Mayuka Kitaguchi

Localized Ocular Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma Treated With Radiation Therapy: A Long-Term Outcome in 86 Patients With 104 Treated Eyes

PURPOSE To evaluate the natural history, behavior of progression, prognostic factors, and treatment-related adverse effects of primary ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma (POAML). METHODS AND MATERIALS Eighty-six patients with histologically proven stage I POAML treated with radiation therapy at National Cancer Center Hospital, Tokyo between 1990 and 2010 were retrospectively reviewed. The median age was 56 years (range, 18-85 years). The median dose administered was 30 Gy (range, 30-46 Gy). Seventy-seven patients (90%) were treated by radiation therapy alone. RESULTS The median follow-up duration was 9 years (range, 0.9-22 years). The 5- and 10-year overall survival (OS) rates were 97.6% and 93.5%, respectively, and no patients died of lymphoma. Patients with tumor sizes ≥4 cm showed a greater risk of contralateral relapse (P=.012). Six patients with contralateral relapse were seen and treated by radiation therapy alone, and all the lesions were controlled well, with follow-up times of 3 to 12 years. There was 1 case of local relapse after radiation therapy alone, and 3 cases of relapse occurred in a distant site. Cataracts developed in 36 of the 65 eyes treated without lens shielding and in 12 of the 39 patients with lens shielding (P=.037). CONCLUSIONS The majority of patients with POAML showed behavior consistent with that of localized, indolent diseases. Thirty gray of local irradiation seems to be quite effective. The initial bilateral involvement and contralateral orbital relapses can be also controlled with radiation therapy alone. Lens shielding reduces the risk of cataract.

Vaginal tolerance of CT based image-guided high-dose rate interstitial brachytherapy for gynecological malignancies

BackgroundPurpose of this study was to identify predictors of vaginal ulcer after CT based three-dimensional image-guided high-dose-rate interstitial brachytherapy (HDR-ISBT) for gynecologic malignancies.MethodsRecords were reviewed for 44 female (14 with primary disease and 30 with recurrence) with gynecological malignancies treated with HDR-ISBT with or without external beam radiation therapy. The HDR-ISBT applicator insertion was performed with image guidance by trans-rectal ultrasound and CT.ResultsThe median clinical target volume was 35.5 ml (2.4-142.1 ml) and the median delivered dose in equivalent dose in 2 Gy fractions (EQD2) for target volume D90 was 67.7 Gy (48.8-94.2 Gy, doses of external-beam radiation therapy and brachytherapy were combined). For re-irradiation patients, median EQD2 of D2cc for rectum and bladder, D0.5cc, D1cc, D2cc, D4cc, D6cc and D8cc for vaginal wall was 91.1 Gy, 100.9 Gy, 260.3 Gy, 212.3 Gy, 170.1 Gy, 117.1 Gy, 105.2 Gy, and 94.7 Gy, respectively. For those without prior radiation therapy, median EQD2 of D2cc for rectum and bladder, D0.5cc, D1cc, D2cc, D4cc, D6cc and D8cc for vaginal wall was 56.3 Gy, 54.3 Gy, 147.4 Gy, 126.2 Gy, 108.0 Gy, 103.5 Gy, 94.7 Gy, and 80.7 Gy, respectively. Among five patients with vaginal ulcer, three had prior pelvic radiation therapy in their initial treatment and three consequently suffered from fistula formation. On univariate analysis, re-irradiation and vaginal wall D2cc in EQD2 was the clinical predictors of vaginal ulcer (p = 0.035 and p = 0.025, respectively). The ROC analysis revealed that vaginal wall D2cc is the best predictor of vaginal ulcer. The 2-year incidence rates of vaginal ulcer in the patients with vaginal wall D2cc in EQD2 equal to or less than 145 Gy and over 145 Gy were 3.7% and 23.5%, respectively, with a statistically significant difference (p = 0.026).ConclusionsRe-irradiation and vaginal D2cc is a significant predictor of vaginal ulcer after HDR-ISBT for gynecologic malignancies. Three-dimensional image-guided treatment planning should be performed to ensure adequate target coverage while minimizing vaginal D2cc in order to avoid vagina ulcer.

Expression of EpCAM and prognosis in early-stage glottic cancer treated by radiotherapy

Treatment of head and neck squamous cell carcinoma (HNSCC) often requires radiotherapy, but relapse can occur. There is, therefore, an urgent need for the identification of a predictive novel biomarker for radiosensitivity. The epithelial cell adhesion molecule (EpCAM) has been shown to promote the transformation of malignant tumors, and EpCAM may have prognostic significance, but it is not known if EpCAM determines prognosis, especially with respect to radiotherapy. Therefore, we determined the incidence of the expression of EpCAM in HNSCC and analyzed the prognostic value in patients with early‐stage glottic cancer treated with radiotherapy.

