Prognostic factors of idiopathic hypereosinophilic syndrome: A nationwide survey in Japan.

Idiopathic hypereosinophilic syndrome (iHES) is a condition wherein persistent hypereosinophilia associated with end-organ damage occurs without any known causes. Due to the rarity of the disease, insufficient knowledge has been accumulated. We therefore conducted a retrospective, multicentre, nationwide survey on iHES in Japan. A total of 57 patients were identified. For 43 patients who received any treatment, all cases were first treated with corticosteroids. An eosinophil percentage of less than 30% in the bone marrow and the absence of oedema were identified as factors associated with steroid dependency. The 5-year overall survival was 88.2%, and five patients died during follow-up; factors associated with worse overall survival were age >50, haemoglobin <12 g/dL, activated partial thromboplastin time >34 s, the presence of dyspnoea, the presence of thrombotic tendency and the presence of renal failure. Given the rarity of fatalities in our cohort, time-to-next-treatment (TTNT) was further analysed; the presence of renal failure, splenomegaly and lung abnormalities were associated with worse TTNT. Our nationwide study not only demonstrated clinical characteristics and the outcome of patients with iHES but also for the first time revealed clinical factors associated with steroid dependency and duration of first-line corticosteroid efficacy.

Association between comorbidities and survival in patients with metastatic urothelial carcinoma treated with pembrolizumab.

BACKGROUND: This study aims to investigate the relationship between comorbidities and survival in patients with mUC treated with pembrolizumab as a second-line treatment. METHODS: From February 2018 to October 2021, we analyzed the data of 185 consecutive patients with metastatic UC who received pembrolizumab as second-line therapy at The Jikei University Hospital and five affiliated hospitals. We used the Charlson Comorbidity Index (CCI) to assess the comorbidities. The outcomes of interest were progression-free survival (PFS) and overall survival (OS). To compare the survival differences, inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves and the IPTW-adjusted Cox regression hazards model were used. RESULTS: After IPTW adjustment, patient characteristics were well-balanced between patients with high CCI and those with low CCI. The IPTW-adjusted Kaplan-Meier curves of PFS and OS based on CCI revealed that the patients with high CCI (2 or more) had a shorter PFS (median, 1.6 vs. 2.8 months) and a shorter OS (median, 12.4 vs. 18.8 months) (0-1). Similarly, in the IPTW-adjusted Cox regression hazards model, patients with high CCI had significantly shorter PFS [HR, 1.84 (95% CI 1.26-2.68; p = 0.002)] and OS [HR, 1.98 (95% CI 1.20-3.27; p = 0.008)] than those with lower CCI. CONCLUSIONS: High CCI was associated with a higher risk of disease progression as well as overall mortality in mUC patients treated with second-line pembrolizumab.

Effectiveness of pembrolizumab in trial-ineligible patients with metastatic urothelial carcinoma.

BACKGROUND: The KEYNOTE-045 trial showed that pembrolizumab therapy improved the survival of patients with advanced urothelial carcinoma (UC). However, its effectiveness in trial-ineligible patients remains unclear. MATERIALS AND METHODS: We conducted a multicenter retrospective study to evaluate the effectiveness of pembrolizumab in patients with metastatic UC who were trial-ineligible. The data of 164 consecutive patients with platinum-treated metastatic UC who received pembrolizumab as second-line therapy were analyzed. Trial eligibility was assessed using the KEYNOTE-045 criteria. Inverse probability of treatment weighting (IPTW) was used to balance patient characteristics. Overall survival (OS) and progression-free survival (PFS) were examined using the IPTW-adjusted Kaplan-Meier method. IPTW-adjusted restricted mean survival times (RMSTs) were compared between ineligible and eligible patients. RESULTS: Seventy-five patients (45.7%) were classified as ineligible based on the KEYNOTE-045 criteria. Baseline hemoglobin concentration of less than 9.0 g/dL was the most common reason for trial protocol violation (N = 23 [14.0%]). An IPTW-adjusted logistic regression model showed that the trial-eligibility was not significantly associated with objective response (OR: 0.65, 95% CI: 0.32 to 1.29, P = 0.22). Ineligible patients had similar RMST for PFS (difference: 3.8 months, 95% CI: -1.6 to 9.3, P = 0.17) and RMST for OS (difference: 1.4 months, 95% CI: -5.4 to 8.2, P = 0.93) compared with eligible patients. CONCLUSIONS: This study suggests that the effectiveness of pembrolizumab may be retained in ineligible patients with platinum-treated metastatic UC. Expanding trial eligibility criteria for these patients may be beneficial.

