Shouko Komori

Definitive Chemoradiation Therapy With Docetaxel, Cisplatin, and 5-Fluorouracil (DCF-R) in Advanced Esophageal Cancer: A Phase 2 Trial (KDOG 0501-P2)

PURPOSE A previous phase 1 study suggested that definitive chemoradiation therapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) is tolerable and active in patients with advanced esophageal cancer (AEC). This phase 2 study was designed to confirm the efficacy and toxicity of DCF-R in AEC. METHODS AND MATERIALS Patients with previously untreated thoracic AEC who had T4 tumors or M1 lymph node metastasis (M1 LYM), or both, received intravenous infusions of docetaxel (35 mg/m(2)) and cisplatin (40 mg/m(2)) on day 1 and a continuous intravenous infusion of 5-fluorouracil (400 mg/m(2)/day) on days 1 to 5, every 2 weeks, plus concurrent radiation. The total radiation dose was initially 61.2 Gy but was lowered to multiple-field irradiation with 50.4 Gy to decrease esophagitis and late toxicity. Consequently, the number of cycles of DCF administered during radiation therapy was reduced from 4 to 3. The primary endpoint was the clinical complete response (cCR) rate. RESULTS Characteristics of the 42 subjects were: median age, 62 years; performance status, 0 in 14, 1 in 25, 2 in 3; TNM classification, T4M0 in 20, non-T4M1LYM in 12, T4M1LYM in 10; total scheduled radiation dose: 61.2 Gy in 12, 50.4 Gy in 30. The cCR rate was 52.4% (95% confidence interval [CI]: 37.3%-67.5%) overall, 33.3% in the 61.2-Gy group, and 60.0% in the 50.4-Gy group. The median progression-free survival was 11.1 months, and the median survival was 29.0 months with a survival rate of 43.9% at 3 years. Grade 3 or higher major toxicity consisted of leukopenia (71.4%), neutropenia (57.2%), anemia (16.7%), febrile neutropenia (38.1%), anorexia (31.0%), and esophagitis (28.6%). CONCLUSIONS DCF-R frequently caused myelosuppression and esophagitis but was highly active and suggested to be a promising regimen in AEC. On the basis of efficacy and safety, a radiation dose of 50.4 Gy is recommended for further studies of DCF-R.

Radiotherapy for patients with unresectable advanced hepatocellular carcinoma with invasion to intrahepatic large vessels: Efficacy and outcomes

To examine the efficacy and outcomes of radiotherapy (RT) in patients who have hepatocellular carcinoma with invasion to intrahepatic large vessels (IHLVs).

A Prospective Quasi-Randomized Comparison of Intraoperatively Built Custom-Linked Seeds Versus Loose Seeds for Prostate Brachytherapy

PURPOSE To compare dosimetric parameters, seed migration rates, operation times, and acute toxicities of intraoperatively built custom-linked (IBCL) seeds with those of loose seeds for prostate brachytherapy. METHODS AND MATERIALS Participants were 140 patients with low or intermediate prostate cancer prospectively allocated to an IBCL seed group (n=74) or a loose seed group (n=66), using quasirandomization (allocated by week of the month). All patients underwent prostate brachytherapy using an interactive plan technique. Computed tomography and plain radiography were performed the next day and 1 month after brachytherapy. The primary endpoint was detection of a 5% difference in dose to 90% of prostate volume on postimplant computed tomography 1 month after treatment. Seed migration was defined as a seed position >1 cm from the cluster of other seeds on radiography. A seed dropped into the seminal vesicle was also defined as a migrated seed. RESULTS Dosimetric parameters including the primary endpoint did not differ significantly between groups, but seed migration rate was significantly lower in the IBCL seed group (0%) than in the loose seed group (55%; P<.001). Mean operation time was slightly but significantly longer in the IBCL seed group (57 min) than in the loose seed group (50 min; P<.001). No significant differences in acute toxicities were seen between groups (median follow-up, 9 months). CONCLUSIONS This prospective quasirandomized control trial showed no dosimetric differences between IBCL seed and loose seed groups. However, a strong trend toward decreased postimplant seed migration was shown in the IBCL seed group.

125Iodine monotherapy for Japanese men with low- and intermediate-risk prostate cancer: outcomes after 5 years of follow-up

Data from 305 Japanese men with low-risk (n = 175) or intermediate-risk (n = 130) prostate cancer who underwent 125I monotherapy were retrospectively analyzed. Of the 305 patients, 93 received hormonal therapy for a median of 6 months (range, 1–33 months) before implantation. The prescribed dose to the prostate plus 3- to 5-mm margin was set at 145 Gy. The mean dose to 90% of the prostate volume at 1 month (D90) and the prostate volume receiving at least 100% dose at 1 month (V100) were 173.4 Gy and 95.8%, respectively. The median follow-up was 66 months (range, 12–94 months). The 5-year biochemical non-evidence of disease rate was 95.5% (low-risk, 94.2%; intermediate-risk, 97.3%). The 5-year freedom from clinical failure rate was 98.9% (low-risk, 98.9%; intermediate-risk, 99.2%).The initial prostate-specific antigen level was identified as a significant predictive factor for biochemical recurrence (P = 0.029). The late Grade 3 genitourinary toxicity rate was 2.0%. No patients displayed late gastrointestinal toxicity of Grade 3 or worse. Monotherapy with 125I showed excellent outcomes with limited morbidity for Japanese men with low- and intermediate-risk prostate cancer after 5 years of follow-up.

