5-year Progression-free Survival Rates Research Articles

Real-word experience of pazopanib and sorafenib in patients with desmoid tumors: A CanSaRCC multi-center study

BackgroundSorafenib and pazopanib, two tyrosine kinase inhibitors (TKI), are widely used in patients with progressive symptomatic desmoid tumors (DT). Limited real-word data is available on long-term outcomes of patients who progressed on, stopped, or continued TKIs. MethodsPatients diagnosed with DTs and treated with sorafenib or pazopanib between 2011 and 2022 at 11 institutions were reviewed. Patient history, response to therapy and toxicity were recorded. Statistical analyses utilized Kaplan-Meier and log-rank tests. Results142 patients with DT treated with sorafenib (n = 126, 88.7 %) or pazopanib (n = 16, 11.3 %) were analyzed. The median treatment duration was 10.8 months (range: 0.07- 73.9). The overall response rate and the disease control rate were 26.0 % and 95.1 %, respectively. The median tumor shrinkage was − 8.5 % (range −100.0 %- +72.5 %). Among responders, the median time to an objective response was 15.2 months (range: 1.1 to 33.1). The 1-year and 2-year progression-free survival rates were 82 % and 80 %. Dose reductions were necessary in 34 (23.9 %) patients. Grade 3 or higher adverse events were reported in 36 (25.4 %) patients. On the last follow-up, 55 (38.7 %) patients continued treatment. Treatment discontinuation (n = 85, 59.9 %) was mainly for toxicity (n = 35, 45.9 %) or radiological or clinical progression (n = 30, 35.3 %). For the entire cohort, 36 (25.4 %) patients required subsequent treatment. In the 32 responders, only 1 (3.1 %) patient required a subsequent treatment. In patients who discontinued TKI, 25 (44.6 %) with stable disease received subsequent treatment compared to 0 (0.0 %) of responders. ConclusionThis retrospective study represents the largest cohort of DT patients treated with sorafenib or pazopanib to date. Discontinuation of treatment in responders is safe. The optimal treatment duration in patients with stable disease remains to be defined.

Tumor necrosis serves as an important pathological characteristic of stage I-II colon cancer.

The long-term prognosis of colon cancer patients remains little changed with relatively high mortality and morbidity. Since the most widely used prognostic parameter TNM staging system is less satisfactory in predicting prognosis in early-stage cancers, numerous clinicopathological factors, including tumor necrosis, have been proposed for prognosis stratification, but substantial evidences are still lacking for early-stage colon cancer. In the retrospective study, a total of eligible 173 stage I-II colon cancer patients, who received tumor radical resection and lymphadenectomy in the local hospital between January 1, 2010, and December 31, 2018, were enrolled for analyzing the prognostic role of tumor necrosis. The primary endpoints included 5-year overall survival (OS) and progression-free survival (PFS). The median follow-up of enrolled early-stage colon cancer patients was 58.3 months. The 2-year and 5-year OS rates were 88.3% and 68.2%, respectively, and the 2-year and 5-year PFS rates were 85.6% and 62.7%, respectively. Seventy-eight patients (45.1%) were diagnosed with tumor necrosis by pathological examination. Demographic analysis revealed a significant association of tumor necrosis with larger tumor size and a marginal association with vascular invasion. Kaplan-Meier survival curves demonstrated that tumor necrosis was associated with worse OS (log-rank P = 0.003) and PFS (log-rank P = 0.002). The independent unfavorable prognostic effect of tumor necrosis was further validated in univariate and multivariate Cox regression analysis (hazard ratio = 1.91 (1.52-2.40), P = 0.004). The current study confirmed the independent prognostic role of tumor necrosis from pathological review in early-stage colon cancer patients. This pathological criterion promises to help in identifying high-risk subgroup from early-stage colon cancer patients, who may benefit from strict follow-up and adjuvant therapy.

