Favorable Prognostic Factor For Progression-free Survival Research Articles

First-line pemetrexed-platinum doublet chemotherapy with or without bevacizumab in non-squamous non-small cell lung cancer: A real-world propensity score-matched study in China.

ObjectiveTo evaluate the efficacy and safety profile of first-line bevacizumab (Bev)-containing pemetrexed-platinum chemotherapy in a real-world Chinese cohort with advanced non-squamous non-small cell lung cancer (NS-NSCLC).MethodsA total of 415 eligible patients with NS-NSCLC who received first-line pemetrexed-platinum chemotherapy at National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between February 2010 and September 2017 were reviewed retrospectively: 309 Bev(−) and 106 Bev(+) cases. Bev was administered at 7.5 mg/kg every 3 weeks in the Bev(+) group. To reduce the risk of a selection bias, a propensity score-matching (PSM) was conducted and 105 pairs of Bev(−) and Bev(+) cases were identified.ResultsThe median duration of follow-up was 15.8 months. The median progression-free survival (PFS) was prolonged significantly in the Bev(+) group than in the Bev(−) group in overall (9.8vs. 7.8 months, P=0.006) and PSM pairs (9.8 vs. 6.6 months, P<0.001). Moreover, patients receiving maintenance therapy with pemetrexed plus Bev had longer PFS than those interrupted after induction chemotherapy, or those receiving mono-maintenance with pemetrexed (12.3vs. 4.8 vs. 8.6 months; P<0.001). Multivariate analyses revealed Bev to be one of the favorable prognostic factors for PFS, along with the predictor of maintenance therapy. ConclusionsFirst-line induction and maintenance therapy with Bev (7.5 mg/kg every 3 weeks) combined with pemetrexed-platinum chemotherapy was efficacious and superior to non-Bev chemotherapy in Chinese patients with advanced NS-NSCLC.

Benefit of Two Additional Cycles of Bortezomib/Thalidomide/Dexamethasone (VTD) Induction Therapy Compared to Four Cycles of VTD for Newly Diagnosed Multiple Myeloma

IntroductionFour cycles of bortezomib/thalidomide/dexamethasone (VTD) induction therapy followed by autologous stem cell transplantation (ASCT) is one of the standard therapy for patients aged less than 65 years with newly diagnosed multiple myeloma (NDMM). Complete remission (CR) status before ASCT is an important prognostic factor for progression-free survival (PFS). We analyzed whether two additional cycles of VTD improved the pre- and post-transplant responses as well as PFS compared to the four cycles of VTD induction therapy.MethodsA total of 222 patients with NDMM between September 2014 and August 2016 from eleven hospitals in South Korea were included in the current study. The patients received at least four or more cycles of VTD induction therapy before administration of high-dose therapy (HDT, melphalan 200mg/m2) followed by ASCT. VTD regimen was consisted of bortezomib subcutaneous infusion (1.3 mg/m2 on days 1, 4, 8, and 11), thalidomide (100 mg daily), and dexamethasone (40 mg on days 1-4, 8-11), which was administered every 4 weeks.ResultsThe median age was 57 years (range 30−64 years), and 120 patients (61.9%) were male. Revised international scoring system (R-ISS) classified 59 (30.4%), 86 (44.3%), and 49 patients (25.3%) as stage I, II, and III, respectively. VTD induction was administered 4 cycles in 194 patients (VTD4, 67.5%) and more than 4 cycles in 63 (VTD6, 32.5%) before HDT. Patient characteristics at diagnosis did not differ between VTD4 and VTD6. CR rate before HDT was significantly higher in VTD6 than VTD4 (31.7% vs 13.0%, P = 0.003). However, CR rate after HDT/ASCT was similar between VTD4 and VTD6 (69.0% vs 65.5%, P = 0.726). There was no difference in the incidence of peripheral neuropathy (PN) (≥ grade 2 or that required dose reduction) between two groups. The median follow-up duration was 18.0 months (range 7.0-43.8 months). The 2-year PFS did not differ between the two groups (51.7 ±5.7% in VTD4 and 62.1±8.6% in VTD6, P = 0.240). Multivariate analysis revealed that the achievement of CR was a favorable prognostic factor for PFS (HR 0.27 [0.08−0.90], P = 0.034). Deletion 17p (HR 2.87 [1.01−7.92], P = 0.048) and t(4;14) (HR 3.38 [1.76−6.48], P < 0.001) in FISH were adverse prognostic factors for PFS. Patients with stage I/II by R-ISS receiving additional two cycles of VTD showed prolonged PFS (median PFS not reached vs. 27.6 months, P = 0.034). In the multivariate analysis, VTD6 was a favorable prognostic factor for PFS for patients with stage I/II by R-ISS, (HR 0.11 [0.02−0.52], P = 0.005).ConclusionCR rates increased with additional cycles of VTD induction therapy for NDMM. However, the PFS benefit was observed only in patients with R-ISS stage I/II. For patients with high-risk MM, intensive induction therapy that overcome poor prognostic factors should be administered to improve long-term outcomes. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Characterization of never-smoking and its association with clinical outcomes in Chinese patients with small-cell lung cancer

