[Prognostic significance of proteins expression by immunohistochemical method in diffuse large B cell lymphoma].

Objective: To analyze the prognostic significance of TP53, Bcl-2, Bcl-6, Myc proteins expression by immunohistochemical method (IHC) in diffuse large B cell Lymphoma (DLBCL) . Methods: Clinical and pathologic data of 223 patients with DLBCL hospitalized in Zhejiang First Hospital from March 2009 to June 2015 were retrospectively analyzed. Results: The 223 cases, a median age of 56 years old with a male predominance, had shown a 39.0% of TP53 positive expression, 38.6% of Myc, 69.1% of Bcl-2, 56.5% of Bcl-6, and 22.7% of Myc/Bcl-2 double expression. According to Hans' classification, 27.4% were GCB and 72.6% were non-GCB. With a median follow-up of 38 (2-97) months, the 3 and 5 years survival rates were 70% and 66% , respectively. By multivariate analysis, TP53 over-expression and Myc/Bcl-2 double expression were independently associated with poor outcomes. 3-year and 5-year overall survival were 59% and 57% for patients with TP53 positive, 77% and 71% for patients with TP53 negative expression. Patients with non-GCB subtype receiving chemotherapy combined with rituximab had a higher OS than those without rituximab. But rituximab did not improve the prognosis of patients with TP53 positive. Conclusion: Myc/Bcl-2 double expression and TP53 over-expression are poor prognosis for DLBCL patients. Patients with Myc/Bcl-2 double expression have shorter OS. Patients with non-GCB subtype who received chemotherapy combined with rituximab have a better OS than those without rituximab. But rituximab does not improve the prognosis of patients with TP53 positive.

[Efficacy and safety analysis of different dose idarubicin plus cytarabine regimen as induction chemotherapy for young patients with de-novo acute myeloid leukemia].

OBJECTIVE: To compare the efficacy, safety and long-term prognosis between different dose idarubicin (IDA) combined with cytarabine (IA) as induction chemotherapy in newly diagnosed young patients of acute myeloid leukemia (AML). METHODS: A total of 149 newly diagnosed young AML patients (APL excluded) between January 2009 to July 2014 was enrolled. According to the dose of IDA, the patients were divided into three groups, high standard- dose IA group (10- 12 mg · m (- 2) · d(- 1)), low standard-dose IA group (8-9 mg·m(-2)·d(-1)) and low-dose IA group (<8 mg·m(-2)·d(-1)). The efficacy, adverse effects and long- term prognosis among the three groups were compared. RESULTS: Of them, 34 patients were in high standard-dose IA group, 53 in low standard-dose IA group and 62 in low-dose IA group. After one cycle of induction chemotherapy, the complete remission (CR) rate was 79.4%, 75.5% and 46.8%, the overall response (OR) rate was 97.1%, 94.3% and 64.5%, and the overall CR rate was 85.3%, 81.1% and 54.8%, respectively. Compared with low- dose IA group, high standard- dose IA group and low standard-dose IA group had significantly better result (P<0.05), but there was no significant difference between the latter two groups (P>0.05). Multivariate analysis also showed that standard-dose IA was favorable factor for induction chemotherapy (P<0.05). The adverse effects were similar in the three group, other than the lowest count of WBC (P=0.002). Low standard-dose IA can improve the OS compared to the low-dose IA (P=0.003), but EFS, RFS was similar in the three groups. CONCLUSIONS: For the newly diagnosed young(<55) AML patients, the standard-dose IA has better CR rate. The adverse effects were similar in the three groups. High-dose IA may improve the OS compared to the low-dose IA.

Homoharringtonine in combination with cytarabine and aclarubicin resulted in high complete remission rate after the first induction therapy in patients with de novo acute myeloid leukemia.

