Takayuki Nose

High-dose-rate brachytherapy as monotherapy for localized prostate cancer: A retrospective analysis with special focus on tolerance and chronic toxicity

PURPOSE To examine retrospectively fractionated high-dose-rate brachytherapy as monotherapy for localized prostate cancer with special focus on tolerance and toxicity, especially chronic toxicity. MATERIALS AND METHODS Between May 1995 and October 2001, 43 patients with localized prostate cancer were treated with high-dose-rate brachytherapy without external beam irradiation at Osaka University Hospital. The stage was T1, T2, T3, and T4 in 8, 14, 18, and 3 patients, respectively. The adenocarcinoma was well, moderately, or poorly differentiated in 12, 16, and 15 patients, respectively. The median initial prostate-specific antigen level was 19.3 ng/mL (range 3.8-233.0). Thirty-eight patients also received hormonal therapy. Metallic needles were implanted transperineally under real-time ultrasound guidance, followed by a dose optimization program. Patients were irradiated twice daily at intervals of >6 h. A total dose of 54 Gy in nine fractions within 5 days (48 Gy in eight fractions within 5 days for the first 7 cases) was administered in one implant session. The median follow-up was 24 months (range 1-76). RESULTS Radiation Therapy Oncology Group acute toxicity of Grade 4, 2, and 1 occurred in 1 (2%), 12 (28%), and 8 (19%) patients, respectively. Five patients had late toxicity: one with rectal ulcer (Grade 2) and four with rectal bleeding (Grade 1). The volume receiving 100% of the prescribed dose showed significant correlations with the incidence of acute and chronic toxicities (p = 0.005 and p = 0.014, respectively). The 3-year actuarial overall survival, local control, and biochemical no evidence of disease rate was 94%, 100%, and 55%, respectively. The crude biochemical control rate for low, intermediate, and high-risk patients was 100% (5 of 5), 80% (8 of 10), and 61% (17 of 28), respectively. CONCLUSIONS High-dose-rate brachytherapy as monotherapy was found to be feasible and well tolerated. It showed a low chronic toxicity rate without any event of Radiation Therapy Oncology Group of Grade 3 or greater.

Needle applicator displacement during high-dose-rate interstitial brachytherapy for prostate cancer

PURPOSE To introduce an effective ambulatory technique in high-dose-rate interstitial brachytherapy (HDR-ISBT) for prostate cancer, we investigated the displacement distance using our novel calculation method. METHODS AND MATERIALS Sixty-four patients treated with HDR-ISBT as monotherapy were examined. Of these, 4, 17, and 43 patients were administered treatment doses of 38 Gy (3 days), 49 Gy (4 days), and 54 Gy (5 days), respectively. For dose administration, we used 776 flexible applicators with a removable template (ambulatory technique). Using CT images, we calculated the relative coordinates of the metal markers and applicators. From these coordinates, to analyze displacement during treatment, we measured the distance between the tip of the needle applicator and the center of gravity of the markers along the average applicator vector. RESULTS The median displacement distance for all applicators was 7 mm (range, -14 to 24), and that of each treatment schedule was 4, 6, and 9 mm for 38, 49, and 54 Gy, respectively. Of the 776 applicators, displacement of >10 mm was seen in 198 (26%) applicators and >15 mm in 57 (7%) applicators. Body height (p<0.0001) and anticoagulant usage (p<0.0001) were significant factors influencing displacement. CONCLUSIONS We investigated needle applicator displacement using our unique method. Additional cranial margins are necessary if there is no repositioning of the dwell position. CT scanning should be performed daily during treatment for checking the position of the applicator to detect and rectify the issue of displacement.

A comparison of the respiratory signals acquired by different respiratory monitoring systems used in respiratory gated radiotherapy