Outcomes of patients in nasopharyngeal adenoid cystic carcinoma in the IMRT era: a single-center experience

ObjectiveNasopharyngeal adenoid cystic carcinoma (NACC) is a rare malignancy with special biological features. Controversies exist regarding the treatment approach and prognostic factors in the IMRT era. This study aimed to evaluate the long-term outcomes and management approaches in NACC.MethodsFifty patients with NACC at our institution between 2010 and 2020 were reviewed. Sixteen patients received primary radiotherapy (RT), and 34 patients underwent primary surgery.ResultsBetween January 2010 and October 2020, a total of 50 patients with pathologically proven NACC were included in our analysis. The median follow-up time was 58.5 months (range: 6.0–151.0 months). The 5-year overall survival rate (OS) and progression-free survival rate (PFS) were 83.9% and 67.5%, respectively. The 5-year OS rates of patients whose primary treatment was surgery and RT were 90.0% and 67.3%, respectively (log-rank P = 0.028). The 5-year PFS rates of patients whose primary treatment was surgery or RT were 80.8% and 40.7%, respectively (log-rank P = 0.024). Multivariate analyses showed that nerve invasion and the pattern of primary treatment were independent factors associated with PFS.ConclusionsDue to the relative insensitivity to radiation, primary surgery seemed to provide a better chance of disease control and improved survival in NACC. Meanwhile, postoperative radiotherapy should be performed for advanced stage or residual tumours. Cranial nerve invasion and treatment pattern might be important factors affecting the prognosis of patients with NACC.

A Retrospective Study of Clinical Outcomes for Patients with Esophageal Cancer Who Were Treated with Radiotherapy Alone

Introduction: Patients with esophageal cancer who are in a poor general condition receive radiotherapy alone, but outcomes are often unsatisfactory. The aim of this study was to clarify recent outcomes of radiotherapy alone for esophageal cancer. Methods: Patients who underwent 50 Gy or more of radiotherapy without chemotherapy were retrospectively reviewed. Endpoints were overall survival (OS), disease-specific survival (DSS), local control (LC), and progression-free survival (PFS). Survival curves were drawn using the Kaplan-Meier method, and predictors were analyzed using the Cox proportional hazards model. Results: Sixty-nine patients were included. The median follow-up period was 17.9 months. The 5-year OS, DSS, LC, and PFS rates were 33.2%, 49.8%, 46.2%, and 16.8%, respectively. In the multivariate Cox proportional hazard model, clinical stage was a significant predictor for OS (hazard ratio [HR]: 4.42, 95% confidence interval [CI]: 1.80–11.17, p = 0.001), DSS (HR: 2.08, 95% CI: 1.43–3.12, p = 0.0001), LC (HR: 1.86, 95% CI: 1.28–2.74, p = 0.001), and PFS (HR: 1.65, 95% CI: 1.25–2.18, p = 0.0004). Radiation dose was a significant predictor for LC (HR: 0.87, 95% CI: 0.78–0.97, p = 0.018) and tumor location was a significant predictor for PFS (HR: 1.55, 95% CI: 1.10–2.19, p = 0.018). In subgroup analysis, the 5-year OS, DSS, LC, and PFS rates for stage I were 60.0%, 80.0%, 71.9%, and 46.1%, respectively. Conclusions: Stage, radiation dose, and tumor location are significant predictors for outcomes. Patients with stage I esophageal cancer can be cured by radiotherapy alone.

Real-world efficacy and safety of BRAF-targeted therapy for patients with advanced melanoma: A single-center retrospective study in Japan.

Most clinical trials investigating targeted therapies for patients harboring BRAF V600 mutations have included mostly White patients, and data for Asian patients are scarce. Although there are several retrospective studies in Japanese patients, they have investigated only the dabrafenib + trametinib regimen, and have had a short follow-up period. We conducted a single-center retrospective study to update previous studies and compare the outcomes with those in White patients. We analyzed 89 patients who received dabrafenib + trametinib or encorafenib + binimetinib, including 11 who received both treatment regimens. The overall response rate was 79.8%, with complete response in 25 patients (28.1%) and partial response in 45 patients (51.7%). The median progression-free survival was 13.7 months, and the median overall survival was 32.9 months. The 3-year progression-free and overall survival rates were 31.8% and 47.9%, respectively. Although the two regimens showed no significant differences in efficacy, their safety profiles differed, as reported in clinical trials. Therefore, the most frequent adverse event associated with the dabrafenib + trametinib regimen was pyrexia (61.3%) and that of encorafenib + binimetinib was blurred vision (32.0%). Switching directly to another targeted therapy after progressive disease showed no clinical response; however, rechallenge followed by immune checkpoint inhibitor therapy showed a certain response. As a prognostic factor, performance status was associated with progression-free survival, and performance status, serum lactate dehydrogenase level, and dose interruption were associated with overall survival in the multivariate analysis. Real-world data on targeted therapy for patients with melanoma in Japan suggest that both dabrafenib + trametinib and encorafenib + binimetinib show similar efficacy and safety in Asian and White patients.