Clinical benefit of continuing pembrolizumab treatment beyond progression in patients with metastatic urothelial carcinoma.

BACKGROUND: There has been no clinical evidence to justify continued pembrolizumab therapy beyond progression in patients with metastatic urothelial carcinoma (UC). MATERIALS AND METHODS: We conducted a multicenter retrospective study evaluating the clinical efficacy of continued use of pembrolizumab beyond progression in patients with metastatic UC. Data from 51 patients with metastatic UC, who developed progression during second-line pembrolizumab therapy, were analyzed. Progression was defined based on the Immunotherapy Response Evaluation Criteria in Solid Tumors. The outcome was overall survival (OS). The association between continued treatment, OS, and the risk of all-cause mortality was tested using log-rank test, conventional and time-dependent Cox regression models. RESULTS: No significant difference in patient characteristics was noted between patients continuing pembrolizumab beyond progression (N = 21) and those discontinuing pembrolizumab (N = 30). Median OS was significantly longer in the continuation group (17.8 vs. 8.8 months; P = 0.038). A multivariable conventional Cox regression model identified continued pembrolizumab administration as a significant independent prognostic factor of all-cause mortality (hazard ratio [HR]: 0.21, 95% confidence interval [CI]: 0.05-0.90, P = 0.036), irrespective of the time from treatment initiation to progression and concurrent clinical progression. Further, longer duration of pembrolizumab treatment beyond progression was independently associated with a reduced risk of all-cause mortality in a multivariable time-dependent Cox regression model, when used as a time-dependent variable (HR: 0.07, 95% CI: 0.01-0.45, P = 0.006). CONCLUSIONS: Continued pembrolizumab administration beyond progression might be beneficial in patients with metastatic UC who were clinically stable.

Comparison of the Immunotherapy Response Evaluation Criteria in Solid Tumours (iRECIST) with RECIST for capturing treatment response of patients with metastatic urothelial carcinoma treated with pembrolizumab.

OBJECTIVE: To evaluate the clinical usefulness of Immunotherapy Response Evaluation Criteria in Solid Tumours (iRECIST) in patients with metastatic urothelial carcinoma (UC) treated with pembrolizumab. The iRECIST is designed to accurately capture the tumour response treated with immunotherapy. PATIENTS AND METHODS: We conducted a multicentre retrospective study evaluating the clinical utility of iRECIST in 91 patients with metastatic UC treated with second-line pembrolizumab. The objective response (OR) and time to progression (TTP) in accordance with both iRECIST and RECIST version 1.1 were compared with overall survival (OS) and risk of all-cause mortality, and analysed using log-rank and multivariable Cox regression models, respectively. Predictive performance of the criteria was studied using Harrell's concordance index (c-index). The clinical usefulness of each criterion was compared using decision curve analysis. RESULTS: Of 57 patients with progressive disease per RECIST, a considerable number of patients were reclassified to immune stable disease (six, 10.5%), immune partial response (two, 3.5%), and immune complete response (two, 3.5%) per iRECIST. Multivariable Cox regression models showed that both OR (hazard ratio [HR] 0.10, 95% confidence interval [CI] 0.03-0.35; P = 0.001) and TTP (HR 0.59, 95% CI 0.46-0.77; P < 0.001) per iRECIST were significantly associated with all-cause mortality. Furthermore, iRECIST had a significant, increased predictability of OS compared with RECIST (OR, c-index: 0.70, increase: 0.04, P = 0.046; TTP, c-index: 0.88, increase: 0.07, P = 0.039). On decision curve analysis, iRECIST presented better net benefit gains than did RECIST. CONCLUSIONS: Compared with RECIST, iRECIST could more accurately predict OS of patients with metastatic UC treated with pembrolizumab. The iRECIST has the potential to be a new standard for tumour response evaluation of these patients.

