Hands-on seminar for image-guided adaptive brachytherapy and intracavitary/interstitial brachytherapy for uterine cervical cancer.

OBJECTIVE: Compared with the implementation speed of image-guided adaptive brachytherapy for uterine cervical cancer, that of intracavitary and interstitial brachytherapy is slow, possible because it requires more invasive procedure of inserting needles directly into tumours. To accelerate the implementation speed of intracavitary and interstitial brachytherapy, a first hands-on seminar for image-guided adaptive brachytherapy and intracavitary and interstitial brachytherapy for uterine cervical cancer was held on 26 November 2022, supported by Japanese Society for Radiology and Oncology. This article deals with this hands-on seminar and difference of degree of confidence of participants in starting intracavitary and interstitial brachytherapy before and after the seminar. METHODS: The seminar consisted of lectures regarding intracavitary and interstitial brachytherapy in the morning and hands-on practice of needle insertion and contouring, as well as dose calculation practice using the radiation treatment system in the evening. Prior to and following the seminar, participants completed a questionnaire asking about their level of confidence in performing intracavitary and interstitial brachytherapy, expressed between 0 and 10 (the higher the number, the stronger the confidence). RESULTS: A total of 15 physicians, six medical physicists and eight radiation technologists from 11 institutions attended the meeting. The median level of confidence before and after the seminar was 3 (range, 0-6) and 5.5 (range, 3-7), respectively, and a statistically significant improvement was observed (P<0.001). CONCLUSION: It was suggested that the hands-on seminar on intracavitary and interstitial brachytherapy for locally advanced uterine cervical cancer improved the level of confidence of the attendees and propelled their motivation, through which it is expected that the implementation of intracavitary and interstitial brachytherapy will be accelerated.

Definitive radiotherapy consisting of external beam radiotherapy without central shielding and 3D image-guided brachytherapy for patients with cervical cancer: feasibility for Japanese patients and dose-response analyses for local control in the low-dose range.

OBJECTIVE: To assess the feasibility of external beam radiotherapy without central shielding in definitive radiotherapy for Japanese patients with cervical cancer. METHODS: We retrospectively analysed the data of cervical cancer patients treated with definitive radiotherapy consisting of external beam radiotherapy without central shielding and three-dimensional-image-guided brachytherapy. RESULTS: The study included 167 patients (T1 + 2 = 108, T3 + 4 = 59) from eight Japanese institutions. For three-dimensional-image-guided brachytherapy, intra-cavitary and interstitial brachytherapy was utilized in 33 patients (20%). The median follow-up was 26.6 months (interquartile range, 20-43.2). The maximum rectal D2 (75 Gy)/bladder D2 (90 Gy) constraints were deviated by 6%/10% and 10%/5% for T1 + 2 and T3 + 4, respectively. The 2-year incidence of ≥grade 3 proctitis/cystitis was 4%/1% for T1 + 2 and 10%/2% for T3 + 4. The 2-year local progression-free survival was 89% for T1 + 2 and 82% for T3 + 4. For T1 + 2, the 2-year local progression-free survival for the high-risk clinical target volume D90 ≥ 68 Gy (indicated by receiver operating characteristic analysis; area under the curve = 0.711) was 92% versus 67% for <68 Gy (log-rank; P = 0.019). Cox multivariate analysis indicated that the high-risk clinical target volume D90 was one of independent predictors of local failure (P = 0.0006). For T3 + 4, the 2-year local progression-free survival was 87% for the high-risk clinical target volume <82 cm3 (area under the curve = 0.67) and 43% for ≥82 cm3 (P = 0.0004). Only the high-risk clinical target volume was an independent predictor of local failure (P = 0.0024). CONCLUSIONS: Definitive radiotherapy consisting of external beam radiotherapy without central shielding and three-dimensional-image-guided brachytherapy was feasible for Japanese patients with cervical cancer. Dose de-escalation from the current global standards is suggested for patients with T1 + 2 disease.

[Bleeding due to acquired factor V inhibitor successfully treated with platelet transfusion during treatment for recurrent prostate squamous cell carcinoma].

