Survival outcomes including salvage therapy of adult head and neck para-meningeal rhabdomyosarcoma: a multicenter retrospective study from Japan.

BACKGROUND: Rhabdomyosarcoma is the most common soft tissue sarcoma in children, but rare in adults. Para-meningeal rhabdomyosarcoma in head and neck (PM-HNRMS) is less applicable for surgery due to the anatomic reason. PM-HNRMS has a poor prognosis in children. However, its clinical outcomes remain unclear in adults due to the rarity. Further, there is almost no detailed data about salvage therapy. METHODS: We retrospectively examined the adult patients with PM-HNRMS treated at institutions belonging to the Kyushu Medical Oncology Group from 2009 to 2022. We evaluated the overall survival (OS) and progression-free survival (PFS) of the patients who received a first-line therapy. We also reviewed the clinical outcomes of patients who progressed against a first-line therapy and received salvage therapy. RESULTS: Total 11 patients of PM-HNRMS received a first-line therapy. The characteristics were as follows: median age: 38 years (range 25 - 63 years), histology (alveolar/spindle): 10/1, and risk group (intermediate/high): 7/4. As a first-line therapy, VAC and ARST0431-based regimen was performed in 10 and 1 patients, respectively. During a first-line therapy, definitive radiation for all lesions were performed in seven patients. The median PFS was 14.2 months (95%CI: 6.0 - 25.8 months): 17.1 months (95%CI: 6.0 - not reached (NR)) for patients with stage I-III and 8.5 months (95%CI: 5.2 - 25.8 months) for patients with stage IV. The 1-year and 3-year PFS rates were 54.5% and 11.3% for all patients. Median OS in all patients was 40.8 months (95%CI: 12.1 months-NR): 40.8 months (95%CI: 12.1 - NR) for patients with stage I-III and NR for patients with stage IV. The 5-year OS rate was 48.5% for all patients. Among seven patients who received salvage therapy, three are still alive, two of whom remain disease-free for over 4 years after completion of the last therapy. Those two patients received multi-modal therapy including local therapy for all detected lesions. CONCLUSION: The cure rate of adult PM-HNRMS is low in spite of a first-line therapy in this study. Salvage therapy might prolong the survival in patients who received the multi-modal therapy including local therapy for all detected lesions.

Contrasting area and yield responses to extreme climate contributes to climate-resilient rice production in Asia.

Climate impacts on crop production components other than yield, i.e., area and cropping intensity, remain under-studied. Here, we clarify climate-crop area relationships by analyzing subnational census area and yield data for six multi-rice cropping countries in South and Southeast Asia. Extreme climate has a greater influence on the departure of area and yield from long-term trends than the average seasonal climate; precipitation and temperature in the sowing period of the wet/rainfed season have a greater influence on variability of the total annual area than in the growing period. In 57% of the country-scenario cases showing significant changes in area and/or yield, the directions of the area and yield responses to climate are not synchronized, deriving non-significant production changes under projected climates. Climate-area relationships not only limit production shocks, but also clarify uncertainties associated with climate mitigation of agricultural land, where area markedly affects the scale of mitigation.

Validation of four-dimensional computed tomography without external reference respiratory signals for radiation treatment planning of lung tumors.

Deviceless four-dimensional (4D) computed tomography (CT) allows the acquisition of respiratory signals from six features without requiring an external device for cine CT processing. This method has been recently introduced in radiation treatment planning of lung tumors. To validate deviceless 4D CT, it must be compared with conventional 4D CT, which requires an external monitoring device. We compared the two methods using a multicell 4D phantom that simulates patient's movement during respiration regarding the target volume (TV), target position (TP), and internal TV for lung tumor radiation therapy. We retrospectively obtained images of 10 patients who underwent radiation treatment planning of lung tumors and compared the two methods, as in the phantom study. For the phantom study, the mean TV, root mean square errors of the TP, and mean internal TV differences between the two methods ranged from -4.5% to 1.2%, 0.7 to 2.6 mm, and -1.1% to 3.4%, respectively. The corresponding results of the clinical study ranged from -1.5% to 14.9%, 0.1 to 5.9 mm, and -9.7% to 10.1%, respectively. The results of deviceless 4D CT for the clinical study were consistent with those of conventional 4D CT, except for target movements with high excursions. Therefore, deviceless 4D CT can be an alternative to conventional 4D CT for radiation treatment planning of lung tumors.

