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Nasopharyngeal carcinoma (NPC) is a common head and neck malignant tumor with high incidence in southern China. Local recurrence is one of the main failure modes of locally advanced NPC. The dose-escalation after radical radiotherapy for locally advanced NPC remains controversial. In the era of modern radiotherapy, the mainstream treatment mode of locally advanced NPC is neoadjuvant chemotherapy plus concurrent chemoradiotherapy. There is no consensus on whether to prescribe dose-escalation, how and when to conduct dose-escalation, how much dose to prescribe for patients with residual lesion proved by MRI or pathology. How to accurately determine the target volume and dose / fraction to maximize the local control of the tumor are the directions of clinical practice for locally advanced NPC, which remain to be further studied.
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Objective:To evaluate the spatial position and functional parameters of 18F-FDG PET-CT and diffusion-weighted imaging (DWI) before and during radiotherapy (RT) based on the medium of 3DCT in patients with esophageal cancer and to explore whether the high-signal area derived from DWI can be used for individualized definition of the volume in need of dose-escalation for esophageal cancer. Methods:Thirty-two patients with esophageal cancer treated with concurrent chemoradiotherapy or neoadjuvant chemoradiation sequentially underwent repeated 3DCT, 18F-FDG PET-CT and enhanced MRI scans before RT and at the 15 th time of RT. All images were fused with the 3DCT images by deformable registration. The gross tumor volume (GTV) was delineated based on PET Edge on the first and second 3DCT, PET-CT and DWI and corresponding T 2-weighted MRI (T 2W-MRI) fused images, and defined as GTV CTpre and GTV CTdur, GTV PETpre, GTV PETdur, GTV DWIpre and GTV DWIdur, respectively. SUV (SUV max, SUV mean, SUV peak), MTV, TLG, ADC (ADC min and ADC mean) values and △SUV (△SUV max, △SUV mean, △SUV peak), △MTV, △TLG, △ADC (△ADC mean and △ADC min) of lesions were measured before and during RT. Results:The differences in SUV (SUV max, SUV mean, SUV peak), MTV, TLG, ADC mean and ADC min of the GTV before and during RT were statistically significant (all P<0.001). The tumor ADC and SUV values before and during RT showed no significant correlation, and there was no correlation between △ADC and △SUV (both P>0.05). The conformity index (CI) of GTV PETpre to GTV DWIpre was significantly higher than that of GTV PETdur to GTV DWIdur ( P<0.001). The shrinkage rate of maximum diameter (△LD DWI)(24%) and the shrinkage rate of tumor volume (VRR DWI)(60%) based on DWI during RT were significantly greater than the corresponding PET-based △LD PET (14%) and VRR PET (41%)( P=0.017 and P<0.001). Conclusions:The location of high residual FDG uptake based on PET-CT yields poor spatial matching compared with the area with residual high signal based on DWI during RT. Tumor ADC and SUV values may play complementary roles as imaging markers for prediction of patterns of failure and for definition of the volume in need of dose-escalation. In addition, the shrinkage rates of tumor maximum diameter/volume based on DWI during RT are significantly faster than those based on PET-CT. Therefore, the feasibility of selecting boosting of the high signal area derived from DWI for individualized definition of the volume for esophageal cancer is not clear.
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RTOG 0617 trial has indicated that no benefit can be obtained in the overall survival of locally advanced non-small cell lung cancer patients by improving the prescribed dose, which promotes the adjustments to the strategies of dose escalation. Currently, multiple studies have been designed to explore more effective approaches to boost dose, such as dose boosts based on increased 18FDG-uptake regions, simultaneous integrated boost intensity-modulated radiotherapy and modulation of dose fractions, which have achieved a series of progress. The widespread application of PET-CT and intensity-modulated radiotherapy offers broad space for the dose escalation and optimization.
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RTOG 0617 trial has indicated that no benefit can be obtained in the overall survival of locally advanced non-small cell lung cancer patients by improving the prescribed dose,which promotes the adjustments to the strategies of dose escalation.Currently,multiple studies have been designed to explore more effective approaches to boost dose,such as dose boosts based on increased 18FDG-uptake regions,simultaneous integrated boost intensity-modulated radiotherapy and modulation of dose fractions,which have achieved a series of progress.The widespread application of PET-CT and intensity-modulated radiotherapy offers broad space for the dose escalation and optimization.