Catheter displacement prior to the delivery of high-dose-rate brachytherapy in the treatment of prostate cancer patients

Purpose The purpose of this work was to report measured catheter displacement prior to the delivery of high-dose-rate brachytherapy (HDR) in the treatment of prostate cancer. Material and methods Data from 30 prostate cancer patients treated with HDR brachytherapy were analyzed retrospectively. Eighteen transperineal hollow catheters were inserted under transrectal ultrasound guidance. Gold marker seeds were also placed transperineally into the base and apex of the prostate gland. Five treatment fractions of 7.5 Gy each were administered over 3 days. The patient underwent CT scanning prior to each treatment fraction. Catheter displacement was measured from the pre-treatment CT dataset reconstructed at 1.25 mm slice thickness. Results Most of catheters were displaced in the caudal direction. Variations of 18 catheters for each patient were small (standard deviations < 1 mm for all but one patient). Mean displacements relative to the apex marker were 6 ± 4 mm, 12 ± 6 mm, 12 ± 6 mm, 12 ± 6 mm, and 12 ± 6 mm from plan to 1st, 2nd, 3rd, 4th, and 5th fractions, respectively. Conclusions Our results indicate that catheter positions must be confirmed and if required, adjusted, prior to every treatment fraction for the precise treatment delivery of HDR brachytherapy, and to potentially reduce over-dosage to the bulbo-membranous urethra.

High-dose-rate brachytherapy and hypofractionated external beam radiotherapy combined with long-term hormonal therapy for high-risk and very high-risk prostate cancer: outcomes after 5-year follow-up

The purpose of this study was to report the outcomes of high-dose-rate (HDR) brachytherapy and hypofractionated external beam radiotherapy (EBRT) combined with long-term androgen deprivation therapy (ADT) for National Comprehensive Cancer Network (NCCN) criteria-defined high-risk (HR) and very high-risk (VHR) prostate cancer. Data from 178 HR (n = 96, 54%) and VHR (n = 82, 46%) prostate cancer patients who underwent 192Ir-HDR brachytherapy and hypofractionated EBRT with long-term ADT between 2003 and 2008 were retrospectively analyzed. The mean dose to 90% of the planning target volume was 6.3 Gy/fraction of HDR brachytherapy. After five fractions of HDR treatment, EBRT with 10 fractions of 3 Gy was administered. All patients initially underwent ≥6 months of neoadjuvant ADT, and adjuvant ADT was continued for 36 months after EBRT. The median follow-up was 61 months (range, 25–94 months) from the start of radiotherapy. The 5-year biochemical non-evidence of disease, freedom from clinical failure and overall survival rates were 90.6% (HR, 97.8%; VHR, 81.9%), 95.2% (HR, 97.7%; VHR, 92.1%), and 96.9% (HR, 100%; VHR, 93.3%), respectively. The highest Radiation Therapy Oncology Group-defined late genitourinary toxicities were Grade 2 in 7.3% of patients and Grade 3 in 9.6%. The highest late gastrointestinal toxicities were Grade 2 in 2.8% of patients and Grade 3 in 0%. Although the 5-year outcome of this tri-modality approach seems favorable, further follow-up is necessary to validate clinical and survival advantages of this intensive approach compared with the standard EBRT approach.

Conversion surgery after combination chemotherapy of docetaxel, cisplatin and S-1 (DCS) for far-advanced gastric cancer

PurposeA triplet regimen of docetaxel, cisplatin, and S-1(DCS) is highly effective against metastatic gastric cancer. We performed this study to clarify the safety and efficacy of surgical resection in patients with initially unresectable gastric cancer, after down-staging or disease control was achieved by DCS chemotherapy.MethodsThe subjects of this retrospective study were 31 consecutive patients with initially unresectable gastric cancer, who underwent surgical resection between October, 2006 and December, 2012, after down-staging or disease control was achieved by DCS chemotherapy. We evaluated the clinicopathological factors and clinical outcomes and assessed radiographic response based on the RECIST criteria, not by central review.ResultBefore DCS chemotherapy, 18 patients had extra-regional lymph node metastasis, 5 had liver metastasis, 8 had macroscopic peritoneal metastasis, and 8 had pancreatic head invasion. Twenty-three (74.2%) of the 31 patients underwent R0 resection. Postoperative morbidity and mortality rates were 16.1 and 0%. During chemotherapy, grade 3/4 toxicities included neutropenia (54.8%), leukopenia (32.3%), and anemia (16.1%). Median progression-free survival and median overall survival (OS) were 42.1 and 56.1 months, respectively. These results were similar for all patients, except those with locally advanced disease alone. In the multivariate analysis for OS, ypN remained an independent negative prognostic factor (p = 0.018).ConclusionSurgical resection after DCS chemotherapy for initially unresectable gastric cancer was safe and provided a reasonable R0 resection rate and good mid-term survival.