To assess the efficacy and toxicity of HAA regimen (homoharritonine 4 mg/m2/day, days 1-3; cytarabine 150 mg/m2/day, days 1-7; aclarubicin 12 mg/m2/day, days 1-7) as an induction therapy in the treatment of de novo acute myeloid leukemia (AML), 48 patients with newly diagnosed AML, aged 35 (14-57) years, were entered into this clinical study. The median follow-up was 26 months. Eighty-three percent of patients achieved complete remission (CR), and the first single course of induction HAA regimen resulted in CR rate of 79%. The CR rate of 100, 82 and 33% were achieved in patients with favorable, intermediate and unfavorable cytogenetics, respectively. For all patients who achieved CR, the median time from the initiation of the induction therapy to the evaluation of the remission status was 32 days. For all patients, the estimated 3 years overall survival (OS) rate was 53%, whereas for patients with M5, the estimated OS rate at 3 years was 75%. The toxicities associated with HAA regimen were acceptable, and the most common toxicity was infection. This study suggested that HAA regimen might be a well-tolerable, effective induction regimen in young adult patients with AML.

Intensity modulated radiation therapy (IMRT) in the management of prostate cancer.

Intensity modulated radiation therapy (IMRT) is gaining widespread use in the radiation therapy community. Prostate cancer is the ideal target for IMRT due to the growing body of literature supporting dose escalation and normal tissue limitations. The need for dose escalation and the limits of conventional radiation therapy necessitate precise patient and prostate localization as well as advanced treatment delivery. The treatment of prostate cancer has been dramatically altered by the introduction of technology that can focus on the target while avoiding normal tissue. IMRT is evolving as the treatment of the future for prostate cancer.

Important prognostic factors in patients with skull base erosion from nasopharyngeal carcinoma after radiotherapy.

PURPOSE: To evaluate the long-term outcome and prognostic factors in patients with skull base erosion from nasopharyngeal carcinoma after initial radiotherapy (RT). METHODS AND MATERIALS: From January 1985 to December 1986, 100 patients (71 males, 29 females) with a diagnosis of nasopharyngeal carcinoma were found on computed tomography (CT) to have skull base erosion. The mean age was 41 years (range 16-66). Ninety-six patients had World Health Organization type III undifferentiated carcinoma, and 4 had type I. The metastatic workup, including chest radiography, liver ultrasound scanning, and liver function test was negative. All patients underwent external beam RT (EBRT) alone to 66-80 Gy during 6-8 weeks. A daily fraction size of 2 Gy was delivered using 60Co or a linear accelerator. No patient received chemotherapy. All patients were followed at regular intervals after irradiation. The median follow-up was 22.3 months (range 2-174). Survival of the cohort was computed by the Kaplan-Meier method. The potential prognostic factors of survival were examined. Multivariate analyses were performed using the Cox regression model. RESULTS: The 1, 2, 5, and 10-year overall survival rate for the cohort was 79%, 41%, 27%, and 13%, respectively. However, the subgroup of patients with both anterior cranial nerve (I-VIII) and posterior cranial nerve (IX-XII) involvement had a 5-year survival of only 7.7%. A difference in the time course of local recurrence and distant metastasis was observed. Both local recurrence and distant metastasis often occurred within the first 2 years after RT. However, local relapse continued to occur after 5 years. In contrast, no additional distant metastases were found after 5 years. The causes of death included local recurrence (n = 59), distant metastasis (n = 21), both local recurrence and distant metastasis (n = 1), and unrelated causes (n = 5). After multivariate analysis, complete recovery of cranial nerve involvement, cranial nerve palsy, and headache after irradiation were found to be independent prognostic factors in this cohort. CONCLUSIONS: We present one of the longest follow-ups of patients with nasopharyngeal carcinoma invading the skull base. Our results demonstrate the importance of cranial nerve involvement, recovery of headache, and cranial nerve palsy. These factors should be carefully evaluated from the history, physical examination, and imaging studies. A subgroup of patients with skull base involvement had long-term survival after RT alone. The findings of this study are important as a yardstick against which more aggressive strategies, such as combined radiochemotherapy and altered fractionation RT can be compared.