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PURPOSE: Glioblastoma (GBM) carries a high propensity for in-field failure despite trimodality management. Past studies have failed to show outcome improvements with dose-escalation. Herein, we examined trends and outcomes associated with dose-escalation for GBM. MATERIALS AND METHODS: The National Cancer Database was queried for GBM patients who underwent surgical resection and external-beam radiation with chemotherapy. Patients were excluded if doses were less than 59.4 Gy; dose-escalation referred to doses ≥66 Gy. Odds ratios identified predictors of dose-escalation. Univariable and multivariable Cox regressions determined potential predictors of overall survival (OS). Propensity-adjusted multivariable analysis better accounted for indication biases. RESULTS: Of 33,991 patients, 1,223 patients received dose-escalation. Median dose in the escalation group was 70 Gy (range, 66 to 89.4 Gy). The use of dose-escalation decreased from 8% in 2004 to 2% in 2014. Predictors of escalated dose were African American race, lower comorbidity score, treatment at community centers, decreased income, and more remote treatment year. Median OS was 16.2 months and 15.8 months for the standard and dose-escalated cohorts, respectively (p = 0.35). On multivariable analysis, age >60 years, higher comorbidity score, treatment at community centers, decreased education, lower income, government insurance, Caucasian race, male gender, and more remote year of treatment predicted for worse OS. On propensity-adjusted multivariable analysis, age >60 years, distance from center >12 miles, decreased education, government insurance, and male gender predicted for worse outcome. CONCLUSION: Dose-escalated radiotherapy for GBM has decreased over time across the United States, in concordance with guidelines and the available evidence. Similarly, this large study did not discern survival improvements with dose-escalation.
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Humans , Male , Bias , Cohort Studies , Comorbidity , Racial Groups , Drug Therapy , Education , White People , Glioblastoma , Insurance , Odds Ratio , Radiotherapy , United StatesABSTRACT
The benefit of androgen-deprivation therapy (ADT) in combination with dose-escalated radiotherapy (DERT) for localized prostate cancer has not been determined in randomized studies. In this study, the benefit of ADT was assessed in patients uniformly treated with dose-escalated intensity-modulated radiation therapy (IMRT) to the prostate and seminal vesicles but not pelvis. In all, 419 patients with localized prostate adenocarcinoma underwent definitive IMRT (cumulative dose 78 Gy), with 32.6%, 33.1%, 32.1%, and 2.1% having T1 through T4 disease, respectively, and 51.2% having high-risk disease. ADT was given to 76.1% of patients. With a median follow-up of 60 months, 5-year biochemical failure-free, disease-free, and overall survival rates were 87%, 86%, and 87%, respectively. T stage was an independent predictor of all three rates. Five-year pelvic nodal recurrence rate was 2.9%. ADT improved biochemical failure-free and disease-free survival but not overall survival. ADT showed benefit in high-risk disease but not intermediate-risk disease. Late gastrointestinal and genitourinary toxicities ≥ grade 2 occurred in 11.0% and 6.7%, respectively. In conclusion, DERT with 78 Gy yields good disease control and low rate of pelvic nodal recurrence. ADT improves disease-free survival in patients with high-risk but not intermediate-risk disease.