A 78-year-old man with prostate squamous cell carcinoma recurrence in his pelvis was admitted to our hospital. Rectal obstruction led to creation of an artificial anus on the transverse colon. Then, docetaxel and radiation therapies were started. A week later, severe hematuria and melena occurred. Activated partial thromboplastin time (APTT) and prothrombin time (PT) were extremely prolonged. Cross-mixing test for APTT and PT revealed an inhibitor pattern, which was diagnosed as acquired factor V inhibitor. Fresh frozen plasma and vitamin K infusions were ineffective, but platelet transfusion successfully stopped the bleeding. Platelet factor V derived from megakaryocytes may affect local hemostasis. The patient received prednisolone (PSL), and the inhibitor disappeared on day 70 and was in remission. PSL could be stopped on day 100. Later, we demonstrated APTT and PT shortening of factor V deficient plasma by the supernatant of activated platelets with collagen.

Radiotherapy for vaginal cancer: a multi-institutional survey study of the Japanese Radiation Oncology Study Group.

PURPOSE: Our aim was to assess the patterns of practice and treatment outcomes of definitive radiotherapy (RT) for vaginal cancer in Japan. MATERIALS AND METHODS: RT methods and outcomes of patients with vaginal cancer treated with definitive RT or chemoradiotherapy at 10 institutes of the Japanese Radiation Oncology Study Group between January 2000 and March 2010 were retrospectively evaluated. RESULTS: A total of 90 patients were enrolled in the study. The clinical stages were I, II, III, and IVA in 34, 36, 16, and 4 patients, respectively. Seventy patients were treated with three-dimensional conformal RT (3DCRT) and brachytherapy (BT), 12 with BT alone, and 8 with 3DCRT alone. Chemotherapy was administered to 29 patients. The 5-year overall survival and local control rates were 77 and 83% with a median follow-up period of 94 months for surviving or lost patients. The 5-year overall survival rates according to stage were 94, 71, 56, and 75% for stages I, II, III, and IVA, respectively. The 5-year local control rates according to stage were 94, 77, 74, and 75% for stages I, II, III, and IVA, respectively. Twenty-nine percent (6 of 21 patients) of local recurrences occurred between 5 and 10 years after RT. The 10-year local control rate of all patients was 71%. Significant prognostic factors for overall survival by univariate and multi-variate analyses were performance status, tumor size, and pelvic lymph node metastasis. Grade 3 late radiation morbidity of the rectum, pelvic bone, urinary bladder, and skin developed in 9% (8 of 90 patients). CONCLUSIONS: Good outcomes similar to those of cervical cancer can be achieved with definitive RT delivered by 3DCRT and/or BT for vaginal cancer. Long follow-up is necessary for a continuing risk of local recurrence after 5 years.

Minimally invasive surgery using intraoperative electron-beam radiotherapy for the treatment of soft tissue sarcoma of the extremities with tendon involvement.

BACKGROUND: When a soft tissue sarcoma (STS) is located at the distal part of an extremity and involves the tendon, a wide excision usually causes severe functional disability. We therefore developed a minimally invasive surgical technique using intraoperative electron-beam radiotherapy (IOERT) to reduce the incidence of post-operative functional disability in patients with peri-/intra-tendinous STS. We assessed the clinical outcomes of the novel minimally invasive surgery. METHODS: The study population included five patients who received treatment for distal extremity STSs. After elevating the tumor mass, including the tendon and nerve from the tumor bed with a wide margin, a lead board was inserted beneath the tumor mass to shield the normal tissue. IOERT (25-50 Gy) was then applied, and the tumor excised with care taken to maintain the continuity of the tendon. RESULTS: In a desmoid patient, local recurrence was observed outside the irradiated field. No cases of neuropathy or bone necrosis were observed. The mean limb function score was excellent in all patients. None of the high-grade sarcoma patients had local recurrence or distant metastasis. CONCLUSIONS: Although the current study is only a pilot study with a small number of patients, it shows that this minimally invasive procedure has the potential to become a standard treatment option for selected patients. TRIAL REGISTRATION: H17-250 (registered 2 November 2005) and H25-250 (modified from H17-250, registered 5 December 2013).

