Programmed cell death ligand-1 expression and survival in a cohort of patients with non-small cell lung cancer receiving first-line through third-line therapy in Denmark

BackgroundPD-L1 expression on tumor cells (TCs) or immune cells (ICs) may be used as a prognostic marker for survival in patients with NSCLC. We characterized PD-L1 expression on TCs or ICs in a patient cohort with NSCLC to determine associations between PD-L1 expression and overall survival (OS), according to EGFR and KRAS mutation status.MethodsDanish patients aged >18 years diagnosed with NSCLC before 2014 on first- (N = 491), second- (N = 368), or third-line (N = 498) therapy were included. Data were extracted from population-based medical registries. Tumor samples from pathology archives were tested for biomarkers. High PD-L1 expression was defined as expression on ≥25 % of TCs or ICs based on first diagnostic biopsy or surgical resection. KRAS and EGFR mutation status were tested using PCR-based assays. Cox regression analysis was used to compute adjusted HRs and associated 95 % CIs.ResultsPD-L1 TC and IC ≥ 25 % were observed in 24.3 %–31.0 % and 11.7–14.7 % of patients, respectively. EGFR and KRAS mutations were detected in 4.7 %–8.8 % and 26.5 %–30.7 % of patients, respectively. PD-L1 TC ≥ 25 % was not associated with survival advantage in first- (HR = 0.96, 95 % CI: 0.75–1.22), second- (1.08, 0.81–1.42), or third-line (0.94, 0.74–1.20) therapy. PD-L1 IC ≥ 25 % was associated with survival advantage in second-line (HR = 0.56, 95 % CI: 0.36–0.86) and third-line (0.69, 0.49–0.97) but not first-line (1.00, 0.70–1.41) therapy.ConclusionNo association was observed between PD-L1 TC ≥ 25 % and OS in any therapy line. PD-L1 IC ≥ 25 % may confer survival benefit among some patients who reach second-line therapy.     

Sequential Capecitabine/Temozolomide and Sunitinib Treatment in Patients With Metastatic Well-Differentiated Grade 1/Grade 2 Pancreatic Neuroendocrine Tumors

ObjectiveThe role of alternate sequential administration of sunitinib and capecitabine/temozolomide (CAPTEM) in metastatic pancreatic neuroendocrine tumors (PanNETs) remains unexplored. We thus aimed to analyze the efficacy and tolerability of this strategy in advanced grade 1/grade 2 PanNETs.MethodsIn total, data of 43 patients with metastatic PanNET were collected from a real-world database of a cancer center. Twenty-four patients were treated with sunitinib followed by CAPTEM (group 1), and 19 patients were treated with CAPTEM followed by sunitinib (group 2).ResultsTwenty-three patients were treated with first-line sunitinib or CAPTEM, and 20 patients were pretreated with somatostatin analog (SSA) or SSA in combination with transcatheter arterial chemoembolization. The objective response rate with first-line treatment was similar in both groups, whereas that with second-line treatment was higher in group 1 than in group 2, albeit with no significant differences (21.1% vs 5.3%, respectively; P = .205). Median progression-free survival (mPFS) for first-line and second-line treatments did not differ between the 2 groups (11 and 12 months vs 12 and 8 months, respectively). Following subgroup analyses, treatment with first-line sunitinib and sunitinib after pretreated SSA had a longer mPFS than that with second-line sunitinib after CAPTEM (11 months vs 8 months, respectively; P = .046), whereas treatment with first-line CAPTEM and CAPTEM after pretreated SSA had an mPFS similar to that of second-line CAPTEM after sunitinib treatment. CAPTEM and sunitinib had similar tolerability.ConclusionAlternating sunitinib and CAPTEM were well tolerated and associated with similar mPFS in grade 1/grade 2 PanNETs. However, larger prospective studies are required to investigate the efficacy of alternate sequential therapies for metastatic PanNET.     

Second-Line Treatment of Her2-Positive Metastatic Breast Cancer: Trastuzumab beyond Progression or Lapatinib? A Population Based Cohort Study

Background

The relative efficacy of lapatinib vs. continuing trastuzumab beyond progression (TBP) in HER2-positive metastatic breast cancer (MBC) patients, who progressed on first-line trastuzumab, is still unclear. The objective of this population based cohort study was to compare outcomes of lapatinib vs. TBP in daily practice.

