Non-pharmacological treatments for anticipatory nausea and vomiting during chemotherapy: a systematic review and meta-analysis of the Clinical Practice Guidelines for Antiemesis 2023.

BACKGROUND: Anticipatory chemotherapy-induced nausea and vomiting (CINV) is a conditioned response influenced by the severity and duration of previous emetic responses to chemotherapy. We aimed to evaluate the efficacy of non-pharmacologic interventions for anticipatory CINV among patients with cancer. METHODS: We conducted a systematic search in databases, including PubMed, the Cochrane Library, CINAHL, and Ichushi-Web, from January 1, 1990, to December 31, 2020. Randomized controlled trials, non-randomized designs, observational studies, or case-control studies that utilized non-pharmacological therapies were included. The primary outcomes were anticipatory CINV, with an additional investigation into adverse events and the costs of therapies. The risk-of-bias for each study was assessed using the Cochrane risk-of-bias tool, and meta-analysis was performed using Revman 5.4 software. RESULTS: Of the 107 studies identified, six met the inclusion criteria. Three types of non-pharmacological treatments were identified: systematic desensitization (n = 2), hypnotherapy (n = 2), and yoga therapy (n = 2). Among them, systematic desensitization significantly improved anticipatory CINV as compared to that in the control group (nausea: risk ratio [RR] = 0.60, 95% confidence interval [CI] = 0.49-0.72, p < 0.00001; vomiting: RR = 0.54, 95% CI = 0.32-0.91, p = 0.02). However, heterogeneity in outcome measures precluded meta-analysis for hypnotherapy and yoga. Additionally, most selected studies had a high or unclear risk of bias, and adverse events were not consistently reported. CONCLUSIONS: Our findings suggest that systematic desensitization may effectively reduce anticipatory CINV. However, further research is warranted before implementation in clinical settings.

2023 Japan Society of clinical oncology clinical practice guidelines update for antiemesis.

BACKGROUND: The Japan Society of Clinical Oncology Clinical Practice Guidelines for Antiemesis 2023 was extensively revised to reflect the latest advances in antineoplastic agents, antiemetics, and antineoplastic regimens. This update provides new evidence on the efficacy of antiemetic regimens. METHODS: Guided by the Minds Clinical Practice Guideline Development Manual of 2017, a rigorous approach was used to update the guidelines; a thorough literature search was conducted from January 1, 1990, to December 31, 2020. RESULTS: Comprehensive process resulted in the creation of 13 background questions (BQs), 12 clinical questions (CQs), and three future research questions (FQs). Moreover, the emetic risk classification was also updated. CONCLUSIONS: The primary goal of the present guidelines is to provide comprehensive information and facilitate informed decision-making, regarding antiemetic therapy, for both patients and healthcare providers.

Adjuvant treatments for locally advanced differentiated thyroid cancer: a nationwide survey in Japan.

The role of adjuvant external-beam radiotherapy (EBRT) for locally advanced differentiated thyroid cancer (DTC) is controversial because of the lack of prospective data. To prepare for a clinical trial, this study investigated the current clinical practice of adjuvant treatments for locally advanced DTC. A survey on treatment selection criteria for hypothetical locally advanced DTC was administered to representative thyroid surgeons of facilities participating in the Japan Clinical Oncology Group Radiation Therapy Study Group. Of the 43 invited facilities, surgeons from 39 (91%) completed the survey. For R1 resection or suspected residual disease, 26 (67%) facilities administered high-dose (100-200 mCi) radioactive iodine (RAI), but none performed EBRT. For R2 resection or unresectable primary disease, 26 (67%) facilities administered high-dose RAI and 7 (18%) performed adjuvant treatments, including EBRT. For complete resection with nodal extra-capsular extension, 13 (34%) facilities administered high-dose RAI and 1 (3%) performed EBRT. For unresectable mediastinal lymph node metastasis, 31 (79%) facilities administered high-dose RAI and 5 (13%) performed adjuvant treatments, including EBRT. Adjuvant EBRT was not routinely performed mainly because of the lack of evidence for efficacy (74%). Approximately 15% of the facilities routinely considered adjuvant EBRT for DTC with R2 resection or unresectable primary or lymph node metastasis disease. Future clinical trials will need to optimize EBRT for these patients.

