Supportive Care Group Research Articles

Palliative radiotherapy versus best supportive care in patients with painful hepatic cancer (CCTG HE1): a multicentre, open-label, randomised, controlled, phase 3 study

Palliative treatment options for painful hepatic cancer can be restricted due to patients eventually becoming refractory to standard treatment. The aim of this study was to determine whether radiotherapy improves hepatic pain from cancer. In this open-label, randomised, controlled, phase 3 trial (CCTG HE1) done in nine cancer centres across Canada, we included patients aged 18 years or older with hepatocellular carcinoma or liver metastases, who were refractory to standard treatment, with an Eastern Cooperative Oncology Group performance status of 0-3, with life expectancy of more than 3 months, and pain or discomfort at its worst in the past 24 hours on the Brief Pain Inventory (BPI) of at least 4 out of 10, which was stable for up to 7 days before randomisation. Patients were randomly assigned (1:1), via a minimisation method after stratification by centre and type of cancer (hepatocellular carcinoma vs liver metastases), to single-fraction radiotherapy (8 Gy) to the liver with 8 mg ondansetron (or equivalent) orally and 4 mg dexamethasone orally given 1-2 h before radiotherapy plus best supportive care (including non-opioid or opioid analgesia, or dexamethasone, or a combination of these) or best supportive care alone. The primary endpoint was improvement in patient-reported liver cancer pain or discomfort of at least 2 points on worst pain intensity on the BPI at 1 month after randomisation. All patients with both baseline and 1-month assessments were included in the primary endpoint analysis. Safety was assessed in all patients randomly assigned to treatment. This trial is registered with ClinicalTrials.gov, NCT02511522, and is complete. Between July 25, 2015, and June 2, 2022, 66 patients were screened and randomly assigned to radiotherapy plus best supportive care (n=33) or best supportive care (n=33). Median age was 65 years (IQR 57-72), 37 (56%) of 66 patients were male, 29 (44%) were female, 43 (65%) had liver metastases, and 23 (35%) had hepatocellular carcinoma (data on race and ethnicity were not collected). As of data cutoff (Sept 8, 2022), median follow-up was 3·2 months (95% CI 3·0-3·4). 24 (73%) of 33 in the radiotherapy plus best supportive care group and 18 (55%) of 33 in the best supportive care only group completed baseline and 1-month assessments. An improvement in hepatic pain of at least 2 points in worst pain intensity on the BPI at 1 month was seen in 16 (67%) of 24 patients in the radiotherapy plus best supportive care group versus four (22%) of 18 patients in the best supportive care group (p=0·0042). The most common grade 3-4 adverse events within 1 month after randomisation were abdominal pain (three [9%] of 33 in the radiotherapy group vs one [3%] of 33 in best supportive care group) and ascites (two [6%] vs one [3%]). No serious adverse events or treatment-related deaths were observed. Single-fraction radiotherapy plus best supportive care improved pain compared with best supportive care alone in patients with liver cancer, and could be considered a standard palliative treatment. Canadian Cancer Society.

Dendritic cells loaded with allogeneic tumour cell lysate plus best supportive care versus best supportive care alone in patients with pleural mesothelioma as maintenance therapy after chemotherapy (DENIM): a multicentre, open-label, randomised, phase 2/3 study

Dendritic cell immunotherapy has proven to be safe and induces an immune response in humans. We aimed to establish the efficacy of dendritic cells loaded with allogeneic tumour cell lysate (MesoPher, Amphera BV, 's-Hertogenbosch, Netherlands) as maintenance therapy in patients with pleural mesothelioma. In this open-label, randomised, phase 2/3 study, patients with histologically confirmed unresectable pleural mesothelioma, aged 18 years or older, with an Eastern Cooperative Oncology Group performance status score of 0-1, and non-progressing disease after four to six cycles of standard chemotherapy (with pemetrexed 500 mg/m2 plus platinum [cisplatin 75 mg/m2 or carboplatin area under the curve of 5]) were recruited from four centres in Belgium, France, and The Netherlands. Participants were randomly assigned (1:1), using block randomisation (block size of 4), stratified by centre and histology (epithelioid vs other), to MesoPher treatment plus best supportive care or best supportive care alone. Patients received up to a maximum of five MesoPher infusions, with treatment administered on days 1, 15, and 29, and weeks 18 and 30. At each timepoint, participants received an injection of 25 × 106 dendritic cells (two-thirds of the dendritic cells were administered intravenously and a third were injected intradermally). Best supportive care was per local institutional standards. The primary endpoint was overall survival, assessed in all participants randomly assigned to treatment (full analysis set) and safety assessed in all randomly assigned participants, and who underwent leukapheresis if they were in the MesoPher group. This study is registered with ClinicalTrials.gov, NCT03610360, and is closed for accrual. Between June 21, 2018, and June 10, 2021, 176 patients were screened and randomly assigned to the MesoPher group (n=88) or best supportive care alone group (n=88). One participant in the MesoPher group did not undergo leukapheresis. Mean age was 68 years (SD 8), 149 (85%) of 176 were male, 27 (15%) were female, 173 (98%) were White, two were Asian (1%), and one (1%) was other race. As of data cutoff (June 24, 2023), after a median follow up of 15·1 months (IQR 9·5-22·4), median overall survival was 16·8 months (95% CI 12·4-20·3; 61 [69%] of 88 died) in the MesoPher group and 18·3 months (14·3-21·9; 59 [67%] of 88 died) in the best supportive care group (hazard ratio 1·10 [95% CI 0·77-1·57]; log-rank p=0·62). The most common grade 3-4 treatment-emergent adverse events were chest pain (three [3%] of 87 in the MesoPher group vs two [2%] of 88 in the best supportive care group), dyspnoea (none vs two [2%]), anaemia (two [2%] vs none), nausea (none vs two [2%]), and pneumonia (none vs two [2%]). No deaths due to treatment-emergent adverse events were recorded. Treatment-related adverse events consisted of infusion-related reactions (fever, chills, and fatigue), which occurred in 64 (74%) of 87 patients in the MesoPher group, and injection-site reactions (itch, erythema, and induration), which occurred in 73 (84%) patients, and all were grade 1-2 in severity. No deaths were determined to be treatment related. MesoPher did not show improvement in overall survival in patients with pleural mesothelioma. Immune checkpoint therapy is now standard of care in pleural mesothelioma. Further randomised studies are needed of combinations of MesoPher and immune checkpoint therapy, which might increase efficacy without adding major toxicities. Amphera BV and EU HORIZON.