Phase I/II trial evaluating combined radiotherapy and in situ gene therapy with or without hormonal therapy in the treatment of prostate cancer--a preliminary report.

PURPOSE: To report the preliminary results of a Phase I/II study combining radiotherapy and in situ gene therapy (adenovirus/herpes simplex virus thymidine kinase gene/valacyclovir) with or without hormonal therapy in the treatment of prostate cancer. METHODS AND MATERIALS: Arm A: low-risk patients (T1-T2a, Gleason score <7, pretreatment PSA <10) were treated with combined radio-gene therapy. A mean dose of 76 Gy was delivered to the prostate with intensity-modulated radiotherapy. Arm B: high-risk patients (T2b-T3, Gleason score >or=7, pretreatment PSA >or=10) were treated with combined radio-gene therapy and hormonal therapy. Hormonal therapy was comprised of a 4-month leuprolide injection and 2-week use of flutamide. Arm C: Stage D1 (positive pelvic lymph node) patients received the same regimen as Arm B, with the additional 45 Gy to the pelvic lymphatics. Treatment-related toxicity was assessed using Cancer Therapy Evaluation Program common toxicity score and Radiation Therapy Oncology Group (RTOG) toxicity score. RESULTS: Thirty patients (13 in Arm A, 14 in Arm B, and 3 in Arm C) completed the trial. Median follow-up was 5.5 months. Eleven patients (37%) developed flu-like symptoms (Cancer Therapy Evaluation Program Grade 1) of fatigue and chills/rigors after gene therapy injection but recovered within 24 h. Four patients (13%) and 2 patients (7%) developed Grade 1 and 2 fever, respectively. There was no patient with weight loss. One patient in Arm B developed Grade 3 elevation in liver enzyme, whereas 11 and 2 patients developed Grade 1 and 2 abnormal liver function tests. There was no Grade 2 or above hematologic toxicity. Three patients had transient rise in creatinine. There was no RTOG Grade 3 or above lower gastrointestinal toxicity. Toxicity levels were as follows: 4 patients (13%), Grade 2; 6 patients (20%), Grade 1; and 20 patients (67%), no toxicity. There was 1 patient with RTOG Grade 3 genitourinary toxicity, 12 patients (40%) with Grade 2, 8 patients (27%) with Grade 1, and 9 patients (30%) with no toxicity. No patient dropped out from the trial or had to withhold treatment because of severe toxicity. CONCLUSIONS: This is the first trial of its kind in the field of prostate cancer that aims to expand the therapeutic index of radiotherapy by combining in situ gene therapy. Initial experience has demonstrated the safety of this approach. There is no added toxicity to each therapy used alone. Long-term follow-up and larger cohort studies are warranted to evaluate long-term toxicity and efficacy.

Intensity-modulated radiation therapy (IMRT) for prostate cancer with the use of a rectal balloon for prostate immobilization: acute toxicity and dose-volume analysis.