Who should receive single-fraction palliative radiotherapy for gastric cancer bleeding?: An exploratory analysis of a multicenter prospective observational study (JROSG 17-3).

Purpose: Although the Palliative Prognostic Index (PPI) has been used to predict survival in various cancers, to our knowledge, no study has examined its applicability in gastric cancer. This study aimed to determine the baseline PPI cutoff value for recommending single-fraction radiotherapy in patients with bleeding gastric cancer. Materials and methods: This was a secondary analysis of the Japanese Radiation Oncology Study Group (JROSG) 17-3, a multicenter prospective study of palliative radiotherapy for bleeding gastric cancer. Discrimination was evaluated using a time-dependent receiver operating characteristic curve, and the optimal cutoff value was determined using the Youden index. A calibration plot was used to assess the agreement between predicted and observed survival. Results: We enrolled 55 patients in JROSG 17-3. The respective median survival times were 6.7, 2.8, and 1.0 months (p = 0.021) for patients with baseline PPI scores of ≤ 2, 2 < PPI ≤ 4, and PPI > 4. The areas under the curve for predicting death within 2, 3, 4, and 5 months were 0.813, 0.787, 0.775, and 0.721, respectively. The negative predictive value was highest when survival < 2 months was predicted and the Youden index was highest when the cutoff PPI value was 2. The calibration curve showed a reasonable agreement between the predicted and observed survival. Conclusion: Baseline PPI is useful for estimating short-term prognosis in patients treated with palliative radiotherapy for gastric cancer bleeding. A cutoff PPI value of 2 for estimating survival ≤ 2 months should be used to recommend single-fraction radiotherapy.

Pain Response Rates After Conventional Radiation Therapy for Bone Metastases Assessed Using International Consensus Pain Response Endpoints: A Systematic Review and Meta-Analysis of Initial Radiation Therapy and Reirradiation.

Previous meta-analysis of conventional radiation therapy for painful bone metastases showed overall response (OR) rates of 72% to 75% (evaluable patients), 61% to 62% (intent-to-treat patients) for initial radiation therapy, and 68% for reirradiation (evaluable patients). However, the definition of pain response differed among the studies included. Hence, we conducted a systematic review and meta-analysis to determine the pain response rates assessed by the International Consensus Pain Response Endpoints (ICPRE) for both initial radiation therapy and reirradiation. The PubMed and Scopus databases were searched for articles published between 2002 and 2021. The inclusion criteria were (1) prospective studies or studies based on prospectively collected data and (2) studies in which pain response was assessed using ICPRE. Our primary outcomes of interest were the OR rates (sum of the complete and partial response rates) for both initial radiation therapy and reirradiation. Of the 6470 articles identified in our database search, 32 and 3 met the inclusion criteria for the analysis of initial radiation therapy and reirradiation, respectively. The OR rates of initial radiation therapy in evaluable patients (n = 4775) and intent-to-treat patients (n = 6775) were 60.4% (95% confidence interval [CI], 55.2-65.4) and 45.4% (95% CI, 38.7-52.4), respectively. The OR rates of reirradiation in evaluable patients (n = 733) and intent-to-treat patients (n = 1085) were 70.8% (95% CI, 15.7-96.9) and 62.2% (95% CI, 5.3-98.0), respectively. Subgroup analyses of initial radiation therapy including the comparison of randomized and nonrandomized studies showed no significant differences in any comparison, indicating similar response rates across different study designs. For initial radiation therapy, we determined the ICPRE-assessed response rates, which were lower than previously reported. The OR and complete response rates should be benchmarks for future randomized and nonrandomized studies. For reirradiation, the wide CIs demonstrate that the response rates based on ICPRE require further investigation.

Protocol for a confirmatory trial of the effectiveness and safety of palliative arterial embolization for painful bone metastases.