Value of a multidisciplinary geriatric oncology committee on patient care in a community-based, academic cancer center.

e13771 Background: The heterogeneity in health and functional ability among older patients makes the management of cancer a unique challenge. The Geriatric Oncology Program at the University of Maryland Baltimore Washington Medical Center (BWMC) was created to optimize cancer management and recommendations for older patients. This study aimed to assess the benefits of the implementation of such a program at a community- based academic cancer center. Materials and Methods: We retrospectively analyzed patients aged ≥80 years presenting to the Geriatric Oncology Program between January 2017 and July 2022. A multidisciplinary team of specialists collectively reviewed each patient using geriatric-specific domains and stratified each patient into one of three management groups- Group 1: those deemed fit to receive standard oncologic care (SOC); Group 2: those recommended to receive optimization services prior to reassessment for SOC; and Group 3: those deemed to be best suited for supportive care and/ or hospice care. ANOVA, chi-square, and Kaplan-Meier analyses were used to assess patient outcomes. Results: Among 233 patients included, 76 (32.6%) received SOC (Group 1), 43 (18.5%) were optimized (Group 2), and 114 (49.0%) received supportive care or hospice referral (Group 3). There was no significant difference in sex, race, or age among all three groups. The Canadian Study of Health and Aging-Clinical Frailty Scale (CSHA-CFS) score was implemented in 2019 (n=90). Patients receiving supportive/ hospice care only had an average score of 5.8, while the averages for those in the optimization and SOC groups were 4.6 and 4.1, respectively (p=< .001). SOC patients had the longest average survival of 2.71 years compared to the optimization (2.30 years) and supportive care groups (0.93 years) (p= <0.001). 69.8% of optimized patients were deemed fit for SOC upon re-evaluation following optimization services. For all patients that underwent surgical interventions, post- operatively, 23 patients (85%) were discharged home and 4 (15%) were discharged to a rehab facility. The average survival after surgery for all patients was 3.16 years, while patients who were optimized prior to surgery had an average survival after surgery of 3.21 years. Conclusions: The present study demonstrates the need for specialized consideration of the heterogeneity that cancer diagnoses present in older individuals. The Geriatric Oncology Program at BWMC is able to maximize treatment outcomes for geriatric patients through the provision of SOC therapies and optimization services, while also minimizing unnecessary interventions on an individual patient-centric level.

A randomized controlled study on perioperative treatment of esophageal squamous cell carcinoma with camrelizumab combined with nab-paclitaxel and cisplatin.

e16122 Background: Neoadjuvant immunochemotherapy for esophageal squamous cell carcinoma (ESCC) has received increasing acceptance due to its effectiveness being confirmed by several phase II studies. CheckMate 577 has determined the efficacy of adjuvant immunotherapy in ESCC patients (pts) with R0 resection after neoadjuvant chemoradiotherapy. However, in the era of neoadjuvant immunotherapy, the optimal adjuvant treatment regimen for pts with ESCC warrant further research. This study aims to explore the efficacy and safety of perioperative treatment with camrelizumab combined with nab-paclitaxel and cisplatin for potentially resectable ESCC. Methods: This study planned to enroll 190 pts with potentially resectable stage II/III/IVa (cT1b-4aN0-3M0) ESCC. Eligible pts received 2-cycle of neoadjuvant camrelizumab (200mg, d1, q3w) combined with nab-paclitaxel (125mg/m2, d1,8, q3w) and cisplatin (75mg/m2, d1, q3w). Pts who reached pathologic complete remission (pCR) were randomly assigned to the immunotherapy group (camrelizumab for 16 cycles) and the best supportive care (BSC) group. Pts who did not reach pCR were randomly assigned to the immunochemotherapy group (camrelizumab combined with nab-paclitaxel and cisplatin for 2-4 cycles and camrelizumab for 12-14 cycles) and the immunotherapy group. Primary endpoints were pCR rate and 3-year DFS rate. Secondary endpoints were major pathologic response (MPR) rate, objective response rate (ORR), disease free survival (DFS), overall survival (OS). Results: As of Jan. 9th 2024, 121 pts (83 males and 38 females) with a median age of 65 years were enrolled in the study. One hundred and thirteen pts completed neoadjuvant treatment and 102 pts were available for imaging evaluation, the ORR was 91.9% and the DCR was 98.9%. Ninety six pts underwent surgery, 95 (98.9%) pts had a R0 resection, 32 (33.3%) pts reached pCR, 33 (34.3%) pts reached MPR. TNM down-staging was observed in 74 (77%) pts. Of 81 pts who underwent randomization, 30 pts reached pCR, 14 pts were randomly assigned to immunotherapy group, and 16 were assigned to BSC group. For 51 pts who did not reach pCR, 26 were randomized to the immunochemotherapy group and 25 were assigned to the immunotherapy group. At date cutoff, 5 pts (distant recurrence) relapsed in the immunochemotherapy group and 2 pts (distant recurrence) relapsed in the immunotherapy group who did not reach pCR. One hundred and twtety-one of 123 pts had AEs, and 33 pts had grade ≥3 AEs. The most common grade ≥3 AEs were anemia (9.9%), decreased lymphocyte count (7.4%), leukopenia (4.1%). Conclusions: This ongoing study again confirmed the safety and efficacy of neoadjuvant immunochemotherapy for resectable ESCC. Further data on optimal adjuvant treatment regimen for pts with or without residual disease will be reported in the future. Clinical trial information: NCT05182944 .