Impact of four-dimensional cone-beam computed tomography on target localization for gastric mucosa-associated lymphoid tissue lymphoma radiotherapy: reducing planning target volume.

BACKGROUND: Radiotherapy of gastric mucosa-associated lymphoid tissue (MALT) lymphoma should be delivered to the entire stomach with planning target volume (PTV) that accounts for variations in stomach volume, respiratory movement, and patient set-up error. In this study, we evaluated whether the use of four-dimensional cone-beam computed tomography (4D-CBCT) reduces the PTV. METHODS: Eight patients underwent radiotherapy with 15 fractions of gastric MALT lymphoma using 4D-CBCT. PTV structures of 5-30 mm margins (5 mm intervals) from the clinical target volume (CTV) delineated based on the 4D-CT images (CTV-4D) were generated. For the target localization, we performed matching based on skin marking (skin matching), bone anatomy (bone matching), and stomach anatomy (4D soft-tissue matching) based on registration between planning CT and 4D-CBCT images from 10 phases. For each patient, we calculated the covering ratio (CR) of the stomach with variable PTV structures, based on the 4D-CBCT images, with a total of 150 phases [CR (%) = (number of covering phases/150 phases) × 100], for three target localization methods. We compared the CR values of the different target localization methods and defined the PTV with an average CR of ≥ 95% for all patients. RESULTS: The average CR for all patients increased from 17.9 to 100%, 19.6 to 99.8%, and 33.8 to 100%, in the skin, bone, and 4D soft-tissue matchings, respectively, as the PTV structures increased from 5 to 30 mm. The CR obtained by 4D soft-tissue matching was superior to that obtained by skin (P = 0.013) and bone matching (P = 0.008) for a PTV structure of 15 mm margin. The PTV required an additional margin of 20 mm (average CR: 95.2%), 25 mm (average CR: 99.1%), and 15 mm (average CR: 98.0%) to CTV-4D for the skin, bone, and 4D soft-tissue matchings, respectively. CONCLUSIONS: This study demonstrates that the use of 4D-CBCT reduces the PTV when applying 4D soft-tissue matching, compared to skin and bone matchings. Additionally, bone matching does not reduce the PTV as compared with traditional skin matching.

Image quality evaluation of in-treatment four-dimensional cone-beam computed tomography in volumetric-modulated arc therapy for stereotactic body radiation therapy.

In this study, the image quality of in-treatment four-dimensional cone-beam computed tomography (In-4D-CBCT) obtained with various prescription doses (PDs) were quantitatively evaluated in volumetric-modulated arc therapy (VMAT) for stereotactic body radiation therapy (SBRT) of the lungs and liver. To assess image quality, we used a dynamic thorax phantom and three-dimensional (3D) abdominal phantom; In-4D-CBCT images were acquired with various PDs (from 5 to 12 Gy). The In-4D-CBCT with various PDs were compared with the reference images (pre-4D-CBCT). The image quality was evaluated using the signal-to-noise ratio (SNR), the contrast-to-noise ratio (CNR), and the Dice similarity coefficient (DSC). The fiducial marker positions with various PDs were compared with those of the reference images. For the dynamic thorax phantom, the difference between pre- and In-4D-CBCT in terms of SNR and CNR decreased, as the PD increased from 6 to 12 Gy. The median DSC ranged from 0.7 to 0.74, and showed good similarity. For the 3D abdominal phantom, the difference between pre- and In-4D-CBCT in terms of SNR and CNR decreased as the PD increased from 5 to 6 Gy; conversely, it increased as the PD increased from 7 to 8 Gy. The fiducial marker positions were within 1.0 mm for all PDs. We concluded that the image quality of In-4D-CBCT degraded compared with the reference image; however, it was sufficiently accurate for assessing the intra-fractional tumor position in VMAT for SBRT of the lungs and liver both in terms of the target volume similarity and accuracy of the fiducial marker position.