Methods

All HER2-positive MBC patients who began second-line anti HER2 therapy between 1st January 2010 and 30th August 2013 were selected from Clalit Health Services’ (CHS) electronic database. Available data on patient and disease characteristics and treatments were analyzed. The primary endpoint was overall survival (OS). Outcomes were compared using the Kaplan-Meier (log-rank) method and Cox proportional hazards model.

Results

64 patients received second-line lapatinib and 93 TBP. The two treatment groups were similar in age and co-morbidity rates, but differed in proportion of prior adjuvant trastuzumab (lapatinib: 29.7%, TBP: 16.1%, P = 0.043) and rates of prior brain metastases (lapatinib: 32.8%, TBP: 10.8%, P = 0.01). Lapatinib median OS was 13.0 months (95% CI: 9.5–16.5) vs. 31.0 for TBP (95% CI: 20.6–41.4), P<0.001. On multivariate analysis, longer OS was preserved for TBP, after controlling for differences in age, adjuvant trastuzumab, duration of first-line trastuzumab therapy, brain metastases, visceral metastases and hormonal treatment [Hazard Ratio (HR) = 0.63, 95% CI: 0.40–0.99, P = 0.045].

Conclusion

In this comparative cohort study, OS of HER2-positive MBC patients treated with TBP was significantly longer than with lapatinib. These results might be especially relevant in settings where ado-trastuzumab-emtansine (TDM-1), the current preferred agent in this setting, is not available yet for patients.     

The Pan-Immune-Inflammation Value predicts the survival of patients with anaplastic lymphoma kinase-positive non-small cell lung cancer treated with first-line ALK inhibitor

BackgroundAnaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have significantly improved the clinical outcomes of patients with ALK-positive non-small cell lung cancer (NSCLC). However, reliable biomarkers to predict the prognostic role of this treatment are lacking. The Pan-Immune-Inflammation Value (PIV) has recently been demonstrated as a novel comprehensive biomarker to predict survival of patients with solid tumors. Our study aimed to evaluate the prognostic power of PIV in this group of patients.Patients and methods94 patients with advanced ALK-positive NSCLC who received first-line ALK inhibitors were enrolled in this study. PIV was calculated as the product of peripheral blood neutrophil, monocyte, and platelet counts divided by lymphocyte count. Kaplan-Meier method and Cox hazard regression models were used for survival analyses.ResultsThe 1-year progression-free survival (PFS) was 63.5%, and the 5-year overall survival (OS) rate was 55.1%. Patients with higher PIV, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune inflammation index (SII) had worse PFS in univariate analysis, but only the PIV (hazard ratio [HR] = 2.90, 95% confidence interval [CI]: 1.79–4.70, p < 0.001) was an independent prognostic factor in multivariate analysis. Similarly, patients with higher PIV, NLR, PLR, and SII had a worse OS in the univariate analysis, but only the PIV (HR = 4.70, 95% CI: 2.00–11.02, p < 0.001) was significantly associated with worse OS in multivariate analysis.ConclusionPIV is a comprehensive and convenient predictor of both PFS and OS in patients with ALK-positive advanced NSCLC who received first-line ALK TKIs. Prospective clinical trials are required to validate the value of this new parameter.     