Integration of the geriatric palliative care in oncological care of elderly patient with cancer.

The objective of this article is to describe the profile of the population attended to by the palliative geriatrics clinic and to evaluate the symptomatic control derived from the care provided. During 2017 a model based on a holistic approach was implemented, in this model the team geriatric palliative care plays a fundamental role by being part of the palliative care team and functioning as a liaison with the oncology team and other required services. We outlined the profile of 100 patients aged 70 and older seen between 2017 and 2019 at our geriatric palliative care clinic. Descriptive statistics were used. In addition, the symptoms and the care clinic model effect on the symptomatic control were analyzed, as well as the complexity of patients in palliative care with IDC-Pal. The patients median age was 83.5 years. Patients were classified by type of management: 47% within the supportive care group and 53% with palliative care only; 58% had metastatic disease and 84% presented at least 1 comorbidity. Frailty was observed in 78% and a Karnofsky scale of 60 or less was observed in 59% of the overall population. Elderly cancer patients have a complex profile and may have multiple needs. Integrating geriatric palliative care can help to provide better and personalized care along with symptomatic control. Further studies are required to establish the ideal care model for these patients. Importantly, a personalized treatment with a geriatric palliative care specialist is a key element.

Value of a multidisciplinary geriatric oncology committee on patient care in a community-based, academic cancer center

IntroductionThe heterogeneity in health and functional ability among older patients makes the management of cancer a unique challenge. The Geriatric Oncology Program at the University of Maryland Baltimore Washington Medical Center (BWMC) was created to optimize cancer management for older patients. This study aimed to assess the benefits of the implementation of such a program at a community-based academic cancer center. Materials and MethodsWe analyzed patients aged ≥80 years presenting to the Geriatric Oncology Program between 2017 and 2022. A multidisciplinary team of specialists collectively reviewed each patient using geriatric-specific domains and stratified each patient into one of three management groups- Group 1: those deemed fit to receive standard oncologic care (SOC); Group 2: those recommended to receive optimization services prior to reassessment for SOC; and Group 3: those deemed to be best suited for supportive care and/or hospice care. ResultsThe study cohort consisted of 233 patients, of which 76 (32.6%) received SOC, 43 (18.5%) were optimized, and 114 (49.0%) received supportive care or hospice referral. Among the optimized patients, 69.8% were deemed fit for SOC upon re-evaluation following their respective optimization services. The Canadian Study of Health and Aging-Clinical Frailty Scale (CSHA-CFS) score was implemented in 2019 (n = 90). Patients receiving supportive/hospice care only had an average score of 5.8, while the averages for those in the optimization and SOC groups were 4.6 and 4.1, respectively (p ≤0.001). Patients receiving SOC had the longest average survival of 2.71 years compared to the optimization (2.30 years) and supportive care groups (0.93 years) (p ≤0.001). For all patients that underwent surgical interventions post-operatively, 23 patients (85%) were discharged home and four (15%) were discharged to a rehabilitation facility. DiscussionThe present study demonstrates the profound impact that the complexities in health status and frailty among older individuals can have during cancer management. The Geriatric Oncology Program at BWMC maximized treatment outcomes for older adults through the provision of SOC therapies and optimization services, while also minimizing unnecessary interventions on an individual patient-centric level.

Optimizing Recurrent Glioblastoma Salvage Treatment: A Multicenter Study Integrating Genetic Biomarkers From the Korean Radiation Oncology Group (21-02).

