Treatments and prognostic factors for bone and soft tissue sarcoma in non-urban areas in Japan.

BACKGROUND: Although bone and soft tissue sarcoma is recognized as a rare cancer that originates throughout the body, few comprehensive reports regarding it have been published in Japan. PATIENTS AND METHODS: Bone and soft tissue sarcomas were tabulated from the Cancer Registries at eight university hospitals in the Chugoku-Shikoku region. Prognostic factors in cases were extracted in a single facility and have been analyzed. RESULTS: From 2016 to 2019, 3.4 patients with bone and soft tissue sarcomas per a general population of 100,000 were treated at eight university hospitals. The number of patients who underwent multidisciplinary treatment involving collaboration among multiple clinical departments has been increasing recently. In the analysis carried out at a single institute (Ehime University Hospital), a total of 127 patients (male/female: 54/73) with an average age of 67.0 y (median 69.5) were treated for four years, with a 5-year survival rate of 55.0%. In the analysis of prognostic factors by multivariate, disease stage and its relative treatment, renal function (creatinine), and a patient's ability of self-judgment, and a patient's mobility and physical capability were associated with patient prognosis regarding bone and soft tissue sarcomas. Interestingly, age did not affect the patient's prognosis (> 70 vs ≦ 70). CONCLUSIONS: Physical and social factors may affect the prognosis of patients with bone and soft tissue sarcomas, especially those living in non-urban areas.

[Development and Verification of an irAEs Self-Reported Interview System(ISRIS)].

A variety of immune-related adverse events(irAEs)occur during the use of immune checkpoint inhibitors, and delayed detection may make it difficult to continue treatment. To detect irAEs as early as possible, we have been administering an irAEs self-reported interview system(ISRIS)to all outpatients using a tablet device. We conducted a retrospective study of outpatients who received pembrolizumab, nivolumab, atezolizumab, ipilimumab, and durvalumab and utilized the ISRIS from June 2019 to May 2020. The survey items were the primary disease, initial symptoms of irAEs, and detected irAEs. The total number of patients was 140, and the total number of interviews was 1,095. Overall, 42 irAEs occurred. The ISRIS is useful for detecting subjective skin disorders. However, its detection rate of myocarditis and thyroid, hepatic, and renal dysfunction was low, and there is room for improvement. We are currently developing an ISRIS application that maintains sensitivity and increases specificity to allow for early detection of irAEs at home.

The prognostic significance of whole-body and spleen MTV (metabolic tumor volume) scanning for patients with diffuse large B cell lymphoma.

BACKGROUND: Positron Emission Tomography-Computed Tomography (PET-CT) has been changing diagnostic and therapeutic strategies for patients with cancers, and several PET-CT-related prognostic factors have been reported. We have focused on metabolic tumor volumes (MTVs) over the whole body and in specific organs using 18F-PET-CT imaging, and have compared clinical data to know the prognosis of patients with diffuse large B cell lymphoma (DLBCL). PATIENTS AND METHODS: From January 2006 to December 2016, patients who were newly diagnosed for de novo DLBCL and who received 18F-FDG PET-CT scans for disease staging at Ehime University Hospital were reviewed. RESULTS: A total of forty out of 108 patients with DLBCL were analyzed. The median and the average follow-up were 3.9 years and 3.6 years. Both MTV50 and MTV60 whole-body searching indicated effective prognostic values for patients with DLBCL statistically (P = 0.027). However, analysis of MTVs in the spleen and in bone marrow did not provide any prognostic value. Receiver operating characteristic (ROC) analysis indicated that the cutoff level 25.8 in MTV60 is the most effective prognostic value (P = 0.022) which predicts patient survival after treatment with R-CHOP chemotherapy. CONCLUSION: MTV60 using whole-body scanning appears to be an effective indicator in DLBCL and indicates the patient prognosis.

[Assessment of Chemotherapy-Induced Adverse Events Using a Sharing System of Patient-Reported Information via a Touch Panel].

Screening for total pain and sharing of patient information including adverse events for patients receiving chemotherapy by medical staff is needed in clinical practice. We introduced a sharing system for patient-oriented outcome sheets via a touch panel at an outpatient chemotherapy clinic. This study aimed to assess whether the system contributes to the improved management of treatment-related adverse events. We retrospectively analyzed data from a total of 215 patients at Ehime University Hospital using their electronic medical records from April to August 2015. Forty of these patients had received interventions relating to treatment-related adverse events. The proportion of a total number of interventions before and after the sharing system was 42/282(14.9%)and 45/215(20.9%), respectively. The proportion of a total number of interventions at the first course of outpatient chemotherapy also increased from 9/40(22.5%)to 14/40(35%)compared with before the sharing system. The purpose of interventions were for insomnia, anorexia, and cancer-related pain, etc., listed in order of degree of frequency. These results suggest that a sharing system of patient-reported interview sheets contributes to tracking treatment -related adverse events and aids in ensuring interventions can be efficiently performed by multidisciplinary team members.