A Real-World Study in Advanced Non–Small Cell Lung Cancer with KRAS Mutations

BACKGROUND: KRAS gene mutations are well known as a key driver of advanced non–small cell lung cancer (NSCLC). The impact of KRAS-mutant subtypes on the survival benefit from salvage chemotherapy is controversial. Here, we present a real-world study in patients across China with advanced NSCLC with KRAS mutations using a website-based patient self-report system. METHODS: We identified a total of 75 patients diagnosed with KRAS-mutant (determined by molecular sequencing) advanced NSCLC between 2014/5/9 and 2019/5/30. KRAS mutation subtypes were divided into G12C and non-G12C groups for statistical analysis. The clinicopathological characteristics and treatment survival benefit in all patients with a KRAS mutation were evaluated. Programmed death-ligand 1 (PD-L1) expression data were collected from 30 patients in the same cohort. RESULTS: In this study, 23 patients with stage IIIB NSCLC and 52 patients with stage IV NSCLC were enrolled with 58 men and 17 women; the median age was 60 years (39–84). All patients received regular chemotherapy/radiotherapy/targeted therapy/immune therapy as per the disease condition. Four main KRAS mutation subtypes were detected: G12C (33%), G12V (19%), G12A (12%), and G12D (12%). Three predominant KRAS comutations were detected: TP53-KRAS (31%), EGFR-KRAS (11%), and STK11-KRAS (8%). Compared with the KRAS non-G12C mutation subtype, patients with the KRAS G12C mutation had potentially longer progression-free survival (PFS) after first-line chemotherapy (4.7 vs. 2.5 months, p < 0.05). Pemetrexed-based chemotherapy appeared to be superior to taxanes- and gemcitabine-based chemotherapies in all patients (PFS: 5.0 vs. 1.5 and 2.3 months, respectively, p > 0.05). Cox regression analysis showed that the KRAS G12C mutation and pemetrexed-based first-line chemotherapy were positive influencers for PFS after first-line (hazard ratios = 0.31 and 0.55, respectively, P < 0.05), but not second-line chemotherapies. CONCLUSION: The KRAS G12C mutation could be a predictive biomarker for better survival benefit from first-line chemotherapy in patients with advanced NSCLC and KRAS mutations. The first-line chemotherapy regimen could possibly influence the outcome in patients with KRAS mutations. Larger and prospective clinical trials are warranted to confirm our conclusions.     

Gemcitabine in the first and second-line chemotherapy of advanced non-small cell lung cancer

Aim of this study was to estimate efficacy of gemcitabine in first and the second-line chemotherapy for patients with advanced non-small cell lung cancer (stage III and IV). In first-line chemotherapy, 120 patients were treated with different chemotherapy regimens. Fifty-nine patients were treated with gemcitabine / cisplatin (PG), 41 with cisplatin / etoposide (PE) and 20 with mitomycin / ifosfamide / cisplatin (MIC). Forty patients, unsuccessfully treated with PE and MIC in first-line therapy were treated with PG (24 pts) and with best supportive care (BSC) (16 pts). In first-line therapy PG was superior to PE and MIC protocol (mean survival (MS) 10 vs. 7 vs. 8.5 months). Response rate (RR) for PG in first-line therapy was 46% and 21% in second-line. We showed also significantly better survival in patients treated with PG in second-line chemotherapy comparing to best supportive care (MS 9 vs. 5.5 months). Toxic side effects for combination PG was acceptable. This study confirmed that PG combination is safe and effective as first and second-line chemotherapy for patients with advanced non-small cell lung cancer.     

Predictors of treatment initiation and mapping the cancer diagnostic pathway: A retrospective observational cohort study of patients with metastatic non-small cell lung cancer

BackgroundHealth-care providers in the US revealed that a substantial proportion of mNSCLC patients do not receive any first-line therapy and the biggest gaps in care are time inefficiencies in the diagnostic process. The goal of this study was to determine whether such gaps are found in Israel where healthcare is universal and participation in a medical insurance plan is free and compulsory.MethodsWe conducted a retrospective, observational cohort study using the computerized data of Maccabi Healthcare Services, a 2.5 million-member state-mandated health-service. Patients with mNSCLC diagnosed between 2017 and 2018 were followed until December 2019.ResultsAmong 434 patients (62% male, mean age 68 y, 74% adenocarcinoma), 345 (79%) initiated first-line treatment. Compared to treated, untreated patients (n = 89) were more likely to be older (mean [SD]=71 years [10] vs. 67 [10], p < 0.001), have a higher co-morbidity index (5.6 ([4.4] vs. 4.0 [3.4], p < 0.001), smokers (84% vs. 66%, p = 0.001), and require hospitalization in the year prior to diagnosis (80% vs 61%, p = 0.002). There was no difference in socioeconomic status. Time from first symptom to imaging was longer for untreated than treated patients (6.51 months [4.24, 7.33] vs 3.48 months [2.76, 4.34] respectively, p = 0.22). Predictors of treatment initiation included age< 70 years, non-smokers, EGFR testing performed, ECOG performance status 0–1 and shorter wait from first symptom to imaging. Median time from first symptom to initiation of 1 L, was 7.76 months (6.51–8.75).ConclusionThe proportion of untreated mNSCLC patients are comparable to those reported in the US; we did not find health disparities between socioeconomic levels. Our data suggest that the main barrier to effective diagnostic process is the wait between symptom complaint and imaging.     

