Kana Takahashi

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.

Impact of concurrent chemotherapy on definitive radiotherapy for women with FIGO IIIb cervical cancer.

The purpose of this retrospective study is to investigate the impact of concurrent chemotherapy on definitive radiotherapy for the International Federation of Gynecology and Obstetrics (FIGO) IIIb cervical cancer. Between 2000 and 2009, 131 women with FIGO IIIb cervical cancer were treated by definitive radiotherapy (i.e. whole pelvic external beam radiotherapy for 40–60 Gy in 20–30 fractions with or without center shielding and concomitant high-dose rate intracavitary brachytherapy with 192-iridium remote after loading system for 6 Gy to point A of the Manchester method). The concurrent chemotherapy regimen was cisplatin (40 mg/m2/week). After a median follow-up period of 44.0 months (range 4.2–114.9 months) and 62.1 months for live patients, the five-year overall survival (OS), loco-regional control (LRC) and distant metastasis-free survival (DMFS) rates were 52.4, 80.1 and 59.9%, respectively. Univariate and multivariate analyses revealed that lack of concurrent chemotherapy was the most significant factor leading to poor prognosis for OS (HR = 2.53; 95% CI 1.44–4.47; P = 0.001) and DMFS (HR = 2.53; 95% CI 1.39–4.61; P = 0.002), but not for LRC (HR = 1.57; 95% CI 0.64–3.88; P = 0.322). The cumulative incidence rates of late rectal complications after definitive radiotherapy were not significantly different with or without concurrent chemotherapy (any grade at five years 23.9 vs 21.7%; P = 0.669). In conclusion, concurrent chemotherapy is valuable in definitive radiotherapy for Japanese women with FIGO IIIb cervical cancer.

Dosimetric variations due to interfraction organ deformation in cervical cancer brachytherapy

We quantitatively estimated dosimetric variations due to interfraction organ deformation in multi-fractionated high-dose-rate brachytherapy (HDRBT) for cervical cancer using a novel surface-based non-rigid deformable registration. As the number of consecutive HDRBT fractions increased, simple addition of dose-volume histogram parameters significantly overestimated the dose, compared with distribution-based dose addition.

Radiation therapy for primary vaginal carcinoma

Brachytherapy plays a significant role in the management of cervical cancer, but the clinical significance of brachytherapy in the management of vaginal cancer remains to be defined. Thus, a single institutional experience in the treatment of primary invasive vaginal carcinoma was reviewed to define the role of brachytherapy. We retrospectively reviewed the charts of 36 patients with primary vaginal carcinoma who received definitive radiotherapy between 1992 and 2010. The treatment modalities included high-dose-rate intracavitary brachytherapy alone (HDR-ICBT; two patients), external beam radiation therapy alone (EBRT; 14 patients), a combination of EBRT and HDR-ICBT (10 patients), or high-dose-rate interstitial brachytherapy (HDR-ISBT; 10 patients). The median follow-up was 35.2 months. The 2-year local control rate (LCR), disease-free survival (DFS), and overall survival (OS) were 68.8%, 55.3% and 73.9%, respectively. The 2-year LCR for Stage I, II, III and IV was 100%, 87.5%, 51.5% and 0%, respectively (P = 0.007). In subgroup analysis consisting only of T2–T3 disease, the use of HDR-ISBT showed marginal significance for favorable 5-year LCR (88.9% vs 46.9%, P = 0.064). One patient each developed Grade 2 proctitis, Grade 2 cystitis, and a vaginal ulcer. We conclude that brachytherapy can play a central role in radiation therapy for primary vaginal cancer. Combining EBRT and HDR-ISBT for T2–T3 disease resulted in good local control.