Treatment-associated outcomes of patients with primary ocular adnexal MALT lymphoma after accurate diagnosis.

BACKGROUND: Differentiation between primary ocular adnexal mucosa-associated lymphoid tissue (POA-MALT) lymphoma and reactive lymphoid hyperplasias sometimes may be difficult. We have examined the treatment-associated mortality of POA-MALT lymphoma after confirmed diagnosis and evaluated their proper treatments. PATIENTS AND METHODS: From 1991 through 2016, cases of POA-MALT lymphoma were retrospectively analyzed based on their pathological and molecular/immunological diagnoses. RESULTS: A total of 78 cases with POA-MALT lymphoma with a median age of 66 years were analyzed over median/mean observations of 6.4/7.1 years. Forty-four patients (56%) were diagnosed with IgH gene clonality and 10 patients (13%) were diagnosed with flow cytometric analysis in addition to the pathological decision. The rest (24 patients, 31%) were diagnosed employing pathological decisions of hemato-pathologists and clinical decisions. All patients, except cases of watchful waiting, achieved complete remission. After initial treatment, 68 patients (87%) presented disease-free during the observation period. As treatment, a radiotherapy-based strategy was followed with 15 patients (19%, group A). Immuno-chemotherapy was administered to 24 patients (31%, B). Surgical extraction only was selected for 36 patients (46%, C). Watchful waiting was selected with three patients (4%). Recurrence after the initial treatment was found in one patient (7%) out of A, in three patients (13%) out of B, and in six patients (17%) out of C, respectively. Progression-free survivals at 5 and 10 years were 100 and 100% in A, 95 and 75% in B, and 88 and 81% in C, respectively. The recurrence rates between the patients who were diagnosed with only pathological decision (n = 24) and the patients who were diagnosed with molecular and immunological procedures (n = 54) did not show any statistical differences. CONCLUSION: Our results indicate that radiotherapy-based treatment strategies for patients with POA-MALT lymphoma show a low rate of recurrence and may improve their prognosis even after the accurate diagnosis. However, contamination of the cases with reactive (polyclonal) lymphoid hyperplasia into those with MALT lymphoma should be carefully removed to avoid unnecessary treatment for malignancies that do not exist.

Retrospective analysis of first-line treatment for follicular lymphoma based on outcomes and medical economics.

BACKGROUND: Follicular lymphoma (FL) is the most common type of non-Hodgkin lymphoma (NHL), with indolent progression. Several treatment options are selected, based not only on disease status, quality of life (QOL), and age of patient, but also on recent increasing medical costs. We retrospectively analysed the first-line treatment of FL with regard to treatment outcomes and medical economics, and discuss the appropriate strategies for FL. METHODS: Data on a total of 69 newly-diagnosed patients with FL was retrospectively collected from 2001 to 2015. RESULTS: The median age of the patients was 60 years and the median follow-up was 58 months. A total of 25 cases with FL were treated with R monotherapy, and 28 cases were treated with R-CHOP as first-line treatment. The factors affecting the decision of physicians to use R or R-CHOP treatment were serum level of lactate dehydrogenase (LDH) and disease stage. The first-line treatment-associated survival did not show any statistical differences between R and R-CHOP. The average hospitalization and average of all medical costs during the first-line treatment were 4.1 days (R) versus 55.7 days (R-CHOP), and JPY 1,707,693 (USD 15,324) (R) versus JPY 2,136,117 (USD 19,170) (R-CHOP), respectively. CONCLUSION: R monotherapy for patients whose diseases show low tumor burden and who are not candidates for local treatment has benefits as a first-line treatment compared to R-CHOP, based on the patients' QOL and medical economics.

A study on the colonization of Pneumocystis jirovecii among outpatients during cancer chemotherapy and among healthy smokers.