Comparison of therapeutic results from radiofrequency ablation and stereotactic body radiotherapy in solitary lung tumors measuring 5 cm or smaller.

BACKGROUNDS: This retrospective study was conducted to compare the clinical outcomes of radiofrequency ablation (RFA) with those of stereotactic body radiotherapy (SBRT) in patients with lung tumors. METHODS: Local tumor progression, adverse events, and overall survival were compared in patients who underwent either RFA or SBRT for a single lung tumor measuring 5 cm or smaller. This study was approved by the institutional review boards of two institutions. Informed consent was waived. RESULTS: During September 2009 to June 2012, 48 patients [30 males and 18 females, with a mean age ± standard deviation (SD) of 75.0 ± 7.5 years] underwent RFA at one institution and 47 patients (21 males and 26 females, with a mean age ± SD of 77.0 ± 7.5 years) underwent SBRT in another. The mean maximum tumor diameter ± SD was 2.0 ± 0.8 cm (range 0.6-3.9 cm) in the RFA group, and 2.1 ± 0.9 cm (range 0.8-4.7 cm, p = 0.539) in the SBRT group. The RFA and SBRT groups showed similar 3-year local tumor progression [9.6%, 95% confidence interval (CI) 3.6-23.9% vs. 7.0%, 95% CI 0.2-20.2%, p = 0.746] and overall survival rates (86.4%, 95% CI 69.2-94.3% vs. 79.6%, 95% CI 60.6-90.1%, p = 0.738). No factor significantly affected local tumor progression. A maximum tumor size of 2 cm was identified as a prognostic factor in both univariate and multivariate analyses. No death was related to treatment procedures. Major complication rates (Grade 3 adverse events) of the RFA (10.4%, 5/48) and SBRT (8.5%, 4/47, p > 0.999) groups were similar. CONCLUSION: For lung tumor patients, lung RFA provided local tumor control and survival that were similar to those achieved using SBRT, with equal safety.

Patterns of care for brachytherapy in Japan.

This study aimed to assess the current state of brachytherapy (BT) resources, practices and resident education in Japan. A nationwide survey was undertaken encompassing 177 establishments facilitating BT in 2022. Questionnaires were disseminated to each BT center, and feedback through online channels or postal correspondence was obtained. The questionnaire response rate was 90% (159/177), and every prefecture had a response in at least one center. The number of centers in each prefecture ranged from 0.6 to 3.6 (median: 1.3) per million population. The annual number of patients in each center ranged from 0 to 272 (median: 31). While most prefectures provided intracavitary (IC) BT for gynecological cancers and interstitial (IS) BT for prostate cancer, only one-third of the prefectures provided IS BT for cancer sites other than the prostate. The institutional image-guided BT implementation rate was 71%. IC and IS BT was performed for 15.4% of IC BT cases of gynecological cancer. Only 47% of the BT training centers answered that they could provide adequate training in BT for residents. The most common reason for this finding was the insufficient number of patients in each center. The results show that, although BT has achieved uniformity in terms of facility penetration, new technologies are not yet widespread enough. Furthermore, IS BT, which requires advanced skills, is limited to a few BT centers, and considerable number of BT training centers do not have sufficient caseloads to provide the necessary experience for their residents.

Intratumor hemodynamics using contrast-enhanced MRI in intra-arterial chemotherapy for head and neck cancer.

OBJECTIVE: The objectives of the study were to estimate the perfusion of tumors by drugs used in intra-arterial chemotherapy for head and neck cancer with magnetic resonance imaging and to establish the factors involved in determining the optimal dose. STUDY DESIGN: Contrast agent was administered intra-arterially into either the lingual or maxillary artery in 43 patients. Triple-phase continuous fast spin echo magnetic resonance imaging was performed. Changes in blood water longitudinal relaxation rate (⊿R1) were measured in relation to imaging phase, type of artery, measurement site, and tumor size. RESULTS: ⊿R1 was significantly higher at the tumor margin than at the center for both arteries, except in the first phase for the lingual artery. ⊿R1 was greatest in the third phase for the lingual artery and in the second phase for the maxillary artery. For both arteries, as the tumor size increased, there was a significant decrease in ⊿R1 at the center of the tumor compared with the margin. CONCLUSIONS: The factors associated with ⊿R1 were imaging phase, type of artery, measurement site, and tumor size. When determining a drug's optimal dose, the type of artery and tumor size must be taken into consideration.