Medication Possession Ratio Predicts Antiretroviral Regimens Persistence in Peru

Objectives

In developing nations, the use of operational parameters (OPs) in the prediction of clinical care represents a missed opportunity to enhance the care process. We modeled the impact of multiple measurements of antiretroviral treatment (ART) adherence on antiretroviral treatment outcomes in Peru.

Design And Methods

Retrospective cohort study including ART naïve, non-pregnant, adults initiating therapy at Hospital Nacional Cayetano Heredia, Lima-Peru (2006-2010). Three OPs were defined: 1) Medication possession ratio (MPR): days with antiretrovirals dispensed/days on first-line therapy; 2) Laboratory monitory constancy (LMC): proportion of 6 months intervals with ≥1 viral load or CD4 reported; 3) Clinic visit constancy (CVC): proportion of 6 months intervals with ≥1 clinic visit.Three multi-variable Cox proportional hazard (PH) models (one per OP) were fit for (1) time of first-line ART persistence and (2) time to second-line virologic failure. All models were adjusted for socio-demographic, clinical and laboratory variables.

Results

856 patients were included in first-line persistence analyses, median age was 35.6 years [29.4-42.9] and most were male (624; 73%). In multivariable PH models, MPR (per 10% increase HR=0.66; 95%CI=0.61-0.71) and LMC (per 10% increase 0.83; 0.71-0.96) were associated with prolonged time on first-line therapies.Among 79 individuals included in time to second-line virologic failure analyses, MPR was the only OP independently associated with prolonged time to second-line virologic failure (per 10% increase 0.88; 0.77-0.99).

Conclusions

The capture and utilization of program level parameters such as MPR can provide valuable insight into patient-level treatment outcomes.     

Sustained Virological Response on Second-Line Antiretroviral Therapy following Virological Failure in HIV-Infected Patients in Rural South Africa

Objective

This study aims to describe the virological, immunological and clinical efficacy of protease inhibitor (PI)-based second-line antiretroviral therapy (ART) in rural South Africa.

Methods

An observational cohort study was performed on 210 patients (including 39 children) who initiated PI-based second-line therapy at least 12 months prior to data collection. Biannual clinical, immunological and virological monitoring was performed. Primary endpoints were adequate virological response (plasma HIV-1 RNA<400 copies/ml), full virological suppression (plasma HIV-1 RNA<50 copies/ml) and treatment failure (virological failure (plasma HIV-1 RNA>1000 after initial virological response) or on-going viremia (plasma HIV-1 RNA never<400 copies/ml for more than six months)). Data were analyzed by an on-treatment (OT) and intention-to-treat (ITT) approach. Analyses were primarily performed on the group of patients who switched following first-line virological failure.

Results

Median duration of follow-up after switch to second-line treatment was 20 months [IQR 11–35]. 191 patients had switched to second-line ART due to first-line virological failure. 139/191 of them (72.8%, ITT) were in care and on treatment at the end of follow-up and 11/191 (5.8%, ITT) had died. After twelve months, an adequate virological response was seen in 92/128 patients (71.9%, OT), of which 78/128 (60.9%, OT) experienced full virological suppression. Virological response remained stable after 24 months. Virological efficacy was similar amongst adult and pediatric patients. As in first-line ART, we observed a lack of correlation between virological failure and WHO-defined immunological failure.

Conclusions

Good virological outcomes following first-line failure can be achieved with PI-based, second-line antiretroviral therapy in both adult and pediatric patients in rural South Africa. Retention rates were high and virological outcomes were sustainable during the two-year follow-up period, although persisting low-level viremia occurred in a subset of patients. The observed viro-immunological dissociation emphasizes the need for virological monitoring.     

Cost-Effectiveness of Tenofovir Instead of Zidovudine for Use in First-Line Antiretroviral Therapy in Settings without Virological Monitoring

Background

The most recent World Health Organization (WHO) antiretroviral treatment guidelines recommend the inclusion of zidovudine (ZDV) or tenofovir (TDF) in first-line therapy. We conducted a cost-effectiveness analysis with emphasis on emerging patterns of drug resistance upon treatment failure and their impact on second-line therapy.

