Intensity-modulated radiation therapy with the central shielding technique for patients with uterine cervical cancer†.

We aimed to examine outcomes and toxicities of intensity-modulated radiation therapy (IMRT) with the central shielding (CS) technique for patients with uterine cervical cancer. This retrospective study included 54 patients with International Federation of Gynecology and Obstetrics IB-IVA cancer. Whole pelvic radiotherapy or extended-field radiotherapy were performed at the dose of 50.4 Gy in 28 fractions with helical tomotherapy (HT). Six patients had para-aortic lymph node metastases. The CS technique with HT was utilized after a total dose of 28.8-41.4 Gy to reduce doses to the rectum and bladder. The prescribed dose of intracavitary brachytherapy was mainly 18-24 Gy in three or four fractions at point A. Concurrent chemotherapy was used for 47 patients (87%). Median follow-up time was 56 months. Seventeen patients (31%) developed recurrence. The recurrence of the cervix was observed in two patients (4%). The 5-year rates of the locoregional control, progression-free survival (PFS) and overall survival were 79, 66 and 82%, respectively. Among several factors evaluated, histological type of adenocarcinoma was only a significantly worse prognostic factor for PFS by multivariate analysis (hazard ratio, 4.9 [95% confidence interval, 1.3-18], P = 0.018). Grade 2 or higher late toxicities were observed in nine patients (17%). Two patients (4%) each had grade 3 proctitis and grade 3 ileus, respectively. No grade 4 toxicity or treatment-related death was observed. The results suggest that IMRT with the CS technique allows a high local control without increasing the risk of complications for cervical cancer patients.

Daily irradiation versus irradiation at two- to three-day intervals in stereotactic radiotherapy for patients with 1-5 brain metastases: study protocol for a multicenter open-label randomized phase II trial.

BACKGROUND: Radiobiological daily changes within tumors are considered to be quite different between stereotactic radiotherapy (SRT) (e.g., 50 Gy in 4 fractions) and conventional radiotherapy (e.g., 60 Gy in 30 fractions). We aim to assess the optimal interval of irradiation in SRT and compare outcomes of daily irradiation with irradiation at two- to three-day intervals in SRT for patients with one to five brain metastases (BM). METHODS: This study is conducted as a multicenter open-label randomized phase II trial. Patients aged 20 or older with one to five BM, less than 3.0 cm diameter, and Karnofsky Performance Status ≥70 are eligible. A total of 70 eligible patients will be enrolled. After stratifying by the number of BMs (1, 2 vs. 3-5) and diameter of the largest tumor (< 2 cm vs. ≥ 2 cm), we randomly assigned patients (1:1) to receive daily irradiation (Arm 1), or irradiation at two- to three-day intervals (Arm 2). Both arms are performed with total dose of 27-30 Gy in 3 fractions. The primary endpoint is an intracranial local control rate, defined as intracranial local control at initially treated sites. We use a randomized phase II screening design with a two-sided α of 0∙20. The phase II trial is positive with p < 0.20. All analyses are intention to treat. This study is registered with the UMIN-clinical trials registry, number UMIN000048728. DISCUSSION: This study will provide an assessment of the impact of SRT interval on local control, survival, and toxicity for patients with 1-5 BM. The trial is ongoing and is recruiting now. TRIAL REGISTRATION: UMIN000048728. Date of registration: August 23, 2022. https://center6.umin.ac.jp/cgi-bin/ctr/ctr_view_reg.cgi?recptno=R000055515 .

Poor local control of ulcerative T1 glottic cancer treated with 2.25-Gy per fraction radiotherapy.