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Objective To investigate dose escalation by metabolic sub-volume based on standard uptake values ( SUV) gradient of pre-treatment positron emission tomography/computed tomography ( PET/CT) for locally advanced non-small cell lung cancer ( NSCLC) radiotherapy. Methods The pre-treatment 18 F-FDG PET/CT images of 29 patients with locally advanced NSCLC were analyzed retrospectively. Gross tumor volume ( GTV) was delineated on the PET/CT fusion images. Tumor metabolic sub-volume was segmented according to the threshold of 50% and 75% maximum standard uptake values ( SUVmax ) . The region that under 50% SUVmax was defined as GTV1. From 50% to 75% SUVmax was defined as GTV2,and over 75% SUVmax was defined as GTV3. PTV (planning target volume), PTV1, PTV2 and PTV3 were extended from GTV, GTV1, GTV2 and GTV3, and different plans were designed subsequently. Plan 1 was designed for PTV with prescription dose 60 Gy, and Plan 2 was designed for PTV1, PTV2 and PTV3 with prescription dose 60-66 Gy, 66-72 Gy and≥72 Gy, respectively. The dosimetric parameters between tumor target and organs at risk (OARs) were compared. Results Compared to Plan 1, the absorbed dose in Plan 2 that covers 2% volume of the PTV ( D2 ) was increased from 66. 5 Gy to 78. 5 Gy and the dose was escalated by about 23. 2%. The average dose of PTV1, PTV2 and PTV3 increased by 2. 8% (62. 7-64. 4 Gy), 10. 3% (63. 5 -70. 0 Gy), 18. 7% (63. 8 -75. 8 Gy), and the average dose of PTV increased by 8. 9% (63. 2-68. 8 Gy). The sub-regional dose had been effectively improved. There was no significant difference in target coverage between Plan 1 and Plan 2 ( P >0. 05 ) . Homogeneity index (HI) was decreased with the escalation of maximum dose for Plan 2(t=23. 3, P<0. 05). There was no statistically significant difference in radiation dose of OARs between two plans ( P>0. 05 ) . Conclusions Dose escalation based on metabolic sub-volume from 18 F-FDG PET/CT was feasible, and radiation dose escalation of sub-volume with high metabolic activity can be achieved without increasing the OARs dose.
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Objective To investigate dose escalation by metabolic sub-volume based on standard uptake values ( SUV) gradient of pre-treatment positron emission tomography/computed tomography ( PET/CT) for locally advanced non-small cell lung cancer ( NSCLC) radiotherapy. Methods The pre-treatment 18 F-FDG PET/CT images of 29 patients with locally advanced NSCLC were analyzed retrospectively. Gross tumor volume ( GTV) was delineated on the PET/CT fusion images. Tumor metabolic sub-volume was segmented according to the threshold of 50% and 75% maximum standard uptake values ( SUVmax ) . The region that under 50% SUVmax was defined as GTV1. From 50% to 75% SUVmax was defined as GTV2,and over 75% SUVmax was defined as GTV3. PTV (planning target volume), PTV1, PTV2 and PTV3 were extended from GTV, GTV1, GTV2 and GTV3, and different plans were designed subsequently. Plan 1 was designed for PTV with prescription dose 60 Gy, and Plan 2 was designed for PTV1, PTV2 and PTV3 with prescription dose 60-66 Gy, 66-72 Gy and≥72 Gy, respectively. The dosimetric parameters between tumor target and organs at risk (OARs) were compared. Results Compared to Plan 1, the absorbed dose in Plan 2 that covers 2% volume of the PTV ( D2 ) was increased from 66. 5 Gy to 78. 5 Gy and the dose was escalated by about 23. 2%. The average dose of PTV1, PTV2 and PTV3 increased by 2. 8% (62. 7-64. 4 Gy), 10. 3% (63. 5 -70. 0 Gy), 18. 7% (63. 8 -75. 8 Gy), and the average dose of PTV increased by 8. 9% (63. 2-68. 8 Gy). The sub-regional dose had been effectively improved. There was no significant difference in target coverage between Plan 1 and Plan 2 ( P >0. 05 ) . Homogeneity index (HI) was decreased with the escalation of maximum dose for Plan 2(t=23. 3, P<0. 05). There was no statistically significant difference in radiation dose of OARs between two plans ( P>0. 05 ) . Conclusions Dose escalation based on metabolic sub-volume from 18 F-FDG PET/CT was feasible, and radiation dose escalation of sub-volume with high metabolic activity can be achieved without increasing the OARs dose.
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PURPOSE: This study aimed to evaluate the effects of radiotherapy (RT) on progression-free survival (PFS) for patients with recurrent colorectal cancer. METHODS: We reviewed the records of 22 patients with recurrent colorectal cancer treated with RT between 2008 and 2014. The median radiation dose for recurrent disease was 57.6 Gy (range, 45-75.6 Gy). Patients were divided into 2 groups according to the type of RT: patients underwent RT without previous history of irradiation (n = 14) and those treated with secondary RT (reirradiation: n = 8) at the time of recurrence. RESULTS: The median follow-up period was 24.9 months (range, 4.5-66.6 months). Progression was observed in 14 patients (including 8 with loco-regional failure and 9 with distant metastases). Distant metastases were related to the RT dose (<70 Gy, P = 0.031). The 2-year loco-regional control (LRC), PFS, and overall survival (OS) rates were 74.6%, 45.1%, and 82.0%, respectively. The LRC rate was not different between the patients treated with RT for the first time and those treated with reirradiation (P = 0.101, 2-year LRC 79.5% vs. 41.7%). However, reirradiation was related to poor PFS (P = 0.022) and OS (P = 0.002). An escalated RT dose (≥70 Gy) was associated with a higher PFS (P = 0.014, 2-year PFS 63.5% vs. 20.8%). CONCLUSION: Salvage RT for locally recurrent colorectal cancer can be offered when surgery is impossible. Dose-escalated RT shows a possible benefit in reducing the risk of progression.
