Interstitial round needles should not be used for cervical cancer patient treated with intracavitary/ interstitial brachytherapy using a Venezia applicator : a case report.

BACKGROUND: Image-guided adaptive brachytherapy (IGABT) demonstrates an excellent local control rate and low toxicity while treating cervical cancer. For intracavitary/interstitial (IC/IS) brachytherapy (BT), several applicators are commercially available. Venezia (Elekta, Sweden), an advanced gynecological applicator, is designed for IC/IS BT for treating locally advanced cervical cancer. There are two types of interstitial needles for the Venezia applicator: the round needle and sharp needle. Generally, a round needle is safer because it has less risk of damaging the organ at risk than a sharp needle. However, there is currently no evidence to suggest that a round needle is better than a sharp needle for the Venezia applicator in IC/IS BT. Herein, we documented our experience of using both round and sharp needles with the Venezia applicator in IC/IS BT for cervical cancer. CASE PRESENTATION: A 71-year-old woman was diagnosed with clinical stage T2bN0M0 and the International Federation of Gynecology and Obstetrics stage IIB cervical squamous cell carcinoma. Definitive therapy, including a high-dose-rate BT boost, was planned using a round needle with the Venezia applicator in IC/IS BT. After inserting four interstitial round needles during the first and second BT sessions, an unexpectedly large gap (1.5 cm) was detected between the cervix and ovoid. We therefore used a sharp needle with the Venezia applicator for IC/IS BT during the third and fourth BT sessions. Three sharp needles were firmly inserted during the third and fourth BT sessions. CONCLUSIONS: The study findings suggest that the interstitial round needle should not be used for cervical cancer patients undergoing IC/IS BT using the Venezia applicator.

A novel intra pre-plan method of interstitial needle optimization for cervical cancer patients treated with Venezia applicator brachytherapy: a technical note.

Purpose: Novel hybrid Venezia applicator enables intracavitary and interstitial brachytherapy (BT) for locally advanced cervical cancer. However, the method to determine the optimal interstitial needle number, position, and depth using this applicator is unknown. Therefore, we aimed to establish a method for reliable needle optimization. Material and methods: We produced a template model of the Venezia applicator with whole needles, and acquired computed tomography (CT) images (template CT). Using this template CT as a map, clinicians could define interstitial needle's insertion route in advance. During treatment, we first placed tandem and ovoid, and acquired a CT (tandem + ovoid CT). This was fused to the template CT by matching the contour of applicators with high accuracy. Then, we determined the optimal interstitial needle number, position, and depth to fit high-risk clinical target volume (HR-CTV) and avoid organs at risk (OARs) on the fused CT (intra pre-plan). Next, we re-inserted the tandem and ovoids with interstitial needle into patient's uterus and vagina. We inserted the optimized interstitial needle using insertion tool of optimal depth immediately following the applicator insertion. Lastly, a real-time treatment planning CT was performed, followed by planning and treatment. Results: We achieved a good dose distribution of Venezia applicator BT using intra pre-plan method to optimize the number of interstitial needles, position, and depth. Conclusions: This novel intra pre-plan method of interstitial needle optimization using template CT fusion provides high reproducibility, efficiency, and safety for patients with cervical cancer treated with brachytherapy using Venezia applicator.

Persistent disturbance of consciousness with bilateral globus pallidus and substantia nigra lesions in 2 patients with severe COVID-19 pneumonia.

With an increasing number of cases of Coronavirus disease 2019 (COVID-19), various neurological complications have been reported; however, some of these have not been fully elucidated. We herein report on 2 cases in which lesions at the bilateral globus pallidus and substantia nigra were observed. The patients were a 27-year-old male and a 61-year-old female. They underwent ventilation management due to COVID-19 pneumonia with hypoxemia. However, even after the sedative had weakened, the state of consciousness disturbance was found to have continued. Brain magnetic resonance imaging was performed for both patients. From the bilateral globus pallidus to the substantia nigra of both, the fluid attenuated inversion recovery images and T2-weighted images indicated high intensity, while the diffusion-weighted image resulted in high intensity and low apparent diffusion coefficient. Regarding the 61-year-old female patient, head computed tomography also indicated low density at the bilateral globus pallidus. The patients did not show any improvement in their neurological findings while hospitalized. Although COVID-19 associated with bilateral globus pallidus and substantia nigra lesions are rare, the neurological prognosis may be poor. We believe that attention should be paid to these imaging findings at the onset of consciousness disturbance.

