Fumiaki Isohashi

Monotherapeutic High-Dose-Rate Brachytherapy for Prostate Cancer: Five-Year Results of an Extreme Hypofractionation Regimen With 54 Gy in Nine Fractions

PURPOSE To evaluate an extreme hypofractionation regimen with 54 Gy in nine fractions provided by high-dose-rate (HDR) brachytherapy as monotherapy for prostate cancer by reporting 5-year clinical results. METHODS AND MATERIALS Between 1996 and 2005, 112 patients with localized prostate cancer were treated with HDR brachytherapy without external beam radiotherapy. Of the 112 patients, 15 were considered low risk, 29 intermediate risk, and 68 as high risk. The prescribed dose was uniformly 54 Gy in nine fractions within 5 days. Of the 112 patients, 94 also received hormonal therapy. The median follow-up time was 5.4 years. RESULTS All the patients safely completed the treatment regimen. The 5-year prostate-specific antigen (PSA) failure-free, local control, disease-free survival, and overall survival rate was 83%, 97%, 87%, and 96%, respectively. The 5-year PSA failure-free rate for low-, intermediate-, and high-risk patients was 85% (95% confidence interval, 66-100%), 93% (95% confidence interval, 83-100%), and 79% (95% confidence interval, 69-89%), respectively. The significant prognostic factors for PSA failure were the initial PSA level (p = .029) and younger age (p = .019). The maximal toxicities observed were Grade 3 using the Common Terminology Criteria for Adverse Events, version 3.0, for both acute and late toxicity (6 and 3 patients had acute and late Grade 3 toxicity, respectively). Late Grade 2 toxicity was observed in 13 patients. CONCLUSION Monotherapeutic HDR brachytherapy with an extreme hypofractionation regimen of 54 Gy in nine fractions associated with hormonal therapy was feasible, and its toxicity was acceptable. The interim tumor control rate at a median 5.4 years was promising, even for patients with locally advanced disease. This dose-fractionation scheme might be referred to by other terms, such as stereotactic body radiotherapy. Studies with longer follow-up periods and from multiple institutions are needed to confirm the efficacy of this novel approach.

Pretreatment leukocytosis is an indicator of poor prognosis in patients with cervical cancer

OBJECTIVES The aim of this study was to investigate the prognostic value of pretreatment leukocytosis in patients with cervical cancer in relation to well-established conventional risk factors. METHODS The baseline characteristics and outcome data from 536 patients treated for cervical cancer between 1996 April to 2007 March were collected and reviewed. Cox proportional hazards regression model was used to identify independent prognostic factors for overall survival. Subsequently, the prognostic significance of pretreatment WBC count was prospectively investigated in 156 patients newly diagnosed cervical cancer from 2007 April to 2010 March. RESULTS In a retrospective analysis, patients with leukocytosis (WBC ≥ 10,000/μl) showed significantly higher treatment failure rate (P < 0.0001) and shorter OS (P < 0.0001) than the patients without leukocytosis. Tumors from patients with leukocytosis showed significantly stronger immunoreactivity for G-CSF than those obtained from patients without leukocytosis. Multivariate analyses revealed that clinical stage, tumor diameter, histology, and elevated WBC count (≥ 10,000/μl) were significant prognostic factors in terms of overall survival. In a prospective investigation, patients with leukocytosis showed significantly higher treatment failure rate (P < 0.0001), shorter PFS (P < 0.0001), and higher serum G-CSF concentrations (p = 0.001) than the patients without leukocytosis. Multivariate analyses revealed that clinical stage, tumor diameter, and elevated WBC count were significant prognostic factors in terms of PFS. CONCLUSION Pretreatment leukocytosis is an independent prognostic factor in patients with cervical cancer. Our finding can be used to identify patients with poor prognosis and to design future tailored clinical trials.