ObjectivesSmall-cell lung cancer (SCLC) has been viewed as a smoking-related disease, with only 2% to 5% patients being never-smokers. This study aimed to investigate the clinical characteristics of never-smoking and its association with treatment outcomes in Chinese SCLC patients in real world. MethodsWe performed a retrospective study of 303 patients with SCLC and grouped into smokers and never-smokers. The clinical characteristics and treatment outcomes of two groups were collected and compared. ResultsIn total, 113 patients with limited-stage (LS) SCLC and 190 patients with extensive-stage (ES) SCLC were enrolled. Sixty-nine (22.8%) patients were never-smokers. Both the median progression-free survival (PFS) and overall survival (OS) were significantly longer in never-smokers than in smokers (PFS, 8.37 vs. 7.10 months, P=0.036; OS, 19.73 vs. 14.40 months, P=0.044) in all populations. Multivariate analysis suggested that never-smoking was a significant favorable prognostic factor for PFS (HR=0.753; P=0.047) instead of OS (HR=0.780; P=0.236) in patients with SCLC. The objective response rate (ORR) to first-line therapy were similar between two group (52.6% vs. 59.4%, P=0.315). Moreover, prophylactic cranial irradiation (PCI) resulted in marginally significantly longer PFS than observation in patients with ES-SCLC who obtained objective response after first-line therapy (10.57 vs. 7.73 months, P=0.075). ConclusionThe current study indicated that never-smokers are increasingly prevalent in Chinese patients with SCLC. Never-smokers with SCLC had significantly longer PFS and OS compared with smokers, and smoking was an independent poor prognostic factor for PFS in patients with SCLC.

Circulating tumor DNA as a predictor for response to treatment in BRAF V600E mutant malignant melanoma.