Methods

We used a stochastic simulation of a generalized HIV-1 epidemic in sub-Saharan Africa to compare two strategies for first-line combination antiretroviral treatment including lamivudine, nevirapine and either ZDV or TDF. Model input parameters were derived from literature and, for the simulation of resistance pathways, estimated from drug resistance data obtained after first-line treatment failure in settings without virological monitoring. Treatment failure and cost effectiveness were determined based on WHO definitions. Two scenarios with optimistic (no emergence; base) and pessimistic (extensive emergence) assumptions regarding occurrence of multidrug resistance patterns were tested.

Results

In the base scenario, cumulative proportions of treatment failure according to WHO criteria were higher among first-line ZDV users (median after six years 36% [95% simulation interval 32%; 39%]) compared with first-line TDF users (31% [29%; 33%]). Consequently, a higher proportion initiated second-line therapy (including lamivudine, boosted protease inhibitors and either ZDV or TDF) in the first-line ZDV user group 34% [31%; 37%] relative to first-line TDF users (30% [27%; 32%]). At the time of second-line initiation, a higher proportion (16%) of first-line ZDV users harboured TDF-resistant HIV compared with ZDV-resistant viruses among first-line TDF users (0% and 6% in base and pessimistic scenarios, respectively). In the base scenario, the incremental cost effectiveness ratio with respect to quality adjusted life years (QALY) was US$83 when TDF instead of ZDV was used in first-line therapy (pessimistic scenario: US$ 315), which was below the WHO threshold for high cost effectiveness (US$ 2154).

Conclusions

Using TDF instead of ZDV in first-line treatment in resource-limited settings is very cost-effective and likely to better preserve future treatment options in absence of virological monitoring.     

The impact of local control timing in Ewing sarcoma

AimTo assess the impact of delay in local control on survival outcomes of Ewing sarcoma (ES) patients.BackgroundThe cornerstone of therapy of localized ES includes chemotherapy and local control with surgery or radiotherapy. We sought to assess the impact of delay (>15 weeks) in timing of local control on survival outcomes of ES patients.MethodsData of consecutive patients with primary non-metastatic ES of the extremities, treated at a single institution were collected. The impact of delay of timing for local control, demographics, and disease characteristics on overall survival (OS) was analyzed.ResultsA total of 43 patients with ES of the extremity were included. All patients received neoadjuvant chemotherapy. Local control was by surgery in 36 patients and definitive radiation in 7. A total of 16 patients had delay in local control. At a median follow of up of 48 months, patients with delay in local control had significantly inferior OS compared to those with optimal local control timing (5-year OS 56% vs. 80%, respectively, p = 0.044). Other factors that predicted inferior OS included definitive radiation as opposed to definitive surgery (5-year OS 25% vs. 79%, respectively, p = 0.041) and tumor necrosis <90% as opposed to ≥90% (5-year OS 55% vs. 90%, respectively, p = 0.01).ConclusionDelay in definitive therapy, local control with radiation as opposed to surgery and poor post-chemotherapy tumor necrosis predict inferior OS in ES. Adopting strategies to minimize delay in local control could improve survival outcomes.     

Mortality in Children with Optic Pathway Glioma Treated with Up-Front BB-SFOP Chemotherapy

Background

In terms of overall survival (OS), limited data are available for the very long-term outcomes of children treated for optic pathway glioma (OPG) with up-front chemotherapy. Therefore, we undertook this study with the aim of clarifying long-term OS and causes of death in these patients.

Methods

We initiated and analyzed a historical cohort study of 180 children with OPG treated in France with BB-SFOP chemotherapy between 1990 and 2004. The survival distributions were estimated using Kaplan-Meier method. The effect of potential risk factors on the risk of death was described using Cox regression analysis.

Results

The OS was 95% [95% CI: 90.6-97.3] 5 years after diagnosis and significantly decreased over time without ever stabilizing: 91.6% at 10 years [95% CI: 86.5-94.8], 80.7% at 15 years [95% CI: 72.7-86.8] and 75.5% [95% CI: 65.6-83] at 18 years. Tumor progression was the most common cause of death (65%). Age and intracranial hypertension at diagnosis were significantly associated with a worse prognosis. Risk of death was increased by 3.1[95% CI: 1.5-6.2] (p=0.002) for patients less than 1 year old at diagnosis and by 5.2[95% CI: 1.5-17.6] (p=0.007) for patients with initial intracranial hypertension. Boys without diencephalic syndrome had a better prognosis (HR: 0.3 [95% CI: 0.1-0.8], p=0.007).

