortezomib monotherapy for the treatment of patients with relapsed/refractory MM. [Table: see text]
A prospective trial of involved field radiation (IFRT) + chemotherapy compared to extended field (EFRT) radiation for favorable Hodgkin disease: Survival differences and implications of mature follow-up for current combined modality therapy
Authors: Horning S. J. , Hoppe R. T. , Advani R. H. , Breslin S. , Allen J. , Hancock S. L. , Rosenberg S. A. 
Published: March 2020

8014 Background: We conducted a prospective randomized trial from 1980–88 comparing IFRT plus VBM (vinblastine, bleomycin, methotrexate) chemotherapy to extended field radiation (EFRT) in patients with favorable stage I-IIIA disease to limit radiation exposure and define an effective treatment regimen that preserved fertility and did not increase the risk of leukemia. Methods: Patients (pt) with favorable, laparotomy-staged disease were defined as those with no bulky mediastinal disease, no or minimal abdominal disease (<5 cm), no or minimal splenic disease, and <1 extranodal site. VBM was given for 6 cycles after 44 Gy IFRT. EFRT was subtotal lymphoid for stage I-IIA and total lymphoid irradiation for I-IIB, IIIA pt. We previously reported (J Clin Oncol 6:1822, 1988) no survival differences in this study. Follow-up was similar for both arms and was further supplemented by an approved SSA Epidemiologic Vital Status Data Record application. Results: 72 pt were randomized, 34 to IFRT + VBM and 38 to EFRT. Median follow-up is 20.8 yr (10.3–25.1) and just 8 pt were censored at <15 yr. Twenty-one yr freedom from progression is 96% for IFRT + VBM vs 74% for EFRT (p= 0.035). A single death at 18 yr was recorded in IFRT + VBM pt (3%) whereas 11 deaths occurred among EFRT pt (29%). Overall survival (OS) at 21 yr is 95% for IFRT + VBM vs 68% for EFRT (p=0.003). As previously reported, fertility was informally assessed, but premature menopause was not observed and both men and women conceived after IFRT + VBM. Conclusion: The reduction of radiation to IFRT, combined with a less toxic chemotherapy in our study, resulted in excellent long-term OS that was significantly superior to EFRT. The survival data with IFRT + VBM also compare favorably with our historical EFRT experience. Moreover, these results have implications for current combined modality therapy where much lower doses of RT, more limited fields and brief chemotherapy should lead to even less late morbidity and mortality. No significant financial relationships to disclose.
Long-term responses to thalidomide and rituximab in Waldenstrom's macroglobulinemia
Authors: Soumerai J. D. , Branagan A. R. , Patterson C. J. , Hunter Z. R. , Treon S. P. 
Published: March 2020

8017 Background: Rituximab is active in Waldenstrom's macroglobulinemia (WM), producing response rates of 40–50%. Lower response rates are observed among patients with the FcγRIIIA-158 FF polymorphism; high B2M (≥3.0 mg/dL), and high serum IgM levels (≥6,000 mg/dL). Thalidomide enhances rituximab-mediated ADCC of lymphoplasmacytic cells and produces response rates of 25% in WM. As such, we conducted this phase II study using thalidomide and rituximab in patients naïve to either agent. Methods: Intended therapy was: Weeks 1–52: Thalidomide (200 mg po qHS for 2 wks, then 400 mg po qHS) Weeks 2–5, 13- 16: Rituximab (375 mg/m2/wk) Twenty-five patients were enrolled, 20 of whom were previously untreated, with a baseline median age of 62 (range 44–86 yrs), BM involvement of 40 (range 5–80%), serum IgM of 3,670 (range 924–8,610 mg/dL), B2M of 2.6 (range 1.4–8.3 mg/L), Hct of 34.1 (range 23.6–42.6%). Results: Grade ≥2 toxicities to thalidomide included neuroparesthesias (n=11); somnolence (n=3); confusion (n=3); rash (n=2); tremors (n=2); bradycardia (n=2) and palpitations (n=1). Among patients experiencing neuroparesthesias, 10 demonstrated resolution to grade 1 (n=3) or complete resolution (n=7) at a median of 6.7 (range 0.4- 22.5 months). Dose reduction of thalidomide occurred in all patients and led to discontinuation in 11 patients. Twenty-three patients were evaluable. Responses among evaluable patients: CR (n=1); PR (n=15); MR (n=2); SD (n=1) for an overall and a major response rate of 78% and 70%, respectively. Median serum IgM decreased from 3,670 (924–8,610 mg/dL) to 1,590 (36–5,230 mg/dL) (p<0.001), while median hematocrit rose from 33.0 (23.6–42.6%) to 37.6 (29.3–44.3%) (p=0.004) at best response. With a median follow-up of 42+ months, the median TTP for all evaluable patients on study was 35 months, and 38+ months for responders. Overall response was associated with median cumulative thalidomide dose: CR/PR/MR (29,275 mg) vs. SD/NR (7,400 mg); p=0.004. Overall responses were unaffected by FcγRIIIA-158 polymorphism status (81% vs. 71% for VV/FV vs. FF); serum IgM (78% vs. 80% for <6,000 vs. ≥6,000 mg/dL); and B2M levels (71% vs. 89% for <3 vs. ≥3 g/dL); p=NS. Conclusions: Thalidomide in combination with rituximab is highly active and produces long- term responses in patients with WM. No significant financial relationships to disclose.
Survival outcomes for multiple myeloma over three decades: A Surveillance, Epidemiology, and End Results (SEER) analysis
Authors: Jawed I. , Lee C. M. , Tward J. D. , Macdonald O. K. , Martincic D. , Vudarla N. , Fairbanks R. K. , Kaya H. 
Published: March 2020