Efficacy and safety of ramucirumab plus modified FOLFIRI for metastatic colorectal cancer.

BACKGROUND: Dose modification of chemotherapy for metastatic colorectal cancer (MCRC) is often needed, especially in second-line and later-line treatments due to adverse events of previous treatment and poor patient condition. No study has focused on ramucirumab plus modified dose of FOLFIRI for MCRC, and whether low relative dose intensity (RDI) affects treatment efficacy has not been clarified. METHODS: MCRC patients who received ramucirumab plus FOLFIRI, which consisted of 150 mg/m2 of irinotecan, at six institutions were retrospectively analyzed. RESULTS: A total of 43 patients were assessed. Median age was 63 years, and 22 patients (51%) were women. Twenty-six patients (60%) were given ramucirumab plus FOLFIRI as second-line therapy, and 17 (40%) as third or later-line. The median relative dose intensity (RDI) of irinotecan was 60.6%, which is lower than that in the pivotal phase 3 study (RAISE), and other agents showed the same trend. Median progression-free survival was 4.8 [95% confidence interval (CI) 3.2-5.7] months for all patients, 5.4 (95% CI 3.5-7.2) months for second-line patients, and 2.8 (95% CI 1.6-5.8) months for third or later-line patients. Median overall survival was 17.3 (95% CI 11.5-22.4) months for all patients. Patients with irinotecan RDI less than 60% showed similar treatment efficacy. Hematological toxicities of grade 3 or worse were observed in 21 patients, but all were manageable. CONCLUSION: Low RDI did not compromise the treatment efficacy of ramucirumab plus modified FOLFIRI for MCRC patients.

The Effectiveness of Hepatic Arterial Infusion Chemotherapy with 5-Fluorouracil/Cisplatin and Systemic Chemotherapy with Ramucirumab in Alpha-Fetoprotein-Producing Gastric Cancer with Multiple Liver Metastases.

Alpha-fetoprotein- (AFP-) producing gastric cancer (AFPGC) is characterized by a high incidence of liver and lymph node metastases and poor prognosis. Although several case reports have described successful multidisciplinary treatment, there are currently no standard therapies for AFPGC. A 57-year-old man presented with upper abdominal pain. His serum AFP level was extremely high (588.9 ng/mL). Computed tomography (CT) revealed multiple liver metastases with several lesions at an imminent risk of rupture. Five days after admission to our hospital, one lesion ruptured. Transarterial chemoembolization (TACE) of the ruptured tumor was performed, and hepatic arterial infusion chemotherapy (HAIC) with 5-fluorouracil (5-FU)/cisplatin (CDDP) to the other liver metastases was administered. The patient's AFP levels decreased to 297.1 ng/mL. Gastrointestinal endoscopy revealed Borrmann type 2 lesion in the pyloric portion. Pathological examination indicated hepatoid adenocarcinoma of the stomach and metastatic liver. The final diagnosis was AFPGC and multiple liver metastases. The patient underwent systemic chemotherapy with capecitabine/CDDP (cape/CDDP) for three months. His AFP level increased extremely, and CT revealed progression of the liver metastases. TACE was performed, and HAIC (5FU/CDDP) was administered to the progressive lesion of the liver. Originating from the gastric lesion, a distal gastrectomy and D2 + α lymph node resection were performed. One month after the operation, the patient underwent systemic chemotherapy with paclitaxel/ramucirumab (PTX/RAM). After eight cycles of chemotherapy, his AFP level had declined, and CT showed a complete response. After three months of drug withdrawal, the patient has undergone maintenance treatment with RAM. It has been two years since the recurrence. Our experience suggests that HAIC with 5-FU/CDDP and systemic chemotherapy with a regimen including RAM may be an effective treatment for AFPGC.