BACKGROUND: Transcatheter arterial embolization (TAE) has long been used for hemostasis of traumatic or postoperative hemorrhage and embolization of tumors. Previous retrospective studies of TAE for painful bone metastases showed 60%-80% pain reduction with a median time to response of 1-2 days. Compared with radiotherapy and bisphosphonates, time to response appeared earlier than that of radiotherapy or bone-modifying agents. However, few prospective studies have examined TAE for this indication. Here, we describe the protocol for a confirmatory study designed to clarify the efficacy and safety profile of TAE. METHODS: This study will be a multicenter, single-arm confirmatory study (phase 2-3 design). Patients with painful bone metastases from any primary tumor are eligible for enrollment. TAE will be the main intervention. Following puncture of the femoral artery under local anesthesia and insertion of an angiographic sheath, angiography will confirm that the injected region includes tumor vasculature. Catheter position will be adjusted so that the embolization range does not include non-target tissues. Spherical embolic material will then be slowly injected into the artery to embolize it. The primary endpoint (efficacy) is the proportion of subjects with pain relief at 72 h after TAE and the secondary endpoint (safety) is the incidence of all NCI Common Terminology Criteria for Adverse Events version 5.0 Grade 4 adverse events and Grade ≥ 3 necrosis of the central nervous system. DISCUSSION: If the primary and secondary endpoints are met, TAE can be a treatment choice for painful bone metastases. Trial registry number is UMIN-CTR ID: UMIN000040794. TRIAL REGISTRATION: The study is ongoing, and patients are currently being enrolled. Enrollment started in March 2021. A total of 36 patients have participated as of Aug 2022. PROTOCOL VERSION: Ver1.4, 13/07/2022.

Patient-reported outcome and quality of life research policy: Japan Clinical Oncology Group (JCOG) policy.

Assessments of patient-reported outcomes and health-related quality of life in cancer clinical trials have been increasingly emphasized recently because patient and public involvement in cancer treatment development has been promoted by regulatory authorities and academic societies. To assess patient experiences during and after cancer treatment, there is interest in implementing patient-reported outcome and health-related quality of life assessments into cancer clinical trials. The Japan Clinical Oncology Group quality of life ad hoc committee previously created a version of the Quality of Life Assessment Policy in 2006. Recently, there has been increasing demand from Japan Clinical Oncology Group researchers to assess patient-reported outcome/health-related quality of life in clinical trials. Although guidelines are available regarding planning and reporting clinical trials that include patient-reported outcome/health-related quality of life as an endpoint, there are still issues regarding the lack of consensus on standardized methods for analysing and interpreting the results. Hence, it was considered necessary to reorganize the Japan Clinical Oncology Group patient-reported outcome/quality of life research committee and to revise the former patient-reported outcome/quality of life research policy to promote patient-reported outcome/health-related quality of life research in future Japan Clinical Oncology Group trials. The purpose of this Japan Clinical Oncology Group patient-reported outcome/quality of life research policy is to define patient-reported outcome/health-related quality of life research and provide guidelines for including patient-reported outcome/health-related quality of life as an endpoint in Japan Clinical Oncology Group trials.

Incidence of and risk factors for non-hematologic toxicity with combined radiotherapy and CDK4/6 inhibitors in metastatic breast cancer using dose-volume parameters analysis: a multicenter cohort study.