8019 Background: There is limited data regarding survival outcomes for multiple myeloma in the literature. The purpose of this study was to analyze how patient characteristics and decade of treatment affect overall survival (OS) and cause-specific survival (CSS) for patients within a large United States (US) population database. Methods: Data were obtained from the Surveillance, Epidemiology, and End Results Program (SEER) of the US National Cancer Institute for the years 1973–2003. Patient characteristics (gender, race, age) and year of diagnosis were analyzed by multivariate Cox regression analysis for both OS and CSS endpoints. Results: 40,538 patients were included in the analysis. The mean age at diagnosis was 68.3 (median 69) years. Mean survival for the entire cohort was 41 (median 24) months. Females had better OS than males, hazard ratio (HR) 0.91 (CI 0.89–0.93, P = 0.0001), and CSS, HR 0.96 (CI 0.93–0.98, P = 0.004). There were no significant differences in OS between white and black race (P = 0.34), but black race was associated with improved CSS, HR 0.89 (CI 0.86–0.93, P = 0.0001). Younger age (age <40, 41–60, 61–70, and 71–80) was associated with improved OS and CSS (all P = 0.0001). Early treatment decade (1973–1985) was associated with diminished OS and CSS on multivariate analysis with HR 1.11 (CI 1.08–1.14, P = 0.0001) and HR 1.12 (CI 1.08–1.16, P = 0.001), respectively. Conclusions: This is the largest reported population analysis of survival outcomes for multiple myeloma. It covers three decades of care in the United States. This study reveals that improved OS and CSS are associated with younger age, female gender, and recent decade of treatment. We believe that survival improvement in recent treatment decades may be due to advances in supportive care and/or earlier diagnosis as the standard treatment for myeloma did not significantly change during this time period. Follow up studies may show dramatic improvements in survival outcomes due to modern myeloma therapies in this decade. No significant financial relationships to disclose. [Table: see text]
Phase II study of total therapy 3 (TT3) with added bortezomib (V) for multiple myeloma (MM)
Authors: Barlogie B. , Anaissie E. , Shaughnessy J. D. , van Rhee F. , Hollmig K. , Pineda-Roman M. , Mohiuddin A. , Zangari M. , Tricot G. , Crowley J. 
Published: March 2020