9564 Background: Available biomarkers LDH and S100B possess limited sensitivity and specificity to predict outcome in melanoma. In this pilot study we evaluated the use of circulating tumor (ct)DNA harboring BRAF and NRAS mutations as a predictive biomarker for treatment response and progression-free survival (PFS) in patients with locally advanced or metastatic melanoma. Methods: We analyzed 89 retrospective plasma samples from 32 unselected pts, and 158 samples from 12 pts included in a prospective trial (DRKS00009507). We included stage III disease with planned resection or stage IV disease before initiation or change of medical treatment. Blood samples were taken at baseline at d +8, d +28, and thereafter at 3 months intervals for up to two years. We developed a hydrolysis probe based, Locked Nucleic Acid assay to detect BRAF V600E and wild type ctDNA by droplet digital PCR. Results were correlated with LDH, S100B and PFS. Results: Sensitivity of BRAF V600E specific assay was 0.01% with a limit of Blank of 0.28 copies/well. Of 31 stage IV pts with retrospective samples, 23 were positive for BRAF V600E ctDNA at least once (74%). Positive pts had a mean of 9 (range: 1-17) and 483 (range: 0.1-16,388) BRAF V600E copies/mL for stage III and stage IV respectively. The presence of ctDNA at baseline predicted poor PFS (hazard ratio [HR] 1.487, 95% CI 0.34-6.45). A negative slope in BRAF V600E ctDNA was a favorable prognostic factor for PFS (hazard ratio [HR] 0.230, 95% CI 0.04-1.20) with a median PFS of 3.42 vs. 2.56 months (Range 1.87-8.9 vs. 0.89-5.02). Residual ctDNA at the first time point after initiation or change of treatment was related to a shorter PFS (hazard ratio [HR] 2.02, 95% CI 0.39-10.53). Based on 144 measurement pairs, BRAF ctDNA strongly correlated with S100 (r = 0.73) and LDH (r = 0.52). Conclusions: Residual ctDNA early after change or institution of treatment predicted tumor progression at first clinical response assessment. A positive to negative conversion or a decrease indicated a more favorable course. These data support the use of ctDNA as an early predictive marker for treatment response. We will examine whether two or more detected mutations indicate clonal heterogeneity and confer adverse prognosis. Clinical trial information: DRKS00009507.

The value of prognostic factors in Chinese patients with small cell lung cancer: A retrospective study of 999 patients.

Little is known about the prognostic factors for small cell lung cancer (SCLC) in Chinese patients. The aim of this retrospective study was to improve our understanding of overall survival (OS) and progression-free survival (PFS) prognostic factors in Chinese patients with SCLC. A retrospective analysis of 999 SCLC cases was performed. Patient characteristics, treatments, and laboratory data, including platelet counts and serum lactate dehydrogenase (LDH) and serum sodium levels, were collected. Potential prognostic factors for OS and PFS were evaluated by univariate and multivariate analyses. The median OS and PFS were 10.6 and 7.0 months, respectively. The multivariate Cox proportional hazards model was used to identify stage, serum LDH, and several therapy-relevant factors, including the initial chemotherapy regimen, number of initial chemotherapy cycles, and combination therapy, as independent prognostic factors for OS. Furthermore, female sex, normal LDH levels, a response to therapy, receiving six cycles of initial chemotherapy, and receiving chemotherapy combined with radiotherapy and/or surgery were favorable prognostic factors for PFS. In addition, patients with hyponatremia had a worse OS; therefore, hyponatremia could not influence survival when a good response to therapy was achieved, and it failed to predict PFS. This study demonstrated that several factors, including patient, tumor, and treatment characteristics and serum LDH levels are independent prognostic factors for OS and PFS in Chinese patients with SCLC. The identification of such factors will help physicians compare different populations and to interpret the contribution of treatment to differences in survival among groups.

Second-line docetaxel-based chemotherapy after failure of fluorouracil-based first-line treatment for advanced esophageal squamous cell carcinoma.

PurposeThis retrospective analysis evaluates the clinical efficacy and toxicity of second-line docetaxel-based chemotherapy after failure of fluorouracil-based first-line treatment for advanced esophageal squamous cell carcinoma (ESCC).MethodsWe retrospectively reviewed patients who had received second-line docetaxel-based chemotherapy for advanced ESCC in Zhejiang Cancer Hospital between January 2008 and December 2011. Survival curves were plotted using the Kaplan–Meier method. The Cox proportional hazard model was used for multivariate analysis.ResultsEighty-five patients received docetaxel-based second-line chemotherapy after the failure of first-line fluorouracil-based treatment. Forty-four patients received docetaxel-platinum chemotherapy, and 41 received docetaxel single-agent treatment. The progression-free survival (PFS) and overall survival (OS) were 3.5 and 5.5 months in all of the patients, respectively. There were no statistically significant differences in PFS and OS between docetaxel-platinum and docetaxel single-agent chemotherapy groups (P-value 0.38 and 0.64, respectively). Response to first-line chemotherapy was a favorable prognostic factor for PFS in uni- and multivariate analyses (P-value 0.005 and 0.028, respectively).ConclusionPatients with docetaxel-based second-line treatment obtained a moderate PFS advantage in advanced ESCC. Response to first-line chemotherapy was a favorable prognostic factor for PFS of second-line chemotherapy in advanced ESCC.