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Humans , Colorectal Neoplasms , Disease-Free Survival , Follow-Up Studies , Neoplasm Metastasis , Radiotherapy , Rectal Neoplasms , RecurrenceABSTRACT
Radiotherapy has an important role in the management of prostate cancer patients. It can be used as definitive treatment in place of surgery, postoperative adjuvant radiotherapy, or salvage treatment when recurrences develop after surgery. During definitive radiotherapy treatment, dose escalation can improve biochemical control but has not led to improved survival to date. Hypofractionated radiotherapy is applied for prostate cancer treatment, since prostate cancer has a low alpha/beta ratio. Contrary to theoretical expectations, hypofractionated treatment does not show improved therapeutic results and decreased toxicity, but it can reduce overall treatment time. Ongoing non-inferiority trials may assist in determining optimal hypofractionated treatment regimens. Adjuvant radiotherapy in patients with pathological T3 or positive resection margins can improve biochemical control and might increase overall survival. However, there is debate regarding the superiority of adjuvant radiotherapy over early salvage radiotherapy in high-risk patients after surgery. To address this issue, it will be necessary to wait for the results of current randomized trials.
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Humans , Prostatic Neoplasms , Proton Therapy , Radiotherapy , Radiotherapy, Adjuvant , RecurrenceABSTRACT
PURPOSE: We analyzed outcomes of patients with prostate cancer undergoing either radical retropubic prostatectomy (RRP) +/- salvage radiation or definitive radiation therapy (RT) +/- androgen deprivation. MATERIALS AND METHODS: From 2003-2010 there were 251 patients who underwent RRP and 469 patients who received RT (> or =7,560 cGy) for prostate cancer. Kaplan-Meier analysis was performed with the log-rank test to compare biochemical control (bCR), distant metastatic-free survival (DMPFS), and prostate cancer-specific survival (PCSS) between the two groups. RESULTS: The median follow-up was 70 months and 61.3% of the men were African American. For low risk disease the 6-year bCR were 90.3% for RT and 85.6% for RRP (p = 0.23) and the 6-year post-salvage bCR were 90.3% vs. 90.9%, respectively (p = 0.84). For intermediate risk disease the 6-year bCR were 82.6% for RT and 59.7% for RRP (p < 0.001) and 82.6% vs. 74.0%, respectively, after including those salvaged with RT (p = 0.06). For high risk disease, the 6-year bCR were 67.4% for RT and 41.3% for RRP (p < 0.001) and after including those salvaged with RT was 67.4% vs. 43.1%, respectively (p < 0.001). However, there were no significant differences between the two groups in regards to DMPFS or PCSS. CONCLUSION: Treatment approaches utilizing RRP +/- salvage radiation or RT +/- androgen deprivation yielded equivalent DMPFS and PCSS outcomes. Biochemical control rates, using their respective definitions, appeared equivalent or better in those who received treatment with RT.