BACKGROUND: There is a lack of data on combined radiotherapy (RT) and cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i) risk factors and toxicity. This study aimed to assess the incidence of and risk factors for non-hematologic toxicities in patients treated with combined RT and CDK4/6i using dose-volume parameter analysis. METHODS: We conducted a retrospective multicenter cohort study of patients with metastatic breast cancer receiving RT within 14 days of CDK4/6i use. The endpoint was non-hematologic toxicities. Patient characteristics and RT treatment planning data were compared between the moderate or higher toxicities (≥ grade 2) group and the non-moderate toxicities group. RESULTS: Sixty patients were included in the study. CDK4/6i was provided at a median daily dose of 125 mg and 200 mg for palbociclib and abemaciclib, respectively. In patients who received concurrent RT and CDK4/6i (N = 29), the median concurrent prescribed duration of CDK4/6i was 14 days. The median delivered RT dose was 30 Gy and 10 fractions. The rate of grade 2 and 3 non-hematologic toxicities was 30% and 2%, respectively. There was no difference in toxicity between concurrent and sequential use of CDK4/6i. The moderate pneumonitis group had a larger lung V20 equivalent dose of 2 Gy per fraction and planning target volume than the non-moderate pneumonitis group. CONCLUSIONS: Moderate toxicities are frequent with combined RT and CDK4/6i. Caution is necessary concerning the combined RT and CDK4/6i. Particularly, reducing the dose to normal organs is necessary for combined RT and CDK4/6i.

Subclinical and latent cardiac dysfunction in obstructive sleep apnea and effectiveness of continuous positive airway pressure.

PURPOSE: Obstructive sleep apnea (OSA) is associated with various cardiovascular disorders. This study aimed to investigate the effects of OSA on left ventricular (LV) function in patients with OSA who were at risk for heart failure but who had not yet developed structural heart changes. The study also sought to determine the effects of continuous positive airway pressure (CPAP) in these patients. METHODS: In a retrospective study, consecutive patients with polysomnographic OSA (apnea-hypopnea index [AHI] >5) were categorized into mild (AHI < 15), moderate (15 ≤ AHI < 30), and severe OSA (AHI ≥ 30) groups. The subjects were patients with OSA and at risk for heart failure who had not yet developed structural heart changes. All study participants underwent echocardiography and two-dimensional speckle tracking analysis, and their global longitudinal strain (GLS) was calculated. RESULTS: Of 275 patients, there were 31 with mild, 92 with moderate, and 152 with severe OSA. Of patients with moderate to severe OSA (AHI ≥ 20), 206 started CPAP and 92 patients underwent follow-up echocardiogram and speckle tracking echo analysis (median period of CPAP use: 283 days [258 to 391]). GLS was significantly reduced in patients with moderate and severe OSA compared with mild OSA (-17.8±3.1 vs. -18.0±2.6 vs. -19.3±2.8%, p=0.038). The proportion of patients with GLS ≥ -18% was significantly higher among the patients with moderate to severe OSA than among those with mild OSA. GLS improved after CPAP therapy in patients with moderate to severe OSA (GLS: -18.1±2.7% to -19.0±2.8%, p=0.004). Significant improvement in GLS was confirmed, particularly among patients with good CPAP adherence. CONCLUSION: Moderate to severe OSA is associated with LV dysfunction and can be significantly improved by CPAP therapy.

Acute Myocardial Infarction Due to Coronary Artery Embolism during Chemotherapy with mFOLFOX-6 Plus Bevacizumab for Metastatic Colon Cancer.

Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, may be associated with arterial embolisms. We herein report a case of acute myocardial infarction caused by coronary embolism during combination chemotherapy with mFOLFOX-6 and bevacizumab in a patient with metastatic colon cancer. Thromboembolism occurred only in the distal right posterolateral branch without stenotic lesions or plaque rupture in the proximal branch of the right coronary artery. Sole thromboaspiration was successfully performed; the final angiogram demonstrated no stenosis in the right coronary artery. Bevacizumab may be associated with acute coronary syndrome in patients with coronary risk factors, despite no significant coronary narrowing.

Emergency Transcatheter Aortic Valve Implantation in a Surgical Aortic Bioprosthetic Valve for Acute Decompensated Heart Failure Caused by Sudden Progression of Structural Valve Deterioration.

Bioprosthetic aortic valves have limited durability. We herein report sudden progression of structural valve deterioration (SVD) and a successful case of emergency transcatheter aortic valve (TAV) implantation for acute decompensated heart failure (ADHF) caused by SVD. A 79-year-old man who had undergone a Bentall operation 11 years prior was diagnosed with ADHF due to suddenly progressive SVD. Emergency TAV implantation in the surgical bioprosthetic valve was selected based on the surgical risk. Ours and previous case reports suggest that SVD can progress suddenly, even after months of stability, and that emergency TAV implantation is effective.