Erratum to “Desmoid Fibromatosis in Pediatric Patients: Management Based on a Retrospective Analysis of 59 Patients and a Review of the Literature”

Background. Only limited data are available concerning desmoid tumor in children. Methods. Fifty-nine children and adolescents with desmoid tumor treated in 2 French cancer centers with a very long followup were retrospectively reviewed. Results. Median age was 6 years (range, 0–15). Tumors mainly involved the limbs (42%). Five cases occurred in a context of genetic disorder. Surgery was first-line treatment in 80% of cases. Resection was microscopically complete in 3 patients (pts), with a microscopic residue in 19 pts and a macroscopic residue in 35 cases. Various adjuvant therapies were used. Overall response to all systemic therapies was 33%. Thirty-eight patients developed one or more recurrences or progressions. After a median followup of 8.5 years, 34 patients were alive in complete remission (CR), including 16 first CR. Seven patients died, 6 from refractory disease and 1 from colorectal carcinoma in a genetic context. Ten-year progression-free survival (PFS) and overall survival were 31% and 88%, respectively. In univariate analysis, age less than 10 years and head-neck site were favorable prognostic factors for PFS. Conclusions. When surgery is required, surgical margins must be negative. Low-dose chemotherapy can be proposed as adjuvant therapy. Prospective trials must be developed to evaluate long-term response and side effects.

Temozolomide Salvage Chemotherapy for Recurrent Anaplastic Oligodendroglioma and Oligo-Astrocytoma

ObjectiveTo evaluate the efficacy of temozolomide (TMZ) chemotherapy for recurrent anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA).MethodsA multi-center retrospective trial enrolled seventy-two patients with histologically proven AO/AOA who underwent TMZ chemotherapy for their recurrent tumors from 2006 to 2010. TMZ was administered orally (150 to 200 mg/m2/day) for 5 days per 28 days until unacceptable toxicity occurred or tumor progression was observed.ResultsTMZ chemotherapy cycles administered was median 5.3 (range, 1-41). The objective response rate was 24% including 8 cases (11%) of complete response and another 23 patients (32%) were remained as stable disease. Severe side effects (≥grade 3) occurred only in 9 patients (13%). Progression-free survival (PFS) of all patients was a median 8.0 months (95% confidence interval, 6.0-10.0). The time to recurrence of a year or after was a favorable prognostic factor for PFS (p<0.05). Overall survival (OS) was apparently differed by the patient's histology, as AOA patients survived a median OS of 18.0 months while AO patients did not reach median OS at median follow-up of 11.5 months (range 2.7-65 months). Good performance status of Eastern Cooperative Oncology Group 0 and 1 showed prolonged OS (p<0.01).ConclusionFor recurrent AO/AOA after surgery followed by radiation therapy, TMZ could be recommended as a salvage therapy at the estimated efficacy equal to procarbazine, lomustine, and vincristine (PCV) chemotherapy at first relapse. For patients previously treated with PCV, TMZ is a favorable therapeutic option as 2nd line salvage chemotherapy with an acceptable toxicity rate.