Severe cellulitis caused by Achromobacter xylosoxidans after allogeneic hematopoietic stem cell transplantation.

Achromobacter xylosoxidans (A. xylosoxidans) is an aerobic gram-negative bacillus and often isolated from aquatic environments. It is supposed to cause infections in patients with malignancy or immunodeficiency. It causes various healthcare-associated infections, but cellulitis is rare. Herein, we report the first case of sever cellulitis by A. xylosoxidans after allogeneic hematopoietic stem cell transplantation (HSCT). A 49-year-old man underwent allogeneic HSCT from 8/8 HLA-matched unrelated donor with myeloablative conditioning for relapsed acute myeloid leukemia. He developed skin chronic graft versus host disease 11 months after HSCT. During the prolonged treatment with prednisolone and cyclosporine, he developed cellulitis on his left leg and admitted to our hospital. Blood and exudate culture revealed A. xylosoxidans. Although empirical therapy with cefepime was ineffective, his symptoms were dramatically improved after administration of meropenem. To our knowledge, this is the first case of A. xylosoxidans cellulitis after allogeneic HSCT. A. xylosoxidans should be considered as a possible cause of cellulitis in post-allogeneic HSCT patients on prolonged immunosuppressive therapy.

Positron Emission Tomography in Segmentectomy for cT1N0M0 Nonsmall Cell Lung Cancer.

BACKGROUND: This study was aimed to examine the significance of fluorodeoxyglucose positron emission tomography in predicting prognosis after segmentectomy in lung cancer. METHODS: This was a retrospective cohort study, including 227 patients with cT1N0M0 nonsmall cell lung cancer who underwent positron emission tomography followed by segmentectomy between 2012 and 2019. Significance of tumor histology, T-stage, tumor size, and standardized uptake value on positron emission tomography in relation to recurrence-free survival were examined using Cox's proportional hazard analysis. Median follow-up period was 56 months (range: 1-95 months). RESULTS: Tumor stages were Tis in 25 patients, T1mi/T1a in 51, T1b in 98, and T1c in 53. Twenty-six patients (11%) experienced recurrences, including local (n = 8) and distant (n = 18). Multivariate analysis showed that the significant variables for recurrence-free survival were T-stage and standardized uptake value (p = 0.002 and 0.015, respectively), whereas tumor histology and tumor size were not significant (p = 0.28 and 0.44, respectively). When tumor size was divided into ≤2 cm and >2 cm for analysis, it was not significant again (p = 0.49), whereas standardized uptake value remained significant (p = 0.008). While standardized uptake value of tumors with recurrences was significantly higher than those without (4.9-2.8 and 2.6-2.5, respectively, p < 0.001), there was no significant difference between local and distant recurrences (p = 0.32). Cut-off value of standardized uptake value for recurrences was 3.2. Five-year recurrence-free survival rates in tumors with standardized uptake value <3.2 and ≥3.2 were 86 and 65%, respectively (p < 0.001). CONCLUSION: Positron emission tomography could predict the prognosis after segmentectomy better than tumor size.

Ribcage procedure after neoadjuvant chemoradiotherapy for non-small cell lung cancer involving the chest wall.