PURPOSE Respiratory monitoring systems are used to detect the respiratory phase of patients during the planning and administration of respiratory gated radiotherapy by using four-dimensional computed tomography (4DCT) or 4D positron-emission tomography/CT (4DPET/CT) and the linear accelerator (linac), respectively. Generally, identical respiratory monitoring systems are used for 4DCT, 4DPET/CT, and linac. However, different systems are sometimes used in combination because the accessibility of the respiratory monitoring systems may differ by manufacturer. The combined use of different respiratory monitoring systems in phase-based gating is of concern because the differences in the timing of tags (end-respiration signals algorithmically determined by the respiratory monitoring system), defined by the two systems, may result in phase differences, The purpose of this study is to estimate this difference and evaluate its effect on 4DCT data. METHODS Ten patients (seven men and three women) with a median age of 75 yr (range: 57-84 yr) were treated by gated stereotactic body radiation therapy between April and December 2009. Two types of respiratory monitoring systems--RPM (Varian Medical Systems) and AZ-733V (Anzai MEDICAL)--were placed on the abdominal surface of the patients, and the respiratory signals were acquired by both systems. The relationship between the amplitude peak and the tag obtained by each respiratory system was analyzed for each patient. Further, the 4DCT images were reconstructed by using the signals obtained from both the RPM and the AZ-733V systems, and the tumor volumes and the tumor centroid positions in the craniocaudal plane were analyzed for each patient. RESULTS The correlation factor between the respiratory signals from the RPM system and AZ-733V system was 0.990 (range: 0.940-0.994). The amplitude peak of the RPM system corresponded well with that of the AZ-733V system. The median +/- standard deviation of the phase difference for all the patients ranged from -4.3 +/- 7.1% to 3.5 +/- 2.2%. In the case of some patients, differences were noted between the two systems in the estimation of the tumor centroid position and tumor shape. CONCLUSIONS The estimation of the position of the tumor centroid and tumor shape may vary with the use of different respiratory monitoring systems. This implies that it is preferable to use the same respiratory monitoring system with 4DCT, 4DPET-CT, and linac.

Adjuvant radiotherapy after radical hysterectomy of the cervical cancer

AimTo investigate prognostic factors and complications after radical hysterectomy followed by postoperative radiotherapy for carcinoma of the uterine cervix.Patients and MethodsOne hundred twenty-eight patients with Tlb-2b carcinoma of the uterine cervix following radical hysterectomy with bilateral pelvic lymphadenectomy and postoperative radiation therapy were reviewed. Pathologic and treatment variables were assessed by multivariate analysis for local recurrence, distant metastases and cause specific survival.ResultsThe number of positive nodes (PN) in the pelvis was the strongest predictor of pelvic recurrence and distant metastases. These 2 failure patterns independently affect the cause specific survival. The 5-year cumulative local and distant failure were PN(0): 2% and 12%, PN(1–2): 23% and 25%, PN(2<): 32% and 57%, respectively (p=0.0029 and p=0.0051). The 5-year cause specific survival rates were PN(0): 90%, PN(1–2): 59% and PN(2<): 42% (p=0.0001). The most common complication was lymphedema of the foot experienced by one-half of the patients (5-year: 42%, 10-year: 49%).ConclusionThese results suggest that patients with pathologic Tlb-T2b cervix cancer with pelvic lymph node metastases are at high risk of recurrence or metastases after radical hysterectomy with pelvic lymphadenectomy and postoperative irradiation.ZusammenfassungZielUntersuchung der prognostischen Faktoren und Komplikationen der adjuvanten Radiotherapie nach radikaler Hysterektomie bei Patienten mit Zervixkarzinom.Patienten und MethodenIn dieser Studie wurden 128 Patientinnen mit Zervixkarzinom untersucht, bei denen die pathologische Untersuchung nach radikaler Hysterektomie mit gleichzeitiger bilateraler pelvischer Lymphadenektomie und postoperativer Radiotherapie die Klassifikation als Tlb-T2b-Karzinome ergab. Dabei wurden pathologische und therapeutische Parameter auf der behandelten Seite mit Hilfe der Multivarianzanalyse auf lokale Rezidive und Fernmetastasen beeinflussende Faktoren hin untersucht.ErgebnisseDie Zahl der metastatischen pelvischen Lymphknoten (PN) war der wichtigste Indikator fur die Wahrscheinlichkeit für das Auftreten von lokalen Rezidiven und Fernmetastasen, wobei beide Parameter die Überlebensrate der Grundkrankheit fast unabhängig voneinander beeinflußten. Die kumulativen Fünf-Jahres-Raten für lokale Rezidive und Fernmetastasen waren jeweils bei PN(0): 2% und 12%, PN(1–2): 23% und 25% und PN(2<): 32% und 57% (p=0,0029 und p=0,0051). Die Fünf-Jahres-Überlebensraten für die Grundkrankheit waren jeweils bei PN(0): 90%, PN(1–2): 59%, PN(2<): 42% (p=0,0001). Die häufigste Komplikation waren Lymphödeme der Füße, die bei etwa der Hälfte der Patienten auftraten (fünf Jahre: 42%, zehn Jahre: 49%).Schlußfolgerung enDiese Ergebnisse deuten darauf hin, daß bei Patientinnen mit pathologisch als Tlb-T2b klassifizierten Zervixkarzinomen mit Lymphknotenmetastasen ein hohes Risiko von Rezidiven oder Metastasen nach radikaler Hysterektomie mit pelvischer Lymphadenektomie und postoperativer Bestrahlung besteht.