Inverse planning for combination of intracavitary and interstitial brachytherapy for locally advanced cervical cancer

The main purpose of this study was to compare three different treatment plans for locally advanced cervical cancer: (i) the inverse-planning simulated annealing (IPSA) plan for combination brachytherapy (BT) of interstitial and intracavitary brachytherapy, (ii) manual optimization based on the Manchester system for combination-BT, and (iii) the conventional Manchester system using only tandem and ovoids. This was a retrospective study of 25 consecutive implants. The high-risk clinical target volume (HR-CTV) and organs at risk were defined according to the GEC-ESTRO Working Group definitions. A dose of 6 Gy was prescribed. The uniform cost function for dose constraints was applied to all IPSA-generated plans. The coverage of the HR-CTV by IPSA for combination-BT was equivalent to that of manual optimization, and was better than that of the Manchester system using only tandem and ovoids. The mean V100 achieved by IPSA for combination-BT, manual optimization and Manchester was 96 ± 3.7%, 95 ± 5.5% and 80 ± 13.4%, respectively. The mean D100 was 483 ± 80, 487 ± 97 and 335 ± 119 cGy, respectively. The mean D90 was 677 ± 61, 681 ± 88 and 513 ± 150 cGy, respectively. IPSA resulted in significant reductions of the doses to the rectum (IPSA D2cm3: 408 ± 71 cGy vs manual optimization D2cm3: 485 ± 105 cGy; P = 0.03) and the bladder (IPSA D2cm3: 452 ± 60 cGy vs manual optimization D2cm3: 583 ± 113 cGy; P < 0.0001). In conclusion, combination-BT achieved better tumor coverage, and plans using IPSA provided significant sparing of normal tissues without compromising CTV coverage.

Radiotherapy for gastric lymphoma: a planning study of 3D conformal radiotherapy, the half-beam method, and intensity-modulated radiotherapy.

During radiotherapy for gastric lymphoma, it is difficult to protect the liver and kidneys in cases where there is considerable overlap between these organs and the target volume. This study was conducted to compare the three radiotherapy planning techniques of four-fields 3D conformal radiotherapy (3DCRT), half-field radiotherapy (the half-beam method) and intensity-modulated radiotherapy (IMRT) used to treat primary gastric lymphoma in which the planning target volume (PTV) had a large overlap with the left kidney. A total of 17 patients with gastric diffuse large B-cell lymphoma (DLBCL) were included. In DLBCL, immunochemotherapy (Rituximab + CHOP) was followed by radiotherapy of 40 Gy to the whole stomach and peri-gastric lymph nodes. 3DCRT, the half-field method, and IMRT were compared with respect to the dose–volume histogram (DVH) parameters and generalized equivalent uniform dose (gEUD) to the kidneys, liver and PTV. The mean dose and gEUD for 3DCRT was higher than for IMRT and the half-beam method in the left kidney and both kidneys. The mean dose and gEUD of the left kidney was 2117 cGy and 2224 cGy for 3DCRT, 1520 cGy and 1637 cGy for IMRT, and 1100 cGy and 1357 cGy for the half-beam method, respectively. The mean dose and gEUD of both kidneys was 1335 cGy and 1559 cGy for 3DCRT, 1184 cGy and 1311 cGy for IMRT, and 700 cGy and 937 cGy for the half-beam method, respectively. Dose–volume histograms (DVHs) of the liver revealed a larger volume was irradiated in the dose range <25 Gy with 3DCRT, while the half-beam method irradiated a larger volume of liver with the higher dose range (>25 Gy). IMRT and the half-beam method had the advantages of dose reduction for the kidneys and liver.

Outcomes of salvage high-dose-rate brachytherapy with or without external beam radiotherapy for isolated vaginal recurrence of endometrial cancer

Purpose This study was designed to retrospectively analyze outcomes of high-dose-rate (HDR) brachytherapy, with or without external beam radiotherapy (EBRT), in patients with vaginal recurrence of endometrial carcinoma, and to identify factors prognostic of patient outcomes. Material and methods The medical records of all patients who underwent HDR brachytherapy for initial recurrence in the vagina of endometrial cancer after definitive surgery between 1992 and 2014 were retrospectively reviewed. All patients underwent either intracavitary brachytherapy (ICBT) or interstitial brachytherapy (ISBT) with or without EBRT. Late toxicity was graded using the EORTC (LENT/SOMA) scale, revised in 1995. Results Thirty-seven patients were identified. The median follow-up time was 48 months (range: 6-225 months). Of these 37 patients, 23 underwent ICBT, 14 underwent ISBT, and 26 underwent EBRT. Tumor size at first examination of initial relapse was significantly larger in the ISBT than in the ICBT group. The 4-year respective overall survival (OS), local control (LC), and progression-free survival (PFS) rates in the entire cohort were 81.0%, 77.9%, and 56.8%, respectively. The interval between diagnosis of first recurrence and radiotherapy (< 3 months, ≥ 3 months) was a significant predictor of LC and PFS. OS and LC rates did not differ significantly in the ICBT and ISBT groups. Two patients experienced grade 2 rectal bleeding, and four experienced grade 2 hematuria. No grade 3 or higher late complications were observed. Conclusions Salvage HDR brachytherapy is an optimal for treating vaginal recurrence of endometrial carcinoma with acceptable morbidity. Early radiotherapy, including brachytherapy, should be considered for women who experience vaginal recurrence of endometrial cancer.