The Tokai Study Group for Therapeutic Radiology and Oncology (TOSTRO) started managing T1 glottic cancer using 2.25 Gy/fraction radiotherapy in 2011. The aim was to evaluate the local control (LC) rate and toxicity with 2.25-Gy radiotherapy in clinical practice and identify prognostic factors.The eligibility criteria were T1 glottic squamous cell carcinoma patients with age ≥20 years, treated with 2.25 Gy/fraction without chemotherapy between 2011 and 2017. LC rates were evaluated based on age, performance status, sex, T-category, tumor type (ulcerative or non-ulcerative), presence of anterior commissure invasion, tumor size, X-ray beam energy, and overall treatment time. Acute and late adverse events were evaluated using CTCAE version 4.0. A total of 202 patients were enrolled. The median follow-up period was 34.2 months. The 2- and 4-year LC rates were 93.8% and 93.1%, respectively. There was a significant difference in the LC rate between non-ulcerative type and ulcerative type (95.2% vs. 74.1% at 2 years, 94.4% vs. 74.1% at 4 years; p = 0.01). On univariate analysis, only tumor type was significantly correlated with a poor LC rate (hazard ratio 4.3; 95% confidence interval 1.2-15.4; p = 0.03). Acute grade 3 adverse events occurred in 17 patients. However, no late adverse events of grade 3 or higher have occurred to date. T1 glottic cancer treatment outcomes using hypofractionated radiotherapy with 2.25 Gy/fraction in clinical practice were comparable to previously reported results. However, ulcerative type tumor was associated with a poor LC rate.

The importance of choosing the right strategy to treat small cell carcinoma of the cervix: a comparative analysis of treatments.

BACKGROUND: Standard treatments for small cell carcinoma of the cervix (SCCC) have not been established. In this study, we aimed to estimate the optimal treatment strategy for SCCC. METHODS: This was a multicenter retrospective study. Medical records of patients with pathologically proven SCCC treated between 2003 and 2016 were retrospectively analyzed. Overall survival (OS) was plotted using the Kaplan-Meier method. Log-rank tests and Cox regression analysis were used to assess the differences in survival according to stage, treatment strategy, and chemotherapy regimen. RESULTS: Data of 78 patients were collected, and after excluding patients without immunohistopathological staining, 65 patients were evaluated. The median age of the included patients was 47 (range: 24-83) years. The numbers of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stages I-IIA, IIB-IVA, IVB were 23 (35%), 34 (52%), and 8 (12%), respectively. Of 53 patients who had undergone chemotherapy, 35 and 18 received SCCC and non-SCCC regimens as their first-line chemotherapy regimen, respectively. The 5-year OS for all patients was 49%, while for patients with FIGO stages I-IIA, IIB-IVA, IVB, it was 60, 50, and 0%, respectively. The 5-year OS rates for patients who underwent treatment with SCCC versus non-SCCC regimens were 59 and 13% (p < 0.01), respectively. This trend was pronounced in locally advanced stages. Multivariate analysis showed that FIGO IVB at initial diagnosis was a significant prognostic factor in all patients. Among the 53 patients who received chemotherapy, the SCCC regimen was associated with significantly better 5-year OS in both the uni- and multivariate analyses. CONCLUSION: Our results suggest that the application of an SCCC regimen such as EP or IP as first-line chemotherapy for patients with locally advanced SCCC may play a key role in OS. These findings need to be validated in future nationwide, prospective clinical studies.

A multicenter survey of stage T1 glottic cancer treated with radiotherapy delivered in 2.25-Gy fractions in clinical practice: An initial 5-year analysis.

The purpose of this study was to evaluate the acute and late toxicity as well as local control (LC) in T1 glottic cancer (GC) patients treated with hypofractionated radiotherapy (RT) in clinical practice. The Tokai Study Group for Therapeutic Radiology and Oncology started RT treatment with a dose of 2.25 Gy for T1 GC in 2011. Ten institutions combined data from 104 patients with T1 squamous cell carcinoma between 2011 and 2015. In total, 104 patients with T1 GC were irradiated with a standard radiation dose of 63 Gy in 28 fractions.The median follow-up duration was 18 (3.7-49.5) months. Acute grade 3 adverse events were observed in 7 patients, with 4 patients (5%) having dermatitis and 3 patients (4%) having mucositis. Late adverse events above grade 3 were not observed. Two patients developed local recurrence. The rates of acute adverse events in the present study were comparable to those in previous studies that have used 2 Gy fractions of RT.

Retrospective case series of 15 patients treated with chemoradiation using 5-FU and nedaplatin for gynecological malignancy: with regard to hemotoxicity.

We conducted a retrospective comparison of the hemotoxicity of the sequential administration of 5-Fluorouracil (5-FU) prior to Nedaplatin (NDP) (FN therapy) and that of its reverse sequence (NF therapy) for gynecological malignancy. From February 2002 to November 2004, a total of 15 gynecological malignancy patients were treated with radiation therapy combined with NDP and 5-FU. Of these 15 patients, 5 were treated with NF therapy, and 10 were treated with FN therapy. No significant differences were detected between the FN and NF groups with regard to white blood cell count (WBC), hemoglobin level (Hb), and platelet count. The results of this study do not show that the FN group has a lesser degree of hemotoxicity than the NF group.