PURPOSE: Non-small cell lung cancer (NSCLC) involving the chest wall is usually treated with en bloc rib resection or parietal pleurectomy; however, the former causes chest wall deformity and the latter is associated with local recurrence. To prevent both these sequalae, we performed the "ribcage" procedure for tumors involving the chest wall after induction chemoradiotherapy. METHODS: This was a single center retrospective study conducted from 2012 to 2018. The "ribcage" procedure is designed to preserve the ribs of patients with lung tumors involving chest wall and involves peeling the intercostal muscles and periosteum from the ribs, resulting in a birdcage-like appearance. Seventeen patients with NSCLC clearly involving the chest wall, but not destroying the ribs, were treated with induction chemoradiotherapy, followed by the ribcage procedure. A negative margin at the ribs was confirmed by intraoperative frozen sections in 16 of these patients, who then underwent the ribcage procedure. RESULTS: Complete resection was achieved in all 16 patients, none of whom experienced major postoperative complications. After a median follow-up period of 37 months, there was no evidence of local recurrence in any of the patients. CONCLUSION: Our findings suggest that the ribcage procedure is the preferable surgical option as it can prevent chest wall deformities as well as local recurrence.

NUT midline carcinoma mimicking a germ cell tumor: a case report.

BACKGROUND: NUT midline carcinoma (NMC) is a rare and highly aggressive malignancy. Although more information on NMC has been recently accumulating in the literature, most oncologists and pathologists remain unfamiliar with the clinical and pathologic features of this disease. The clinical features of NMC sometimes mimic those of other malignancies, and NMC can therefore be overlooked if the diagnosis is not suspected. We present the case of a young male with NMC arising in the mediastinum with elevated serum alpha-fetoprotein levels suggestive of an extragonadal nonseminomatous germ-cell tumor. CASE PRESENTATION: A 28-year-old Japanese male presented with cough and left-sided chest pain for 6 weeks. The patient had a mediastinal tumor with metastases to the right lung, lymph nodes, and bones at initial presentation. Nonseminomatous germ cell tumor was suspected due to the young age, location of the tumors, and elevated serum alpha-fetoprotein. However, biopsy confirmed the diagnosis of NMC with immunohistochemistry. The tumor briefly responded to cytotoxic chemotherapy but subsequently progressed and became refractory to the chemotherapy regimen. External beam radiotherapy was administered with dramatic shrinkage of the tumor and a metabolic response on 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan. However, the patient died 4.5 months after the diagnosis of NMC. CONCLUSIONS: Serum levels of alpha-fetoprotein may be elevated in patients with NMC. Regardless of the level of tumor markers, immunohistochemistry for NUT should be performed in cases of poorly differentiated carcinomas without glandular differentiation arising in the midline structures. 18F-FDG PET/CT is useful for staging and assessing responses to therapy.

Nivolumab, an Anti-Programmed Cell Death-1 Antibody, Induces Fulminant Type 1 Diabetes.

Programmed cell death-1 (PD-1), an immunoreceptor, is located on T cells and pro-B cells and interacts with its ligands to inhibit T cell activation and proliferation, thereby promoting immunological self-tolerance. Nivolumab, an anti-PD1 antibody, blocks PD-1 and can restore anticancer immune responses by abrogating PD-1 pathway-mediated T-cell inhibition. Autoimmune adverse events are expected with PD-1 therapy. Fulminant type 1 diabetes is the subtype of type 1 diabetes. The clinical feature is the extremely rapid progression of hyperglycemia and ketoacidosis. Here we describe a 66-year-old woman with advanced melanoma who was treated with nivolumab. After 4 months and six doses of the medicine, the patient was admitted to the hospital with complaints of nausea and vomiting. The laboratory data showed ketonuria, hyperglycemia (531 mg/dl), high anion gap metabolic acidosis, HbA1c (7.3%), and absence of insulin-secreting capacity. These data are compatible with the criteria of fulminant type 1 diabetes. The patient was diagnosed with diabetic ketoacidosis because of fulminant type 1 diabetes. The findings of this case indicated that nivolumab can cause fulminant type 1 diabetes. Diabetic ketoacidosis due to fulminant type 1 diabetes is potentially fatal condition. Thus, diabetic ketoacidosis due to fulminant type 1 diabetes should be considered in the differential diagnosis when patients treated with nivolumab complain of gastrointestinal symptoms.