Prostate-specific antigen nadir after high-dose-rate brachytherapy predicts long-term survival outcomes in high-risk prostate cancer

Purpose To evaluate the prognostic value of prostate-specific antigen nadir (nPSA) after high-dose-rate (HDR) brachytherapy in clinically non-metastatic high-risk prostate cancer patients. Material and methods Data from 216 patients with high-risk or locally advanced prostate cancer who underwent HDR brachytherapy and external beam radiation therapy with long-term androgen deprivation therapy (ADT) between 2003 and 2008 were analyzed. The median prostate-specific antigen (PSA) level at diagnosis was 24 ng/ml (range: 3-338 ng/ml). The clinical stage was T1c-2a in 55 cases (26%), T2b-2c in 48 (22%), T3a in 75 (35%), and T3b-4 in 38 (17%). The mean dose to 90% of the planning target volume was 6.3 Gy/fraction of HDR brachytherapy. After 5 fractions, external beam radiation therapy with 10 fractions of 3 Gy was administered. All patients initially underwent neoadjuvant ADT for at least 6 months, and adjuvant ADT was continued for 36 months. The median follow-up was 7 years from the start of radiotherapy. Results The 7-year PSA relapse-free rate among patients with a post-radiotherapy nPSA level of ≤ 0.02 ng/ml was 94%, compared with 23% for patients with higher nPSA values (HR = 28.57; 95% CI: 12.04-66.66; p < 0.001). Multivariate analysis revealed that the nPSA value after radiotherapy was a significant independent predictor of biochemical failure, whereas pretreatment predictive values for worse biochemical control including higher level of initial PSA, Gleason score ≥ 8, positive biopsy core rate ≥ 67%, and T3b-T4, failed to reach independent predictor status. The 7-year cancer-specific survival rate among patients with a post-radiotherapy nPSA level of ≤ 0.02 ng/ml was 99%, compared with 82% for patients with higher nPSA values (HR = 32.25; 95% CI: 3.401-333.3; p = 0.002). Conclusions A post-radiotherapy nPSA value of ≤ 0.02 ng/ml was associated with better long-term biochemical tumor control even if patients had pretreatment predictive values for worse control.

Clinical outcomes in patients with cancer of unknown primary site treated by gastrointestinal oncologists

Abstract Objective To evaluate the clinical outcomes in patients with cancer of an unknown primary site (CUP), who were treated by gastrointestinal oncologists. Methods We retrospectively studied 29 patients with CUP who were presented at the Department of Gastroenterology, Kitasato University Hospital from October 2005 to October 2013, and were treated by the gastrointestinal oncologists. The patients were divided into two groups, namely chemotherapy group and symptomatic therapy group, and the clinical characteristics and survival times were compared. The clinical course was studied according to the histologic type (adenocarcinoma or non-adenocarcinoma), prognostic subset (favorable or unfavorable), and the presence or absence of chemotherapy. Results The chemotherapy group comprised 19 patients, and the symptomatic therapy group comprised 10 patients. The median survival time was 11 months in the chemotherapy group and 3 months in the symptomatic therapy group. Twenty-two patients had adenocarcinoma, and 7 had non-adenocarcinoma. Of the 22 patients with adenocarcinoma, 2 belonged to the favorable prognostic subset and received chemotherapy. One of these patients died of cancer at 47 months, and the other was alive and disease free at 58 months. Among the 20 patients with adenocarcinoma in the unfavorable prognostic subset, 16 received chemotherapy and had a median survival of 16 months. Seven (44%) of these patients survived for at least 21 months, and 3 patients who could receive 3 or more regimens survived for at least 46 months. Conclusion It might be appropriate for gastrointestinal oncologists to treat CUP on the basis of clinical experience, depending on the situation.

Assessment of transposed ovarian movement: how much of a safety margin should be added during pelvic radiotherapy?

Abstract The purpose of this study was to analyze transposed ovarian movement. Data from 27 patients who underwent ovarian transposition after surgical treatment for uterine cancer were retrospectively analyzed. Computed tomography (CT) images including transposed ovaries were superimposed on other CT images acquired at different times, and were matched on bony structures. Differences in ovarian position between the CT images were measured. The planning organ at risk volume (PRV) margins were calculated from the formula of the 90% reference intervals (RIs) and the 95% RI, which were defined as mean ± 1.65 standard deviation (SD) and mean ± 1.96 SD, respectively. The 90% RI in the cranial, caudal, anterior, posterior, left and right directions were 1.5, 1.5, 1.4, 1.0, 1.7 and 0.9 cm, respectively. The 95% RI in the corresponding directions were 1.5, 2.0, 1.7, 1.2, 1.9 and 1.2 cm, respectively. These data suggest that bilateral ovaries need a PRV margin of ∼2 cm in all directions. The present study suggests that a transposed ovary needs the same PRV margin as a normal ovary (∼2 cm). Even after transposition, ovaries should be kept away from the radiation field to take into consideration the degree of ovarian movement.