CORRELATION BETWEEN DOSIMETRIC PARAMETERS AND LATE RECTAL AND URINARY TOXICITIES IN PATIENTS TREATED WITH HIGH-DOSE-RATE BRACHYTHERAPY USED AS MONOTHERAPY FOR PROSTATE CANCER

PURPOSE To evaluate the correlation between dosimetric parameters and late rectal and urinary toxicities in high-dose-rate brachytherapy (HDR-BT) used as monotherapy for prostate cancer. METHODS AND MATERIALS The data of 83 patients treated with HDR-BT alone for prostate cancer from 2001 through 2005 at Osaka University Hospital were analyzed. Median follow-up time was 36 months (range, 18-70). The total prescribed dose was 54 Gy in nine fractions over 5 days. Correlation between dosimetric parameters and late toxicities was examined. RESULTS The means of V30, V40, V50, V60, V70, D1cc, D2cc, D5cc, and D10cc of the rectum were significantly higher in 18 patients who presented with late rectal toxicity (Grades 1-3 rectal bleeding) than in the other 65 patients who did not. A significant difference was observed for D1cc-10cc but not for D5-90. The statistically most significant difference was observed for V40 and D5cc. Late rectal toxicity rate was significantly higher for patients with rectal V40 >or= 8 cc than those with the rectal V40 < 8 cc (42% vs. 8%; p < 0.001), as well as for patients with rectal D5cc >or= 27 Gy compared with those with rectal D5cc < 27 Gy (50% vs. 11%; p < 0.001). Dosimetric parameters of the urethra of 15 patients with late urinary toxicity were not significantly different from the 68 patients without toxicity. CONCLUSION Rectal V40 < 8 cc and D5cc < 27 Gy may be dose-volume constraints in HDR-BT used as monotherapy for prostate cancer.

Postoperative concurrent nedaplatin-based chemoradiotherapy improves survival in early-stage cervical cancer patients with adverse risk factors

OBJECTIVES The aim of this study was to evaluate the efficacy of postoperative nedaplatin-based concurrent chemoradiotherapy (CCRT) in patients with FIGO stage IA2-IIB cervical cancer with adverse risk factors. METHODS We retrospectively reviewed the medical records of 183 patients with early-stage cervical cancer who had undergone radical surgery between April 1997 and March 2006. Of these, 68 patients displayed high-risk prognostic factors such as positive pelvic lymph nodes, parametrial involvement, or a positive surgical margin. Fifty-seven patients demonstrated intermediate-risk prognostic factors including deep stromal invasion, capillary lymphatic space involvement, or large tumor diameter. These patients were treated postoperatively with CCRT or radiotherapy alone (RT). Fifty-eight patients showed no risk factors and, therefore, received no adjuvant therapy after surgery. The 3-year recurrence rate, progression free survival (PFS), and overall survival (OS) were compared between the treatment groups. RESULTS CCRT was significantly superior to RT alone with regard to recurrence rate, PFS, and OS in patients that displayed high-risk and intermediate-risk prognostic factors. The frequencies of acute grade 3-4 toxicities were significantly higher in patients treated with CCRT than in those treated with RT alone. However, no statistically significant difference was observed with regard to severe late toxicities. CONCLUSIONS Postoperative nedaplatin-based CCRT was safely performed and improved the prognosis of FIGO stage IA2-IIB cervical cancer patients displaying high-risk or intermediate-risk prognostic factors. This treatment can be considered as an alternative to cisplatin-based chemoradiotherapy in this patient population.

Prognostic factors for survival in patients with recurrent cervical cancer previously treated with radiotherapy.

Introduction: The aim of this study was to identify the prognostic factors and to establish a model for the prediction of life expectancy in patients with recurrent cervical cancer that had previously been treated with radiotherapy. Methods: The records of consecutive women with recurrent cervical cancer after radiotherapy were retrospectively reviewed. Primary disease, follow-up, and recurrence data were collected. Univariate and multivariate analyses of prognostic factors of survival were performed. Results: A total of 162 patients were included in our database. The median survival after recurrence was 15 months. Multivariate analysis revealed that symptom status, the site of relapse, prior chemoradiotherapy, and treatment modality were significant prognostic factors in terms of survival after recurrence. Patient survival was inversely correlated with the number of these prognostic factors. When the patients were divided into 3 prognostic groups, (low risk: patients with no poor prognostic factors; intermediate: patients with one poor prognostic factor; and high-risk: patients with more than 2 poor prognostic factors), the patients in the high-risk group had a significantly shorter survival (median, 10 months) than those with one risk factor (median, 20 months) or no risk factors (median, 36 months). Conclusions: Symptom status, the site of relapse, prior chemoradiotherapy, and treatment modality are significant prognostic factors in patients with recurrent cervical cancer that had previously been treated with radiotherapy. Our prognostic model, composed of 4 clinical variables, may enable physicians to predict survival more accurately. Abbreviations: CT - Computed tomography, PET-CT - Positron emission tomography in combination with computed tomography, ISBT - Interstitial brachytherapy, DFI - Disease-free interval

Impact of the addition of concurrent chemotherapy to pelvic radiotherapy in surgically treated stage IB1-IIB cervical cancer patients with intermediate-risk or high-risk factors: a 13-year experience.

