Diagnostic accuracy of periapical radiolucency using periapical radiography and cone-beam computed tomography

Objectives: This research is aimed to compare the accuracy of periapical radiography in detecting periapical radiolucency with that of Cone-beam Computed Tomography (CBCT) and to assess the additional information that CBCT provides. Materials and Methods: 96 patients with a primary diagnosis of endodontic problem had been studied retrospectively. Each root was examined for the presence or absence of periapical lesions according to the Periapical Index (PAI) Score. Roots and root canals identified through perapical radiography and CBCT were recorded. Additional information from CBCT regarding effects of lesions in cortical bone and maxillary sinus was also noted. Sensitivity, specificity, positive predictive value, and negative predictive value were analyzed. Results: The result showed that accuracy of periapical radiography as expressed by its sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) was 0.65, 0.90, 0.86, 0.75, respectively. Conclusion: Periapical radiography has a low sensitivity in detecting periapical lesions compared to CBCT. CBCT also provides more detailed information that is useful in endodontic treatment

Incidence and Risk Factors of Hypomagnesemia in Head and Neck Cancer Patients Treated with Cetuximab

Background Hypomagnesemia is a common adverse event during cetuximab (Cmab) treatment. However, few reports have investigated the incidence and risk factors of hypomagnesemia in head and neck cancer patients treated with Cmab. Methods We retrospectively reviewed 131 head and neck cancer patients who received Cmab-containing therapy. Main eligibility criteria were ≥3 Cmab administrations, no prior EGFR-directed therapy, and no prophylactic Mg supplementation.Results Median baseline serum Mg level and number of Cmab administrations were 2.2 mg/dl and eight, respectively. Overall incidence of hypomagnesemia was 50.4% (grade 1, 46.6%; grade 2, 3.1%; grade 3, 0%; grade 4, 0.8%) and differed between patients treated with palliative chemotherapy and bioradiation (Cmab and radiation) (63% vs. 24%; p<0.01). Independent risk factors were low baseline serum Mg [Odds ratio (OR) 161.988, 95% confidence interval (CI) 9.436-2780.895], ≥7 Cmab administrations (OR 3.56, 95% CI 1.16-13.98), and concurrent administration of platinum (cisplatin; OR 23.695, 95% CI 5.219-107.574, carboplatin; OR 5.487, 95% CI 1.831-16.439). Respective incidence of hypomagnesemia in patients in high- (concurrent platinum and ≥7 Cmab administrations) and low-risk (no concurrent platinum and <7 Cmab administrations) groups was 66.0% and 6.6% (P<0.001, OR 28.0). Conclusion Cmab is associated with a significant risk of hypomagnesemia in patients with head and neck cancer with longer term administration and concurrent platinum therapy. High-risk patients should be treated with particular care

Predictive Value of Cetuximab-Induced Skin Toxicity in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and NECK

Background: Skin toxicity is a common adverse event during cetuximab (Cmab) treatment. However, few reports have investigated the correlation between skin toxicity and the efficacy of Cmab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).Methods: We retrospectively reviewed 112 R/M SCCHN patients who received palliative chemotherapy with Cmab. Main eligibility criteria included primary disease in the oral cavity, hypopharynx, nasopharynx, oropharynx, or larynx; no prior history of EGFR-directed therapy; receipt of Cmab plus chemotherapy as first-line therapy for recurrent or metastatic disease; and follow-up for more than 90 days. We analyzed the time to first occurrence and time of maximum grade skin toxicity, and its predictive value with regard to treatment efficacy.Results: After a median follow-up of 393 days (range 109–1501 days), 105 (94%) and 20 (18%) patients had skin toxicity of any grade and grade 3, respectively. Among them, 8 patients with grade 3 acneiform rash, skin rash, or paronychia within 90 days after treatment initiation (“early skin toxicity”) had improved progression-free survival (PFS) (log-rank test, P = 0.045; 2-year PFS, 25.0 vs. 2.9%) and overall survival (OS) (log-rank test, P = 0.023, 2-year OS, 50.0 vs. 14.4%) compared with those with &lt; grade 3 toxicity. A greater proportion of patients with early skin toxicity than patients without this toxicity could proceed with Cmab maintenance (88 vs. 44%, P = 0.021). Multivariate analysis identified early skin toxicity as an independent predictor of better PFS (hazard ratio [HR] = 0.363, 95% confidence interval [CI] 0.142–0.924, P = 0.034) and OS (HR = 0.187, 95% CI: 0.045–0.781, P = 0.022).Conclusion: Grade 3 Cmab-induced skin toxicity within 90 days was associated with better survival in R/M SCCHN. Effective rash management therefore seems necessary to realize the benefit of Cmab treatment

Robust and highly efficient hiPSC generation from patient non-mobilized peripheral blood-derived CD34+ cells using the auto-erasable Sendai virus vector