Usefulness of Endoscopic Managements in Patients with Ceftriaxone-Induced Pseudolithiasis Causing Biliary Obstruction.

Ceftriaxone (CTRX) is known to cause reversible biliary stones/sludge, which is called biliary pseudolithiasis. We report two rare cases of biliary obstruction by pseudolithiasis shortly after completing CTRX treatment. Stones and sludge, which had not been detected before CTRX administration, appeared in the gallbladder and common bile duct and led to biliary obstruction and acute cholangitis. The obstructions were successfully treated with endoscopic retrograde biliary drainage and endoscopic sphincterotomy. CTRX-induced biliary pseudolithiasis has been reported mainly in children and adolescents but is also seen in adults with similar incidence rate. Although CTRX-induced biliary pseudolithiasis is usually asymptomatic and disappears spontaneously after discontinuing the drug, some patients develop biliary obstruction. Endoscopic managements should be considered in such cases.

Effects of the Maximum Luminance in a Medical-grade Liquid-crystal Display on the Recognition Time of a Test Pattern: Observer Performance Using Landolt Rings.

This study was conducted to measure the recognition time of the test pattern and to investigate the effects of the maximum luminance in a medical-grade liquid-crystal display (LCD) on the recognition time. Landolt rings as signals of the test pattern were used with four random orientations, one on each of the eight gray-scale steps. Ten observers input the orientation of the gap on the Landolt rings using cursor keys on the keyboard. The recognition times were automatically measured from the display of the test pattern on the medical-grade LCD to the input of the orientation of the gap in the Landolt rings. The maximum luminance in this study was set to one of four values (100, 170, 250, and 400 cd/m(2)), for which the corresponding recognition times were measured. As a result, the average recognition times for each observer with maximum luminances of 100, 170, 250, and 400 cd/m(2) were found to be 3.96 to 7.12 s, 3.72 to 6.35 s, 3.53 to 5.97 s, and 3.37 to 5.98 s, respectively. The results indicate that the observer's recognition time is directly proportional to the luminance of the medical-grade LCD. Therefore, it is evident that the maximum luminance of the medical-grade LCD affects the test pattern recognition time.

Enantiomeric separation of racemic 1-benzyl-N-methyltetrahydroisoquinolines on chiral columns and chiral purity determinations of the O-methylated metabolites in plant cell cultures by HPLC-CD on-line coupling in combination with HPLC-MS.

Effective enantiomeric separations of 1-benzyl-N-methyltetrahydroisoquinolines were achieved using commercially available Chiralcel OD-H and OJ-H columns. Online LC-CD analysis allowed for the establishment of a correlation between the absolute configuration of the separated enantiomers and their characteristic CD transitions. LC-MS combined with LC-CD analysis permitted chiral purity determinations of O-methylated metabolites of nine phenolic 1-benzyl-N-methyltetrahydroisoquinolines in cell cultures of Corydalis, Macleaya, and Nandina species.

Artificial DNA made exclusively of nonnatural C-nucleosides with four types of nonnatural bases.

We describe a new class of DNA-like oligomers made exclusively of nonnatural, stable C-nucleosides. The nucleosides comprise four types of nonnatural bases attached to a deoxyribose through an acetylene bond with the beta-configuration. The artificial DNA forms right-handed duplexes and triplexes with the complementary artificial DNA. The hybridization occurs spontaneously and sequence-selectively, and the resulting duplexes have thermal stabilities very close to those of natural duplexes. The artificial DNA might be applied to a future extracellular genetic system with information storage and amplifiable abilities.