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Humans , Male , Follow-Up Studies , Kaplan-Meier Estimate , Prostate , Prostatectomy , Prostatic NeoplasmsABSTRACT
Background and purpose: Malignant tumors often relapsed or metastasized after first-line chemotherapy and needed second-line or above treatment. We conducted this study to deifne the maximum-tolerated dose (MTD) of lobaplatin with ifxed docetaxel for Chinese patients in previously treated solid tumors. Methods:Escalating doses of lobaplatin with fixed docetaxel were administered in a modified Fibonacci sequence. The initial doses were lobapla-tin 30 mg/m2 and docetaxel 60 mg/m2, respectively. Escalating doses was 5 mg/m2. The regimen was repeated every 21 days. If no dose-limiting toxicity (DLT) was observed, the next dose level was applied. The procedures were repeated until DLT appeared. The MTD was declared to be one dose level below the level at which DLT appeared. Results:Seventeen patients received fifty-eight cycles chemotherapy at lobaplatin of levelⅠ(30mg/m2), levelⅡ(35 mg/m2)and levelⅢ(40 mg/m2). Cases of complete response (CR), partial response (PR), stable disease (SD) and progression disease (PD) for the whole group were 0, 1, 10 and 3, respectively. Response rate (RR, CR+PR) and disease control rate (DCR, CR+PR+SD) were 7.1%(1/14) and 78.6%(11/14), respectively. The most common toxicity was leukopenia. Three DLTs occurred in 3 patients in the whole group, including 2 DLTs in dose levelⅢ. We declared thus levelⅡwas MTD. Conclusion:MTD of lobaplatin in our re-search was 35 mg/m2 combined with fixed dose of docetaxel. This combination regimen was well tolerated.
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CONTEXT: Rigosertib, a potent, multi-kinase inhibitor that selectively induces mitotic arrest and apoptosis in cancer cells and is non-toxic to normal cells, is being developed for the treatment of solid tumors and hematological malignancies. AIMS: To determine the safety, doselimiting toxicities, and clinical activity of rigosertib administered by 2-, 4-, or 8-hour continuous IV infusion twice-a-week for 3 weeks out of a 4-week cycle in patients with advanced solid tumor or hematological malignancies; and to confirm the safety and tolerability of the recommended phase 2 dose (RPTD). SETTINGS AND DESIGN: Phase 1, open-label, dose-escalation study in men and women ≥18 years of age. MATERIALS AND METHODS: An escalation phase optimized the duration of infusion (2, 4, or 8 hours) of 3200 mg rigosertib twice-a-week for 3 weeks of a 4-week cycle; an expansion phase confirmed the maximum tolerated dose (MTD). STATISTICAL ANALYSIS USED: All data summaries were descriptive. PK parameters were estimated using compartmental analysis. RESULTS: 25 patients (16 male, 9 female, 26- 66 years, all Asian) were treated with rigosertib, 16 in the escalation phase; 9 in the expansion phase. MTD was determined to be 3200 mg as a 4-hour infusion and 2400 mg over 4 hours was declared to be the RPTD. Best response was stable disease in 5 of 14 evaluable patients, with a mean (range) of 90 (43-108) days. CONCLUSIONS: 2400 mg rigosertib as a 4-hour infusion was identified as the RPTD. Five patients achieved stable disease lasting 6-16 weeks.
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Adult , Aged , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacokinetics , Cohort Studies , Dose-Response Relationship, Drug , Female , Follow-Up Studies , Glycine/administration & dosage , Glycine/analogs & derivatives , Glycine/pharmacokinetics , Humans , Infusions, Intravenous , Male , Maximum Tolerated Dose , Middle Aged , Neoplasm Staging , Neoplasms/drug therapy , Neoplasms/metabolism , Neoplasms/pathology , Prognosis , Sulfones/administration & dosage , Sulfones/pharmacokinetics , Time Factors , Tissue DistributionABSTRACT
PURPOSE: To study the long-term outcomes and tolerance in our patients who received dose escalated radiotherapy in the early salvage post-prostatectomy setting. MATERIALS AND METHODS: The medical records of 54 consecutive patients who underwent radical prostatectomy subsequently followed by salvage radiation therapy (SRT) to the prostate bed between 2003-2010 were analyzed. Patients included were required to have a pre-radiation prostate specific antigen level (PSA) of 2 ng/mL or less. The median SRT dose was 70.2 Gy. Biochemical failure after salvage radiation was defined as a PSA level >0.2 ng/mL. Biochemical control and survival endpoints were analyzed using the Kaplan-Meier method. Univariate and multivariate Cox regression analysis were used to identify the potential impact of confounding factors on outcomes. RESULTS: The median pre-SRT PSA was 0.45 ng/mL and the median follow-up time was 71 months. The 4- and 7-year actuarial biochemical control rates were 75.7% and 63.2%, respectively. The actuarial 4- and 7-year distant metastasis-free survival was 93.7% and 87.0%, respectively, and the actuarial 7-year prostate cancer specific survival was 94.9%. Grade 3 late genitourinary toxicity developed in 14 patients (25.9%), while grade 4 late genitourinary toxicity developed in 2 patients (3.7%). Grade 3 late gastrointestinal toxicity developed in 1 patient (1.9%), and grade 4 late gastrointestinal toxicity developed in 1 patient (1.9%). CONCLUSION: In this series with long-term follow-up, early SRT provided outcomes and toxicity profiles similar to those reported from the three major randomized trials studying adjuvant radiation therapy.