Short- and Long-Term Prognosis in Hemodynamically Stable Pulmonary Embolism With Unresectable or Metastatic Malignancies: The Role of Performance Status.

BACKGROUND: The simplified Pulmonary Embolism Severity Index (sPESI) has limitations when evaluating acute pulmonary embolism (PE) in patients with concurrent malignancy. Despite its utility in predicting outcomes among cancer patients, the role of the Eastern Cooperative Oncology Group Performance Status (ECOG PS) in acute PE remains underexplored. This study aims to assess the prognostic significance of ECOG PS ≥ 3 on short- and long-term mortality in acute PE with malignancy, correlating it with the sPESI. METHODS AND RESULTS: We retrospectively analyzed 44 hemodynamically stable acute PE patients with unresectable or metastatic malignancies ineligible for curative treatment at Kameda Medical Center, a tertiary medical facility in Japan, from April 1, 2019, to March 2, 2023. Of these patients, 16 (36.4%) had ECOG PS ≥ 3. No 30-day mortality occurred in patients with ECOG PS ≤ 2, compared to 18.8% in those with ECOG PS ≥ 3 (p = 0.04). Groups were similar in the sPESI scores, hospital-onset PE proportion, and initial treatments. Post PE diagnosis, 92.9% of ECOG PS ≤ 2 patients and 50% of ECOG PS ≥ 3 patients received chemotherapy (p = 0.002). Cox regression analysis revealed ECOG PS ≥ 3 was independently associated with increased overall survival hazard (adjusted HR = 4.0; P = 0.002). CONCLUSIONS: ECOG PS ≥ 3 suggests a poorer short-term prognosis and independently predicts a worse long-term prognosis in hemodynamically stable acute PE patients with advanced malignancies.

Combination Therapy of Atezolizumab, Bevacizumab, Carboplatin, and Paclitaxel for Metastatic Non-squamous Non-small Cell Lung Cancer With Epidermal Growth Factor Receptor (EGFR)-Tyrosine Kinase Inhibitor Resistance and EGFR Mutations.

INTRODUCTION: Atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) combination therapy has a potential efficacy in a specific subset of non-squamous non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations following tyrosine kinase inhibitor (TKI) treatment. However, there is a dearth of investigations on the effectiveness of ABCP therapy as the primary outcome of EGFR-TKI use. METHODS: A single-center retrospective analysis was performed on 24 cases of stage IV EGFR-positive non-squamous NSCLC patients who received one or more lines of EGFR-TKI therapy and subsequently initiated ABCP therapy within the timeframe of April 1, 2019, to April 30, 2023. This study assessed overall survival and progression-free survival associated with ABCP therapy, further analyzing the overall survival data based on EGFR subgroups. RESULTS: The mean age of the cohort was 65 ± 9 years with 14 females (58%). The performance status (PS) was recorded as 0 in 13 out of 24 patients (54%) and 1 in 11 out of 24 patients (46%). Thirteen (54%) patients had a history of smoking. Adenocarcinoma histology was prevalent in all cases. The EGFR mutations included Ex19del in 14 patients (58%) and L858R in 10 (42%) patients. At ABCP therapy initiation, liver metastases were evident in three cases (13%) and brain metastases in eight (33%). Programmed death ligand 1 (22C3) expression levels varied, with <1%, 1-49%, and ≥50% observed in five, 11, and five cases, respectively, while data were missing for three cases. The median follow-up duration was 14.1 months, with median overall survival estimated at 23.6 months (95% CI: 14.5 months - not reached) and median progression-free survival at 5.6 months (95% CI: 4.9-11.5 months). The EGFR L858R mutation showed a favorable trend in overall survival compared with the EGFR Ex19del mutation (not evaluated vs. 23.6 months). CONCLUSIONS: ABCP therapy for EGFR-positive non-squamous NSCLC is a promising option, similar to immune checkpoint inhibitor-free platinum-based combination therapy. Therefore, prospective trials are necessary to confirm the efficacy of these treatments.