Conclusions

This study shows that i) in children with OPG, OS is not as favorable as previously described and ii) patients can be classified into 2 groups depending on risk factors (age, intracranial hypertension, sex and diencephalic syndrome) with an OS rate of 50.4% at 18 years [95% CI: 31.4-66.6] in children with the worst prognosis. These findings could justify, depending on the initial risk, a different therapeutic approach to this tumor with more aggressive treatment (especially chemotherapy) in patients with high risk factors.     

Significant impact on the oncologic outcomes with intensity modulated radiotherapy and conformational radiotherapy over conventional radiotherapy in cervix cancer patients treated with radiotherapy

ObjectiveWe designed a retrospective cohort of women with cervix cancer treated by radiation therapy with an extended follow-up to evaluate if the incorporation of modern radiation techniques was a prognostic factor.Material and methodsWe studied a cohort of patients with cervix cancer FIGO stage I-IVa treated in the last fifteen years. Patients were treated with radiotherapy alone (RT) or chemoradiation alone (CRT) using conventional radiotherapy (2DRT), conformational radiotherapy (3DRT), or intensity-modulated radiotherapy (IMRT) followed by high dose rate brachytherapy. Univariate and multivariate analysis was conducted to identify significant prognostic factors (p < 0.05).Results228 patients with cervix cancer were included. The treatment groups were CRT (64.8%), and RT (34.2%), with 31.6% submitted to 2DRT and 68.4% to IMRT/3DRT. The median follow-up was 6.3 years, the OS in 5 years according to the treatment groups was 48% for CRT, and 27.8% for RT (p < 0.001). The early-stage I-IIa (p = 0.001), CRT, and IMRT/3DRT were significant factors for better overall survival (OS) in the multivariate analysis. For the cancer-specific survival (CSS), chemoradiation, age <60 years, and IMRT/3DRT were significant. Treatment with IMRT/3DRT was the only prognostic factor associated with event-free survival (EFS).ConclusionIn a long-term follow-up, chemoradiation, early-clinical stage, and age <60 years were significant factors associated with better OS and CSS at 5 and 8 years. The incorporation of new radiation techniques, such as IMRT/3DRT, over time has a significant impact on all endpoints (EFS, OS, and CSS) of this cohort. These outcomes are useful to decide about the radiation technique to achieve satisfactory oncological results outside a clinical trial.     

Myoepithelial carcinoma of major salivary glands: Analysis of population-based clinicopathologic and prognostic features

BackgroundThis study aimed to investigate the effect of demographic characteristics and disease stage on the survival outcomes of patients with myoepithelial carcinoma (MECA) of the salivary glands, and to assess the role of radiotherapy in these patients.MethodsThe Epidemiology, Surveillance and End Results database was queried from 2000 to 2018 to identify patients with MECA. Data pertaining to the tumor stage, size, histological grade, and demographic characteristics were analyzed. The relationship between clinicopathological features and overall survival (OS) was assessed using statistical analyses.ResultsIn total, 290 patients (137 men and 153 women) were identified. The parotid gland was the most common tumor location (76.6% patients). Approximately half of the patients had locally advanced tumors, and 14.5 and 6.6% had lymph node and distant organ involvement, respectively. The median OS was 142 months, while the survival rates at 120 months and 180 months were 53% and 39%, respectively. In the cohort, 160 patients (55.2%) underwent surgery alone, while 130 patients (44.8%) underwent surgery combined with radiotherapy. Multivariate Cox analysis revealed that histopathological grade, stage, T3 stage (hazard ratio [HR]: 2.47, P = 0.039), T4 stage (HR: 3.33, P = 0.011), N2 stage (HR: 6.59, P = 0.002), and M1 stage (HR: 2.72, 95%confidence interval [CI]: 1.03–7.19; P = 0.044) were associated with poor prognosis. Radiotherapy (HR: 0.58, P = 0.042) was a favorable factor for OS, and it reduced the mortality risk by 42%.ConclusionsHistological grade, stage, and radiotherapy are independent risk factors for OS. The decision to administer chemotherapy for MECA should be made with caution. Adjuvant radiotherapy is recommended in high-risk patients.     