Transition Zone Biopsy in the Detection of Prostate Cancer

Objective: About 25% of all prostate cancers occur in the transition zone (TZ). We analyzed the impact of 4 systematic TZ and 2 systematic apex (AP) biopsies in addition to systematic sextant biopsies in an effort to establish the diagnostic importance of early prostate cancer.Methods: One hundred and thirty patients underwent systematic transperineal multipoint prostate biopsy (biopsy of 12 sites, including 4 TZ and 2 AP biopsies).Results: Forty–one of 130 men (31.5%) had biopsy specimens positive for cancer, and cancer originated in the TZ alone in 4 of these 41 patients (9.8%). Fourteen patients underwent radical retropubic prostatectomy. We compare the pathological findings of radical prostatectomy specimens and biopsy results. Prostate cancers predicted to be stage T2c by TZ biopsy were all classified as pT2c or greater.Conclusions: Routine TZ biopsy does not substantially increase the prostate cancer detection rate; however, it can be useful in patients who require repeat biopsy.

New ambulatory implant technique of high-dose-rate interstitial brachytherapy for prostate cancer

PurposeThe aim of this study was to improve the performance status of prostate cancer patients during high-dose-rate interstitial brachytherapy (HDR-ISBT). To this end, we have developed a new ambulatory implant technique.Materials and methodsTen prostate cancer patients were treated with HDR-ISBT as monotherapy from October 2003 until March 2004. We utilized a new removable template, a flexible applicator with a nonmetallic bead and button stopper, and an inner catheter connecting the applicator and the transfer tube of the brachytherapy unit. We shortened the connector end of the flexible applicator to enable the patient to sit down and walk freely during the treatment time.ResultsAll 10 patients could walk without any support. No problem in the application was observed.ConclusionOur new ambulatory implant technique for HDR-ISBT was able to improve the performance status of prostate cancer patients.

High-dose-rate brachytherapy as monotherapy for prostate cancer: technique, rationale and perspective

High-dose-rate (HDR) brachytherapy as monotherapy is a comparatively new brachytherapy procedure for prostate cancer. Although clinical results are not yet mature enough, it is a highly promising approach in terms of potential benefits for both radiation physics and radiobiology. In this article, we describe our technique for monotherapeutic HDR prostate brachytherapy, as well as the rationale and theoretical background, with educational intent.

Late effects of post-high-dose-rate brachytherapy for oropharyngeal carcinoma: are they severer than post-low-dose-rate?

Background:Late effects by high-dose-rate (HDR) brachytherapy have been believed severer than low-dose-rate (LDR) provided tumor control was constant. Local control of oropharyngeal carcinoma with HDR at Osaka Medical Center was comparable to LDR series from Centre Alexis Vautrin (82%, 79.5%, respectively). To assess the feasibility of HDR brachytherapy, the late effects were compared.Patients and Methods:The data of 29 HDR and 24 LDR patients (median follow-up of 27 and 29.5 months, respectively; p = 0.89) were collected. The HDR schedule was 21 Gy/3.5 fractions/2 days following 46 Gy/23 fractions external beam, while 25 Gy/3 days following 50 Gy/25 fractions external beam was for LDR. Late changes were evaluated using RTOG/EORTC late morbidity scoring scheme. For subclinical late changes, mucosa chapter of Dische score was modified for brachytherapy. Scores were discussed through photos and were agreed on by authors. Late sequelae were estimated, by reviewing charts, concerning frequency, severity, and duration of mucosal damages (erosion and ulcer).Results:Late changes were of no difference (p = 0.12 for EORTC/RTOG, and p = 0.45, 0.47, 1.00, 0.12, 0.16, 0.95, 0.27, 0.21 for erythema, ulceration, edema, thinning, pallor, telangiectasia, mobility impairment of tongue/faucial pillars, respectively, of the modified Dische score). Late sequelae showed no differences (p = 0.90, 0.12, 0.40 for frequency, severity, duration, respectively, of mucosal damages).Conclusion:The late effects by HDR were not severer than by LDR. HDR oropharyngeal brachytherapy is as safe as LDR.Hintergrund:Bisher wurde angenommen, dass Spätwirkungen nach Brachytherapie mit hoher Dosisleistung (HDR) schwerwiegender sind als nach niedriger Dosisleistung (LDR), sofern die Tumorkontrolle dabei gleich war. Lokale Kontrollen von im Osaka Medical Center mit HDR behandelten Patienten mit Oropharyngealkarzinom wurden mit einer im Centre Alexis Vautrin durchgeführten Studienserie mit LDR (jeweils 82% und 79,9%) verglichen. Dabei wurden die Spätwirkungen verglichen, um die Anwendbarkeit der HDR-Brachytherapie zu ermitteln.Patienten und Methoden:Die Daten von 29 mit HDR und 24 mit LDR behandelten Patienten (durchschnittliche Beobachtungszeit jeweils 27 und 29,5 Monate (p = 0,89)) wurden gesammelt. Das HDR-Protokoll umfasste 21 Gy/3,5 Fraktionen/2 Tage, gefolgt von 46 Gy in 23 Fraktionen durch externe Bestrahlung, während für die LDR 25 Gy/3 Tage, gefolgt von 50 Gy in 25 Fraktionen durch externe Bestrahlung, eingesetzt wurden. Verzögerte Änderungen wurden mit Hilfe des RTOG/EORTC-Morbiditätspunktsystems bewertet. Für subklinische verzögerte Änderungen wurde der Mukosaabschnitt der Dische-Punktbewertung für die Brachytherapie modifiziert. Die Autoren besprachen und einigten sich auf Punktbewertungen an Hand von Fotos. Spätfolgen wurden durch Revision von Tabellen hinsichtlich Frequenz, Schwere und Dauer der Mukosaschäden abgeschätzt (Erosionen und Geschwüre).Ergebnisse:Es fanden sich keine Unterschiede bei den verzögerten Änderungen (p = 0,12 für RTOG/EORTC und p = 0,45, 0,47, 1,00, 0,12, 0,16, 0,95, 0,27 und 0,21, jeweils entsprechend der modifizierten Dische-Punktbewertung für Erythem, Ulzeration, Ödem, Verdünnung, Blässe, Teleangiektasie, Mobilitätsstörungen der Zunge/Gaumenbogen). Hinsichtlich Frequenz, Schwere und Dauer der Mukosaschäden fanden sich keine Unterschiede in den Spätfolgen (p = 0,90, 0,12, 0,40).Schlussfolgerungen:Die Spätwirkungen der HDR waren nicht schwerwiegender als die der LDR. Daher ist die oropharyngeale HDR-Brachytherapie so sicher wie die LDR.