Long-term oral administration of Huaier granules improves survival outcomes in hepatocellular carcinoma patients within Milan criteria following microwave ablation: a propensity score matching and stabilized inverse probability weighting analysis.

This study aimed to elucidate the therapeutic effects of Huaier granules on hepatocellular carcinoma (HCC) within the Milan criteria in patients who underwent microwave ablation (MWA). A total of 228 patients were included, with 97 in the Huaier group and 131 in the control group. We evaluated progression-free survival (PFS), overall survival (OS), and extrahepatic metastasis survival (EMS) using Kaplan-Meier (KM) curves with a log-rank test. Propensity Score Matching (PSM) and Stabilized Inverse Probability of Treatment Weighting (IPTW) were performed to minimize selection and confounding biases. Following PSM, the 1-, 3-, and 5-year PFS rates in the Huaier and control groups were 83.5% vs 70.7%, 57.7% vs 42.6%, and 43.6% vs 31.9% (p = 0.030), respectively. The 1-, 3-, and 5-year OS rates were 98.9% vs 95.6%, 83.9% vs 72.3%, and 72.2% vs 53.7% (p = 0.023), respectively. The corresponding 1-, 3-, and 5-year EMS rates were 98.9% vs 93.4%, 91.7% vs 83.7%, and 91.7% vs 78.5% (p = 0.039), respectively. Stabilized IPTW analysis of KM curves yielded results similar to those of the PSM analysis. Additionally, administering Huaier granules for at least 6 months significantly improved PFS and OS. Huaier granules can reduce the risk of recurrence and improve the OS of patients with HCC within the Milan criteria following MWA. Administering Huaier granules for over 6 months proved beneficial.

Chemoradiotherapy versus surgery after neoadjuvant chemoimmunotherapy in patients with stage III NSCLC: a real-world multicenter retrospective study

PurposeThe optimal treatment after neoadjuvant chemoimmunotherapy for patients with stage III non-small cell lung cancer (NSCLC) is unclear. This study aimed at comparing the efficacy and safety of chemoradiotherapy and surgery after neoadjuvant chemoimmunotherapy in stage III NSCLC.Materials and methodsWe conducted a real-world multicenter retrospective study on patients with stage III NSCLC who received surgery or chemoradiotherapy after neoadjuvant chemoimmunotherapy between October 2018 and December 2022. Progression-free survival (PFS) and overall survival (OS) were assessed from the initiation of neoadjuvant treatment and estimated by the Kaplan‒Meier method. Univariate and multivariate Cox regression models were used to examine potential prognostic factors. One-to-one propensity score matching (PSM) was used to further minimize confounding.ResultsA total of 239 eligible patients were enrolled, with 104 (43.5%) receiving surgery and 135 (56.5%) receiving CRT. After 1:1 PSM, 1- and 2-year PFS rates in patients receiving radical surgery (rSurgery group) vs. patients receiving definitive cCRT (dCCRT group) were 80.0% vs. 79.2% and 67.2% vs. 53.1%, respectively (P = 0.774). One- and 2-year OS rates were 97.5% vs. 97.4% and 87.3% vs. 89.9%, respectively (P = 0.558). Patients in the dCCRT group had a numerically lower incidence of distant metastases compared to those in the rSurgery group (42.9% vs. 70.6%, P = 0.119). The incidence of treatment-related adverse events was similar in both groups, except that the incidence of grade 3/4 hematological toxicity was significantly higher in the dCCRT group (30.0% vs. 10.0%, P = 0.025).ConclusionFollowing neoadjuvant chemoimmunotherapy, definitive concurrent chemoradiotherapy may achieve noninferior outcomes to radical surgery in stage III NSCLC.

Active surveillance and emerging medical treatment options for desmoid: when and for whom?

This article discusses the evolving approaches to desmoid tumors management, shedding light on recent developments. Active surveillance has become the primary approach for managing primary peripheral desmoid tumors. This strategy was initially based on evidence from retrospective studies. Roughly 50% of cases managed with active surveillance show spontaneous stabilization or regression. Recent prospective trials conducted in Italy, The Netherlands, and France (2022-2023) confirm the efficacy of active surveillance, revealing 3-year progression-free survival rates ranging from 53.4 to 58%. For the patients under active surveillance, decisions regarding treatment are based on significant tumor growth or progressive symptoms. Moreover, three contemporary randomized trials investigated medical treatments for progressive or recurrent desmoid tumors. Sorafenib, pazopanib, and nirogacestat demonstrated clinical activity, as evidenced by favorable progression-free survival and objective response rates. Active surveillance has solidified its position as the primary management approach for desmoid tumors, validated by three robust prospective studies. Three recent randomized trials explored medical treatment for progressive or recurrent desmoid tumors, revealing promising clinical activities.