Anti-asparaginyl tRNA synthetase (Anti-KS) antibody-positive pneumonitis in a patient with immune checkpoint inhibitor treatment: A case report and literature review.

In recent years, the use of immune checkpoint inhibitors (ICI) has increased and there have been case reports of anti- aminoacyl tRNA synthetase (ARS) antibody syndrome during ICI treatment. However, these cases are limited, and their clinical characteristics are not fully understood. We report the first case of anti ARS antibody syndrome with KS antibody during ICI therapy. This report presents our case, along with a literature review of other anti ARS antibody syndrome cases that developed after ICI use, discussing their clinical characteristics and possible mechanisms of onset. Considering the widespread use of ICI in cancer therapy, we should aware of anti ARS antibody syndrome that develops during use of ICI .

[Locally advanced squamous cell carcinoma of the buttocks, which had complete remission induced by chemoradiotherapy with carboplatin].

The patient was a 72-year-old male who had locally advanced squamous cell carcinoma(10×7 cm)in his buttocks that developed 18 months prior to admission. The lesion was unresectable because of the size and its invasion to the sacrum. We performed concomitant chemoradiotherapy with curative intent. External beam radiotherapy(68 Gy)was given with weekly carboplatin(AUC 2)and paclitaxel(30mg/m2). Because he developed cellulites in the irradiated skin, the concurrent chemotherapy was stopped during treatment(at 10 Gy). After improvement of the cellulites, paclitaxel was switched to S-1(80 mg/body/day)and concurrent chemoradiotherapy was completed without further toxicities. Progression of the tumor outside the irradiated field was seen 4 months after the treatment. Four courses of carboplatin (AUC 5)+infusional 5-FU(1, 000mg/m2 day 1-4)was administered as the tumor regressed. He died of sepsis 36 months post-treatment but the tumor remained stable without progression. Chemoradiotherapy may be an option for locally advanced non-melanoma skin cancer.

Autologous nonmyeloablative hematopoietic stem cell transplantation in patients with severe anti-TNF refractory Crohn disease: long-term follow-up.

We evaluated the safety and clinical outcome of autologous nonmyeloablative hematopoietic stem cell transplantation (HSCT) in patients with severe Crohn disease (CD) defined as a Crohn Disease Activity Index (CDAI) greater than 250, and/or Crohn Severity Index greater than 16 despite anti-tumor necrosis factor therapy. Stem cells were mobilized from the peripheral blood using cyclophosphamide (2.0 g/m(2)) and G-CSF (10 µg/kg/day), enriched ex vivo by CD34(+) selection, and reinfused after immune suppressive conditioning with cyclophosphamide (200 mg/kg) and either equine antithymocyte globulin (ATG, 90 mg/kg) or rabbit ATG (6 mg/kg). Eighteen of 24 patients are 5 or more years after transplantation. All patients went into remission with a CDAI less than 150. The percentage of clinical relapse-free survival defined as the percent free of restarting CD medical therapy after transplantation is 91% at 1 year, 63% at 2 years, 57% at 3 years, 39% at 4 years, and 19% at 5 years. The percentage of patients in remission (CDAI < 150), steroid-free, or medication-free at any posttransplantation evaluation interval more than 5 years after transplantation has remained at or greater than 70%, 80%, and 60%, respectively. This trial was registered at www.clinicaltrials.gov as NCT0027853.

Lobectomy versus segmentectomy: a propensity score-matched comparison of postoperative complications, pulmonary function and prognosis.