Phase I study of concurrent chemoradiotherapy with weekly cisplatin and paclitaxel chemotherapy for locally advanced cervical carcinoma in Japanese women.

The purpose of this study was to evaluate the use of concurrent chemoradiotherapy involving weekly administration of cisplatin and paclitaxel for the treatment of locally advanced cervical carcinoma in Japanese women. Twenty Japanese patients were registered for this phase I study. Radiation therapy was performed using external irradiation and high-dose rate intracavitary irradiation of the pelvis. Chemotherapy was performed once a week until termination of the radiation therapy. The dose of cisplatin was decided as 30 mg/m2, and the initial dose of paclitaxel was set as 30 mg/m2, with a planned incremental increase of 10 mg/m2 up to 70 mg/m2. When 3 to 6 patients were registered at each dose level and dose-limiting toxicity (DLT) was noted in more than 3 patients, the dose level was assumed to be the maximum tolerated dose. Among the 20 patients, 1 patient experienced DLT during 2 courses because of dehydration and arrhythmia. In another patient, chemotherapy was discontinued after 4 courses because of a hypersensitivity reaction to paclitaxel at dose level 3. No patient experienced DLT resulting from hematologic toxicities. All patients underwent radiation therapy according to schedule without any discontinuations. A complete response was obtained in 16 patients. Based on the results obtained from this study, weekly administration of 30 mg/m2 cisplatin and 50 mg/m2 paclitaxel with concurrent chemoradiotherapy can be considered a tolerable and safe dose for the treatment of locally advanced cervical carcinoma in Japanese women.

Breast-conserving treatment after neoadjuvant chemotherapy in large breast cancer.

Several recent trials have demonstrated that neoadjuvant chemotherapy can allow more patients to successfully undergo breast-conserving treatment (BCT), and does not confer a survival disadvantage compared with standard adjuvant chemotherapy. In addition, the pathological response of primary breast tumors to neoadjuvant chemotherapy appears to be a surrogate marker for patient outcome.In our series, during the period from May 1995 to December 2000, 86 patients with tumors between 3.1 and 6.0 cm in diameter received epirubicin-based neoadjuvant chemotherapy. There were 55 (64.0%) responders and ultimately 64 patients (74.4%) were treated with BCT. The margin positive rate was 14.1% (9/64), similar to the rate after BCT for early-stage breast cancers, the largest diameter of which was smaller than 3 cm. At a median follow-up of 30 months, only 3 patients in the BCT group have developed local recurrence; the local recurrence rate appears to be comparable to that after BCT for early stage breast cancers. Long term follow-up is required, however, to establish whether this procedure is a safe alternative to mastectomy for patients with large breast cancers.