PURPOSE: To report acute toxicity and to evaluate the relationship between dose-volume effects and acute toxicity in patients with localized prostate cancer, treated with intensity-modulated radiation therapy (IMRT). METHODS AND MATERIALS: Acute toxicity (both lower gastrointestinal [GI] and genito-urinary [GU]) in 100 patients treated with IMRT definitively to a prescribed dose of 70 Gy were assessed using RTOG scoring criteria. A rectal balloon was used for prostate immobilization. Mean doses to seminal vesicles, prostate, bladder, and rectum were recorded. Average irradiated bladder and rectal volumes above 65, 70, and 75 Gy were assessed. A relationship between dose volume and clinical toxicity was evaluated. All patients completed the full duration of acute toxicity assessment. RESULTS: Mean doses to the prostate and seminal vesicles were 75.8 and 73.9 Gy. This represents a moderate dose escalation. Acute GI toxicity profile was very favorable. Eleven percent and 6% of the patients had grade 1 and 2 GI toxicity, respectively, while 83% had no GI complaint. For GU complaints, 38% and 35% had grade 1 and 2 toxicity, respectively, while 27% had no complaints. There was no grade 3 or higher acute GI or GU toxicity. Mean doses to the bladder were 22.8, 23.4, and 26.1 Gy for grade 0, 1, and 2 GU toxicity, respectively (p = 0.132). There is no statistically significant relationship between acute GU toxicity and the bladder volume receiving > 65 Gy, > 70 Gy, or > 75 Gy. In evaluating acute GI toxicity, there are very few grade 1 and 2 events. No relationship was found between acute rectal toxicity and mean rectal dose or irradiated rectal volumes receiving more than 65, 70, and 75 Gy. CONCLUSION: The findings are important with regard to the safety of IMRT, especially in reducing acute GI toxicity. Dose escalation with IMRT using a prostate immobilization technique is feasible. The findings are also important because they contribute to the clinical and dosimetric correlation aspect in the use of IMRT to treat prostate cancer. A larger cohort may be needed to determine if there is a relationship between acute GU toxicity and (a) mean bladder dose and (b) irradiated bladder volume receiving > 65 Gy, > 70 Gy, or > 75 Gy. A larger cohort of patients treated to a higher dose may be needed to show a relationship between dose volume and acute GI toxicity.

Intensity modulated radiation therapy (IMRT) following prostatectomy: more favorable acute genitourinary toxicity profile compared to primary IMRT for prostate cancer.

PURPOSE: To report our initial experience on postprostatectomy IMRT (PPI), addressing acute genitourinary (GU) toxicity in comparison to primary IMRT (PI) for prostate cancer. METHODS AND MATERIALS: From April 1998 to December 1999, 40 postprostatectomy patients were treated with intensity modulated radiation therapy (IMRT) to a median prescribed dose of 64 Gy (mean dose of 69 Gy). The Radiation Therapy Oncology Group (RTOG) scoring system was used to assess acute GU toxicity. Target volume and maximum and mean doses were evaluated. The mean doses to the bladder and irradiated bladder volume receiving >65 Gy were assessed. These were compared to those of 125 patients treated with PI to a prescribed dose of 70 Gy (mean dose of 76 Gy). RESULTS: The acute GU toxicity profile is more favorable in the PPI group with 82.5% of Grade 0-1 and 17.5% of Grade 2 toxicity compared to 59.2% and 40.8%, respectively, in the PI group (p < 0.001). There was no Grade 3 or higher toxicity in either group. The target volume was larger in the PPI group, while the maximum and mean doses to the target were higher in the PI group. The mean dose delivered to the bladder was higher in the PPI group. The irradiated bladder volume receiving >65 Gy was significantly larger in the PI group (p < 0.001). CONCLUSIONS: PPI can be delivered with acceptable ute GU toxicity. The larger PPI target volume may be related to the difficulty in delineating prostatic fossa. Despite a larger target volume and a higher mean dose to the bladder, PPI produced a more favorable acute GU toxicity profile. This may be related to a combination of lower mean and maximum doses and smaller bladder volumes receiving >65 Gy in the PPI group, as well as urethral rather than bladder irradiation. The findings have implications in the evaluation of IMRT treatment plan for prostate cancer, whereby the irradiated bladder volumes above 65 Gy may be more meaningful than the mean dose to the bladder. Longer term toxicity results are awaited.

The use of intensity modulated radiotherapy for the treatment of extensive and recurrent juvenile angiofibroma.

These case series are presented to describe the application and advantages of intensity modulated radiotherapy (IMRT) for the treatment of extensive and/or recurrent juvenile angiofibroma. Two patients were diagnosed with recurrence at 11 and 13 months postoperatively, and one was surgically unresectable. The affected areas included the base of skull, cavernous sinus, pterygopalatine fossa, infratemporal fossa, posterior orbit and nasopharynx. Highly conformal IMRT was delivered with limited radiation doses to the optic nerves, optic chiasm, brainstem, brain, spinal cord, lens, retina, mandible, and parotid. The total dose delivered to the tumor varied from 3400 to 4500 cGy. The tumor shrunk radiographically in all three cases and there was no endoscopic evidence of disease in two cases at 15 months and 40 months. There was no acute toxicity. Late toxicity was limited to one episode of epistaxis and persistent rhinitis in one patient. In conclusion, IMRT provides several advantages over conventional radiotherapy in the treatment of recurrent juvenile angiofibroma.