Bias due to statistical handling of death and reirradiation in the assessment of duration of response after palliative radiotherapy: a scoping review and analysis of clinical data.

OBJECTIVES: We investigated the influence of handling death and reirradiation on the estimation of duration of response (DOR). METHODS: First, we performed a scoping review on methods to assess DOR in palliative radiotherapy. Second, we performed three different analyses on a subgroup of patients from a previously published prospective study. The first analysis was a competing risks analysis considering relapse of pain as the event of interest and death and reirradiation as competing events (Analysis A). The second and third analyses were standard survival analyses where the event of interest was a composite outcome of relapse of pain, death, or reirradiation (Analysis B) and relapse of pain (Analysis C), respectively. RESULTS: Death was considered as an event of interest in less than half of the papers, while reirradiation was not considered in any of the studies. Competing risks analysis was not performed in any of the studies. In the analysis of clinical data, competing risks analysis showed that relapse of pain predominated as the cause of the end of response. Median DOR was correctly estimated to be 4.1 months in Analyses A and B, but was overestimated to be 8.1 months in Analysis C. CONCLUSIONS: Death and reirradiation should be treated as the events of interest that mark the end of response (as in Analyses A and B) to avoid overestimation of treatment efficacy and an invalid assumption of independent censoring. ADVANCES IN KNOWLEDGE: The definition of end of response remains inconclusive in the assessment of DOR. We recommend competing risks analysis (Analysis A), by which we can estimate cumulative incidence of each event type and evaluate the necessity of reirradiation.

Intravenous immunoglobulin for acute exacerbation of fibrotic idiopathic interstitial pneumonias.

BACKGROUND AND AIM: Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is a fatal condition with no established treatment. Intravenous immunoglobulin (IVIG) is a unique therapy with both anti-inflammatory and anti-infective effects. Therefore, we hypothesized that IVIG may have a positive effect on AE of interstitial pneumonia. This study aimed to determine the effect of IVIG in patients with AE of fibrotic idiopathic interstitial pneumonias (IIPs), including IPF. METHODS: We retrospectively analyzed consecutive patients who were diagnosed with AE of fibrotic IIPs and treated with pulse corticosteroid therapy (methylprednisolone 500-1000 mg/day for 3 days) between April 2018 and May 2021 at Kagawa Rosai Hospital and KKR Takamatsu Hospital. RESULTS: This study included 52 patients with AE of fibrotic IIPs (IPF,41; fibrotic IIPs other than IPF,11). Thirteen patients received IVIG (5 g/day for 3-5 days) concurrently with pulse corticosteroid therapy. The remaining 39 patients were assigned to the control group. The survival rate on day 90 was significantly higher in the IVIG group than that in the control group (76.9% vs. 38.5%, p = 0.02). IVIG administration (odds ratio [OR], 0.11; 95% confidence interval [CI], 0.02-0.69; p = 0.02) and C- reactive protein (OR, 1.19; 95% CI, 1.06-1.33, p < 0.01) were independently associated with 90-day mortality. CONCLUSIONS: The results indicate that administration of IVIG may improve the survival of patients with AE of fibrotic IIPs. We are now conducting a prospective study to confirm the effect of IVIG on AE of IPF since May 2022 (jRCT1061220010).

Availability of and factors related to interventional procedures for refractory pain in patients with cancer: a nationwide survey.