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Humans , Follow-Up Studies , Medical Records , Prostate , Prostate-Specific Antigen , Prostatectomy , Prostatic Neoplasms , RadiotherapyABSTRACT
Objective To investigate the maximum-tolerated dose (MTD) of cisplatin in docetaxel,cisplatin,and fluorouracil (TPF) induction chemotherapy followed by intensity-modulated radiotherapy (IMRT) and concomitant chemotherapy as well as the safety and short-term efficacy of TPF induction chemotherapy in the treatment of locally advanced nasopharyngeal carcinoma (NPC).Methods Thirtythree patients with locally advanced NPC were enrolled in this trial.The MTD of cisplatin was determined by dose escalation study,and the short-term efficacy and toxicities were evaluated.Results When the doses of docetaxel and fluorouracil were 60 mg/m2 d1 and 550 mg/m2 d1-5,respectively,the MTD of cisplatin was 65 mg/m2 d1.In this regimen (repeated every 3 weeks),grade 3-4 toxicities included neutropenia (67％),febrile neutropenia (9％),diarrhea (21％),and oral mucositis (6％).Except those who experienced dose-limited toxicity,other patients completed the whole treatment schedule.After TPF induction chemotherapy,the overall response rate was 97％,and the complete response rate was 21％.Conclusions In the endemic areas of NPC,induction chemotherapy with docetaxel (60 mg/m2 d1),cisplatin (65 mg/m2 d1),and fluorouracil (550 mg/m2 d1-5),which is repeated every 3 weeks,is proved safe and effective for Asian patients with locally advanced NPC.
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Background & objectives: Since cabergoline has a long half-life and sustained occupancy of dopamine (D2) receptors in lactotrophs, its doses are slowly built up either monthly or two monthly. This possibly results in delayed normalization of serum prolactin and slow reduction in tumour size. This study was planned to assess the efficacy and safety of rapid escalation of cabergoline doses in men with macroprolactinomas. Materials: Fifteen consecutive men with macroprolactinomas underwent evaluation for anterior pituitary functions, visual fields, quality of life (QOL) score and magnetic resonance imaging (MRI), at baseline and after 6 months of cabergoline therapy. Serum prolactin and testosterone levels were assessed at monthly intervals. Cabergoline was started at a dosage of 0.5 mg twice per week and increased to 1.5 mg twice per week (3 mg ) by the third week, as 3 mg is usually considered as effective dose. Subsequent increase in doses was done as per protocol. Results: The mean age of patients at presentation was 31.7 ± 3.3 yr and duration of symptoms was 25.0 ± 3.6 months. Serum prolactin at baseline was 6249.3 ± 3259.2 μg/l with a tumour volume of 28.9 ± 8.3 cm3. Eighty six per cent of the patients had visual field defects while 53 per cent had decreased visual acuity. The mean dose of cabergoline required was 3.2 mg/wk. Symptoms improved in majority (93%) of patients after four weeks of cabergoline therapy with a dramatic fall in serum prolactin by 99 per cent from 6249.3 ± 3259.2 to 46.9 ± 14.9 μg/l and it was normalized in 93 per cent of the patients by 8.2 wk. Improvement in visual field defects was noted in all but one, after one month and there was further improvement at 6 months. All patients had >25 per cent reduction in tumour size, and 73 per cent had > 50 per cent reduction after six months of cabergoline therapy. Basal circulating testosterone levels were low in 11 (73%) patients and started improving from first month of cabergoline therapy and became normal in around half of the patients after 6 months. No major side effects were observed requiring discontinuation of cabergoline therapy. Interpretation & conclusions: Our preliminary findings show that rapid build-up of cabergoline doses increases its efficacy as well as rapidity of response in terms clinical improvement, normalization of serum prolactin and gonadal functions and reduction in tumour size, without compromising its safety in men with macroprolactinomas. Further studies with a larger sample size and control group for comparison need to be done to confirm these findings.