Elevation of serum vascular endothelial growth factor in male patients with metastatic nasopharyngeal carcinoma.

BACKGROUND: Angiogenesis is essential for tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is the most potent angiogenic factor identified to date. The authors investigated the correlation between the levels of serum VEGF (S-VEGF) in patients with nasopharyngeal carcinoma (NPC) and disease progression. METHODS: The sera from 65 male patients with nonmetastatic NPC, 22 male patients with metastatic NPC, and 27 healthy male volunteers were obtained. A quantitative enzyme-linked immunosorbent assay was performed to measure the concentrations of S-VEGF in the sera. RESULTS: The mean S-VEGF levels were 371.0 pg/mL(-1) (range, 128.5-691.1 pg/mL(-1)) for healthy controls, 375.6 pg/mL(-1) (range, 72.9-1202.5 pg/mL(-1)) for patients with nonmetastatic NPC, and 958.6 pg/mL(-1) (range, 264.4-3744.9 pg/mL(-1)) for patients with metastatic NPC. The mean S-VEGF level in patients with metastatic NPC was significantly higher than in either patients with nonmetastatic NPC (P < 0.001) or healthy controls (P < 0.001). However, there was no statistical difference between these results for healthy controls and patients with nonmetastatic NPC. At the level of 900 pg/mL(-1), S-VEGF indicated distant dissemination of NPC with a specificity of 95.4%, a sensitivity of 31.8%, a positive predictive value of 70.0%, and a negative predictive value of 80.5%. No significant differences in the levels of S-VEGF were found among various T classifications, N classifications, and clinical stages of nonmetastatic NPC. CONCLUSIONS: The levels of S-VEGF were significantly elevated in male patients with metastatic NPC. These levels did not correlate with locoregional progression of NPC. The usefulness of detecting S-VEGF in the early diagnosis of NPC appears to be limited.

Enhanced expression of TGF-beta 1 by peritoneal macrophages in CAPD patients.

Peritoneal macrophages are the predominant cells in peritoneal dialysate. To clarify the role of the macrophage in fibrosis of the peritoneum in long-term continuous ambulatory peritoneal dialysis (CAPD) patients, we studied the transforming growth factor beta (TGF-beta 1) mRNA expression by peritoneal macrophages from peritoneal dialysis patients. Macrophages were obtained when the catheter was inserted and one month later. TGF-beta 1 mRNA was measured by slot-blot hybridization using a cDNA probe. The result was that TGF-beta 1 expression was significantly higher in macrophages from peritoneal dialysate than that of macrophages obtained during catheter insertion. This suggests that peritoneal macrophages play a role in the pathogenesis of fibrosis of peritoneum in peritoneal dialysis patients. It also suggests that peritoneal macrophages in dialysate have been somewhat activated.

Influence of peritoneal dialysis on the progression of chronic renal failure.

To determine whether an early start of peritoneal dialysis is beneficial to the preservation of residual renal function, we studied the effect of peritoneal dialysis on the progression of glomerular sclerosis in subtotal nephrectomy rats. Four weeks after subtotal nephrectomy, Wistar rats were treated with peritoneal dialysis (PD) (through a silicone catheter, two exchanges per day with 20 mL 1.5% dextrose solution per exchange for 8 weeks, n = 10). Then the kidneys were checked. The sclerosis index was significantly lower in the PD group than that of the control group, which was 1.12 +/- 0.13, 1.64 +/- 0.19, respectively (p < 0.05). This suggests that peritoneal dialysis may suppress the progression of chronic renal failure. An early start of PD may benefit the preservation of renal function in uremic patients.