Objectives To identify groups of patients who derive clinical benefit from postoperative adjuvant concurrent chemoradiotherapy (CCRT), we retrospectively investigated the survival outcomes of surgically treated early-stage cervical cancer patients. Methods We reviewed the medical records of 316 patients with FIGO stage IB1-IIB cervical cancer who had been treated with adjuvant radiotherapy (RT) (n = 124, RT group) or adjuvant CCRT (n = 192, CCRT group) after radical hysterectomy between January 1996 and December 2009. Of these, 187 patients displayed high-risk prognostic factors (high-risk group), and 129 displayed intermediate-risk prognostic factors (intermediate-risk group). Sixty patients with 1 intermediate-risk prognostic factor who received no adjuvant therapy were also identified and used as controls (NFT group). Survival was calculated using the Kaplan-Meier method and compared using the log-rank test. Results In the high-risk group, adjuvant CCRT was significantly superior to RT alone with regard to recurrence rate, progression-free survival (PFS), and overall survival. In the intermediate-risk group, CCRT was superior to RT with regard to recurrence rate and PFS in patents with 2 or more risk factors. Among the patients with only 1 intermediate-risk factor, although no survival benefit of CCRT over RT was observed, addition of adjuvant treatment resulted in significantly improved PFS compared with the NFT group in patients with deep stromal invasion (log-rank, P = 0.012). Conclusions Postoperative CCRT improved the prognosis of FIGO stage IB1-IIB cervical cancer patients in the high-risk group and patients who displayed 2 or more intermediate-risk factors. Patients who displayed deep stromal invasion alone also derived clinical benefit from adjuvant treatment.

Radical hysterectomy with adjuvant radiotherapy versus definitive radiotherapy alone for FIGO stage IIB cervical cancer

OBJECTIVES The aim of this study was to compare the treatment outcomes and adverse effects of radical hysterectomy followed by adjuvant radiotherapy with definitive radiotherapy alone in patients with FIGO stage IIB cervical cancer. METHODS We retrospectively reviewed the medical records of FIGO stage IIB cervical cancer patients who were treated between April 1996 and December 2009. During the study period, 95 patients were treated with radical hysterectomy, all of which received adjuvant radiotherapy (surgery-based group). In addition, 94 patients received definitive radiotherapy alone (RT-based group). The recurrence rate, progression-free survival (PFS), overall survival (OS), and treatment-related complications were compared between the two groups. RESULTS Radical hysterectomy followed by adjuvant radiotherapy resulted in comparable recurrence (44.2% versus 41.5%, p=0.77), PFS (log-rank, p=0.57), and OS rates (log-rank, p=0.41) to definitive radiotherapy alone. The frequencies of acute grade 3-4 toxicities were similar between the two groups (24.2% versus 24.5%, p=1.0), whereas the frequencies of grade 3-4 late toxicities were significantly higher in the surgery-based group than in the RT-based group (24.1% versus 10.6%, p=0.048). Cox multivariate analyses demonstrated that treatment with surgery followed by adjuvant radiotherapy was associated with an increased risk of grade 3-4 late toxicities, although the statistical significance of the difference was marginal (odds ratio 2.41, 95%CI 0.97-5.99, p=0.059). CONCLUSIONS Definitive radiotherapy was found to be a safer approach than radical hysterectomy followed by postoperative radiotherapy with less treatment-related complications and comparable survival outcomes in patients with FIGO stage IIB cervical cancer.

Concurrent Weekly Nedaplatin, External Beam Radiotherapy and High-Dose-Rate Brachytherapy in Patients with FIGO Stage IIIb Cervical Cancer: A Comparison with a Cohort Treated by Radiotherapy Alone