The role of interstitial brachytherapy in the management of primary radiation therapy for uterine cervical cancer

Purpose The aim of this study was to report the clinical results of uterine cervical cancer patients treated by primary radiation therapy including brachytherapy, and investigate the role of interstitial brachytherapy (ISBT). Material and methods All consecutive uterine cervical cancer patients who were treated by primary radiation therapy were reviewed, and those who were treated by ISBT were further investigated for clinical outcomes and related toxicities. Results From December 2008 to October 2014, 209 consecutive uterine cervical cancer patients were treated with primary radiation therapy. Among them, 142 and 42 patients were treated by intracavitary and hybrid brachytherapy, respectively. Twenty-five patients (12%) were treated by high-dose-rate (HDR)-ISBT. Five patients with distant metastasis other than para-aortic lymph node were excluded, and 20 patients consisted of the analysis. Three-year overall survival (OS), progression-free survival (PFS), and local control (LC) rate were 44.4%, 38.9%, and 87.8%, respectively. Distant metastasis was the most frequent site of first relapse after HDR-ISBT. One and four patients experienced grade 3 and 2 rectal bleeding, one grade 2 cystitis, and two grade 2 vaginal ulcer. Conclusions Feasibility and favorable local control of interstitial brachytherapy for locally advanced cervical cancer was demonstrated through a single institutional experience with a small number of patients.

A total EQD2 greater than 85 Gy for trachea and main bronchus D2cc being associated with severe late complications after definitive endobronchial brachytherapy.

Purpose The endobronchial brachytherapy (EBBT) is an established treatment method for tumors of the tracheobronchial system, however, little is known about the tolerance dose for organ at risk (OAR) in EBBT. The purpose of this study is to analyze patients with superficial bronchial carcinoma treated with definitive EBBT, and to investigate a relationship between late complications and dose for OAR. Material and methods Endobronchial brachytherapy was performed 6 Gy per fraction for three to four fractions with or without external beam radiation therapy (EBRT). For the purpose of dosimetric analysis, the wall of the lower respiratory tract (LRT: trachea, main bronchus, and lobar bronchiole), trachea, and main bronchus (TMB) was extracted. D0.5cc, D1cc, and D2cc of LRT and TMB were calculated in each EBBT session and added together. V100, V150, and V200 of LRT were also calculated. Results Between March 2008 and April 2014, EBBT was performed in 14 patients for curative intent. The 2-year overall survival (OS), progression-free survival (PFS), and local recurrence free survival (LRFS) was 82.1%, 77.9%, and 91.7%, respectively. There was one patient with grade 5, one grade 4, and three grade 3 obstruction of trachea or bronchus. The mean EQD2 of LRT D2cc, TMB D2cc, D1cc, and D0.5cc of patients with or without late severe respiratory complications was significantly different between two groups (p = 0.018, 0.008, 0.009, and 0.013, respectively). The 2-year incidence rates of late severe complications in patients with TMB D2cc ≤ 85 Gy in EQD2 and > 85 Gy were 0% and 83.3%, respectively with a statistically significance (p = 0.014). Conclusions It was discovered that TMB D2cc > 85 Gy in EQD2 is a strong risk factor for severe late respiratory complication after EBBT.

Acute Radiation Esophagitis Caused by High-Dose Involved Field Radiotherapy with Concurrent Cisplatin and Vinorelbine for Stage III Non-small Cell Lung Cancer

Purpose of this study is to obtain dose-volume histogram (DVH) predictors and threshold values for radiation esophagitis caused by high-dose involved field radiotherapy (IFRT) with concurrent chemotherapy in patients with stage III non-small cell lung cancer (NSCLC). Thirty-two patients treated by 66 Gy/33 Fr, 72 Gy/36 Fr, and 78 Gy/39 Fr thoracic radiotherapy without elective nodal irradiation plus concurrent cisplatin and vinorelvine were reviewed. Acute radiation esophagitis was evaluated according to common terminology criteria for adverse events version 4.0, and correlations between grade 2 or worse radiation esophagitis and DVH parameters were investigated. Grade 0–1, 2, 3, and 4–5 of radiation esophagitis were seen in 11 (34.4%), 20 (62.5%), 1 (3.1%), and 0 (0%) of the patients, respectively. Multivariate analysis revealed that whole esophagus V35 is a predictor of radiation esophagitis (OR = 0.74 [95%CI; 0.60–0.91], p = 0.006). There is a significant difference (38.4% vs. 89.4%, p = 0.027) in the cumulative rates of acute esophagitis according to V35 values of more than 20% versus less. As compared with other factors concerning patient and tumor and treatment factors, V35 < 20% of the esophagus was an independent predictor (HR = 0.29 [95%CI; 0.09–0.85], p = 0.025). In conclusion, whole esophagus V35 < 20% is proposed in high-dose IFRT with concurrent chemotherapy for stage III NSCLC patients.

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.