Japanese Society for Radiation Oncology Consensus Guidelines of combined intracavitary and interstitial brachytherapy for gynecological cancers.

It has been postulated that the combination of intracavitary and interstitial brachytherapy (IC/IS) is effective and safe for large and irregularly shaped uterine cervical cancer patients. However, due to its invasiveness compared to conventional intracavitary brachytherapy (ICBT), it has to be said that the implementation speed of IC/IS is slow. Until now, there have been no guidelines for required equipment, human resources, and procedural guide focusing solely on IC/IS. The purpose of this guideline is to provide radiation oncologists and medical physicists who wish to start IC/IS with practical and comprehensive guidance for a safe IC/IS introduction and to help accelerate the spread of the utilization of IC/IS nationwide. This is the English translation of the Japanese IC/IS Guidelines, and it was created in an effort to share the Japanese approach to the management of locally advanced uterine cervical cancer worldwide.

Initial Experience of Intra-Arterial Chemotherapy Using a Novel External Carotid Arterial Sheath System Combined with Radiotherapy and Systemic Chemotherapy for Locally Advanced Tongue Cancer.

We retrospectively evaluated the safety and effectiveness of an external carotid arterial sheath (ECAS) for intra-arterial chemotherapy (IACT) for locally advanced tongue cancer. Thirty-one patients with the Union for International Cancer Control's 8th TNM stage III-IV tongue cancer underwent IACT using the ECAS combined with RT and systemic chemotherapy with either cisplatin and fluorouracil (FP) or docetaxel, cisplatin, and fluorouracil (TPF) between October 2015 and February 2021. The ECAS was inserted retrogradely via the superficial temporal artery, and the tip was placed in the external carotid artery between the maxillary and facial arteries. A microcatheter was inserted into each tumor-feeding artery through the ECAS under fluoroscopy, wherein cisplatin 50 mg/m2 was administered. IACT was performed weekly with neutralization using sodium thiosulfate. Complete response of the primary lesion was achieved in 28/31 (90%) patients. The median follow-up for all patients was 39 months. The 3-year overall survival, progression-free survival, and local control rates were 81.6%, 74.2%, and 83.4%, respectively. Grade 3 and greater toxicities included oral mucositis (45%), neutropenia (39%), nausea (13%), anemia (10%), thrombocytopenia (10%), dry mouth (10%), and fever (3%). There were no severe complications associated with IACT. In conclusion, the ECAS is feasible and effective for locally advanced tongue cancer.

Prediction of out-of-field recurrence after chemoradiotherapy for cervical cancer using a combination model of clinical parameters and magnetic resonance imaging radiomics: a multi-institutional study of the Japanese Radiation Oncology Study Group.

We retrospectively assessed whether magnetic resonance imaging (MRI) radiomics combined with clinical parameters can improve the predictability of out-of-field recurrence (OFR) of cervical cancer after chemoradiotherapy. The data set was collected from 204 patients with stage IIB (FIGO: International Federation of Gynecology and Obstetrics 2008) cervical cancer who underwent chemoradiotherapy at 14 Japanese institutes. Of these, 180 patients were finally included for analysis. OFR-free survival was calculated using the Kaplan-Meier method, and the statistical significance of clinicopathological parameters for the OFR-free survival was evaluated using the log-rank test and Cox proportional-hazards model. Prediction of OFR from the analysis of diffusion-weighted images (DWI) and T2-weighted images of pretreatment MRI was done using the least absolute shrinkage and selection operator (LASSO) model for engineering image feature extraction. The accuracy of prediction was evaluated by 5-fold cross-validation of the receiver operating characteristic (ROC) analysis. Para-aortic lymph node metastasis (p = 0.003) was a significant prognostic factor in univariate and multivariate analyses. ROC analysis showed an area under the curve (AUC) of 0.709 in predicting OFR using the pretreatment status of para-aortic lymph node metastasis, 0.667 using the LASSO model for DWIs and 0.602 using T2 weighted images. The AUC improved to 0.734 upon combining the pretreatment status of para-aortic lymph node metastasis with that from the LASSO model for DWIs. Combining MRI radiomics with clinical parameters improved the accuracy of predicting OFR after chemoradiotherapy for locally advanced cervical cancer.