A population-based study of soft tissue sarcoma incidence and survival in Australia: An analysis of 26,970 cases

BackgroundSoft tissue sarcomas (STS) are rare, often fatal tumors, but little is known of the epidemiology and survival in the Australian population. This study aims to provide the first epidemiological analysis of incidence and survival rates of STS in the Australian population.MethodsA retrospective population-based observational study was conducted between 1982 and 2009 of all patients with a diagnosis of STS using the Australian Institute of Health and Welfare (AIHW) Australian Cancer Database. Incidence rates per 100,000; incidence rate ratios, age-standardized incidence rates, prevalence and incidence rates of subtypes of STS, median, one-year and 5-year survival rates were examined.ResultsA total of 26,970 patients were identified. Between 1982 and 2009 STS incidence rates significantly increased from 3.99 [95% CI 3.68–4.32] to 6.12 [95% CI 5.80–6.46] per 100,000 Australian population, with a peak incident rate ratio (IRR) of 1.59 [95% CI 1.51–1.69] (p < 0.0001) in 2001. Median age at diagnosis increased from 58 to 63 years. Incidence rates were stable across all 10-year age cohorts, except for people aged over 70 where it increased. Overall, age-standardized incidence rates increased from 4.70 [95% CI 4.42–5.00] in 1982 to 5.87 [95% CI 5.63–6.11] per 100 000 Australians in 2009. Leiomyosarcoma (20.43%), malignant fibrous histiocytoma (16.14%), and soft tissue tumors/sarcomas, not otherwise specified (10.18%) were the most common STS subtypes. Median survival from diagnosis increased from 5.80 years [95% CI 5.06–6.54] in 1985–1989 cohort to 8.18 years [95% CI 7.54–8.81] in the 2000–2004 cohort (log-rank test p < 0.0001).ConclusionThe incidence of STS is increasing in Australia, most noticeably in those aged over 70 years, with a small but statistically significant increase in overall survival rates.     

Seasonal variation in effect of anti-PD-1 initiation on overall survival among patients with advanced melanoma

Melanoma is a highly immunogenic cancer, and circannual rhythms influence the activity of the immune system. We retrospectively collected information on all cases with metastatic melanoma (ocular melanoma excluded) that initiated treatment with BRAF-inhibitor-based therapy (BRAFi) or anti-PD-1 monotherapy (PD-1). Cases were divided in two groups based on treatment initiation in the summer half-year (April to September) or winter half-year (October to March). We collected a total of 1054 (BRAF-i) and 1205 (PD-1) patient cases. Median follow-up was 39.7 (BRAFi) and 47.5 (PD-1) months. We did not observe differences in outcomes across patients who were treated in summer versus winter in the BRAFi cohort. Furthermore, we did not observe significant differences in ORR, CRR, and PFS in the PD-1 cohort. However, in patients with BRAF wild-type disease of the PD-1 cohort, treatment initiation in summer was associated with an improved OS (mOS 39.7 months [summer] versus 21.3 months [winter]; HR 0.70, 95% CI 0.57–0.86, p = .0007). This result remained robust to multivariable proportional hazards adjustment (HR 0.70, 95% CI 0.57–0.87, p = .001). Initiation of immunotherapy in summer is associated with prolonged survival in patients with BRAF wild-type melanoma living in Denmark.     

Anti-PD1 checkpoint inhibitor with or without chemotherapy for patients with recurrent and metastatic nasopharyngeal carcinoma

PurposeTo compare the efficacy and safety of anti-PD1 checkpoint inhibitor plus chemotherapy with anti-PD1 checkpoint inhibitor alone in recurrent and metastatic nasopharyngeal carcinoma (R/M NPC) progressing after first or subsequent-line therapy.Methods and materialsA total of 67 patients with recurrent and metastatic nasopharyngeal carcinoma from our hospital were included. All patients were sorted into two arms: anti-PD1 checkpoint inhibitor+ chemotherapy arm and anti-PD1 checkpoint inhibitor arm. We retrospectively estimated objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) in patients of both arms. Chi-square test and Kaplan–Meier methodology were used to analyze.ResultsFrom September 2018 to March 2020, this research included 67 patients. For anti-PD1 checkpoint inhibitor+ chemotherapy arm, partial response and stable disease were observed in fourteen and 11 patients, respectively, for an ORR of 53.8%. For anti-PD1 checkpoint inhibitor arm, complete response and partial response were observed in one and 5 patients, respectively, for an ORR of 14.6%. The incidence of hyperprogressive disease was higher in the anti-PD1 checkpoint inhibitor group compared with anti-PD1 checkpoint inhibitor+ chemotherapy group (39.0% vs 3.8%, p<0.05). Univariable analyses discovered that 6-month PFS and OS benefits were observed for anti-PD1 checkpoint inhibitor+ chemotherapy arm compared to anti-PD1 checkpoint inhibitor arm (65.4% vs. 28.6%, P = 0.001; 100.0% vs. 73.5%, P = 0.014).ConclusionIn present study, we revealed that adding chemotherapy to anti-PD1 checkpoint inhibitor significantly improved 6-month PFS and OS for patients with R/M NPC progressing after first-line therapy. It warrants further study.     