Few studies have used real-world patient data to compare overall treatment patterns and survival outcomes for recurrent glioblastoma (rGBM). This study aimed to evaluate postprogression survival (PPS) according to the treatment strategy for rGBM by incorporating biomarker analysis. We assessed 468 adult patients with rGBM who underwent standard temozolomide-based chemoradiation. The impact of predictors on PPS was evaluated in patients with isocitrate dehydrogenase wild-type rGBM (n = 439) using survival probability analysis. We identified patients who would benefit from reirradiation (re-RT) during the first progression. Median PPS was 3.4, 13.8, 6.6, and 10.0 months in the best supportive care (n = 82), surgery (with/without adjuvant therapy, n = 112), chemotherapy alone (n = 170), and re-RT (with/without chemotherapy, n = 75) groups, respectively. After propensity score matching analysis of the cohort, both the surgery and re-RT groups had a significantly better PPS than the chemotherapy-only group; however, no significant difference was observed in PPS between the surgery and re-RT groups. In the surgery subgroup, surgery with chemotherapy ( P = .024) and surgery with radio(chemo)therapy ( P = .039) showed significantly improved PPS compared with surgery alone. In the no-surgery subgroup, radio(chemo)therapy showed significantly improved PPS compared with chemotherapy alone ( P = .047). Homozygous deletion of cyclin-dependent kinase inhibitor 2A/B, along with other clinical factors (performance score and progression-free interval), was significantly associated with the re-RT survival benefit. Surgery combined with radio(chemo)therapy resulted in the best survival outcomes for rGBM. re-RT should also be considered for patients with rGBM at first recurrence. Furthermore, this study identified a specific genetic biomarker and clinical factors that may enhance the survival benefit of re-RT.

Scheduled and Breakthrough Opioid Use for Cancer Pain in an Inpatient Setting at a Tertiary Cancer Hospital.

Background: Our aim was to examine the frequency and prescription pattern of breakthrough (BTO) and scheduled (SCH) opioids and their ratio (BTO/SCH ratio) of use, prior to and after referral to an inpatient supportive care consult (SCC) for cancer pain management (CPM). Methods and Materials: Patients admitted at the MD Anderson Cancer Center and referred to a SCC were retrospectively reviewed. Cancer patients receiving SCH and BTO opioids for ≥24 h were eligible for inclusion. Patient demographics and clinical characteristics, including the type and route of SCH and BTO opioids, daily opioid doses (MEDDs) of SCH and BTO, and BTO/SCH ratios were reviewed in patients seen prior to a SCC (pre-SCC) and during a SCC. A normal BTO ratio was defined as 0.5-0.2. Results: A total of 665/728 (91%) patients were evaluable. Median pain scores (p < 0.001), BTO MEDDs (p < 0.001), scheduled opioid MEDDs (p < 0.0001), and total MEDDs (p < 0.0001) were higher, but the median number of BTO doses was fewer (2 vs. 4, p < 0.001), among patients seen at SCC compared to pre-SCC. A BTO/SCH ratio over the recommended ratio (>0.2) was seen in 37.5% of patients. The BTO/SCH ratios in the pre-SCC and SCC groups were 0.10 (0.04, 0.21) and 0.17 (0.10, 0.30), respectively, p < 0.001. Hydromorphone and Morphine were the most common BTO and SCH opioids prescribed, respectively. Patients in the early supportive care group had higher pain scores and MEDDs. Conclusions: BTO/SCH ratios are frequently prescribed higher than the recommended dose. Daily pain scores, BTO MEDDs, scheduled opioid MEDDs, and total MEDDs were higher among the SCC group than the pre-SCC group, but the number of BTO doses/day was lower.

Pediatric transplant–associated thrombotic microangiopathy health care utilization and implications of eculizumab therapy

AbstractThe health care use (HCU) burden of transplant-associated thrombotic microangiopathy (TA-TMA) and its treatments are unknown. The objective of this study was to investigate inpatient costs associated with meeting criteria for TA-TMA in the first year after hematopoietic cell transplant (HCT). This institutional review board–approved retrospective multicenter study included serial children who underwent HCT from 1 January 2015 to 1 July 2019. A standardized unit cost (adjusted for geographic location, differences in cost of living, and inflation) for inpatient hospitalization was extracted from the Pediatric Health Information System data and linked to clinical data. Both total cost and cost per day from 15 days before stem cell infusion to 1-year after HCT were calculated. Among allogeneic (allo) transplant recipients, after adjusting for severe grade 3/4 acute graft-versus-host disease (GVHD), infections, and HLA mismatch, costs were not different in TA-TMA (n = 137) vs no TA-TMA (n = 238). Severe GVHD was significantly associated with increased costs. Among allo high-risk (HR) TMA-TMA, unadjusted costs were significantly higher in the eculizumab-treated cohort (n = 19) than in the supportive care group (n = 36). However, after adjusting for gastrointestinal bleeding that occurred disproportionately in the eculizumab (n = 6) vs supportive care (n = 0) cohort, eculizumab treatment was not associated with increased total costs. More studies are needed to determine the etiology of increased HCU costs in those with HR-TA-TMA and predict those more likely to benefit from eculizumab, reducing HCU and improving outcomes.

Impact of COVID-19 Pandemic on Advanced Non-small Cell Lung Cancer Treatment at a Japanese Hospital.

The COVID-19 pandemic has forced medical institutions to scale back their practice. Changes in patient behavior seemed to be having an impact. We conducted a survey with the aim of reviewing lung cancer treatment during the pandemic period and identifying problems. We examined the medical records of all patients pathologically diagnosed with non-small cell lung cancer (NSCLC) in our hospital from 2017 to 2022. NSCLC patients were divided into two groups: those diagnosed between 2017 and 2019 (first period) and those diagnosed between 2020 and 2022 (second period). Within the study period, 267 NSCLC patients (first period: 147 patients, second period: 121 patients) were diagnosed in our hospital. The patients in the two study periods did not differ significantly in age (p=0.613), ECOG performance status (p=0.125), and clinical stage (p=0.354). Tumor size was significantly larger in the second period with a mean of 5.88 cm ± 3.02, compared to 4.24 cm ± 1.76 in the first period (p<0.001). In the standard treatment group, the median survival time was 457 days in the first period and 313 days in the second period (p=0.063). In the best supportive care group, median survival time was 122 days in the first period and 57 days in the second period (p=0.004). Patients themselves refrained from seeking consultation for lung cancer treatment during the pandemic period. It is inconclusive how to reduce the delay due to the suppression of consultations, but this is an important issue for the future.