Smoking-induced radiation laryngeal necrosis after definitive radiotherapy alone for T1a glottic squamous cell carcinoma: A case report.

BACKGROUND: We report the case of a patient with smoking-induced radiation laryngeal necrosis (RLN) after undergoing definitive radiotherapy (RT) alone for T1a glottic squamous cell carcinoma. CASE: The patient was a 63-year-old man who had a history of heavy smoking. He quit smoking when he was diagnosed with glottic squamous cell carcinoma. The RT dose was 63 Gy, delivered in 28 fractions with the three-dimensional conventional RT technique for the larynx. After RT completion, the initial treatment response was complete response. He then underwent follow-up examinations. At 13 months after RT, the patient resumed smoking. At 2 months after resuming smoking, he had severe sore throat and hoarseness. Laryngoscopy revealed a large tumor in the glottis. Surgical excision was performed, and the patient was histologically diagnosed with RLN, as late toxicity without cancer recurrence. At 3 weeks postoperatively, the patient had dyspnea, and laryngoscopy revealed total laryngeal paralysis. Thus, he underwent an emergent tracheostomy. The administration of steroids affected RLN, and laryngeal paralysis gradually improved. CONCLUSIONS: This case suggests that smoking may have the potential to induce RLN after RT. Moreover, continuing smoking cessation is significantly important for patients with glottic cancer who receive RT. Rather than leaving smoking cessation up to the patient, it would be necessary for clinicians to actively intervene to help patients continue their effort to quit smoking.

Laminaria tent insertion in preplanning MRI for CT-based cervical cancer brachytherapy.

PURPOSE: Preplanning magnetic resonance imaging (MRI) is routinely used in image-guided adaptive brachytherapy (IGABT) for cervical cancer. However, a preplanning MRI performed without an applicator does not have good accuracy of image fusion with a planning computed tomography (CT) performed with an applicator. This study aimed to evaluate the efficacy of laminaria tent insertion during pre-planning MRI for cervical cancer brachytherapy (BT). METHODS AND MATERIALS: Sixteen patients with cervical cancer were enrolled in the study. Images obtained from a single preplanning MRI performed with a laminaria tent inserted into the cervix were fused with images from the planning CT performed with an applicator during each BT session. The alignment between the high-risk clinical target volume on MRI (HR-CTVMRI) and planning CT (HR-CTVCT) was assessed. Image fusion accuracy was classified as follows: maximum misalignment between HR-CTVMRI and HR-CTVCT <5 mm was excellent, 5-10 mm as available, and >10 mm as not available. Image fusion accuracy was reviewed by two radiation oncologists. RESULTS: Fifty-nine BT sessions were analyzed. Fusion images for 39 (66%) sessions were categorized as excellent, and those for the remaining 12 (20%) sessions were available, and 8 (14%) were not available. Complications reported after laminaria tent insertion were grade-1 fever for 5 (8%) BT sessions in 5 patients and grade-1 pain for 8 (13%) sessions in 5 patients. CONCLUSION: Laminaria tent insertion during pre-planning MRI may improve the accuracy of image fusion with planning CT and may help delineate the HR-CTV in CT-based IGABT for cervical cancer.

The 5-year outcomes of moderately hypofractionated radiotherapy (66 Gy in 22 fractions, 3 fractions per week) for localized prostate cancer: a retrospective study.

BACKGROUND: Hypofractionated radiotherapy using fewer and larger fractional doses may be more beneficial than conventional external-beam radiotherapy for localized prostate cancer. We evaluated the 5-year outcomes of moderately hypofractionated radiotherapy for localized prostate cancer. METHODS: We retrospectively evaluated 195 patients with localized prostate cancer (T1-3N0M0) who underwent intensity-modulated radiotherapy (IMRT) (66 Gy delivered in fractions of 3 Gy every other weekday) between May 2005 and December 2011. Patients received androgen deprivation therapy depending on the perceived intermediate or high risk of their disease. A prostate-specific antigen nadir +2.0 ng/ml indicated biochemical failure. We assessed toxicity using the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria, and patient-reported outcomes using the Expanded Prostate Cancer Index Composite (EPIC). RESULTS: The risk classifications (proportion) were low risk (13.8%), intermediate risk (35.9%), and high risk (50.3%). The median follow-up was 69 months. Thirteen (6.66%) patients experienced biochemical failure within a median of 40 months (interquartile range, 25-72 months). The 5-year overall survival rate and no biological evidence of disease rate were 97.7% and 92.4%, respectively. Based on the RTOG/EORTC criteria, no patient experienced acute or late toxicity of grade 3 or higher. The EPIC scores revealed significant differences in the average value of all domains (p < 0.01). At 1 month postradiotherapy completion, the general urinary and bowel domain scores had decreased, but these scores returned to baseline level by 3 months post radiotherapy. CONCLUSIONS: The moderately hypofractionated radiotherapy protocol yielded short-term satisfactory clinical outcomes with acceptable toxicity.