Preliminary results of reduced myocardial blood flow in the subacute phase after radiation therapy for thoracic esophageal cancer: A quantitative analysis with stress dynamic myocardial computed tomography perfusion imaging.

BACKGROUND AND PURPOSE: Late adverse cardiac events after radiation therapy (RT) for thoracic malignancies are known, but the underlying mechanisms are poorly understood. This study aimed to determine the radiation dose that can cause MBF alterations in the subacute phase after RT for thoracic esophageal cancer using stress dynamic myocardial computed tomography perfusion imaging (CTP). MATERIALS AND METHODS: Twenty-five patients with esophageal cancer scheduled for RT were prospectively enrolled. The quantitative analysis of MBF by CTP was performed before and 3 months after RT. The mean radiation dose and hyperemic MBF in 15 segments of the left ventricular (LV) myocardium were determined. ΔMBF was calculated in each segment as MBFafter RT - MBFbeforeRT. The myocardial segments were classified into the following 5 groups according to the mean radiation dose: group A, <10 Gy; B1, 10-15 Gy; B2, 15-20 Gy; C, 20-30 Gy; and D, >30 Gy. RESULTS: The final cohort included 22 patients who completed pre- and post-RT CTP. A one-way analysis of variance revealed a significant difference (p=0.005) in ΔMBF among the five groups of LV segments classified by the mean radiation dose. ΔMBF was significantly lower in group C (-7.7 ± 28.9 mL/min/100 g, p=0.020) and group D (-8.4 ± 34.8 mL/min/100 g, p=0.004) in comparison to ΔMBF in group A (4.9 ± 26.1 mL/min/100 g). CONCLUSIONS: This study using CTP early after RT demonstrated a significant reduction of the MBF in the LV segments with ≥20 Gy of radiation. The results might provide important insights into preventing radiotherapy-induced cardiac events.

Verification of the junctional dose for irradiation of the chest wall and supraclavicular regions under the circumstances of advanced technologies.

A single-isocenter half-beam technique is commonly used when irradiating the chest wall and supraclavicular regions in patients with high-risk breast cancer. However, several studies have reported that underdosage can occur at the junction of the chest wall and supraclavicular regions due to a "tongue-and-groove" effect. This study verified the efficacy of an open leaf technique (OL-tech) that involves placing a multileaf collimator 5 mm outside from the beam central axis to remove the effect of the multileaf collimator in a single-isocenter half-beam technique. We compared the junction doses of the OL-tech with those of a conventional technique (C-tech) in square and clinical plans, using 4 and 10 MV x-rays in the Clinac iX and 6 and 10 MV x-rays in the Trilogy accelerators (Varian Medical Systems, Palo Alto, CA). EBT3 radiochromic films were used for measurements. Measurements were performed at a depth of 3 cm when verifying field matching. The EBT3 films in the square plan indicated junction doses for the C-tech of 78.3% with the Clinac iX accelerator and 73.6% with the Trilogy accelerator. By contrast, the corresponding doses for the OL-tech were 107.2% and 99.8%, respectively. In the clinical plan, the junction doses for the C-tech were 76.5% with the Clinac iX accelerator and 72.6% with the Trilogy accelerator; the corresponding doses for the OL-tech were 108.3% and 101.7%, respectively. As with the square plan, variations in the junction dose were much smaller using the OL-tech than using the C-tech. Our results suggest that the OL-tech can be useful for improving dose homogeneity at the junction of the chest wall and supraclavicular regions.

Endobronchial brachytherapy combined with surgical procedure for synchronous multiple primary lung cancer: A case report.