Immunosuppression versus Supportive Care on Kidney Outcomes in IgA Nephropathy in the Real-World Setting.

The efficacy of immunosuppression in the management of immunoglobulin A (IgA) nephropathy remains highly controversial. The study was conducted to assess the effect of immunosuppression, compared with supportive care, in the real-world setting of IgA nephropathy. A cohort of 3946 patients with IgA nephropathy, including 1973 new users of immunosuppressive agents and 1973 propensity score-matched recipients of supportive care, in a nationwide register data from January 2019 to May 2022 in China was analyzed. The primary outcome was a composite of 40% eGFR decrease of the baseline, kidney failure, and all-cause mortality. A Cox proportional hazard model was used to estimate the effects of immunosuppression on the composite outcomes and its components in the propensity score-matched cohort. Among 3946 individuals (mean [SD] age 36 [10] years, mean [SD] eGFR 85 [28] ml/min per 1.73 m 2 , and mean [SD] proteinuria 1.4 [1.7] g/24 hours), 396 primary composite outcome events were observed, of which 156 (8%) were in the immunosuppression group and 240 (12%) in the supportive care group. Compared with supportive care, immunosuppression treatment was associated with 40% lower risk of the primary outcome events (adjusted hazard ratio, 0.60; 95% confidence interval, 0.48 to 0.75). Comparable effect size was observed for glucocorticoid monotherapy and mycophenolate mofetil alone. In the prespecified subgroup analysis, the treatment effects of immunosuppression were consistent across ages, sexes, levels of proteinuria, and values of eGFR at baseline. Serious adverse events were more frequent in the immunosuppression group compared with the supportive care group. Immunosuppressive therapy, compared with supportive care, was associated with a 40% lower risk of clinically important kidney outcomes in patients with IgA nephropathy.

A randomized controlled study on perioperative treatment of esophageal squamous cell carcinoma with camrelizumab combined with nab-paclitaxel and cisplatin.

e16075 Background: Neoadjuvant immunochemotherapy for esophageal squamous cell carcinoma (ESCC) has received increasing acceptance due to its effectiveness being confirmed by several phase II studies. CheckMate 577 has determined the efficacy of adjuvant immunotherapy in ESCC patients (pts) with R0 resection after neoadjuvant chemoradiotherapy. However, in the era of neoadjuvant immunotherapy, the optimal adjuvant treatment regimen for pts with ESCC warrant further research. This study aims to explore the efficacy and safety of perioperative treatment with camrelizumab combined with nab-paclitaxel and cisplatin for potentially resectable ESCC. Methods: This study planned to enroll 130 pts with potentially resectable stage II/III/IVa (cT1b-4aN0-3M0) ESCC. Eligible pts received 2-cycle of neoadjuvant camrelizumab (200mg, d1, q3w) combined with nab-paclitaxel (125mg/m2, d1,8, q3w) and cisplatin (75mg/m2, d1, q3w). Pts who reached pathologic complete remission (pCR) were randomly assigned to the immunotherapy group (camrelizumab for 16 cycles) and the best supportive care (BSC) group. Pts who did not reach pCR were randomly assigned to the immunochemotherapy group (camrelizumab combined with nab-paclitaxel and cisplatin for 2-4 cycles and camrelizumab for 12-14 cycles) and the immunotherapy group. Primary endpoints were pCR rate and 3-year DFS rate. Secondary endpoints were major pathologic response (MPR) rate, objective response rate (ORR), disease free survival (DFS), overall survival (OS). Results: As of Feb. 9th 2023, 72 pts (52 males and 20 females) with a median age of 64 years were enrolled in the study. Sixty-three pts completed neoadjuvant treatment and 54 pts were available for imaging evaluation, the ORR was 92.5% and the DCR was 98.1%. Fifty-three pts underwent surgery, 52 (98.1%) pts had a R0 resection, 19 (35.8%) pts reached pCR, 15 (28.3%) pts reached MPR. TNM down-staging was observed in 41 (77.3%) pts. Of 44 patients who underwent randomization, 16 pts reached pCR, 8 pts were randomly assigned to immunotherapy group and BSC group respectively. For pts who did not reach pCR, 15 were randomized to the immunochemotherapy group, and 13 were assigned to the immunotherapy group. The median follow-up was 6.1 months, and the median DFS had not yet reached. Sixty-eight out of 72 pts had AEs, and 25 pts had grade ≥3 AEs. The most common grade ≥ 3 AEs were anemia (9.7%), leukopenia (8.3%), hypokalemia (5.5%). There were 2 treatment-related deaths, one was due to postoperative complication and one due to bone marrow suppression, diarrhea and immunotherapy-related myocarditis. Conclusions: This ongoing study again confirmed the safety and efficacy of neoadjuvant immunochemotherapy for resectable ESCC. Further data on optimal adjuvant treatment regimen for pts with or without residual disease will be reported in the future. Clinical trial information: NCT05182944 .