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Adult , Dopamine Agonists/administration & dosage , Dopamine Agonists/therapeutic use , Dose-Response Relationship, Drug , Ergolines/administration & dosage , Ergolines/therapeutic use , Humans , Male , Middle Aged , Prolactinoma/drug therapy , Quality of LifeABSTRACT
Objective To decrease radiation induced toxicities especially mucostis in patients with locally advanced nasopharyngeal carcinoma( NPC ) who underwent concurrent radiochemotherapy, the maximum tolerated dose and dose limited toxicities of capecitabine combination with cisplatin were observed. Methods From Aug 2006 to Oct 2007, 24 patients with intensity modulated radiotherapy(IMRT) and concurrent chemotherapy with capecitabine and cisplatin for nasopharyngeal carcinoma(stages Ⅲ-Ⅳ) were enrolled in this study. There were four dose-level groups of Capecitabine[625-1250 mg/(m2 ·d) , d1-14]and fixed cisplatin dose[20 mg/(m ·d) ,d1-5) ]MRI and CT scan were used for evaluation of tumor shrinkage. Treatment related toxicities were evaluated according to the common toxicity criteria( NCI-CTC Version 3.0). Results The acute side-effects include Grade 3 or Grade 4 mucosal toxicity(lasting for at least 5 d) and Grade 3 or Grade 4 non-mucosal toxicity were evaluated. Group 625 mg/m2 and Group 825 mg/m2 had none, Group 1000 mg/m2 had 6 patients and Group 1250 mg/m2 had 3 patients for mucosal toxicity, which were the main dose-limited toxicity and relevant to the dose of capecitabine apparently( P < 0. 05 ). There was also a trend of increase by the dose level of capecitabine for other toxicities. The median follow-up time for all patients was 28. 5 months. The locoregional recurrence occurred in 2 patients and distant metastasis in 2 patients. Two-year overall survival rate and locoregional control rate were 100% and 91.7%, respectively.Complete response and partialresponse were found on MRI or CT scan in patients of 29. 2% at the end of treatment and 83. 3% after three months, respectively. Conclusions The combination regimen of capecitabine and cisplatin is safe and effective according to the preliminary result. Toxicities related to radiochemotherapy for NPC were significantly associated with the dose level of chemotherapy.
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Objective To investigate the efficacy and toxicity of sorafenib dose escalation in treating patients with advanced renal cell carcinoma who progressed after rutine dosage of sorafenib.Methods Twenty-four patients with advanced renal cell carcinoma who progressed after 4-22 months' rutine sorafenib treatment(400 mg bid po.) received dose escalation therapy.Nineteen cases were male,5 were female,with the average age of 52 years.Ten cases added their doses to 600 mg bid,and 14 cases escalated to 800 mg bid.Results Four cases(16.7%) progressed after one month's treatment of sorafenib dose escalation,and quited the study.In the other 20 cases,1(4.2%) reached partial remission with a tumor shrinkage of 42.5% and 19(79.2%) maintained stable disease for more than 12 weeks.To Jul 2009,another 10 cases progressed,and the median progression free survival(PFS) for the PR and SD patients was 7 months(3-14 months).The disease control rate was 79.2%,and the median PFS was 5 months(0-14 months) for the entire group of 24 cases.Common toxicities after dose escalation of sorafenib were similar to those of rutine dosage.Although the grade of hand-foot reaction,diarrhea,fatigue,and neutropenia were more severe,no grade 4 toxicities were observed during the treatment.Grade of toxicities would decrease when the time of treatment prolonged.Conclusions Sofafenib dose escalation is a feasible and effective treatment for the patients with advanced renal cell carcinoma who failed to rutine dosage of sorafenib.The disease control rate of this therapy is relatively high.The toxicities do not increase much,and could be well tolerated by most patients.