AIMS: Pneumocystis Jirovecii (PJ) is regarded as an agent of fungal infection and in cases of pneumocystis pneumonia (PCP) in immune-compromised patients including cancer patients. It is not clear what kinds of cancer, treatments, and environment need prophylaxis for PCP. In this study, we have analyzed the detectability of PJ DNA from sputum, and discussed prophylaxis and risk factors regarding PCP. METHODS: A total of forty-nine materials (twenty-four from outpatients during cancer chemotherapies and twenty-five from healthy control subjects) was collected. Their PJ DNAs were amplified using nested PCR with specific primers of the PJ gene (the mitochondrial small subunit rRNA gene). RESULTS: PJ DNA was detectable in 46% of specimens (sputum) from cancer patients during chemotherapies, and incidences of not significantly different among types of cancer and chemotherapy regimens. Prophylactic use of Sulfamethoxazole/Trimetoprim (ST) reduced the detection of PJ DNA. Detection of PJ DNA is not high among healthy non-smokers (20%) and high among healthy smokers (47%). CONCLUSIONS: Prophylactic use of ST may be necessary for cancer patients during chemotherapies. Also, smoking may be associated with PJ colonization in the airway and air vesicles, and may increase the mortality rate for PCP. All patients undergoing cancer chemotherapies should cease smoking.

Distinguishing Axillary Lymphadenopathy after COVID-19 Vaccination from Malignant Lymphadenopathy.

Objectives: To study the differences between malignant hypermetabolic axillary lymphadenopathy (MHL) and COVID-19 vaccine-associated axillary hypermetabolic lymphadenopathy (VAHL) using clinical imaging. Methods: A total of 1096 patients underwent Positron Emission Tomography-Computed Tomography (PET-CT) between 1 June 2021 and 30 April 2022 at Ehime University Hospital. In total, 188 patients with axillary lymphadenopathy after the COVID-19 vaccination were evaluated. The patients were classified into three groups such as VAHL (n = 27), MHL (n = 21), and equivocal hypermetabolic axillary lymphadenopathy (EqHL; n = 140). Differences in lymph node (LN) swellings were statistically analyzed using clinical imaging (echography, CT, and 18F-FDG PET). Results: MHL included a higher female population (90.5%) owing to a higher frequency of breast cancer (80.9%). Axillary LNs of MHL did not show any LN fatty hilums (0%); however, those of VAHL and EqHL did (15.8 and 36%, respectively). After the logistic regression analysis of the patients who had axillary lymphadenopathy without any LN fatty hilums, the minor axis length and ellipticity (minor axis/major axis) in the largest axillary LN, SUVmax, and Tissue-to-Background Ratio (TBR) were useful in distinguishing malignant lymphadenopathies. A receiver-operating characteristic (ROC) analysis indicated that a cut-off value of ≥7.3 mm for the axillary LN minor axis (sensitivity: 0.714, specificity: 0.684) and of ≥0.671 for ellipticity (0.667 and 0.773, respectively) in the largest LN with the highest SUVmax and TBR were predictive of MHL. Conclusions: Axillary lymphadenopathy of the minor axis and ellipticity in LN without fatty hilums may be useful to be suspicious for malignancy, even in patients who have received COVID-19 vaccination. Further examinations, such as 18F-FDG PET, are recommended for such patients.

Evaluation of infrared-reflection absorption spectroscopy measurement and locally weighted partial least-squares for rapid analysis of residual drug substances in cleaning processes.

The usefulness of infrared-reflection absorption spectroscopy (IR-RAS) for the rapid measurement of residual drug substances without sampling was evaluated. In order to realize the highly accurate rapid measurement, locally weighted partial least-squares (LW-PLS) with a new weighting technique was developed. LW-PLS is an adaptive method that builds a calibration model on demand by using a database whenever prediction is required. By adding more weight to samples closer to a query, LW-PLS can achieve higher prediction accuracy than PLS. In this study, a new weighting technique is proposed to further improve the prediction accuracy of LW-PLS. The root-mean-square error of prediction (RMSEP) of the IR-RAS spectra analyzed by LW-PLS with the new weighting technique was compared with that analyzed by PLS and locally weighted regression (LWR). The RMSEP of LW-PLS with the proposed weighting technique was about 36% and 14% smaller than that of PLS and LWR, respectively, when ibuprofen was a residual drug substance. Similarly, LW-PLS with the weighting technique was about 39% and 24% better than PLS and LWR in RMSEP, respectively, when magnesium stearate was a residual excipient. The combination of IR-RAS and LW-PLS with the proposed weighting technique is a very useful rapid measurement technique of the residual drug substances.

Treatment and prognosis of patients with both cancer and impaired decision-patient with both cancer and dementia making as a symptom of dementia.