Primary Central Nervous System Lymphoma in Elderly Patients: Clinical Outcomes and Prognosis

AbstractAbstract 5083In this retrospective study, we sought to describe the demographics, diagnoses, management, and outcomes of elderly patients with primary CNS lymphoma (PCNSL) at a single institution. Patients and MethodsAfter obtaining IRB approval, the Cleveland Clinic Brain Tumor and Neuro-Oncology Center's database was used to identify patients with newly diagnosed PCNSL who were older than 60 years between 1986 and 2010. We excluded patients who were HIV positive or had systemic lymphoma. During individual chart review, we confirmed the diagnosis and collected information of patients' demographics, disease presentation, diagnostic procedures, initial and salvage therapy, and clinical outcome. ResultsA total of 84 patients were older than 60 years of age when they were diagnosed with PCNSL at our institution from 1986 to 2010. The median age was 67. 9 years (range: 60. 3–89. 2 years). The median Karnofsky performance status (KPS) of these patients at the diagnosis was 70 (range: 20–90), which stayed the same at the subsequent disease relapses. The median duration of symptoms was 1. 5 months (range: 0. 1–13 months).The initial treatment regimens included whole brain radiation therapy (WBRT), chemotherapy with or without consolidation WBRT. Five patients (6%) received WBRT alone. 43 patients (51%) received chemotherapy alone. Six patients (7%) received chemotherapy followed by consolidation WBRT. Among the patients who received chemotherapy with or without WBRT, 40 of them (48%) received methotrexate-based therapy; 9 patients (11%) received non-methotrexate-based therapy.Among the patients who received initial treatment, 20 of them (37%) achieved complete response (CR), while 19 patients (35%) had disease progression during the treatment. The median progression free survival (PFS) was 8. 0 months (95% CI 2. 7–22 months). The median overall survival (OS) was 15. 5 months (95% CI 6. 6–38. 5 months). We also compared the benefit of individual initial treatment regimens although the reason of their allocation was not determined. It turned out that patients with chemotherapy followed by consolidation WBRT had significantly higher response rate and longer survival than patients with WBRT alone (Figure 1). Unfortunately, no patient who received WBRT alone achieved CR. In addition, the methotrexate-based chemotherapy offered significantly longer PFS than non-methotrexate-based chemotherapy (P = 0. 0008).In univariate analysis, we evaluated potential prognostic factors such as gender, age, KPS, symptom duration, prior malignancy, year of diagnosis, symptoms, and multiple site involvement for response rate, PFS, and OS. Recursive partitioning analysis identified 70 years as the cutoff point for age and 70 as the cutoff point for KPS. We found that no factors can predict response to therapy. However, younger age, higher KPS, more recent diagnosis, and the presence of ocular symptoms were favorable factors for longer OS. Age is the only favorable prognostic factor for PFS, although higher KPS has a trend (P = 0. 08) toward longer PFS. When these factors were subjected to multivariable analysis, age older than 70 years and KPS less than 70 were the only poor prognostic factors for both OS and PFS. With this information in hand, we divided the patients into three prognostic groups based on the number of poor prognostic factors (Table 1). The median OS and PFS for the group with no poor prognostic factors were 65 months and 24 months, respectively. The median OS and PFS for the group with all poor prognostic factors were 1. 0 month and 0. 6 month, respectively. ConclusionsChemotherapy followed by consolidation WBRT had significantly higher response rate and longer survival than patients with WBRT alone. Age and performance status were the only independent predictor of either PFS or OS. [Display omitted] [Display omitted] Table-1Prognostic GroupsNo. of poor prognostic featuresPatient groupNo. of patient (%)Median OS (months)PMedian PFS (months)P0 (good)age≤70 and KPS≥7029 (40%)65 (33-NR)<0.000124 (5.0–60)<0.00011 (medium)age>70 and KPS≥70 OR age≤70 and KPS<7029 (40%)28 (9.7–54)8.0 (2.3–22)2 (poor)age>70 and KPS<7014 (20%)1.0 (0.5–3.0)0.6 (0.3–NR) Disclosures:No relevant conflicts of interest to declare.