The management of synchronous multiple primary lung cancer is a challenge. In this report, we describe our experience in a patient with three synchronous multiple cancers. The first lesion was completely surgically removed, the second lesion received postoperative irradiation, and the third lesion was treated with radiotherapy alone. Radiation therapies were performed using a combination of external irradiation and endobronchial brachytherapy. Endobronchial brachytherapy is an effective radiation therapy for endobronchial tumors owing to its advantage of high-dose concentration. However, adverse events (AEs) such as hemoptysis or severe bronchitis are a problem. Thus, we have developed an applicator to keep the radioactive source in the center of the bronchial lumen. A total of 28 months after treatment, the patient had not experienced any relapses or AEs. Endobronchial brachytherapy using an applicator can be an alternative treatment for cases in which surgery is expected to lead to pulmonary dysfunction.

Early alteration in apparent diffusion coefficient and tumor volume in cervical cancer treated with chemoradiotherapy or radiotherapy: Incremental prognostic value over pretreatment assessments.

PURPOSE: Our study aimed to evaluate a prognostic value of early changes in apparent diffusion coefficients (ADC) and tumor volume during treatment in patients with cervical cancer treated with chemoradiotherapy or radiotherapy, and to assess whether the early changes provided an incremental value to pre-treatment ADC and tumor volume in predicting disease recurrences. METHODS AND MATERIALS: A total of 103 patients with stage IB-IVA cervical cancer including 76 (74%) patients with stage ≥IIIA who underwent magnetic resonance imaging before and during (25 ± 4.6 days after start) the treatment were enrolled. Eighty-one patients received chemoradiotherapy and the remaining 22 had radiotherapy. Both a volumetric ADC and volume of a tumor before and during treatment were measured. %ADC increase and %Volume reduction were defined as changes in the ADCs and tumor volume before and during treatment, respectively. RESULTS: During a median follow-up of 2.7 years, 42 (41%) patients had disease recurrences. Univariate Cox regression analysis revealed that pre-treatment ADC (Hazard ratio [HR] = 2.8; p = 0.002), %ADC increase (HR = 6.8; p < 0.001), and %Volume reduction (HR = 2.7; p = 0.003) were significant predictors for disease recurrences. On multivariate analysis, %ADC increase was the only independent predictor (adjusted HR = 5.2; p < 0.001) for disease recurrences when adjusted for %Volume reduction and pre-treatment ADC. Global chi-square analysis demonstrated that %ADC increase and %Volume reduction had an additional prognostic value over pre-treatment ADC and tumor volume (p < 0.05). Kaplan-Meier curve analysis showed that both smaller %ADC increase and %Volume reduction were associated with worse prognosis in disease-free survival (log-rank, p < 0.001 and p = 0.002, respectively). CONCLUSIONS: Among patients with cervical cancer treated with chemoradiotherapy or radiotherapy, early changes in tumor ADCs and tumor volume during treatment are associated with better prognosis. %ADC increase and %Volume reduction during the treatment have an additional prognostic value for predicting tumor recurrence to pre-treatment ADC and tumor volume.

Drug concentration estimation using contrast-enhanced MRI in intra-arterial chemotherapy for head and neck cancers.

OBJECTIVE: In cases of head and neck cancer treated with intra-arterial chemotherapy, no objective indices are available for determining the distribution of anticancer drugs administered to multiple arteries. To establish such indices, noninvasive measurements of drug concentrations are required in the arterial perfusion area of each artery. In MRI, changes in 1/T1 (Δ1/T1) are correlated with the contrast agent concentration. We focused on these properties and investigated whether it is possible to estimate anticancer drug concentrations within tissue based on Δ1/T1. METHODS: We employed the fast spin echo (FSE) sequence to determine optimum imaging parameters using a phantom. Subsequently, contrast agent was administered via the lingual and external carotid arteries for seven cases of tongue cancer. Δ1/T1 were then measured in tumor and nontumor tissues. The results of this study were compared with those of a previous study in which intratumor concentrations of anticancer agent were measured in excised specimens. RESULTS: The optimum imaging parameters for the FSE was two repetition times (TR, 500 and 1000 ms). When compared with the external carotid artery administration, the lingual artery administration of contrast agent resulted in significantly higher Δ1/T1 in both tumor and nontumor tissues (2.13 and 2.62 times, respectively). The multiplying factor for the nontumor tissue and high homogeneity of the contrast agent concentration were reasonably consistent with the results of the previous study. CONCLUSION: This method can be applied to estimating intratissue concentrations of intra-arterially administered anticancer drugs, thus possibly providing useful information in determining the distribution of anticancer drugs.