Intensity-modulated radiation therapy for small cell carcinoma of the prostate: A case report.

Small cell carcinomas (SCC) make up only 1% of malignancies of the prostate. Reports of several case series have described outcomes of surgery and chemotherapy for SCC of the prostate, but few reports address radiotherapy. We treated a case of SCC of the prostate with intensity-modulated radiation therapy (IMRT) consisting of 70 Gy administered in 35 fractions followed by hormonal therapy using only luteinizing hormone-releasing hormone (LH-RH) agonist. The tumor volume decreased remarkably by 4 months after IMRT. The rapid decrease in tumor size of this SCC of the prostate seemed to suggest a similar high radiosensitivity to that of SCC of the lung, but the tumor increased rapidly thereafter within the radiation fields, and pelvic lymph node metastases had developed by 24 months after IMRT. By 28 months after IMRT, multiple lung metastases developed, and the patient died of SCC of the prostate 31 months after initial diagnosis.

Multicenter Phase 2 Study of Cisplatin and 5-Fluorouracil With Concurrent Radiation Therapy as an Organ Preservation Approach in Patients With Squamous Cell Carcinoma of the Cervical Esophagus.

PURPOSE: To clarify, in a multicenter, single-arm, phase 2 study (UMIN Clinical Trials Registry no. UMIN000001439), the clinical profile of chemoradiotherapy (CRT) for cervical esophageal cancer. PATIENTS AND METHODS: Patients with operable cervical esophageal cancer, excluding candidates for endoscopic resection, were enrolled. Protocol treatment consisted of CRT and adjuvant chemotherapy (CT). First, patients received concurrent CRT with 5-fluorouracil (5-FU) plus cisplatin (CDDP). Chemotherapy consisted of 5-FU at 700 mg/m2 intravenous on days 1 to 4 and CDDP at 70 mg/m2 intravenous on day 1, repeated every 4 weeks for 2 cycles. Radiation therapy consisted of 60 Gy in 30 fractions. After completion of CRT, 2 additional cycles of CT with 5-FU (800 mg/m2, days 1-5) and CDDP (80 mg/m2, day 1) were repeated at a 4-week interval. The primary endpoint was 3-year overall survival. RESULTS: Thirty patients were enrolled across 8 institutions in Japan, consisting of 26 men and 4 women with a median age of 64.5 years (range, 50-75 years). No grade 4 hematologic toxicity was seen in the CRT phase, and 1 grade 4 thrombocytopenia was seen in the CT phase. Grade 3 nonhematologic acute toxicities in the CRT phase were nausea (10%), mucositis (13.3%), and dysphagia (13.3%). No treatment-related death in either phase occurred. Overall complete response rate was 73%, and 3-year overall and laryngectomy-free survival were 66.5% and 52.5%, respectively. Regarding T4 disease, 3-year overall and laryngectomy-free survival were 58.3% and 38.5%, respectively. CONCLUSIONS: This study, the first prospective study for cervical esophageal cancer, showed that CRT has sufficient efficacy and safety for use as an alternative to surgery for these patients.

Dropped head syndrome induced by chemoradiotherapy for nasopharyngeal carcinoma: a case report.

'Dropped head syndrome' (DHS) is characterized by severe weakness of the muscles of the back of the neck, resulting in chin-on-chest deformity. Dropped head syndrome induced by radiotherapy is very rare. We report a case of DHS following chemoradiotherapy with a total of 64.8 Gy in 36 fractions for nasopharyngeal carcinoma.

Evaluation of anxiety and salivary chromogranin a secretion in women receiving breast conserving surgery followed by radiation therapy.