Multi-institutional analysis of early glottic cancer from 2000 to 2005.

BACKGROUND: The purpose of this study is to analyze the outcome of patients with early glottic cancer (GC) treated with radiotherapy (RT) with or without chemotherapy at 10 institutions in the Tokai District, Japan. METHODS: Ten institutions combined data from 279 patients with T1-T2 GC treated with RT with or without chemotherapy between 2000 and 2005. The overall survival rate, disease-specific survival rate, and local control rate were evaluated in 270 patients, except for incomplete cases due to issues such as discontinuation, using the method of Kaplan-Meier and compared using the log-rank test. Results were considered statistically significant at the level of p < 0.05. RESULTS: For 122 patients, the tumors were classified as T1a, while 64 patients had T1b tumors, and 84 patients had T2 tumors. In three cases of T1 tumors, the subtype was unknown. Combined chemoradiotherapy (CRT) was administered during each stage, and various chemotherapy drugs and regimens were used. The median follow-up period was 55.4 months. The 5-year LC rates for T1a, Tb, and T2 tumors in all patients were 87.9%, 82.7%, and 74.1%, respectively. The difference between T1a and T2 was statistically significant (p = 0.016). The 5-year LC rates for T1a, Tb, and T2 with CRT were 92.7%, 78.6%, and 80.7%, respectively, while the rates with radiation alone were 86.5%, 83.8%, and 64.4%, respectively. The difference between CRT and RT alone was not statistically significant in each stage. CONCLUSIONS: In this survey, CRT was performed for early GC at most institutions in clinical practice. Our data showed no statistical difference in the LC rates between CRT and RT alone in each stage. However, there was a tendency for the LCRs of the CRT group to be more favorable than those of the RT group in the T2-stage.

A case of cervical multicentric Castleman disease treated with intensity-modulated radiation therapy using helical tomotherapy.

Castleman disease (CD) is a rare lymphoproliferative disorder. Two clinical entities are described: a unicentric form with disease confined to a single lymph node region and a multicentric form characterized by generalized lymphadenopathy and systemic symptoms. Although surgery is regarded as standard therapy for the unicentric form, no consensus has been reached concerning the standard treatment for multicentric CD. We report here a case of cervical multicentric CD treated with intensity-modulated radiation therapy (IMRT), using helical tomotherapy to minimize xerostomia in comparison with conventional radiotherapy. A 29-year-old woman complained of neck swelling. Computed tomography showed lymphadenopathy in both sides of the neck. The patient was diagnosed with the plasma cell subtype of CD on biopsy. After initial treatment with prednisone, IMRT was planned to avoid normal structures, for example the parotid gland. The cervical lymphadenopathy shrank gradually during IMRT with 44 Gy in 22 fractions. Four years and 3 months after IMRT, regrowth of cervical lymph nodes has not been detected. The parotid function improved dramatically on quantitative salivary scintigraphy between 3 and 12 months after IMRT. Radiotherapy could be an option for multicentric CD, and IMRT is an effective means of minimizing xerostomia in head and neck lesions.

Combined chemoradiotherapy for early glottic cancer in clinical practice in Japan: analysis of 10 institutions.

AIM: To conduct a retrospective analysis regarding treatment strategies for early glottic cancer (GC) at ten institutions. PATIENTS AND METHODS: A questionnaire-based survey was used to obtain personal and medical information on patients who started radiation therapy for T1 or T2 GC between January 2000 and December 2005. RESULTS: A total of 279 patients were registered for the survey, of whom 124 patients were classified as T1a, with 65 patients as T1b and 87 patients as T2. The rates of chemoradiotherapy for T1a, T1b and T2 were 24%, 23% and 60%, respectively. A comparison of results for academic and non-academic hospitals showed statistically different rates of combination therapy for T1a (6.9% vs. 39.3%, respectively; p<0.001) and T1b (11.4% vs. 36.6%, respectively; p<0.05) but not for T2 (70.0% vs. 54.4%, respectively; p = 0.158). CONCLUSION: In clinical practice, combined chemoradiotherapy was performed for early GC at most institutions in Tokai District, Japan.