BACKGROUND: Cancer pain may be refractory to standard pharmacological treatment. Interventional procedures are important for quality of analgesia. The aim of the present study was to clarify the availability of four interventional procedures (celiac plexus neurolysis/splanchnic nerve neurolysis, phenol saddle block, epidural analgesia, and intrathecal analgesia), the number of procedures performed by specialists, and their associated factors. In addition, we aimed to establish how familiar home hospice physicians and oncologists are with the different interventional procedures available to manage cancer pain. METHODS: A cross-sectional survey using a self-administered questionnaire was conducted. Subjects were certified pain specialists, interventional radiologists, home hospice physicians, and clinical oncologists. RESULTS: The numbers of valid responses/mails were 545/1,112 for pain specialists, 554/1,087 for interventional radiology specialists, 144/308 for home hospice physicians, and 412/800 for oncologists. Among pain specialists, depending on intervention, 40.9-75.2% indicated that they perform each procedure by themselves, and 47.5-79.8% had not performed any of the procedures in the past 3 years. Pain specialists had performed the four procedures 4,591 times in the past 3 years. Among interventional radiology specialists, 18.1% indicated that they conduct celiac plexus neurolysis/splanchnic nerve neurolysis by themselves. Interventional radiology specialists had performed celiac plexus neurolysis/splanchnic nerve neurolysis 202 times in the past 3 years. Multivariate analysis revealed that the number of patients seen for cancer pain and the perceived difficulty in gaining experience correlated with the implementation of procedures among pain specialists. Among home hospice physicians and oncologists, depending on intervention, 3.5-27.1% responded that they were unfamiliar with each procedure. CONCLUSIONS: Although pain specialists responded that the implementation of each intervention was possible, the actual number of the interventions used was limited. As interventional procedures are well known, it is important to take measures to ensure that pain specialists and interventional radiology physicians are sufficiently utilized to manage refractory cancer pain.

Stereotactic body radiotherapy versus conventional radiotherapy for painful bone metastases: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is a promising approach in treating painful bone metastases. However, the superiority of SBRT over conventional external beam radiotherapy (cEBRT) remains controversial. Therefore, this systematic review and meta-analysis of randomised controlled trials was conducted to compare SBRT and cEBRT for the treatment of bone metastases. METHODS: A search was conducted using PubMed on January 22, 2022, with the following inclusion criteria: (i) randomised controlled trials comparing SBRT with cEBRT for bone metastases and (ii) endpoint including pain response. Effect sizes across studies were pooled using random-effects models in a meta-analysis of risk ratios. RESULTS: A total of 1246 articles were screened, with 7 articles comprising 964 patients (522 and 442 patients in the SBRT and cEBRT arms, respectively) meeting the inclusion criteria. The overall pain response (OR) rates of bone metastases at 3 months were 45% and 36% in the SBRT and cEBRT arms, respectively. The present analyses showed no significant difference between the two groups. In four studies included for the calculation of OR rates of spinal metastases at three months, the OR rates were 40% and 35% in the SBRT and cEBRT arms, respectively, with no significant difference between the two groups. The incidence of severe adverse effects and health-related quality of life outcomes were comparable between the two arms. CONCLUSIONS: The superiority of SBRT over cEBRT for pain palliation in bone metastases was not confirmed in this meta-analysis. Although SBRT is a standard of care for bone metastases, patients receiving SBRT should be selected appropriately.

Tumor response and survival outcomes of salvage concurrent chemoradiotherapy with three-dimensional conformal radiotherapy and 5-fluorouracil/platinum-based chemotherapy for postoperative locoregional recurrence of esophageal squamous cell carcinoma.

BACKGROUND: Salvage concurrent chemoradiotherapy is effective against locoregional recurrence after curative resection of esophageal squamous cell carcinoma. However, there is no consensus on its application. We investigated the outcomes of salvage concurrent chemoradiotherapy (60 Gy in 30 fractions) with three-dimensional conformal radiotherapy and 5-fluorouracil/platinum-based chemotherapy. METHODS: We retrospectively investigated the outcomes and prognostic factors in 51 patients with esophageal squamous cell carcinoma treated with salvage concurrent chemoradiotherapy. RESULTS: The median follow-up was 17.5 (range, 2.8-116.1) months. The overall response, complete response, and partial response rates were 74.5%, 49.0%, and 25.5%, respectively. The median progression-free survival was 8.2 months; the 3-year progression-free survival rate was 22.9%. The median overall survival was 23.1 months; the 3-year overall survival rate was 40.7%. Overall survival was significantly longer in patients with a complete response than in those without (median overall survival: not reached vs. 15.3 months); 3-year overall survival rate: 62.5% vs. 20.3% (hazard ratio: 0.222; P < 0.001). Multivariate analysis showed that the independent prognostic factor for overall survival was < 25 mm longest diameter of metastatic lymph nodes (hazard ratio: 3.71). CONCLUSIONS: Salvage concurrent chemoradiotherapy (60 Gy in 30 fractions) with three-dimensional conformal radiotherapy and 5-fluorouracil/platinum-based chemotherapy was an effective and safe treatment for locoregional recurrence after curative resection of esophageal squamous cell carcinoma, especially in those approaching a complete response. Additionally, a shorter longest diameter of metastatic lymph nodes may be associated with better long-term survival.