Clinical value of serum biomarkers, squamous cell carcinoma antigen and apolipoprotein C-II in follow-up of patients with locally advanced cervical squamous cell carcinoma treated with radiation: A multicenter prospective cohort study.

There are currently no reliable, established serum biomarkers to predict the prognosis of radiotherapy for advanced cervical cancer. We aimed to identify serum biomarkers for survival after radiotherapy for cervical cancer. In this multicenter prospective cohort study, the usefulness of pre- and posttreatment serum protein levels of potential biomarkers, including squamous cell carcinoma antigen (SCC-Ag), apolipoprotein C-II (ApoC-II), matrix metalloproteinase (MMP)1, and MMP2, were evaluated together with clinical factors in 145 cervical cancer patients in order to determine their suitability to predict survival. Progression-free survival (PFS) was the primary endpoint, and overall survival (OS), pelvic PFS (PPFS), and distant metastasis-free survival (DMFS) were the secondary endpoints. Blood samples were collected before and 1 month after radiotherapy to measure serum biomarker levels. ApoC-II was measured using a monoclonal antibody-based enzyme-linked immunosorbent assay, which was developed for this purpose. Kaplan-Meier method, log-rank test, and univariate and multivariate Cox proportional hazards models were used for statistical analyses. In multivariate analysis, larger tumor size was independently associated with shorter PFS, OS, PPFS, and DMFS, while longer overall treatment time was independently associated with shorter PPFS. Higher pretreatment SCC-Ag (P < 0.001) was associated with shorter DMFS. Higher posttreatment SCC-Ag (P = 0.017) was also associated with shorter DMFS. Pretreatment ApoC-II was associated with PPFS in univariate analysis (P = 0.048), but not in multivariate analysis. Patients with pretreatment ApoC-II levels ≤ 25.8 µg/ml had shorter PPFS than those with pretreatment ApoC-II levels > 25.8 µg/ml (P = 0.023, log-rank test). Pre- and posttreatment serum SCC-Ag and pretreatment serum ApoC-II levels may be important biomarkers to predict survival outcomes of patients with cervical cancer after radiotherapy. Pre- and posttreatment SCC-Ag and pretreatment ApoC-II might be useful in clinical settings for screening patients to improve treatment strategies in cervical cancer.

Primary central nervous system lymphoma in Japan: changes in clinical features, treatment, and prognosis during 1985-2004.

We have conducted nationwide surveys of primary central nervous system lymphoma (PCNSL) treated since 1985. In the present study, we newly collected data between 2000 and 2004 and investigated changes in clinical features and outcome over time. A total of 739 patients with histologically proven PCNSL under going radiotherapy were analyzed. Seventeen institutions were surveyed, and data on 131 patients were collected. These data were compared with updated data that were previously obtained for 466 patients treated during 1985-1994 and 142 patients treated during 1995-1999. Recent trends toward decrease in male/female ratio, increase in aged patients, and increase in patients with multiple lesions were seen. Regarding treatment, decrease in attempts at surgical tumor removal and increases in use of systemic chemotherapy and methotrexate (MTX)-containing regimens were observed. The median survival time was 18, 29, and 24 months for patients seen during 1985-1994, 1995-1999, and 2000-2004, respectively, and the respective 5-year survival rates were 15%, 30%, and 30%. In groups seen during 1995-1999 and during 2000-2004, patients who received systemic or MTX-containing chemotherapy had better prognosis than those who did not. Multivariate analysis of all patients seen during 1985-2004 suggested the usefulness of MTX-containing chemotherapy as well as the importance of age, lactate dehydrogenase level, and tumor multiplicity as prognostic factors. Thus, this study revealed several notable changes in clinical features of PCNSL patients. The prognosis improved during the last 10 years. Advantage of radiation plus chemotherapy, especially MTX-containing chemotherapy, over radiation alone was suggested.