Prospective Randomized Trial of Docetaxel Versus Best Supportive Care in Patients With Non-Small-Cell Lung Cancer Previously Treated With Platinum-Based Chemotherapy.

To evaluate whether treatment with single-agent docetaxel would result in longer survival than would best supportive care in patients with non-small-cell lung cancer who had previously been treated with platinum-based chemotherapy. Secondary end points included assessment of response (docetaxel arm only), toxicity, and quality of life. One hundred four patients (103 of whom were eligible for entry onto the study) were well balanced for prognostic factors. Of 84 patients with measurable lesions, six (7.1%) achieved partial responses (three patients at each dose level). Time to progression was longer for docetaxel patients than for best supportive care patients (10.6 v 6.7 weeks, respectively; P < .001), as was median survival (7.0 v 4.6 months; log-rank test, P = .047). The difference was more significant for docetaxel 75 mg/m2 patients, compared with corresponding best supportive care patients (7.5 v 4.6 months; log-rank test, P = .010; 1-year survival, 37% v 11%; χ2 test, P = .003). Febrile neutropenia occurred in 11 patients treated with docetaxel 100 mg/m2, three of whom died, and in one patient treated with docetaxel 75 mg/m2. Grade 3 or 4 nonhematologic toxicity, with the exception of diarrhea, occurred at a similar rate in both the docetaxel and best supportive care groups. Treatment with docetaxel is associated with significant prolongation of survival, and at a dose of 75 mg/m2, the benefits of docetaxel therapy outweigh the risks.

Efficacy of immune checkpoint inhibitor treatment for head and neck mucosal melanoma recurrence in patients treated with carbon-ion radiotherapy.

Carbon-ion radiotherapy (C-ion RT) is effective for head and neck mucosal melanoma (HN-MM), including radioresistant mucosal melanoma. Melanoma also responds effectively to immune checkpoint inhibitors (ICIs). Data on the efficacy and safety of ICIs for HN-MM are insufficient. To analyze the efficacy and safety of ICI salvage therapy in patients with HN-MM recurrence after C-ion RT. This retrospective study analyzed the medical records of 52 patients with HN-MM treated with C-ion RT between 2012 and 2020. A dose of 57.6 or 64.0 Gy (relative biological effectiveness) was provided in 16 fractions. The primary endpoint was 3-year overall survival (OS) rate. The median follow-up time was 26.8 months for all patients. A total of 29 patients had local recurrence or distant metastasis, and 16 patients who received ICI therapy. The 3-year OS rate in the ICI group (n = 16) and best supportive care group (n = 13) were 53.8% and 0.0%, respectively (p = 0.837); the difference was not statistically significant. There were no deaths after 1 year among patients who underwent ICI therapy. No adverse events associated with C-ion RT were related to or exacerbated by ICI. ICI salvage therapy is effective and safe for patients with HN-MM recurrence after C-ion RT.

Main causes of death in advanced biliary tract cancer.

There are no previous reports on the main causes of death in biliary tract cancer (BTC) patients. This study aimed to evaluate the main causes of death and survival rates in patients with BTC. We retrospectively evaluated 143 patients who were diagnosed with unresectable BTC between August 2010 and March 2020. We classified the main causes of death based on laboratory data, imaging studies, and medical records. The main causes of death evaluated included liver failure, cholangitis, cachexia, other causes associated with tumor progression, and complications. We also analyzed survival rates for each main cause of death. After excluding patients who were lost to follow-up, living patients, and patients who had no records of laboratory data within 30 days before the date of death, 108 patients were analyzed. The main cause of death was cholangitis in 33 (30.6%), cachexia in 22 (20.4%), liver failure in 10 (9.3%), other causes associated with tumor progression in 18 (16.7%), and complications in 25 (23.2%) patients. Median overall survival (OS) was 334.0 days in the chemotherapy group and 75.0 days in the best supportive care (BSC) group. Survival analyzed according to the main cause of death was significantly different between the chemotherapy and BSC groups; OS for cachexia, cholangitis, liver failure, other causes associated with tumor progression, and complications, respectively, were 453.0, 499.0, 567.0, 205.0, and 327.5 days (p=0.003) in the chemotherapy group and 219.0, 69.0, 34.0, 93.0, and 56.0 days (p=0.001) in the BSC group. The main causes of death in patients with advanced BTC are cholangitis, cachexia, liver failure, other causes associated with tumor progression, and complications. Other causes associated with tumor progression in the chemotherapy group, and liver failure in the BSC group as the main causes of death shortened the survival of BTC patients.