Quality Indicators in Palliative Radiation Oncology: Development and Pilot Testing.

PURPOSE: A quality indicator (QI) is a valuable tool to evaluate the quality of health care systems. In palliative radiation oncology, only a few related QIs have been developed to date. In this study, we sought to develop and pilot test QIs that assess the quality of care in palliative radiation therapy. METHODS AND MATERIALS: A modified Delphi method was used to establish consensus with an expert panel. The panel consisted of 8 radiation oncologists who have expertise in palliative radiation oncology and 1 expert on Delphi methodology. Online panel meetings and e-mail surveys were conducted to develop QIs on palliative radiation therapy for bone and brain metastases. Feasibility of measurement was assessed though pilot surveys that were conducted by radiation oncologists at 5 facilities. RESULTS: After 3 online meetings and 2 e-mail surveys, we developed 4 QIs on bone metastases and 3 QIs on brain metastases. Two email surveys and 2 pilot surveys confirmed the validity of QIs and the feasibility of measurement, respectively. CONCLUSIONS: We developed valid and feasible QIs on palliative radiation therapy for bone and brain metastases. Our work may contribute to reduce the evidence-practice gaps in palliative radiation oncology.

Preoperative Chemoradiotherapy plus Nivolumab before Surgery in Patients with Microsatellite Stable and Microsatellite Instability-High Locally Advanced Rectal Cancer.

PURPOSE: Preoperative chemoradiotherapy (CRT) and surgical resection are the standard treatment for locally advanced rectal cancer (LARC). Combining immune checkpoint inhibitors with radiation suggests a promising approach for enhancing efficacy. We investigated the efficacy of CRT followed by nivolumab and surgery in patients with LARC. PATIENTS AND METHODS: In phase I, we investigated the feasibility of sequentially combined CRT, 5 cycles of nivolumab, and radical surgery. In phase II, patients with microsatellite stable (MSS) and microsatellite instability-high (MSI-H) LARC were evaluated. RESULTS: Three patients in phase I received full courses of CRT and nivolumab without dose modification; the schedule was recommended for phase II. A pathologic complete response (pCR) was centrally confirmed in 30% [11/37; 90% confidence interval (CI), 18%-44%] and 60% (3/5) of the MSS and exploratory MSI-H cohorts, respectively. While immune-related severe adverse events were observed in 3 patients, no treatment-related deaths were observed. In 38 patients with MSS who underwent surgery, pCR rates of 75% (6/8) and 17% (5/30; P = 0.004, Fisher exact test) were observed in those with programmed cell death ligand 1 (PD-L1) tumor proportion score ≥1% and <1%, respectively; IHC staining was performed using pre-CRT samples. In 24 patients with MSS, pre-CRT samples were analyzed by flow cytometry; pCR rates of 78% (7/9) and 13% (2/15; P = 0.003, Fisher exact test) were observed for CD8+ T cell/effector regulatory T cell (CD8/eTreg) ratios of ≥2.5 and <2.5, respectively, in tumor-infiltrating lymphocytes. CONCLUSIONS: CRT followed by consolidation nivolumab could increase pCR. PD-L1 expression and an elevated CD8/eTreg ratio were positive predictors in patients with MSS LARC.