OBJECTIVES: To demonstrate the differences in clinical outcomes between lobectomy and segmentectomy for non-small cell lung cancer using propensity score matching. METHODS: A single-centre, retrospective, matched cohort study was conducted in clinical T1N0M0 non-small cell lung cancer patients treated by surgery between 2012 and 2019. Differences in freedom from recurrence, overall survival, postoperative complications, chest drainage and preservation of pulmonary function between lobectomy and segmentectomy were evaluated using the propensity score model. Matched variables of patients were age, sex, comorbidity index and pulmonary function. Matched variables of tumours were tumour size, T-stage, fluorodeoxyglucose uptake on positron emission tomography, histopathology, lobe site and tumour distance ratio from the hilum. RESULTS: Of the 112 patients treated by lobectomy and 233 patients treated by segmentectomy, 93 patients each from both groups were selected after the matching. The median tumour distance ratio from hilum was 0.7 in lobectomy and 0.8 in segmentectomy group (P = 0.59), i.e. almost outer third tumour location. There were no significant differences in freedom from recurrence (P = 0.38), overall survival (P = 0.51), postoperative complications (P = 0.94), drainage period (P = 0.53) and prolonged air leakage (P = 0.82) between the two. Median preservation of pulmonary function was 93.2% after segmentectomy, which was significantly higher than 85.9% after lobectomy (P < 0.001). CONCLUSIONS: Freedom from recurrence, overall survival, postoperative complications and chest drainage were similar between segmentectomy and lobectomy. Segmentectomy could be one of the options for clinical T1N0M0 non-small cell lung cancer located outer third as well as being able to preserve pulmonary function better than lobectomy.

Effectiveness of pembrolizumab in patients with urothelial carcinoma receiving proton pump inhibitors.

BACKGROUND: The association of concurrent proton pump inhibitor (PPI) use with treatment outcome of metastatic urothelial carcinoma (UC) remains controversial. MATERIALS AND METHODS: We retrospectively analyzed the records of 227 patients with platinum-treated metastatic UC treated with pembrolizumab. The primary outcome was overall survival (OS). Immune progression-free survival (iPFS) and objective response per immune response evaluation criteria in solid tumors were also compared. Inverse probability of treatment weighting (IPTW)-adjusted multivariable Cox regression models and an IPTW-adjusted multivariable logistic regression model were used to evaluate the oncological outcomes. Furthermore, the heterogeneity of the treatment effect on OS was examined using interaction terms within the IPTW-adjusted univariate Cox regression models. RESULTS: Overall, 86 patients (37.9%) used PPIs. After weighting, no significant differences in patient characteristics were observed between PPI users and non-users. PPI use was significantly associated with a shorter OS (hazard ratio [HR]: 2.02, 95% confidence interval [CI]: 1.28-3.18, P = 0.003) and iPFS (HR: 1.70, 95% CI: 1.23-2.35, P = 0.001). Although not statistically significant, PPI use was associated with objective response as well (OR: 0.61, 95% CI: 0.36-1.02, P = 0.06). The interaction analyses showed that the effect of PPI significantly decreased with age (HR: 0.97, 95% CI: 0.93-1.00, P[interaction] = 0.048) and was increased in males (HR: 2.97, 95% CI: 1.10-8.05, P[interaction] = 0.032). CONCLUSIONS: PPI use was significantly associated with worse survival of patients with metastatic UC treated with pembrolizumab. Furthermore, the results suggested that its effects decreased with age and was increased in males.

Psychological barriers to the use of opioid analgesics for treating pain in patients with advanced recurrent cancer (BAROC): protocol for a multicentre cohort study.

INTRODUCTION: Opioid analgesics are essential for treating cancer pain. However, patients are sometimes reluctant to use them because of concerns about addiction and dependence. Rapid pain relief following opioid administration may help overcome the psychological barriers to opioid analgesic use. This study aims to determine the relationship between psychological resistance to strong opioid analgesic use and pain amelioration speed in patients with advanced recurrent cancer. METHODS AND ANALYSIS: This ongoing, multicentre, observational study enrols patients aged 20 years or older with distant metastasis or advanced recurrent cancer receiving strong opioid analgesics for cancer pain for the first time. All participants, both inpatient and outpatient, were recruited from five Japanese hospitals. We are investigating the relationship between psychological barriers at the start of treatment and pain relief during the first week of treatment in these patients. The primary outcome is the Japanese version of the Barriers Questionnaire-II score at baseline. The secondary outcomes are the relationships between psychological barriers to strong opioid analgesic use and changes in pain over time. The participants are asked to fill out an electronic patient-reported outcome daily during the first week of treatment. The sample size was determined based on the number of patients in the year prior to study commencement who used strong opioid analgesics, met the eligibility criteria and could be expected to consent to participate in the study. ETHICS AND DISSEMINATION: The study protocol was approved by the ethics committee (approval ID B200600091) of Yokohama City University on 24 August 2020. The protocol has been reviewed by the institutional review boards at the four participating study sites. The results will be published in a peer-reviewed journal and will be presented at a relevant meeting. TRIAL REGISTRATION NUMBER: UMIN000042443.