8020 Background: Building on the success of TT2 with OS exceeding a median of 8 yr, TT3 incorporated V into induction and consolidation/maintenance of melphalan (MEL)-based tandem transplants. Methods: Newly diagnosed patients with MM up to age 75 yr (>59 yr, 47%) were enrolled in TT3, consisting of 2 cycles of V, thalidomide, dexamethasone, cisplatin, adriamycin, cyclophosphamide, etoposide (VTD-PACE) as induction prior to and as consolidation after MEL transplants, followed by maintenance with monthly VTD in year 1 and TD in years 2 and 3. The primary endpoint was complete response (CR). Results: 303 eligible patients were accrued between 02/04 and 07/06; median follow-up is 19 mo. Tandem transplants were completed in 84% with TT3 and 66% with TT2 (p<0.0001) with similar 12-mo TRM (4% v 5%). At 24 mo, 84% v 68% achieved n-CR including 59% v 44% CR (both p<0.0001). 24-mo EFS is superior (83% v 75%, p=0.02; <65 yr: 86% v 76%, p=0.008) while 24-mo OS is still similar (86% v 85%, p=0.44; <65 yr: 88% v 85%, p=0.16). In gene array-based high-risk MM, 24-mo EFS was 62% v 27% (p=0.006) and 24-mo OS was 74% v 43% (p=0.06). Independent adverse parameters for OS with TT3 were LDH>=190 U/L (27%; HR=3.78, p=0.002), high-risk gene array (14%; HR=3.30, p=0.006) and age >=65 yr (29%; HR=2.23, p=0.044). Compared to the T arm of TT2, fewer patients in TT3 experienced grade >2 tremor (3% v 13%, p<0.001), constipation (6% v 14%, p=0.002), syncope (1% v 12%, p<0.001) and thrombo-embolic events (27% v 38%, p=0.004). Conclusion: Compared to TT2, added V and shortened induction in TT3 increased tandem transplant compliance, effected higher CR and n-CR rates and extended EFS with a strong trend for superior OS in high-risk MM in patients <65 yr. TT3 toxicity was reduced in comparison with the T arm of TT2. No significant financial relationships to disclose.
Final results of a phase II PETHEMA trial of alternating bortezomib and dexamethasone as induction regimen prior autologous stem cell transplantation (ASCT) in younger patients with multiple myeloma (MM): Efficacy and clinical implications of tumor response
Authors: Rosiñol L. , Oriol A. , Mateos M. , Sureda A. , Díaz-Mediavilla J. , Herrero C. , Liu X. , Van de Velde H. , San Miguel J. , Bladé J. 
Published: March 2020

8024 Background: Dexamethasone-based combinations are the standard induction regimens for younger patients with MM prior ASCT. This is the first study in which bortezomib and dexamethasone were administered on an alternating basis. Aims: efficacy and kinetics of response. Methods: patients with newly diagnosed MM under the age of 66 years were treated with bortezomib at 1.3 mg/m2 on days 1, 4, 8 and 11 (cycles 1, 3, 5) and dexamethasone 40 mg p.o. on days 1–4, 9–12 and 17–20 (cycles 2, 4 and 6), followed by ASCT with melphalan-200. Responses were evaluated by the EBMT criteria but a VGPR was included. Random effects models were utilized to analyze the tumor response kinetics to bortezomib and dexamethasone with the absolute value of M-protein overtime and decrease by cycle. Because the nonlinearity in the change of M-protein overtime, a piecewise linear model was employed. Results: between August, 2005 and March, 2006, 40 patients (median age 57) were enrolled. The response rate was 82% with 12% CR plus 10% VGPR. The response was quick with 82% M-protein reduction achieved with the first 2 cycles. There was no further decrease of the mean M-protein in cycles 5 and 6. The M-protein decrease was not different with dexamethasone and with bortezomib (p=0.48). Chromosome 13 deletion as well as t(4;14) and t(14;16) did not had a negative impact on response. Toxicity was very low: ten (25%) patients had mild peripheral neuropathy (grade 1:9 cases, grade 2:1 case) and 11 grade 1 thrombocytopenia. Grade 3 toxicity was observed in 7 patients (neutropenia 6, skin/liver 1 case). No patient developed grade 4 toxicity. In all patients stem cells could be adequately collected (median of CD34+ 5 ×106/Kg). The overall response rate after ASCT was 90% with 40% CR plus 20% VGPR. Conclusions: Bortezomib alternating with dexamethasone is highly effective as up-front therapy in patients with MM, and is associated with a very low toxicity. The results of the tumor response kinetics analysis support a short program of alternating bortezomib and dexamethasone (i.e., maximum of 4 cycles) as an effective and safe therapy for younger myeloma patients prior ASCT. [Table: see text]