CAR T cells vs bispecific antibody as third- or later-line large B-cell lymphoma therapy: a meta-analysis

AbstractThis meta-analysis evaluates the efficacy and safety of chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). We searched MEDLINE, Embase, and Cochrane databases until July 2023 for trials assessing CAR T-cell therapies and CD20×CD3 bispecific antibodies as third or subsequent lines in R/R DLBCL. Random-effects models estimated the complete response (CR) rate and secondary outcomes, with meta-regressions adjusting for relevant covariates. Sixteen studies comprising 1347 patients were included in the pooled analysis. The pooled CR rate for bispecific antibodies was 0.36 (95% confidence interval [CI], 0.29-0.43), compared with 0.51 (95% CI, 0.46-0.56) for CAR T-cell therapy (P < .01). This superiority persisted when comparing the CAR T-cell–naive patients within the bispecific antibody group, with a CR rate of 0.37 (95% CI, 0.32-0.43). Multivariable meta-regression also revealed better efficacy of CAR T cells with adjustment for the proportion of double-hit lymphoma. The pooled 1-year progression-free survival rate mirrored these findings (0.32 [95% CI, 0.26-0.38] vs 0.44 [95% CI, 0.41-0.48]; P < .01). For adverse events of grade ≥3, the bispecific antibody had incidences of 0.02 (95% CI, 0.01-0.04) for cytokine release syndrome, 0.01 (95% CI, 0.00-0.01) for neurotoxicity, and 0.10 (95% CI, 0.03-0.16) for infections. The CAR T cell had rates of 0.08 (95% CI, 0.03-0.12), 0.11 (95% CI, 0.06-0.17), and 0.17 (95% CI, 0.11-0.22), respectively, with significant differences observed in the first 2 categories. In summary, CAR T-cell therapy outperformed bispecific antibody in achieving higher CR rates, although with an increase in severe adverse events.

Effects of concurrent chemoradiotherapy with or without Endostar on the regression of retropharyngeal lymph node and prognosis of patients with locally advanced nasopharyngeal carcinoma: a retrospective study

Background and PurposeTo investigate the effect of combining Endostar with concurrent chemoradiotherapy (ECCRT) compared to concurrent chemoradiotherapy (CCRT) on the regression rate of retropharyngeal lymph nodes (RLNs) and the relationship between regression rate of RLNs and prognosis of patients with locally advanced nasopharyngeal carcinoma (LANPC).MethodsA total of 122 LANPC patients with RLNs metastasis were included. Metastatic RLNs were delineated both before and after treatment slice by slice on the magnetic resonance images cross-section. The regression rate of RLNs, adverse effects (AE) were evaluated. The median regression rate of RLNs was taken as the cut-off value, and the patients were furtherly divided into high regression rate (HRR) group and low regression rate (LRR) group, then survival times were evaluated.ResultsThe median regression rates of RLNs in the ECCRT and CCRT groups were 81% and 50%, respectively (P < 0.001). There was no statistically significant difference in the incidence of grade 3/4 AEs between the two groups, except for oral mucositis (ECCRT 26.23% vs. CCRT 44.26%, P = 0.037). The 3-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional failure-free survival (LRFFS) rates in the HRR and LRR groups were 85.48% and 86.67% (P = 0.983), 80.65% and 68.33% (P = 0.037), 83.87% and 85% (P = 0.704), 93.55% and 81.67% (P = 0.033), respectively.ConclusionsPatients in the ECCRT group had higher regression rates of RLNs and lower incidence of severe oral mucositis. Furthermore, patients in the HRR group had a better 3-year PFS and LRFFS rate than those in the LRR group.

Dose-escalated Salvage Whole-pelvic Radiotherapy for Biochemical Recurrence After Radical Prostatectomy for High-risk Prostate Cancer.