Intrafraction esophageal motion in patients with clinical T1N0 esophageal cancer

Aim To investigate the intrafraction movement of the esophagus using fiducial markers. Background Studies on intrafraction esophageal motion using the fiducial markers are scarce. Materials and methods We retrospectively analyzed patients with clinical T1N0 esophageal cancer who had received fiducial markers at our hospital between July 2007 and December 2013. Real-Time Position Management System to track the patients respiration was used, and each patient underwent three-dimensional computed tomography of the resting expiratory and inspiratory level. We used the center of the marker to calculate the distance between the expiratory and inspiratory breath-holds, which were measured with the radiotherapy treatment planning system in three directions: left-right (LR), superior-inferior (SI), and anterior-posterior (AP). The movements at each site were compared with the Kruskal-Wallis analysis and Wilcoxon rank sum test with a Bonferroni correction. Results A total of 101 patients with 201 fiducial markers were included. The upper, middle and lower thoracic positions had 40, 77, and 84 markers, respectively. The mean absolute magnitudes of the shifts (standard deviation) were 0.18 (0.19) cm, 0.68 (0.46) cm, and 0.24 (0.24) cm in the LR, SI, and AP directions, respectively. From the cumulative frequency distribution, we assumed that 0.35 cm LR, 0.8 cm SI, and 0.3 cm AP in the upper; 0.5 cm LR, 1.55 cm SI, and 0.55 cm AP in the middle; and 0.75 cm LR, 1.9 cm SI, and 0.95 cm AP in the lower thoracic esophagus covered 95% of the cases. Conclusions The internal margin based on the site of esophagus was estimated.

Long-term observations of radiation-induced creatinine clearance reduction and renal parenchymal volume atrophy

PURPOSE The kidney is a dose-limiting organ for upper abdominal radiotherapy. In this study, radiation-induced kidney injury represented by changes of creatinine clearance (Ccr) and renal parenchymal volume measured by computed tomography (CT) were evaluated by analysing dose-volume histograms (DVHs) in patients with primary gastric diffuse large B-cell lymphoma (PGDLBCL) treated with chemoradiotherapy. MATERIALS AND METHODS Thirty-eight PGDLBCL patients (seventy-six kidneys) treated with chemoradiotherapy were included in this study. At least 4 years of follow-up was required for eligibility. Patients underwent (immuno-) chemotherapy followed by radiotherapy with approximately 40Gy to the whole stomach and perigastric lymph nodes. Ccr and CT were obtained at least annually. Changes of Ccr and renal parenchymal volume before and 4years after radiotherapy were compared using DVH parameters. RESULTS Mean Ccr decreased significantly from 82.7mL/min (range, 39-124mL/min) before radiotherapy to 70.4mL/min (range, 35-109mL/min) (p=0.01) 4years after radiotherapy. Mean reduction of bilateral renal parenchymal volume was 12% (range, -5-37%) in the same time period. Ccr and renal parenchymal volume tended to lower over time more than 4years after radiotherapy. Concerning DVH analysis, V20Gy⩾26.6% and D30%⩾19Gy had a significant risk of bilateral renal atrophy of ⩾14% and reduction of the Ccr⩾20mL/min. CONCLUSION This study revealed that there was a definite relationship between DVH, renal atrophy and Ccr reduction. V20Gy<26.6% and D30%<19Gy appeared to be safe dose constraints for a Ccr reduction of <20mL/min 4years after radiotherapy.

Early-onset dropped head syndrome after radiotherapy for head and neck cancer: dose constraints for neck extensor muscles

Dropped head syndrome (DHS) is a famous but unusual late complication of multimodality treatment for head and neck carcinoma. We reported this early-onset complication and analyzed the dose to the neck extensor muscles. We examined the records of three patients with DHS after radiotherapy. The doses to the neck extensor muscles were compared between three patients with DHS and nine patients without DHS. The mean dose to the neck extensor muscles of the three patients with DHS were 58.5 Gy, 42.3 Gy and 60.9 Gy, while the dose was <50 Gy in all nine patients in the control group. The onset of this syndrome was 5 months, 6 months and 15 months. The early-onset DHS may have something to do with dose to the neck extensor muscles. The proposed dose to the neck extensor muscles might be <46 Gy (or at least <50 Gy).