Genetic Variants of NBS1 Predict Clinical Outcome of Platinum-based Chemotherapy in Advanced Non-small Cell Lung Cancer in Chinese

NBS1 plays a key role in the repair of DNA double-strand break (DSB). We conducted this study to investigate the effect of two critical polymorphisms (rs1805794 and rs13312840) in NBS1 on treatment response and prognosis of advanced non-small cell lung cancer (NSCLC) patients with platinum-based chemotherapy. Using TaqMan methods, we genotyped the two polymorphisms in 147 NSCLC patients. Odds ratios (ORs) and their 95% confidential intervals (CIs) were calculated as a measure of difference in the response rate of platinum-based chemotherapy using logistic regression analysis. The Kaplan-Meier and log-rank tests were used to assess the differences in progression-free survival (PFS) and overall survival (OS). Cox proportional hazards model was applied to assess the hazard ratios (HRs) for PFS and OS. Neither of the two polymorphisms was significantly associated with treatment response of platinum-based chemotherapy. However, patients carrying the rs1805794 CC variant genotype had a significantly improved PFS compared to those with GG genotype (16.0 vs. 8.0 months, P = 0.040). Multivariable cox regression analysis further showed that rs1805974 was a significantly favorable prognostic factor for PFS [CC/CG vs. GG: Adjusted HR = 0.62, 95% CI: 0.39-0.99; CC vs. CG/GG: Adjusted HR = 0.56, 95% CI: 0.32-0.97). Similarly, rs13312840 with a small sample size also showed a significant association with PFS (CC vs. CT/TT: Adjusted HR = 25.62, 95% CI: 1.53-428.39). Our findings suggest that NBS1 polymorphisms may be genetic biomarkers for NSCLC prognosis especially PFS with platinum-based chemotherapy in the Chinese population.

Prognostic and predictive value of p53 in low MGMT expressing glioblastoma treated with surgery, radiation and adjuvant temozolomide chemotherapy

Objective: To assess the prognostic and predictive significance of p53 protein expression in low O6-methylguanine-DNA methyltransferase (MGMT) expressing glioblastoma multiform (GBM) treated with combined therapy.Methods: The authors reviewed the clinical outcomes of 46 low MGMT expressing GBM patients who had undergone surgery, conventional local radiotherapy and temozolomide chemotherapy. Correlation between p53 expression level and clinical outcomes were analysed with univariate and multivariate Cox model.Results: Patients with low p53 expression had a significantly improved progression free survival (PFS) (p=0·015) and overall survival (OS) (p=0·047) compared to those with high expression. On both univariate and multivariate analyses, low p53 expression persisted as a significant independent favorable prognostic factor for PFS (p=0·017). Pre-operative Karnofsky performance status score (p=0·029), tumor resection extent (p=0·045) and p53 expression level (p=0·038) were significant independent prognostic factors for OS.Conclusion: In these low MGMT expressing GBM patients with combined treatment, low p53 expression was a significant independent favorable prognostic factor for both PFS and OS. In addition to MGMT, p53 may be another stratification variable in the future therapeutic trials.

Expression of Hypoxia-Inducible Factor (HIF) Is An Independent Favorable Prognostic Factor in Diffuse Large B-Cell Lymphoma (DLBCL) Treated with R-CHOP