Defibrotide plus best standard of care compared with best standard of care alone for the prevention of sinusoidal obstruction syndrome (HARMONY): a randomised, multicentre, phase 3 trial

Sinusoidal obstruction syndrome, also known as veno-occlusive disease, is a potentially life-threatening complication of haematopoietic stem-cell transplantation (HSCT). We aimed to compare defibrotide prophylaxis plus best supportive care versus best supportive care alone for sinusoidal obstruction syndrome prevention after HSCT. This open-label, randomised, multicentre, phase 3 trial was done in 104 centres in 14 countries. Patients who were at least 1 month old, were scheduled to receive allogeneic HSCT (adult [aged >16 years] or paediatric [aged >1 month to ≤16 years] patients) or autologous HSCT (paediatric patients only), and were at high risk or very high risk of developing sinusoidal obstruction syndrome were eligible for inclusion. Patients were randomly assigned (1:1) by an interactive web response system to receive intravenous defibrotide 25 mg/kg per day (four equal doses [6·25 mg/kg per dose]) and best supportive care (determined by individual institutional guidelines; defibrotide prophylaxis group) or best supportive care only (best supportive care group). Randomisation was stratified by sinusoidal obstruction syndrome risk, age, and country. The primary endpoint, sinusoidal obstruction syndrome-free survival at day 30 after HSCT, was assessed by an independent Endpoint Adjudication Committee in the intention-to-treat (ITT) population. Safety was assessed in all patients who received protocol treatment. The trial is registered with ClinicalTrials.gov, NCT02851407. Between Jan 11, 2017, and Oct 20, 2020, 372 patients (172 [46%] women and 200 [54%] men; median age 14·0 years [IQR 4·0-41·0] were randomly assigned to the defibrotide prophylaxis group (n=190) or best supportive care group (n=182; ITT population). On the basis of recommendations from the Independent Data Monitoring Committee following completion of the planned interim analysis in the first 280 recruited patients on April 29, 2020, enrolment was prematurely stopped for presumed futility. At the final analysis, sinusoidal obstruction syndrome-free survival by day 30 after HSCT was 67% (95% CI 58-74) in the defibrotide prophylaxis group and 73% (62-80) in the best supportive care group (HR 1·27 [95% CI 0·84-1·93]; p=0·85). Treatment-emergent adverse events were similar between groups during the randomised prophylaxis phase; most treatment-emergent adverse events were related to the transplantation rather than to study drug. The most common grade 3 or 4 treatment-emergent adverse events were stomatitis (grade 3, 52 [29%] of 181 patients in the defibrotide prophylaxis group and 56 [32%] of 174 patients in the best supportive care group; grade 4, two [1%] in the defibrotide prophylaxis group and two [1%] in the best supportive care group) and febrile neutropaenia (grade 3, 51 [28%] in the defibrotide prophylaxis group and 52 [30%] in the best supportive care group; grade 4, no patients in the defibrotide prophylaxis group and three [2%] in the best supportive care group). Serious treatment-emergent adverse events occurred in 74 (41%) of 181 patients in the defibrotide prophylaxis group and 61 (35%) of 174 patients in the best supportive care group. In the rescue phase, when patients in both treatment groups received defibrotide as rescue treatment, fatal treatment-related adverse events occurred in one (4%) of 25 patients in the defibrotide prophylaxis group (intracranial haemorrhage) and one (3%) of 31 patients in the best supportive care group (sinusoidal obstruction syndrome). Defibrotide did not show a benefit in the prophylaxis of sinusoidal obstruction syndrome. Additional studies of carefully selected patients at high risk of sinusoidal obstruction syndrome after HSCT are warranted. Jazz Pharmaceuticals.

Use of Antibiotics in Poisonous Ingestions of Corrosives and Organophosphates: A Retrospective Cohort Study.

The use of antibiotics following oral poisoning by corrosives and organophosphates is controversial. We assessed the clinical outcomes of using antibiotics in acute poisonous ingestion involving corrosives or organophosphates by conducting a retrospective cohort study of patients presenting to the emergency department following ingestion of corrosives or organophosphates who received either antibiotics or supportive care. The endpoints included clinical stability, length of stay (LOS), and mortality. Of 95 patients, 40 received antibiotics and 55 received supportive care. The median age was 2.1 and 2.7 years, respectively (p = 0.053). Bacterial growth was shown in only 2 of 28 cultures (both were respiratory), but with hospital-acquired organisms as it was shown ≥4 days post-admission. Clinical stability rates were 60% and 89.1% in the antibiotic and supportive care groups, respectively (p < 0.001). Median LOS was 3 vs. 0 days (p < 0.001), and no mortality was recorded. NG/G-tube placement was the only factor associated with clinical failure (OR, 20.97; 95% CI, 2.36-186.13). Antibiotic use was not associated with higher chances of clinical stability, which may suggest that their use was unnecessary. Clinicians are encouraged to use antibiotics wisely, and only in the presence of a clear indication of an infection. This study provides a basis for future prospective studies to confirm its findings.

The clinical efficacy of fluticasone propionate combined with ACEI/ARB in the treatment of immunoglobulin A nephropathy

BackgroundImmunoglobulin A nephropathy (IgAN) is the most common primary glomerulopathy worldwide, and lacks the effective treatment. The study was aimed to investigate the clinical efficacy of fluticasone propionate aerosol combined with angiotensin converting enzyme inhibitor / angiotensin receptor blocker (ACEI/ARB) in the treatment of IgAN.Methods142 patients with biopsy-proven IgAN at Shenzhen People?s hospital from June 2018 to June 2020 were enrolled. The patients were randomly divided into the supportive care plus fluticasone group and the supportive care group. The patients of the supportive care plus fluticasone group were treated with fluticasone propionate aerosol (250 ?g Bid) combined with ACEI/ARB, while the supportive care group was merely treated with ACEI/ARB. The patients were followed up at 3, 6 and 9 months after enrollment. Primary outcomes include changes in proteinuria and estimated glomerular filtration rate (eGFR).ResultsThe level of proteinuria in the supportive care plus fluticasone group was significantly lower compared with the supportive care group at 0, 3, 6 and 9 months. Meanwhile, during the follow-up period, no serious adverse events were recorded during the study in either group. However, fluticasone treatment did not alleviate the decline in eGFR.ConclusionFluticasone propionate aerosol combined with ACEI/ARB can reduce the level of proteinuria in thetreatment of IgAN, and has no significant effects on renal function.