A comparison of two types of microcatheters used for a novel external carotid arterial sheath system for intra-arterial chemotherapy of head and neck cancer.

PURPOSE: We developed an external carotid arterial sheath (ECAS) for performing intra-arterial chemotherapy (IACT) via the superficial temporal artery for head and neck cancer. This study aimed to assess the potential of a novel microcatheter with a steerable tip inserted through the ECAS in comparison to an existing hook-type microcatheter. MATERIALS AND METHODS: The same operator used two types of microcatheters alternately for each weekly IACT session with the same patient, and the fluoroscopy time required for catheterization and the arterial selectivity of each microcatheter were compared. RESULTS: Ten patients with advanced head and neck cancer were enrolled. The steerable microcatheter significantly shortened the fluoroscopy time required for catheterization in comparison to the hook-type microcatheter (45.9 ± 4.8 vs 70.2 ± 9.8 s, p < 0.02). The arterial selectivity was equivalent [97.1%, (34/35) vs 88.6%, (31/35), p = 0.36]. No serious adverse events were observed in association with the procedure. CONCLUSION: In combination with an ECAS, the steerable microcatheter might be more useful than the hook-type microcatheter.

Long-term follow-up of intensive chemotherapy followed by reduced-dose and reduced-field irradiation for intracranial germ cell tumor.

OBJECTIVE The authors analyzed the efficacy of intensive chemotherapy followed by reduced-dose and reduced-field irradiation for intracranial germ cell tumors (GCTs) and evaluated the long-term late effects caused by chemoradiotherapy (CRT). METHODS The authors performed a retrospective study. The subjects were 24 patients who received CRT between April 1994 and April 2015. After surgery, intensive chemotherapy followed by reduced-dose and reduced-field irradiation was administered. For those with pure germinoma, who comprised the "good prognosis" group, five courses of conventional-dose chemotherapy (CDC) were administered, and radiotherapy (24 Gy) was applied to the whole ventricle. For all others, defined as the "intermediate and poor prognosis" group, two or three courses of CDC and high-dose chemotherapy were administered with peripheral blood stem cell transplantation and radiotherapy (24­30 Gy) applied to the whole ventricle or a larger field with or without local boost irradiation (20 Gy), which was applied as needed. RESULTS The median period of follow-up was 112.5 months (range 28­261 months), and the 5-/10-year overall and progression-free survival rates were 100%/83.5% and 91.3%/86.5%, respectively. The 5-/10-year overall survival rates determined based on the histological subtypes were 100%/100% for pure germinoma and 93.8%/78.7% for others, respectively. The late toxicities were as follows: endocrine disorder (33% in pure germinoma, 56% in others), involuntary movements (17% in pure germinoma, 39% in others), ear and labyrinth disorders (17% in pure germinoma, 33% in others), and psychiatric disorders (0% in pure germinoma, 33% in others). Nineteen of 24 patients underwent MRI (T2*- or susceptibility-weighted imaging) after radiotherapy, and 16 (84%) of those 19 patients had microbleeds detected, while 2 (10.5%) had radiation-induced cavernous vascular malformations detected. CONCLUSIONS Intensive chemotherapy followed by reduced-dose and reduced-field irradiation for intracranial GCTs had the same outcome as that reported in the literature, but late adverse effects after treatment were observed. Almost all of the complications were relatively mild but had the potential to lead to psychiatric disorders and intracranial hemorrhaging. ABBREVIATIONS AFP = alpha-fetoprotein; CDC = conventional-dose chemotherapy; CMB = cerebral microbleed; CRT = chemoradiotherapy; CSI = craniospinal irradiation; EP = etoposide and cisplatin; GCT = germ cell tumor; HCG = human chorionic gonadotropin; HDC = high-dose chemotherapy; ICE = ifosfamide, cisplatin, and etoposide; NGGCT = nongerminomatous GCT; OS = overall survival; PBSCT = peripheral blood stem cell transplantation; PFS = progression-free survival; RICM = radiation-induced cavernous malformation; STGC = syncytiotrophoblastic giant cell; SWI = susceptibility-weighted imaging.