Objectives: The aim of this study was to evaluate whether nedaplatin-based concurrent chemoradiotherapy (CCRT) using high-dose-rate intracavitary brachytherapy (HDR-ICBT) is superior to radiotherapy (RT) alone in patients with FIGO stage IIIb cervical cancer. Methods: The records of 41 consecutive women treated either with nedaplatin-based CCRT using HDR-ICBT (n = 20) or RT alone (nonrandomized control group, n = 21) for stage IIIb cervical cancer were retrospectively reviewed. The activity and toxicity were compared between the two treatment groups. Progression-free survival (PFS) and overall survival (OS) were the main endpoints. Results: The 5-year overall survival rates in the CCRT and RT groups were 65 and 33.3%, respectively. The median OS of the CCRT and RT groups were 60 and 29 months, respectively. CCRT was significantly superior to RT alone with regard to PFS (p = 0.0015) and OS (p = 0.0364). The frequency of acute grade 3–4 toxicity was significantly higher in the CCRT group than in the RT group. However, no statistically significant difference was observed with regard to severe late toxicity. Conclusions: Nedaplatin-based concurrent chemoradiotherapy was safely performed and significantly improved the prognosis of patients with FIGO stage IIIb cervical cancer. This treatment can be considered as an alternative to cisplatin-based chemoradiotherapy in this patient population.

Postoperative whole pelvic radiotherapy plus concurrent chemotherapy versus extended-field irradiation for early-stage cervical cancer patients with multiple pelvic lymph node metastases

OBJECTIVES The aim of this study was to compare the efficacy of postoperative pelvic radiotherapy plus concurrent chemotherapy with that of extended-field irradiation (EFRT) in patients with FIGO Stage IA2-IIb cervical cancer with multiple pelvic lymph node metastases. METHODS We retrospectively reviewed the medical records of patients with FIGO Stage IA2-IIb cervical cancer who had undergone radical surgery between April 1997 and March 2008. Of these, 55 patients who demonstrated multiple pelvic lymph node metastases were treated postoperatively with pelvic radiotherapy plus concurrent chemotherapy (n=29) or EFRT (n=26). Thirty-six patients with single pelvic node metastasis were also treated postoperatively with pelvic radiotherapy plus concurrent chemotherapy. The recurrence rate, progression free survival (PFS), and overall survival (OS) were compared between the treatment groups. RESULTS Pelvic radiotherapy plus concurrent chemotherapy was significantly superior to EFRT with regard to recurrence rate (37.9% vs 69.2%, p=0.0306), PFS (log-rank, p=0.0236), and OS (log-rank, p=0.0279). When the patients were treated with pelvic radiotherapy plus concurrent chemotherapy, there was no significant difference in PFS or OS between the patients with multiple lymph node metastases and those with single node metastases. With regards to grade 3-4 acute or late toxicities, no statistically significant difference was observed between the two treatment groups. CONCLUSIONS Postoperative pelvic radiotherapy plus concurrent chemotherapy is superior to EFRT for treating patients with FIGO Stage IA2-IIb cervical cancer displaying multiple pelvic lymph node metastases.

Reirradiation using high-dose-rate interstitial brachytherapy for locally recurrent cervical cancer: a single institutional experience.

Objectives This study aimed to evaluate the effectiveness and feasibility of reirradiation using high-dose-rate interstitial brachytherapy (HDR-ISBT) in patients with recurrent cervical cancer. Methods The records of 52 consecutive women with central pelvic recurrence who were salvaged with HDR-ISBT–based reirradiation were retrospectively reviewed. Data regarding the primary disease, follow-up findings, recurrence, the treatment outcome, and toxicities were collected. Multivariate analysis was performed using the Cox proportional hazards regression model to identify predictors of the response to HDR-ISBT. Survival rate was calculated using the Kaplan-Meier method and compared using the log-rank test. Results A total of 52 patients who had been treated with HDR-ISBT–based reirradiation were included in our database. The local control rate was 76.9% (40/52), and the median postrecurrence survival period was 32 months. Grade 3 or 4 late toxicities were observed in 13 patients (25%). Multivariate analysis revealed that tumor size and the treatment-free interval were significant poor prognostic factors of postrecurrence survival. In a comparison between the patients who were salvaged with HDR-ISBT–based reirradiation (ISBT group) and those who were treated with palliative therapy alone (palliative group), we found that among the patients who displayed 0 or 1 poor prognostic factors, the patients in the ISBT group survived significantly longer than those in the palliative group. In contrast, similar survival rates were seen in both groups among the patients with 2 or more poor prognostic factors. Conclusions Reirradiation using HDR-ISBT is effective and feasible in patients with recurrent cervical cancer. Our 2-clinical variable prognostic model might enable physicians to identify patients who would not derive clinical benefit from HDR-ISBT and offer them the opportunity to receive other types of treatment.