We conducted a prospective study to assess the anxiety and salivary Chromogranin A (CgA), which is considered to be a biomarker of the stress response, in outpatients receiving breast conserving surgery followed by radiation therapy (RT) to the whole breast. Fifty consecutive patients who received whole-breast RT were enrolled in this study. The anxiety levels were measured by the State-Trait Anxiety Inventory (STAI) at the beginning of RT (baseline), 30 Gy, completion of RT, and 1 and 3 months after RT. Salivary CgA levels were also measured at the same time. The mean state anxiety score for all patients was 46.16 with a standard error (SE) of 1.57 at the beginning of RT (baseline) which continued to decline during and after RT. It reached its lowest score with 36.34 ± 1.56 at 3 months after RT (p < 0.0001). The mean trait anxiety score for all patients was 43.10 ± 1.54 at baseline and remained constant during RT but began to decline after completion of RT and reached a low level at 3 months after RT (p = 0.0021). The mean salivary CgA concentration for all patients demonstrated no consistent trends over time, but at 30 Gy the concentration showed a significant decreasing pattern (p = 0.0473). Salivary CgA concentrations and state anxiety and trait anxiety scores at all time points showed no correlation. The mean anxiety scores measured by STAI showed no positive correlation with salivary CgA concentration for breast cancer patients undergoing radiation therapy following breast conserving surgery.

Sphingosine 1-phosphate inhibits nitric oxide production induced by interleukin-1beta in rat vascular smooth muscle cells.

Sphingosine 1-phosphate (S1P) is a lipid mediator that exerts potent and diverse biological effects on several cardiovascular cells. We investigated the effect of S1P on interleukin (IL)-1beta-induced nitric oxide (NO) production and inducible NO synthase (iNOS) expression in rat vascular smooth muscle cells (VSMCs). S1P inhibited NO production at concentrations higher than 0.1 muM; this was associated with the inhibition of iNOS protein and mRNA expression. S1P also inhibited IL-1beta-induced GTP cyclohydrolase I (GTPCH) mRNA expression. Pertussis toxin (PTX) partially attenuated the inhibitory effects of S1P on NO production and iNOS protein induction, whereas it completely blocked the inhibitory effects on iNOS and GTPCH mRNA expression. S1P inhibited iNOS expression in Ca(2+)-depleted conditions; PTX did not modify this effect. The Rho kinase inhibitor Y 27632 partially but significantly attenuated the inhibitory effect of S1P on iNOS expression in Ca(2+)-depleted condition but did not affect it in the presence of Ca(2+). S1P significantly inhibited IL-1beta-induced persistent activation of extracellular signal-regulated kinase (ERK) but had no effect in Ca(2+)-depleted conditions. Thus, S1P inhibits IL-1beta induction of NO production and iNOS expression in rat VSMCs through multiple mechanisms involving both PTX-sensitive and -insensitive G proteins coupled to S1P receptors. Furthermore, Ca(2+)-dependent ERK inhibition and Ca(2+)-independent Rho kinase activation might be involved in the inhibitory mechanism of iNOS expression. Through its action on NO production by VSMCs, S1P may play an important role in the progression of local vascular injury associated with thrombosis, atherosclerosis, and hypertension.

Sphingosine 1-phosphate induces cyclooxygenase-2 via Ca2+-dependent, but MAPK-independent mechanism in rat vascular smooth muscle cells.

The effects of sphingosine 1-phosphate (S1P) on prostaglandin I(2) (PGI(2)) production and cyclooxygenase (COX) expression in cultured rat vascular smooth muscle cells (VSMCs) were investigated. S1P stimulated PGI(2) production in a concentration-dependent manner, which was completely suppressed by NS-398, a selective COX-2 inhibitor, as determined by radioimmunoassay. S1P stimulated COX-2 protein and mRNA expressions in a concentration- and time-dependent manner, while it had no effect on COX-1 expression. S1P(2) and S1P(3) receptors mRNA were abundantly expressed in rat VSMCs. Suramin, an antagonist of S1P(3) receptor, almost completely inhibited S1P-induced COX-2 expression. Pretreatment of VSMCs with pertussis toxin (PTX) partially, but significantly inhibited S1P-induced PGI(2) production and COX-2 expression. S1P also activated extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK). However, neither PD 98059, a selective inhibitor of ERK activation, nor SB 203580, a selective inhibitor of p38 MAPK, had a significant inhibitory effect on S1P-induced COX-2 expression, suggesting that the MAPK activation does not play main roles in S1P-induced COX-2 induction. S1P-induced COX-2 expression was inhibited by PP2, an inhibitor of Src-family tyrosine kinase, Ca(2+) depletion, and GF 109203X, an inhibitor of protein kinase C (PKC). These results suggest that S1P stimulates COX-2 induction in rat VSMCs through mechanisms involving Ca(2+)-dependent PKC and Src-family tyrosine kinase activation via S1P(3) receptor coupled to PTX-sensitive and -insensitive G proteins.