Phase I/II study of adding intraperitoneal paclitaxel in patients with pancreatic cancer and peritoneal metastasis.

BACKGROUND: Intraperitoneal chemotherapy using paclitaxel is considered an experimental approach for treating peritoneal carcinomatosis. This study aimed to determine the recommended dose, and to evaluate the clinical efficacy and safety, of the combination of intravenous gemcitabine, intravenous nab-paclitaxel and intraperitoneal paclitaxel in patients with pancreatic cancer and peritoneal metastasis. METHODS: The frequencies of dose-limiting toxicities were evaluated, and the recommended dose was determined in phase I. The primary endpoint of the phase II analysis was overall survival rate at 1 year. Secondary endpoints were antitumour effects, symptom-relieving effects, safety and overall survival. RESULTS: The recommended doses of intravenous gemcitabine, intravenous nab-paclitaxel and intraperitoneal paclitaxel were 800, 75 and 20 mg/m2 respectively. Among 46 patients enrolled in phase II, the median time to treatment failure was 6·0 (range 0-22·6) months. The response and disease control rates were 21 of 43 and 41 of 43 respectively. Ascites disappeared in 12 of 30 patients, and cytology became negative in 18 of 46. The median survival time was 14·5 months, and the 1-year overall survival rate was 61 per cent. Conversion surgery was performed in eight of 46 patients, and those who underwent resection survived significantly longer than those who were not treated surgically (median survival not reached versus 12·4 months). Grade 3-4 haematological toxicities developed in 35 of 46 patients, whereas non-haematological adverse events occurred in seven patients. CONCLUSION: Adding intraperitoneal paclitaxel had clinical efficacy with acceptable tolerability.

ANTECEDENTES: La quimioterapia intraperitoneal con paclitaxel se considera una terapia experimental para el tratamiento de la carcinomatosis peritoneal. Este estudio tuvo como objetivo determinar la dosis recomendada y evaluar la eficacia clínica y la seguridad de la combinación de gemcitabina intravenosa, nab-paclitaxel intravenoso y paclitaxel intraperitoneal en pacientes con cáncer de páncreas y metástasis peritoneales. MÉTODOS: Se evaluaron las frecuencias de las toxicidades limitantes de la dosis, y la dosis recomendada se determinó en la fase I. El objetivo principal de la fase II fue la tasa de supervivencia global a 1 año. Los objetivos secundarios fueron los efectos antitumorales, los efectos de alivio de los síntomas, la seguridad y la supervivencia global. RESULTADOS: Las dosis recomendadas de gemcitabina intravenosa, nab-paclitaxel intravenoso y paclitaxel intraperitoneal fueron de 800, 75 y 20 mg/m2 , respectivamente. De los 46 pacientes incluidos en la fase II del estudio, la mediana de tiempo hasta el fracaso del tratamiento fue de 6,0 meses (rango, 0-22,6). Las tasas de respuesta y de control de la enfermedad fueron del 45% y 95%, respectivamente. La ascitis desapareció en el 40% de los pacientes, y la citología se negativizó en el 39% de los pacientes. La mediana del tiempo de supervivencia fue de 14,5 meses y la tasa de supervivencia global a 1 año del 60,9%. La cirugía de rescate se realizó en ocho (17%) pacientes, y los que se sometieron a cirugía sobrevivieron significativamente más tiempo que los que no fueron tratados quirúrgicamente (mediana de supervivencia no alcanzada versus 12,4 meses). Las toxicidades hematológicas de grado 3/4 ocurrieron en el 76% de los pacientes, mientras que los eventos adversos no hematológicos se presentaron en el 15% de los pacientes. CONCLUSIÓN: Agregar paclitaxel intraperitoneal tuvo eficacia clínica con una tolerabilidad aceptable. (UMIN000018878).

Physical Frailty and Hemoglobin-to-Red Cell Distribution Width Ratio in Japanese Older Outpatients.

The Frailty screening should be widely performed; however, simple and inexpensive biomarkers are missing. Biomarkers that can be routinely assessed in many patients are desirable. Recently, the hemoglobin-to-red cell distribution width ratio (Hb/RDW, HRR) has been suggested as a new prognostic marker and has been reported to be associated with inflammation, one of the factors contributing to frailty. Therefore, we aimed to address the role of HRR in frailty among 557 older outpatients (aged 65-96 years). Frailty was assessed using the Japanese version of the Cardiovascular Health Study criteria, and HRR was calculated from clinical records. Participants were classified into five groups based on a sex-stratified quintile of HRR (Q1-Q5). Of the participants, 20.3% were frail. Using multiple logistic regression models with the Q5 group as a reference, after adjusting for sex, age, body mass index, polypharmacy, pre-orthopedic surgery, and the use of iron medications, the multivariable-adjusted odds ratios (95% confidence intervals) of the Q4 to Q1 groups were 0.92 (0.58-1.47), 1.04 (0.67-1.61), 1.29 (0.84-1.96), and 1.85 (1.22-2.82), respectively, indicating that a lower HRR was significantly associated with frailty. The robustness of these results was also shown in the multiple imputation analysis. The results suggest that HRR measurement may be one of the indicators to identify frail older adults in routine practice.