To investigate the institutional experience of dose-escalated salvage whole-pelvic radiotherapy (WPRT) with the simultaneous integrated boost (SIB) technique in patients with biochemical recurrence (BCR) after radical prostatectomy for high-risk prostate cancer. This retrospective study included 21 patients with BCR who received radical prostatectomy for high-risk prostate cancer and underwent salvage RT. Clinical target volume (CTV) of the whole pelvis (CTV56) included the prostate bed, common iliac, external iliac, internal iliac, and obturator lymph node regions. The boost CTV (CTV66) included the prostate bed. Planning target volumes (PTV) were generated by adding a margin of 6-8 mm to CTV (PTV56 and PTV66). Doses of 56.1 and 66 Gy in 33 fractions were delivered to PTV56 and PTV66, respectively. The 5-year biochemical progression-free survival, overall survival, and cause-specific survival rates were 72%, 94%, and 94%, respectively. A grade 3 late genitourinary toxicity event of gross hematuria was observed in one patient (4%). Acute and late toxicities of grade ≥3, other than gross hematuria, were not observed in any patient. Dose-escalated salvage WPRT using the SIB technique provides appropriate tumor control without increasing the incident of significant toxicities.

Conversion surgery intervention versus continued systemic therapy in patients with a response after PD-1/PD-L1 inhibitor-based combination therapy for initially unresectable biliary tract cancer: a retrospective cohort study.

The role of conversion surgery in patients with unresectable biliary tract cancer who responded positively to PD-1/PD-L1 inhibitor-based therapy remains unclear. This study aimed to assess the outcomes in patients with or without conversion surgery. In this cohort study, patients with advanced biliary tract cancer who received combination therapy with PD-1/PD-L1 inhibitors from July 2019 to January 2023 were retrospectively. Patients who exhibited positive responses and met the criteria for conversion surgery were enrolled, and their surgical and oncological outcomes were analyzed. Out of 475 patients, 34 who met the conversion resection criteria were enrolled. The median follow-up was 40.5 months postinitiation of systemic therapy. Ultimately, 13 patients underwent conversion surgery, while 21 received continuation of systemic treatment alone (nonsurgical group). The median interval from the initial antitumor therapy to surgery was 6.7 [interquartile range (IQR) 4.9-9.2] months. Survival with conversion surgery was significantly longer than the nonsurgical cohort, with a median progression-free survival (PFS) [unreached vs. 12.4 months; hazard ratio 0.17 (95% CI: 0.06-0.48); P =0.001] and overall survival (OS) [unreached vs. 22.4 months; hazard ratio 0.28 (95% CI: 0.09-0.84); P =0.02], respectively. After a median postoperative follow-up of 32.2 months in the surgical cohort, eight patients survived without recurrence. The estimated 3-year OS, PFS, and recurrence-free survival rate in the surgical cohort were 59.9, 59.2, and 60.6%, respectively. The R0 resection rate reached 92.3%, with two achieving a pathological complete response. One patient experienced a Clavien-Dindo grade 3 complication without surgery-related mortality. No serious adverse events or surgical delays were observed. Multivariate analysis indicated that conversion surgery was independently associated with OS ( P =0.03) and PFS survival ( P =0.003). Conversion surgery appears safe and offers survival benefits to patients responding to immune checkpoint inhibitors-based combinations. However, further studies are required to validate this strategy in the era of immunotherapy.

The burden of skull base chordomas: insights from a meta-analysis of observational studies.