HIF is a transcription factor that regulates gene expression in response to decreases in cellular oxygenation (hypoxia). Genes activated by HIF are involved in glycolysis, glucose transport, angiogenesis, cell proliferation, cell migration, cell metabolism, and cell survival. Many of these genes confer protection against the consequences of oxygen deprivation while others enhance resistance to chemotherapy or radiotherapy. Clinically, evidence of elevated HIF protein correlates with poor prognosis in lung, breast, colorectal, brain, pancreatic, ovarian, renal, and bladder cancers. Our preliminary tissue micro array (TMA) data suggested that HIF is frequently stabilized in lymphoma (BJH 2008; 141:676), especially among patients with diffuse large B-cell lymphoma (DLBCL). We also found that constitutive expression of HIF-1α and/or HIF-2α is stabilized in a set of established lymphoma cell lines, underscoring the potential impact of HIF in lymphoma. To further investigate the importance of HIF, we examined TMAs for HIF-1α expression from 153 patients with DLBCL treated with CHOP or rituximab-CHOP (R-CHOP) at the BCCA between 1999–2002. Treatment was before (pre-rituximab) and after (post-rituximab) institution of a policy recommending the combination of rituximab with CHOP for all patients with newly diagnosed advanced-stage DLBCL (March 2001). Tissue sections were stained with monoclonal antibody to HIF-1α and expression (nuclear) was scored by computer (Automated Cellular Imaging System) and validated by pathology review. HIF was dichotomized as either negative (neg; no HIF staining) or positive (pos; score of 1 or greater). Of the 153 patients, 78 were consecutively treated with R-CHOP, while 75 had received CHOP. We found HIF pos expression in 63% (49/78) of patients treated with R-CHOP and 59% (44/75) treated with CHOP (p=NS). Further, based on the Hans algorithm, HIF was expressed in 62% of germinal center (GC) patients and 59% of non-GC patients (P=NS). In the R-CHOP group (see Figure 1A and 1B), the 5-year progression-free survival (PFS) was 45% for HIF neg patients vs 62% for HIF pos (log rank p=0.0187); while the 5-year overall survival (OS) was 48% for HIF neg vs 76% for HIF pos (log rank p=0.025).In patients treated with CHOP, there was no difference in outcome between HIF pos and HIF neg subsets. In multivariate analysis in the R-CHOP treated group, controlling for the International Prognostic Index (IPI), HIF pos expression remained a significant independent predictor for OS (p=0.03), while the IPI was of borderline significance (p=0.051). Comparison with other biomarkers showed that HIF did not correlate with expression of bcl-2, CD10, MUM-1, or FOXP1; while a high correlation was detected with bcl-6 and HIF (among HIF pos R-CHOP patients, 94% were bcl-6 pos and 6% were bcl-6 neg; p=0.004). We conclude that expression of HIF-1α is an important and heretofore undiscovered independent favorable prognostic factor for PFS and OS in DLBCL patients treated with R-CHOP, but not in patients treated with CHOP. These data suggest there may be an important biological interaction between CD20 monoclonal antibody-based therapy and HIF or downstream genes regulated by HIF. Further study of this observation is warranted. [Display omitted]

Radiation Therapy Combined with (or without) Cisplatin-based Chemotherapy for Patients with Nasopharyngeal Cancer: 15-years Experience of a Single Institution in Korea

This retrospective study was carried out to evaluate the efficacy and toxicity of radiation therapy (RT) with/without cisplatin-based chemotherapy in nasopharyngeal cancer (NPC). One hundred forty six patients with NPC received curative RT and/or cisplatin-based chemotherapy. Thirty-nine patients were treated with induction chemotherapy (IC), including cisplatin and 5-fluorouracil followed by RT. Another 63 patients were treated with concurrent chemoradiotherapy (CCRT) using cisplatin, and 22 patients were treated with IC followed by CCRT. The remaining 22 patients were treated with RT alone. One hundred four (80.0%) patients achieved complete response (CR), and 23 (17.7%) patients achieved partial response (PR). The patterns of failure were: locoregional recurrences in 21.2% and distant metastases in 17.1%. Five-year overall survival (OS) and progression free survival (PFS) were 50.7% and 45.0%, respectively. Multivariate Cox stepwise regression analysis revealed CR to chemoradiotherapy to be a powerful prognostic factor for OS. CR to chemoradiotherapy and completion of radiation according to the time schedule were favorable prognostic factors for PFS. A comparison of each treatment group (IC --> RT vs. CCRT vs. IC --> CCRT vs. RT alone) revealed no significant differences in the OS or PFS. However, subgroup analysis showed significant differences in both OS and DFS in favor of the combined chemoradiotherapy group compared with RT alone, for stage IV and T3-4 tumors. Grade 3-4 toxicities were more common in the combined chemoradiotherapy arm, particularly in the CCRT group. This study was limited in that it was a retrospective study, much time was required to collect patients, and there were imbalances in the number of patients in each treatment group. Combined chemoradiotherapy remarkably prolonged the OS and PFS in subgroup patients with stage IV or T3-4 NPC.