Extent of Segmentectomy That Achieves Greater Lung Preservation Than Lobectomy.

BACKGROUND: This study sought to clarify the extent of segmentectomy that achieves greater lung preservation than lobectomy. METHODS: This was a single-center retrospective cohort study involving 374 patients with lung cancer who were treated with either lobectomy or segmentectomy between 2013 and 2018. The percentage of preserved pulmonary function (%PPF) after surgery was compared among patients who underwent lobectomy (n = 164), segmentectomy of 2 or more segments (Seg ≥2S; n = 42), and segmentectomy of less than 2 segments (Seg <2S; n = 168). Using perfusion scintigraphy, forced expiratory volume in 1 second of the preserved target lobe was measured to examine its effect on the %PPF. The number of resected subsegments (SSs) in segmentectomy that made the %PPF higher than that observed with lobectomy was also examined. RESULTS: Mean %PPF was lowest in those patients who underwent lobectomy (86%), followed by Seg ≥2S (89%) and Seg <2S (95%) (P < .001), but the difference between the lobectomy and Seg ≥2S was not significant (P = .21). The forced expiratory volume in 1 second of the preserved target lobe was significantly lower in the Seg ≥2S group than in the Seg <2S group (P < .001). The number of resected SSs was 6 to 12 in lobectomy, 4 to 7 in Seg ≥2S, and 1 to 4 in Seg <2S. Although the %PPF after segmentectomy of less than 5 SSs (Seg <5SS) was significantly higher than that after lobectomy (P < .001), the %PPF after segmentectomy of 5 or more SSs (Seg ≥5SS) was not significantly different from that after lobectomy (P = .68). CONCLUSIONS: Both the Seg ≥2S and Seg ≥5SS groups did not differ from lobectomy in %PPF because of the low function of preserved target lobe.

Differences between lung adenocarcinoma and squamous cell carcinoma in histological distribution of residual tumor after induction chemoradiotherapy.

AIMS: To facilitate dose planning for convergent beam radiotherapy in non-small cell lung cancer (NSCLC), tumor response and histological distribution of residual tumors after induction chemoradiotherapy (ICRT) were compared between adenocarcinoma (AD) and squamous cell carcinoma (SQ). METHODS: Ninety-five patients with N1-2 or T3-4 NSCLC were treated with ICRT followed by surgery; 55 had AD and 40 had SQ. For the evaluation of distribution of residual tumors, the location of the external margin of residual tumors was assessed on surgical materials as follows: radius of whole tumor ("a"); distance between the center of tumor and the external margin of residual tumor ("b"); and its location ("b/a"). RESULTS: Of the 55 AD cases, 8 (15%) showed pathological complete remission, which was significantly less frequent than 22 of 40 SQ cases (55%) (p < 0.001). AD showed the residual tumors at the most periphery of tumor (b/a = 1.0) more frequently than SQ, i.e., 39/55 (71%) versus 6/40 (15%), respectively (p < 0.001). Even in 65 cases other than the pathological complete remission, external margins in 47 AD cases located more periphery than those in 18 SQ cases, of which mean b/a values were 0.97 ± 0.17 and 0.70 ± 0.29, respectively (p < 0.001). CONCLUSION: AD showed worse tumor response to ICRT than SQ. After ICRT, AD remained at the periphery of primary tumor more frequently than SQ. It seems that, also in the convergent beam radiotherapy, the periphery part of AD would be more resistant than that of SQ.