The aim of this study was to provide a quantitative synthesis of the survival outcomes for patients with skull base chordomas, focusing on the role of 1) the extent of resection (gross-total [GTR] vs non-GTR), 2) the type of surgery (primary vs revision), 3) tumor histology, and 4) the different use of adjuvant therapies (proton beam radiotherapy [PBRT], photon radiotherapy [RT], or none). A systematic review with a meta-analysis was conducted following the 2020 PRISMA guidelines. Observational studies describing adult and pediatric patient cohorts harboring skull base chordomas were included. The primary outcome measures were represented by the 5-year overall survival (OS) and progression-free survival (PFS) rates. The main intervention effects were represented by the extent of resection (GTR vs non-GTR), type of surgical excision (primary vs revision surgeries), tumor histology, and the different use of adjuvant therapies (PBRT, RT, or none). The pooled estimates were calculated using random forest models. The risk of bias was evaluated using the Joanna Briggs Institute checklist for case series. Six hundred forty-four studies were identified through a database and register search. After study selection, 51 studies and 3871 patients were included in the meta-analysis. The overall 5-year OS rate was 73%, which increased to 84% among patients undergoing GTR. The overall 5-year PFS rate was 52%, increasing to 74% for patients receiving GTR. The 5-year OS and PFS rates for patients undergoing PBRT were 86% and 71%, compared with 71% and 54% for patients receiving RT, and 55% and 25% when no adjuvant treatments were used. Patients undergoing their first surgery had 2.13-fold greater chances of being disease-free and 1.4-fold greater chances of being alive at 5 years follow-up compared with patients who received a revision surgery. Patients harboring chondroid chordomas had 1.13- and 1.9-fold greater chances of being alive at 5 years compared with patients with conventional and de-differentiated chordomas, respectively. The overall risk of bias was low in the included studies. The results of this comprehensive meta-analysis highlight the tremendous impact of GTR and adjuvant PBRT on improving OS and PFS of patients harboring skull base chordomas, with better survival rates demonstrated for patients with chondroid tumors. Even in experienced hands, the rate of surgical morbidity remains high. Proper management in high-volume centers is mandatory to reach the expected resection goal at the first surgical attempt and to reduce surgical morbidity. The introduction of the endoscopic endonasal approach was related to improved surgical and functional outcomes.

The impact of purified protein derivative prior to intravesical bacillus Calmette-Guérin for the treatment of patients with non-muscle invasive bladder cancer.

The aim of this study is to investigate the impact of the intradermal injection of purified protein derivative (PPD) and PPD skin test reactions on the oncological outcomes of patients with non-muscle invasive bladder cancer (NMIBC) treated by trans-urethral resection of bladder tumor (TURBT) and adjuvant intravesical BCG. The study included 100 consecutive patients with NMIBC prospectively given intradermal PPD 1-2 weeks before starting BCG therapy. Another 100 patients with NMIBC not given intradermal PPD before starting BCG were chosen as a historical control. The control group was chosen to be matching with the study group regarding baseline characteristics. The study group was divided into 2 subgroups with positive and negative reaction to PPD skin test. Oncological outcomes, immunological markers (TNF-α and IL-6) changes and BCG side effects were evaluated. There were no significant differences between patients who received PPD or not regarding the 2-year recurrence free survival (RFS) rates and progression-free survival (PFS) rates and immunological markers changes. The 2-year RFS and PFS rates were significantly higher in patients with positive reactions. Post-induction values of immunological markers increased in all patients with a significant increase in patients with positive reactions. BCG side effects were significantly higher in patients with positive reactions. The intradermal injection of PPD before intravesical BCG has no impact on oncological outcomes of patients with NMIBC treated with TURBT and intravesical BCG. However, the PPD skin test reactions before BCG therapy can predict the oncological outcomes, BCG side effects and the immunological outcomes of patients.

Real-world experience of commercial relmacabtagene autoleucel (relma-cel) for relapsed/refractory central nervous system lymphoma: a multicenter retrospective analysis of patients in China

BackgroundRelapsed/refractory (R/R) central nervous system lymphomas (CNSLs) are associated with a poor prognosis. Relmacabtagene autoleucel (relma-cel), expressing the same chimeric antigen receptor (CAR) as lisocabtagene maraleucel, with an optimized commercial-ready...

Long-term clinical outcomes of hypofractionated stereotactic radiotherapy using the CyberKnife robotic radiosurgery system for jugular foramen schwannomas.