Efficacy and safety of sequential immunosuppressive treatment for severe IgA nephropathy: A retrospective study.

Background: This study compared the efficacy and safety of sequential immunosuppressive therapy in patients with non-end-stage IgA nephropathy (IgAN) with Lee's classification of IV ∼ V and provided evidence for the use of immunotherapy in patients with severe IgAN. Methods: We retrospectively analyzed the clinical data of patients with Lee's IV ∼ V non-end-stage IgA nephropathy. Results: 436 patients were diagnosed with IgAN, and 98 patients who met the inclusion criteria were included in this retrospective study. Of these, 17 were in the supportive care group, 20 in the P group (prednisone-only), 35 in P + CTX group (the prednisone combined with cyclophosphamide followed by mycophenolate mofetil), and 26 in the P + MMF group (prednisone combined with mycophenolate mofetil). The four groups showed differences in the segmental glomerulosclerosis score and the proportion of patients with Lee's grade IV (p < 0.05), but no differences in other indicators. Compared with the baseline values, urine protein-to-creatinine ratio (PCR) significantly decreased and serum albumin increased (p < 0.05), but there was no significant difference between the groups. The estimated Glomerular Filtration Rate (eGFR) of the P, P + MMF, and P + CTX groups were higher than that of the supportive care group at the 6th and 24th month after treatment (all p < 0.05). At the 24th month, the eGFR in the P + CTX group was higher than that in the P + MMF group (p < 0.05). The effective remission rate of the P + CTX group was higher than that of the supportive care group (p < 0.05). At 12months, the effective remission rate of the P group was higher than that of the supportive care group (p < 0.05). At the 24th month, there was no significant difference in the effective remission rates among the three groups (P, P + MMF, and P + CTX). Nine patients with severe IgA nephropathy reached the endpoint. Conclusion: This study showed that immunosuppressive therapy insevere IgAN patient scan effectively reduce urinary protein, increase albumin, and protect renal function in the early stages of IgAN. P + CTX is the most commonly used, which has a high effective remission rate of urine protein and a low incidence of end-point events.

Effectiveness of Mycophenolate Mofetil Among Patients With Progressive IgA Nephropathy

The role of mycophenolate mofetil (MMF) in management of immunoglobulin A nephropathy (IgAN) remains highly controversial. To evaluate the efficacy and safety of MMF in patients with IgAN at high risk of kidney function loss. This randomized clinical trial with open-label, blinded end-point design was conducted among adults with IgAN, proteinuria greater than 1.0 g/d, and estimated glomerular filtration rate (eGFR) greater than 30 and less than 60 mL/min/1.73m2 or with persistent hypertension from September 2013 to December 2015. During a 3-month run-in period, 238 patients received optimized supportive care (SC), including losartan. Patients with a urinary protein excretion rate of 0.75 g/d or greater despite of 3 months optimized SC were enrolled into the trial for 3 years. Survivors of the trial who did not receive dialysis or transplant were followed up after the trial for a median (IQR) of 60 (47-76) months. Data were analyzed from March through June 2022. A total of 170 participants were randomized in a 1:1 ratio to receive MMF (initially, 1.5 g/d for 12 months, maintained at 0.75-1.0 g for at least 6 months) plus SC or SC alone. The primary outcomes were (1) a composite of doubling of serum creatinine, end-stage kidney disease (dialysis, transplant, or kidney failure without receiving kidney replacement therapy), or death due to kidney or cardiovascular cause and (2) progression of chronic kidney disease. Among 170 randomized patients (mean [SD] age 36.6 [9.4] years; 94 [55.3%] male patients), 85 patients received MMF with SC and 85 patients received SC alone. The mean (SD) eGFR was 50.1 (17.9) mL/min/1.73m2 and mean (SD) proteinuria level was 1.9 (1.7) g/d; 168 patients (98.8%) completed the trial, and 157 participants (92.4%) survived and did not receive dialysis or transplant. Primary composite outcome events occurred in 6 patients (7.1%) in the MMF group and 18 patients (21.2%) in the SC group (adjusted hazard ratio [aHR], 0.23; 95% CI, 0.09-0.63). Progression of chronic kidney disease occurred in 7 participants (8.2%) in the MMF group and 23 participants (27.1%) in the SC group (aHR, 0.23; 95% CI, 0.10-0.57). The effect of MMF treatment on primary outcomes was consistent across prespecified subgroups, with no significant interaction per subgroup. During posttrial follow-up, annual loss of eGFR accelerated after discontinuation of MMF; mean (SD) annual eGFR loss during the study period was 2.9 (1.0) mL/min/1.73m2 in the MMF group and 6.1 (1.2) mL/min/1.73m2 among 66 patients in the MMF group who discontinued MMF after the trial. Serious adverse events were not more frequent with MMF vs SC alone. This study found that addition of MMF to SC compared with SC alone significantly reduced risk of disease progression among patients with progressive IgAN. ClinicalTrials.gov Identifier: NCT01854814.