Temporal Profiles of Symptom Scores After Palliative Radiotherapy for Bleeding Gastric Cancer With Adjustment for the Palliative Prognostic Index: An Exploratory Analysis of a Multicentre Prospective Observational Study (JROSG 17-3).

AIMS: Although palliative radiotherapy for gastric cancer may improve some symptoms, it may also have a negative impact due to its toxicity. We investigated whether symptoms improved after radiotherapy with adjustment for the Palliative Prognostic Index (PPI) considering that patients with limited survival tend to experience deterioration of symptoms. MATERIALS AND METHODS: This study was an exploratory analysis of the Japanese Radiation Oncology Study Group study (JROSG 17-3). We assessed six symptom scores (nausea, anorexia, fatigue, shortness of breath, pain at the irradiated area and distress) at registration and 2, 4 and 8 weeks thereafter. We tested whether symptoms linearly improved after adjusting for the baseline PPI. Shared parameter models were used to adjust for potential bias in missing data. RESULTS: The present study analysed all 55 patients enrolled in JROSG 17-3. With time from registration as the only explanatory variable in the model, a significant linear decrease was observed in shortness of breath, pain and distress (slopes, -0.26, -0.22 and -0.19, respectively). Given that the interaction terms (i.e. PPI × time) were not significantly associated with symptom scores in any of the six symptoms, only PPI was included as the main effect in the final multivariable models. After adjusting for the PPI, shortness of breath, pain and distress significantly improved (slope, -0.25, -0.19 and -0.17; P < 0.001, 0.002 and 0.047, respectively). An improvement in fatigue and distress was observed only in patients treated with a biologically effective dose ≤14.4 Gy. CONCLUSION: Shortness of breath, pain and distress improved after radiotherapy. Moreover, a higher PPI was significantly associated with higher symptom scores at all time points, including baseline. In contrast, PPI did not seem to influence the improvement of these symptoms. Regardless of the expected survival, patients receiving radiotherapy for gastric cancer can expect an improvement in shortness of breath, pain and distress over 8 weeks. Multiple-fraction radiotherapy might hamper the improvement in fatigue and distress by its toxicity or treatment burden.

A multicenter cohort study of osimertinib compared with afatinib as first-line treatment for EGFR-mutated non-small-cell lung cancer from practical dataset: CJLSG1903.

BACKGROUND: FLAURA, the prospective trial of osimertinib as a first-line therapy compared with first-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), did not show superior survival benefit for osimertinib in either the subgroup of Asians or the subgroup with the L858R mutation. In addition, the superiority of osimertinib compared with second-generation EGFR-TKI is thus far unclear. PATIENTS AND METHODS: We reviewed the clinical data of all consecutive patients who were treated with osimertinib or afatinib as first-line therapy between May 2016 and October 2019 from 15 institutions in Japan. We defined the groups based on first-line EGFR-TKI as the afatinib group and the osimertinib group. Outcomes included time to discontinuation of any EGFR-TKI (TD-TKI), overall survival (OS), and time to treatment failure, with propensity score analysis carried out as an exploratory analysis in the survival and subgroup analyses. RESULTS: A total of 554 patients were enrolled. Data on 326 patients in the osimertinib group, and 224 patients in the afatinib group were analyzed. TD-TKI adjusted by propensity score in the afatinib and osimertinib groups was 18.6 months (95% confidence interval 15.8 to 22.0) and 20.5 months (95% confidence interval 13.8 to not reached), respectively, without significant difference (P = 0.204). OS adjusted by propensity score favored the afatinib group with a significant difference (P = 0.018). Subgroup analysis with propensity score showed that patients with L858R and without brain metastasis had superior survival benefit with afatinib compared with osimertinib (P < 0.001). CONCLUSIONS: TD-TKI in the afatinib group was not significantly prolonged compared with the osimertinib group in the practical data. In the exploratory analysis of patients with L858R-mutated non-small-cell lung cancer without brain metastasis, afatinib showed more benefit in OS over osimertinib.

SARC-F as a Screening Tool for Sarcopenia and Possible Sarcopenia Proposed by AWGS 2019 in Hospitalized Older Adults.