Jugular foramen schwannomas (JFSs) are rarely seen, benign tumors with slow growth. Today, management options for JFSs include observation, surgery, and radiation. However, the optimal treatment strategy remains controversial. Stereotactic radiosurgery serves as a minimally invasive alternative or adjuvant therapeutic regimen of microsurgery. Gamma Knife radiosurgery is suitable for patients with JFS who have small- and medium-sized tumors and normal cranial nerve (CN) function. Hypofractionated stereotactic radiotherapy (HSRT) offers a potential radiobiological advantage and may result in better preservation of normal structures compared to single-fraction stereotactic radiosurgery. The aim of the article was to review the clinical and radiographic outcomes of patients with JFS who were treated using HSRT. The authors retrospectively analyzed 74 patients with JFS who received HSRT between January 2009 and January 2020 in the authors' center. Among them, 53 patients were newly diagnosed with JFS, 19 patients had a previous history of microsurgical resection, and the other 2 patients underwent CyberKnife because of tumor recurrence after Gamma Knife radiosurgery. A total of 73 patients had preexisting CN symptoms and signs. The median tumor volume was 14.8 cm3 (range 0.5-41.2 cm3), and most of them (70.3%) were ≥ 10 cm3. The radiation dose regimen was prescribed depending on the tumor size, and more fractions were used in larger tumors. The median margin doses prescribed were 18.2 Gy/2 fractions, 21.0 Gy/3 fractions, and 21.6 Gy/4 fractions. The median follow-up was 103 months (range 18-158 months). After treatment, 42 (56.8%) patients had tumor regression, 27 (36.5%) patients had stable tumors, and 5 (6.8%) experienced tumor progression. Among them, MRI revealed that 1 patient had a complete response. Three patients received surgery at a median of 25 months because of tumor progression. One patient underwent ventriculoperitoneal shunt insertion for hydrocephalus that developed after HSRT independent of tumor progression. The 5-year progression-free survival rate was 93.2%. Preexisting cranial neuropathies improved in 46 patients, remained stable in 14, and worsened in 14. HSRT proved to be a safe and effective primary or adjuvant treatment strategy for JFSs, although 14 patients (18.9%) experienced some degree of delayed symptomatic deterioration posttreatment. This therapeutic option was demonstrated to provide both excellent tumor control and improvement in CN function.

Second Chance for Cure: Stereotactic Ablative Radiotherapy in Oligometastatic Disease.

Local ablative therapy, such as radiotherapy or surgery, plays a key role in treatment of patients with oligometastatic disease. Stereotactic ablative body radiotherapy (SABR) comes to the fore as a safe and effective treatment for patients with a limited number of metastases, even those located in hard-to-reach body sites. Many researchers have suggested that metastatsis-directed therapy could improve long-term progression-free survival (PFS) and overall survival (OS) in patients with oligometastases. This was a retrospective, single-arm, observational study conducted between July 2015 and February 2022. In our institute, 60 patients with controlled primary tumors and one to five metastases were treated with SABR. Prescribed radiation doses ranged from 12 to 60 Gy administered in one to seven fractions. We aimed to determine whether metastatic-directed therapy using SABR for all oligometastases affects OS and PFS and whether the primary tumor or metastatic site influences OS/PFS. The most common primary malignancy types were prostate (n = 14), colorectal (n = 10), lung (n = 7), and breast cancers (n = 6). The median follow-up was 30 months, ranging from 9 to 79. The 1-, 3-, and 5-year PFS and OS rates were 54.9%, 37.0%, and 37.0% and 98.3%, 84.4%, and 73.8%, respectively, and the median time to first progression was 15 (range, 2-32) months. Twenty-four (40%) patients had no recurrence. In our analysis, primary tumor site was not an independent prognostic factor. The metastatic site may influence on patient outcome in cases of localized bone and liver metastases. In our retrospective analysis, SABR was associated with favorable levels of PFS and OS in patients with oligometastases. The limitations of our study were lacking high-level evidence, and randomized studies to compare SABR and palliative standard of care are mandatory.

Association of preexisting anti-thyroid antibodies and body mass index with prognosis of lung cancer patients treated with PD-1/PD-L1 inhibitors

Abstract Objectives Immune checkpoint inhibitors are a new beneficial medication in the treatment of cancer. Whether preexisting TPOAb was related to longer overall survival (OS) is controversial. This retrospective study analyzed the OS and progression-free survival (PFS) of patients with lung cancer, and explored predictive factors associated with the efficacy of PD-1/PD-L1 inhibitors treatment. Methods Patients with lung cancer who were hospitalized in the First Affiliated Hospital of Wenzhou Medical University between January 1, 2020 and December 30, 2020 were enrolled. Thyroid function, TPOAb, TGAb, and prognostic nutritional index levels and body mass index were analyzed. Supervising physicians independently assessed patient staging, OS, and PFS. Demographic data, pathological type, and previous treatment history were also collected. Results In total, this study enrolled 69 patients, with ages of 46–80 years old. Patients with lower weight showed reduced OS and PFS rates relative to those with normal weight and overweight (p&lt;0.05). The single patient with large cell neuroendocrine carcinoma (LCNEC) exhibited a 1-, 1.5- and 2-year OS rate lower than that of the patients diagnosed with squamous cell carcinoma, small cell lung cancer, or adenocarcinoma (p&lt;0.05). This LCNEC patient also had lower 1-, 1.5-, and 2-year PFS rates compared to adenocarcinoma patients (p&lt;0.05). TPOAb and TGAb levels were unrelated to OS or PFS. Multivariate Cox regression analyses revealed a positive association between body mass index, OS, and PFS. Conclusions Patients with lower body weight were predictive of poorer survival outcomes when receiving PD-1/PD-L1 inhibitors treatment as compared to patients with normal weight and overweight. However, positive baseline TGAb and TPOAb levels were not associated with increased OS or PFS in patients with lung cancer.