AIM: In our aging society, the number of patients with both cancer and dementia has recently been increasing. One of the major clinical questions is whether patients with dementia could receive appropriate cancer treatment. The purpose of this study is to know the prognosis of patients with both cancer and impaired decision-making as a symptom of dementia, and to discuss the proper cancer treatment of the patients with dementia. METHODS: Patients newly diagnosed with both cancer and impaired decision-making as a symptom of dementia at Ehime University Hospital between January 2010 and December 2016 were reviewed. The data of patients with cancer were retrospectively analyzed using an electronic medical record system. RESULTS: In total, 9354 cases were diagnosed with cancer in the Ehime University Hospital over 7 years, and only 105 (1.1%) cases with impaired decision-making as a symptom of dementia were recorded by medical professionals, probably due to poor attention to the cognitive functions of patients with cancer. Analysis of the cancer prognosis of these patients showed that a better prognosis was seen in patients with any therapeutic interventions than in those with no treatment for the cancer itself. However, the prognosis of patients was not significantly different between standard and non-standard treatments. CONCLUSIONS: This study suggests that the poor interest of medical professionals in the cognitive function of patients with cancer at the time of diagnosis of cancer and the lack of any guidelines for patients with both cancer and dementia are major problems in our aging society. Geriatr Gerontol Int 2021; 21: 1105-1110.

Verification of model development technique for NIR-based real-time monitoring of ingredient concentration during blending.

There has been a considerable research on the process analytical technology (PAT) and real-time monitoring based on NIR, but the model development is still an important issue and persons in charge have difficulty in building good models. In this study, to realize efficient NIR-based real-time monitoring of ingredient concentration and establish a model development method, we investigated the effect of a calibration set, spectral preprocessing, wavelengths, and other factors on the prediction error through pilot and commercial scale blending experiments. The results confirmed that the small prediction error was realized by a calibration set, including dynamic measurement spectra acquired with the target blender. In addition, the results demonstrated that locally weighted partial least squares (LW-PLS) achieved the smaller prediction error than conventional PLS. The present study has also clarified that spectral preprocessing methods and wavelengths selected to build a model affect the prediction error of ingredient concentration interactively. A wide wavelength range should be selected when the spectral preprocessing does not lessen the effect of baseline variation, while a narrow wavelength range should be selected when it strongly decreases the effect.

Real-time monitoring of lubrication properties of magnesium stearate using NIR spectrometer and thermal effusivity sensor.

Real-time monitoring techniques based on an NIR spectrometer and a thermal effusivity sensor for lubrication properties of magnesium stearate (Mg-St) are proposed. The lubrication properties of Mg-St are defined by its concentration distribution and flatting state in a mixture. The concentration distribution of Mg-St significantly affects the absorbance in the NIR wavelength region between 1128 nm and 1240 nm. Thus, the absorbance area in this region after baseline correction was selected as a monitoring index (MI). In laboratory-scale experiments, the difference of Mg-St concentration distribution could be detected by the proposed MI with high sensitivity. In addition, experimental results using spherical mannitol granules confirmed that the changes of the flatting state of Mg-St could also be detected by the proposed MI. Similar experiments with spherical mannitol granules and the thermal effusivity sensor confirmed that effusivity could also be used to detect the changes of the flatting state of Mg-St. The applicability of these monitoring techniques was verified using a 2000 L commercial-scale blender equipped with the NIR spectrometer and the thermal effusivity sensor. The results showed that both lubrication properties could be monitored by the proposed MI, and that the flatting state of Mg-St could be monitored more sensitively by using the effusivity.

Estimation of active pharmaceutical ingredients content using locally weighted partial least squares and statistical wavelength selection.

Development of quality estimation models using near infrared spectroscopy (NIRS) and multivariate analysis has been accelerated as a process analytical technology (PAT) tool in the pharmaceutical industry. Although linear regression methods such as partial least squares (PLS) are widely used, they cannot always achieve high estimation accuracy because physical and chemical properties of a measuring object have a complex effect on NIR spectra. In this research, locally weighted PLS (LW-PLS) which utilizes a newly defined similarity between samples is proposed to estimate active pharmaceutical ingredient (API) content in granules for tableting. In addition, a statistical wavelength selection method which quantifies the effect of API content and other factors on NIR spectra is proposed. LW-PLS and the proposed wavelength selection method were applied to real process data provided by Daiichi Sankyo Co., Ltd., and the estimation accuracy was improved by 38.6% in root mean square error of prediction (RMSEP) compared to the conventional PLS using wavelengths selected on the basis of variable importance on the projection (VIP). The results clearly show that the proposed calibration modeling technique is useful for API content estimation and is superior to the conventional one.