OBJECT: The SARC-F questionnaire is a sarcopenia screening tool. However, the validity of the SARC-F score ≥4 (SARC-F≥4) for the evaluation of sarcopenia in the hospital setting has not been investigated. This study investigated the validity of SARC-F≥4 as a screening tool for sarcopenia among hospitalized older adults. DESIGN: Cross-sectional retrospective study. SETTING: A university hospital. PARTICIPANTS: This study included older adult patients (age ≥65 years) who were hospitalized at, and subsequently discharged from, the hospital between April and September 2019 and underwent a nutritional assessment by the nutrition support team during their hospitalization. MEASUREMENTS: SARC-F was recorded at the time of admission, and the criteria specified by the Asia Working Group for Sarcopenia in 2019 (AWGS 2019) were applied to diagnose sarcopenia and possible sarcopenia. Appendicular muscle mass was estimated through validated equations, and three different models were developed for sarcopenia diagnosis. The sensitivity, specificity, and positive/negative likelihood ratios were calculated to analyze the accuracy of the SARC-F≥4 for sarcopenia and possible sarcopenia. Receiver-operating characteristic analyses were conducted to calculate the area under the curve (AUC). RESULTS: In total, 1,689 patients (mean age: 77.2±7.3 years; male: 54.4%) were analyzed, and 636 patients (37.7%) had SARC-F≥4. Patients with SARC-F≥4 had a statistically significant higher prevalence of AWGS 2019-defined sarcopenia than patients with SARC-F <4 in the models (65.4-78.9% vs 40.9-45.2%, p<0.001). The sensitivity, specificity, and positive/negative likelihood ratios of SARC-F≥4 for sarcopenia and possible sarcopenia were 49.1-51.3%, 73.9-81.2%, and 1.88-2.72/0.60-0.69 and 48.0%, 84.5%, and 3.11/0.62, respectively. The AUC for sarcopenia and possible sarcopenia were 0.644-0.695 and 0.708, respectively. The AUC of SARC-F for possible sarcopenia was equivalent to or larger than that for sarcopenia (DeLong test p=0.438, 0.088, and <0.001 vs the three models). CONCLUSIONS: SARC-F≥4 is suitable as a screening tool for sarcopenia in hospitalized older adults. SARC-F assessment could facilitate the detection and exclusion of sarcopenia at hospitalization and may lead to early adoption of a therapeutic and preventive approach.

Diagnostic role of mean platelet volume in tonsillitis with and without peritonsillar abscess.

OBJECTIVE: To assess the diagnostic role of mean platelet volume in tonsillitis with and without peritonsillar abscess. METHODS: Mean platelet volume and other laboratory data were retrospectively investigated. RESULTS: Mean platelet volume was significantly lower in the tonsillitis group (7.8 per cent ± 0.7 per cent) than in the control group (8.7 per cent ± 0.6 per cent; p < 0.0001), and it was significantly lower in the abscess group (7.5 per cent ± 0.6 per cent) than in the no abscess group (8.0 per cent ± 0.7 per cent; p = 0.0277). White blood cell counts and C-reactive protein levels were not significantly different between patients with an abscess and those without. The mean platelet volume cut-off values for the diagnosis of tonsillitis and peritonsillar abscess were 7.95 fl and 7.75 fl, respectively. CONCLUSION: Our results suggest that a decreased mean platelet volume is associated with the development and severity of tonsillitis. This finding provides useful diagnostic information for physicians treating patients with tonsillitis.

A pre-operative predictive score for the outcome of eccentric rotational acetabular osteotomy in the treatment of acetabular dysplasia and early osteoarthritis of the hip in adults.

AIMS: The influence of identifiable pre-operative factors on the outcome of eccentric rotational acetabular osteotomy (ERAO) is unknown. We aimed to determine the factors that might influence the outcome, in order to develop a scoring system for predicting the prognosis for patients undergoing this procedure. PATIENTS AND METHODS: We reviewed 700 consecutive ERAOs in 54 men and 646 women with symptomatic acetabular dysplasia or early onset osteoarthritis (OA) of the hip, which were undertaken between September 1989 and March 2013. The patients' pre-operative background, clinical and radiological findings were examined retrospectively. Multivariate Cox regression analysis was performed using the time from the day of surgery to a conversion to total hip arthroplasty (THA) as an endpoint. A risk score was calculated to predict the prognosis for conversion to THA, and its predictive capacity was investigated. RESULTS: The congruity of the hip, age, the pre-operative minimum width of the joint space and range of abduction were identified as factors predicting conversion to THA. For three groups of patients (scoring 0 to 5, 6 to 7, and 8 to 9 points), the Kaplan-Meier event-free rates of survival at 15 years post-operatively for conversion to THA were 99.6%, 85.2% and 67.3%, respectively. CONCLUSION: These four pre-operative factors are easily measured and predict the prognosis for patients following ERAO. They may be used for decision making when offering surgical treatment to patients with acetabular dysplasia and early onset osteoarthritis. Cite this article: Bone Joint J 2016;98-B:1326-32.

Agenesis of the internal carotid artery with a large hemangioma of the tongue.

A case of agenesis of the left internal carotid artery combined with a large cavernous hemangioma of the tongue is reported. The detailed angiographic findings are demonstrated together with the poly- or computed tomographic findings of the skull. A review of the pertinent literature is presented.