Long-term remission and survival in patients with relapsed or refractory multiple myeloma after treatment with LCAR-B38M CAR T cells: 5-year follow-up of the LEGEND-2 trial

BackgroundThe autologous anti–B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy LCAR-B38M has been approved for the treatment of relapsed and refractory multiple myeloma in many countries across the world under the name ciltacabtagene autoleucel. LEGEND-2 was the first-in-human trial of LCAR-B38M and yielded deep and durable therapeutic responses. Here, we reported the outcomes in LEGEND-2 after a minimal 5-year follow-up.MethodsParticipants received an average dose of 0.5 × 106 cells/kg LCAR-B38M in split or single unfractionated infusions after cyclophosphamide-based lymphodepletion therapy. Investigator-assessed response, survival, safety and pharmacokinetics were evaluated.ResultsSeventy-four participants enrolled and had a median follow-up of 65.4 months. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 21.0% and 49.1%, with progressive flattening of the survival curves over time. Patients with complete response (CR) had longer PFS and OS, with 5-year rates of 28.4% and 65.7%, respectively. Twelve patients (16.2%) remained relapse-free irrespective of baseline high-risk cytogenetic abnormality and all had normal humoral immunity reconstituted. An ongoing CR closely correlated with several prognostic baseline indices including favorable performance status, immunoglobulin G subtype, and absence of extramedullary disease, as well as a combination cyclophosphamide and fludarabine preconditioning strategy. Sixty-two (83.8%) suffered progressive disease (PD) and/or death; however, 61.1% of PD patients could well respond to subsequent therapies, among which, the proteasome inhibitor-based regimens benefited the most. Concerning the safety, hematologic and hepatic function recovery were not significantly different between non-PD and PD/Death groups. A low rate of second primary malignancy (5.4%) and no severe virus infection were observed. The patients who tested positive for COVID-19 merely presented self-limiting symptoms. In addition, a sustainable CAR T population of one case with persistent remission was delineated, which was enriched with indolently proliferative and lowly cytotoxic CD4/CD8 double-negative functional T lymphocytes.ConclusionsThese data, representing the longest follow-up of BCMA-redirected CAR T-cell therapy to date, demonstrate long-term remission and survival with LCAR-B38M for advanced myeloma.Trial registrationLEGEND-2 was registered under the trial numbers NCT03090659, ChiCTRONH-17012285.

The efficacy and safety of stereotactic body radiotherapy combined with systematic therapy for metastatic renal cell carcinoma: a systematic review and meta-analysis.

There is considerable interest in the potential of stereotactic body radiation therapy (SBRT) combined with systemic therapy such as tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitors (ICIs). However, its efficacy and safety remain unclear. The purpose of this study was to evaluate the efficacy and safety of conducting SBRT during ICI or TKI treatment in different disease settings for patients with metastatic renal cell carcinoma (mRCC). A total of 16 studies were ultimately included. Under the random effects model, the pooled 1-year local control rate (1-yr LCR) and objective response rate (ORR) were 90% (95% confidence interval [CI]: 80%-95%, I 2=67%) and 52% (95% CI: 37%-67%, I 2=90%), respectively. SBRT concomitant with different systemic therapy yield significant different 1-yr LCR (p<0.01) and ORR (p=0.02). Regarding survival benefits, the pooled 1-year progression-free survival (1-yr PFS) and 1-year overall survival (1-yr OS) rates were 45% (95% CI: 29%-62%, I 2=91%) and 85% (95% CI: 76%-91%, I 2=66%), respectively. 1-yr PFS and 1-yr OS in different disease settings demonstrated significant difference (p<0.01). As for toxicity, the pooled incidence of grade 3-4 adverse events was 14% (95% CI: 5%-26%, I 2=90%). This study highlights the feasibility of utilizing these strategies in mRCC patients, especially those with a low metastatic tumor burden.