Long-term outcomes of relmacabtagene autoleucel in Chinese patients with relapsed/refractory large B-cell lymphoma: Updated results of the RELIANCE study

Background aimsThe RELIANCE study has demonstrated the activity and safety of relmacabtagene autoleucel (relma-cel) (JW Therapeutics [Shanghai] Co, Ltd, Shanghai, China), a CD19-targeted chimeric antigen receptor T-cell product, in patients with heavily pre-treated relapsed/refractory large B-cell lymphoma (r/r LBCL). This study aimed to report the updated 2-year data of the RELIANCE study.MethodsThe RELIANCE study (NCT04089215) was an open-label, multi-center, randomized, phase 1/2 registrational clinical trial conducted at 10 clinical sites in China. Adult patients with heavily pre-treated r/r LBCL were enrolled and received lymphodepletion chemotherapy followed by infusion of 100 × 10⁶ or 150 × 10⁶ relma-cel. The primary endpoint was objective response rate (ORR) at 3 months, as assessed by investigators. Secondary endpoints were duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety profiles.ResultsFrom November 2017 to January 2022, a total of 68 patients were enrolled, and 59 patients received relma-cel infusion. As of March 29, 2022, a total of 59 patients had a median follow-up of 17.9 months (range, 0.3–25.6). ORR was 77.59% (95% confidence interval [CI], 64.73–87.49) and complete response rate was 53.45% (95% CI, 39.87–66.66). Median DoR was 20.3 months (95% CI, 4.86–not reached [NR]) and median PFS was 7.0 months (95% CI, 4.76–24.15). Median OS was NR and 1-year and 2-year OS rates were 75.0% and 69.3%, respectively. Three (5.1%) patients experienced grade ≥3 cytokine release syndrome and two (3.4%) patients had grade ≥3 neurotoxicity.ConclusionsThe updated data of the RELIANCE study demonstrate durable response with and manageable safety profile of relma-cel in patients with heavily pre-treated r/r LBCL.     

Outcomes following stereotactic radiosurgery or whole brain radiation therapy by molecular subtype of metastatic breast cancer

BackgroundThis study quantified clinical outcomes by molecular subtype of metastatic breast cancer (BC) following whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS). Doing so is important for patient counseling and to assess the potential benefit of combining targeted therapy and brain radiotherapy for certain molecular subtypes in ongoing trials.Materials and methodsThe National Cancer Database was queried for BC (invasive ductal carcinoma) cases receiving brain radiotherapy (divided into WBRT and SRS ). Statistics included multivariable logistic regression to determine factors associated with SRS delivery, Kaplan-Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling.ResultsOf 1,112 patients, 186 (16.7%) received SRS and 926 (83.3%) underwent WBRT. Altogether, 410 (36.9%), 195 (17.5%), 162 (14.6%), and 345 (31.0%) were ER+/HER2−, ER+/HER2+, ER−/HER2+, and ER−/HER2−, respectively. In the respective molecular subtypes, the proportion of subjects who underwent SRS was 13.4%, 19.4%, 24.1%, and 15.7%. Respective OS for WBRT patients were 12.9, 22.8, 10.6, and 5.8 months; corresponding figures for the SRS cohort were 28.3, 40.7, 15.0, and 12.9 months (p < 0.05 for both). When comparing OS between treatment different histologic subtypes, patients with ER−/HER2+ and ER−/HER2− disease had worse OS than patients with ER+/HER2− disease, for both patients treated with SRS and for patients treated with WBRT.ConclusionsMolecular subtype may be a useful prognostic marker to quantify survival following SRS/WBRT for metastatic BC. Patients with HER 2-enriched and triple-negative disease had the poorest survival following brain irradiation, lending credence to ongoing studies testing the addition of targeted therapies for these subtypes.