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PURPOSE: To investigate the effects of radiation dose-escalation on the treatment outcome, complications and the other prognostic variables for glioblastoma patients treated with 3D-conformal radiotherapy (3D-CRT). MATERIALS AND METHODS: Between Jan 1997 and July 2002, a total of 75 patients with histologically proven diagnosis of glioblastoma were analyzed. The patients who had a Karnofsky Performance Score (KPS) of 60 or higher, and received at least 50 Gy of radiation to the tumor bed were eligible. All the patients were divided into two arms; Arm 1, the high-dose group was enrolled prospectively, and Arm 2, the low-dose group served as a retrospective control. Arm 1 patients received 63~70 Gy (Median 66 Gy, fraction size 1.8~2 Gy) with 3D-conformal radiotherapy, and Arm 2 received 59.4 Gy or less (Median 59.4 Gy, fraction size 1.8 Gy) with 2D-conventional radiotherapy. The Gross Tumor Volume (GTV) was defined by the surgical margin and the residual gross tumor on a contrast enhanced MRI. Surrounding edema was not included in the Clinical Target Volume (CTV) in Arm 1, so as to reduce the risk of late radiation associated complications; whereas as in Arm 2 it was included. The overall survival and progression free survival times were calculated from the date of surgery using the Kaplan-Meier method. The time to progression was measured with serial neurologic examinations and MRI or CT scans after RT completion. Acute and late toxicities were evaluated using the Radiation Therapy Oncology Group neurotoxicity scores. RESULTS: During the relatively short follow up period of 14 months, the median overall survival and progression free survival times were 15+/-1.65 and 11+/-0.95 months, respectively. There was a significantly longer survival time for the Arm 1 patients compared to those in Arm 2 (p=0.028). For Arm 1 patients, the median survival and progression free survival times were 21+/-5.03 and 12+/-1.59 months, respectively, while for Arm 2 patients they were 14+/-0.94 and 10+/-1.63 months, respectively. Especially in terms of the 2-year survival rate, the high-dose group showed a much better survival time than the low-dose group; 44.7% versus 19.2%. Upon univariate analyses, age, performance status, location of tumor, extent of surgery, tumor volume and radiation dose group were significant factors for survival. Multivariate analyses confirmed that the impact of radiation dose on survival was independent of age, performance status, extent of surgery and target volume. During the follow-up period, complications related directly with radiation, such as radionecrosis, has not been identified. CONCLUSION: Using 3D-conformal radiotherapy, which is able to reduce the radiation dose to normal tissues compared to 2D-conventional treatment, up to 70 Gy of radiation could be delivered to the GTV without significant toxicity. As an approach to intensify local treatment, the radiation dose escalation through 3D-CRT can be expected to increase the overall and progression free survival times for patients with glioblastomas.
Subject(s)
Humans , Arm , Diagnosis , Disease-Free Survival , Edema , Follow-Up Studies , Glioblastoma , Magnetic Resonance Imaging , Multivariate Analysis , Neurologic Examination , Prospective Studies , Radiotherapy , Retrospective Studies , Survival Rate , Tomography, X-Ray Computed , Treatment Outcome , Tumor BurdenABSTRACT
PURPOSE AND BACKGROUND: Korean Topiramate Study Group (KTSG) was organized to evaluate the efficacy and safety of lower dose (300 mg/day) and slower dose-titration of topiramate as add-on therapy in medically intractable partial epilepsies. METHODS: This study was a multicenter open clinical trial consisting of each 8 weeks of baseline phase, titration phase, and maintence phase. The patient should have partial epilepsies refractory to the maximally tolerable doses of one to two antiepileptic drugs and should have at least two or more episodes of clinical seizures every 4 weeks during the baseline phase. The target dose of topiramate (TPM) was 300 mg/day. TPM was started at the initial dose of 25 mg/day and increased by 25 mg/day every week until 100 mg/day was reached. Thereafter, the dose was increased by 50 mg/day every week. RESULTS: A total of 213 patients entered to the titration phase, 198 patients entered to the maintenance phase, and 182 patients finished the trial as planned. Median baseline seizure frequency was 3.7 episodes/4 weeks which was decreased to 2.1 episodes/4 weeks after the introduction of TPM. Median seizure frequency reduction rate (MSFRR) was 44.8%, responder rate was 47.6% and seizure free rate (SFR) was 9%. Adverse events (AE) occurred in 22% of patients with dizziness being the most common (10.0%). Premature withdrawl from the study due to AE occurred in 13 patients (6.1%). CONCLUSION: TPM 300 mg/day was as effective as TPM 600 mg/day and safety was markedly improved by a slower dose titration. We did not find any dose-response relationship of TPM in this study.