Background: Disease modeling with patient-derived induced pluripotent stem cells (iPSCs) is a powerful tool forelucidating the mechanisms underlying disease pathogenesis and developing safe and effective treatments. Patientperipheral blood (PB) cells are used for iPSC generation in many cases since they can be collected with minimuminvasiveness. To derive iPSCs that lack immunoreceptor gene rearrangements, hematopoietic stem and progenitorcells (HSPCs) are often targeted as the reprogramming source. However, the current protocols generally requireHSPC mobilization and/or ex vivo expansion owing to their sparsity at the steady state and low reprogrammingefficiencies, making the overall procedure costly, laborious, and time-consuming.Methods: We have established a highly efficient method for generating iPSCs from non-mobilized PB-derivedCD34+ HSPCs. The source PB mononuclear cells were obtained from 1 healthy donor and 15 patients and werekept frozen until the scheduled iPSC generation. CD34+ HSPC enrichment was done using immunomagnetic beads,with no ex vivo expansion culture. To reprogram the CD34+-rich cells to pluripotency, the Sendai virus vectorSeVdp-302L was used to transfer four transcription factors: KLF4, OCT4, SOX2, and c-MYC. In this iPSC generationseries, the reprogramming efficiencies, success rates of iPSC line establishment, and progression time wererecorded. After generating the iPSC frozen stocks, the cell recovery and their residual transgenes, karyotypes, T cellreceptor gene rearrangement, pluripotency markers, and differentiation capability were examined.Results：We succeeded in establishing 223 iPSC lines with high reprogramming efficiencies from 15 patients with 8 different disease types. Our method allowed the rapid appearance of primary colonies (~ 8 days), all of which were expandable under feeder-free conditions, enabling robust establishment steps with less workload. After thawing, the established iPSC lines were verified to be pluripotency marker-positive and of non-T cell origin. A majority of the iPSC lines were confirmed to be transgene-free, with normal karyotypes. Their trilineage differentiation capability was also verified in a defined in vitro assay.Conclusion：This robust and highly efficient method enables the rapid and cost-effective establishment of transgene-free iPSC lines from a small volume of PB, thus facilitating the biobanking of patient-derived iPSCs and their use for the modeling of various diseases

Subsequent chemotherapy with paclitaxel plus cetuximab-based chemotherapy following immune checkpoint inhibitor in recurrent or metastatic squamous cell carcinoma of the head and neck

BackgroundImmune checkpoint inhibitors (ICIs) are essential in treating recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). However, the overall response rate (ORR) is limited to 10-20%, and subsequent chemotherapy is critical to maximizing the subjects’ prognosis.MethodsWe retrospectively reviewed 59 patients with R/M SCCHN treated with paclitaxel+cetuximab (PE)-based chemotherapy (PCE, paclitaxel+carboplatin+cetuximab; or PTX+Cmab, paclitaxel+cetuximab) following disease progression after either pembrolizumab or nivolumab monotherapy.ResultsOf 59 patients, 15 were treated with pembrolizumab, with an ORR of 13.3%, and the remaining 44 with nivolumab, with an ORR of 11.4%. All patients in the pembrolizumab cohort had platinum-sensitive disease. Following ICI treatment, 19 patients were treated with PCE and the remaining 40 with PTX+Cmab. PE-based chemotherapy induced favorable and prompt tumor shrinkage even in cases where ICI was not effective, with a median change in the summed dimensions of target lesions of -43.4%, resulting in an ORR of 62.7%. Median time to response was 1.8 months. The patients in the pembrolizumab cohort appeared to have a numerically higher response rate than those receiving nivolumab (80.0% vs. 56.8%). For the 59 patients, progression-free survival and overall survival, calculated from the initiation of PE-based chemotherapy, were 4.6 months and 17.1 months, respectively. Grade ≥3 adverse events occurred in 40.7%, and no treatment-related death was observed.ConclusionPE-based chemotherapy following ICI is encouraging for its robust antitumor efficacy in R/M SCCHN

Efficacy of anti-PD-1 monotherapy for recurrent or metastatic olfactory neuroblastoma

BackgroundOlfactory neuroblastoma (ONB) is a rare malignant tumor of the head and neck. Due to its rarity, standard systemic therapy for this condition has yet to be established. In particular, the use of immune checkpoint inhibitors (ICIs) for the recurrent or metastatic (R/M) ONB population remains unclear.MethodsWe retrospectively evaluated 11 patients with R/M ONB who received any systemic chemotherapy at two Japanese institutions (National Cancer Center Hospital East and Kyushu Medical Center) between January 2002 and March 2022 and analyzed outcomes by use of anti-PD-1 antibody (nivolumab or pembrolizumab) monotherapy.ResultsOf the 11 patients, 6 received ICI (ICI-containing treatment group) and the remaining 5 were treated with systemic therapy but not including ICI (ICI-non-containing treatment group). Overall survival (OS) was significantly longer in the ICI-containing group (median OS: not reached vs. 6.4 months, log-rank p-value: 0.035). The fraction of ICI systemic therapy in the entire treatment period of this group reached 85.9%. Four patients (66.7%) in the ICI-containing treatment group experienced immune-related adverse events (irAE), with grades of 1/2. No irAE of grade 3 or more was seen, and no patient required interruption or discontinuation of treatment due to toxicity.ConclusionICI monotherapy appears to be effective and to contribute to prolonged survival in R/M ONB