Control Rates For Patients Research Articles

The Objective Response and Disease Control Rates in Patients with Liver Metastastic Breast Cancer Receiving Transarterial Radioembolization: A Meta-Analysis

Aim: To meta-analyze the utility of transarterial radioembolization (TARE) in patients with liver metastatic breast cancer (BC), based on the objective response rate (ORR) and disease control rate (DCR). Methods: A literature search was performed retrieving studies with (1) at least 10 patients with liver metastatic BC treated with TARE and (2) adequate information to derive ORR and DCR. The ORR is the ratio between patients with liver lesions showing complete response (CR) or partial response (PR) over the total number of patients treated with TARE; the DCR is the ratio between patients with CR, PR, or stable disease (SD) over the total number of patients treated with TARE. Results: Eighteen studies (650 patients) were eligible; the ORR of TARE resulted 50.71% (95% C.I.: 40.04–61.36) and the DCR resulted 88.37% (95% C.I.: 81.89–93.57). Taking into account resin spheres (395 patients), the ORR was 60.35% (95% C.I.: 46.55–73.36) and the DCR was 92.73% (95% C.I.: 87.17–96.80%). Considering glass spheres (144 patients), the ORR was 32.38% (95% C.I.: 18.43–48.16) and the DCR was 82.69% (95% C.I.: 59.29–97.26). Conclusions: This meta-analysis favors the use of TARE in patients with liver metastatic BC either with resin or glass spheres.

Abstract P116: Hypertension Treatment and Control in Canadians with Diabetes

Introduction: 3 million Canadians and 23 million Americans have concurrent hypertension and diabetes. Blood pressure (BP) control reduces the risk of heart attacks, strokes, retinopathy, and kidney disease. We investigated hypertension control rates in patients with diabetes, responses to uncontrolled BP measurements, and use of antihypertensive drug classes. Methods: We performed an observational study of adults with diabetes and hypertension drawing from the IQIVA primary care database (contains data on 1.2 million Canadians). Our first outcome was mean BP at 3, 6, 12, and 24 months after inclusion. Our second outcome was the number of uncontrolled BP measurements (≥130/80) followed by a physician BP check, medication dose/frequency increase, or new medication in the subsequent 6 weeks. Our third outcome (for a subset of individuals with medication data available) was the number of individuals prescribed renin-angiotensin-aldosterone-system inhibitors (RAASi), dihydropyridine calcium channel blockers (DHP-CCBs), or thiazide/thiazide-like diuretics. Results: We identified 10,814 individuals identified with both diabetes and hypertension. Mean BP (in mmHg) remained largely unchanged over 24 months: 136.7/78.6 at 3 months, 135.5/82.2 at 6 months, 137.2/82.8 at 12 months, and 136.6/82.3 at 24 months. Over the two years of follow-up there were 55,381 uncontrolled BP events, and in the subsequent 6 weeks only 27,877 (50.3%) were followed by ≥1 physician BP checks. Among individuals with medication data, there were 16,364 uncontrolled BP events, 33.4% followed by a new antihypertensive medication and 18.2% followed by an antihypertensive dose/frequency change. Of the 6,919 individuals for whom we had medication data, 6,216 (89.8%) were prescribed a RAASi, 2,371 (34.3%) were prescribed a DHP-CCB, and 1,672 (24.2%) were prescribed thiazide/thiazide like diuretic. Conclusion: Over two-thirds (68.8%) of people with diabetes and hypertension had uncontrolled blood pressure that persisted over 2 years during which half of uncontrolled BPs were followed by a physician BP check in 6 weeks, and one-fifth by a antihypertensive dose/frequency change. While almost 90% were treated with RAASi, over a third were on a DHP-CCB and less than one quarter were treated with a thiazide/thiazide like diuretic. Therapeutic inertia and under-prescribing of dual and triple therapy contribute to persistently high BP thus represent opportunities for improvement.

Application of Individual Case Management Nursing Model in Blood Lipid Management of Patients with Coronary Heart Disease

Objective: To explore the effect of the case management nursing model on lipid management in patients with coronary heart disease. Methods: Coronary heart disease patients admitted to the cardiology department of a tertiary hospital in Henan Province from April 2023 to March 2024 were randomly divided into a conventional care group and a case management group. The case management model was implemented, and a 3-month follow-up was conducted. Data were collected and analyzed. Results: There were no statistically significant differences in baseline data between the two groups. After 3 months of case management, the case management group showed better medication adherence, greater reductions in lipid levels, and higher lipid control rates. Conclusion: The case management nursing model can improve medication adherence and lipid control rates in patients with coronary heart disease.

Predicting locoregional recurrence in triple-negative breast cancer using novel molecular subtyping.

e12549 Background: Triple-negative breast cancer (TNBC) presents a poorer prognosis compared to other breast cancer subtypes, characterized by a higher likelihood of early recurrence and increased incidence of visceral metastases. Evidence from numerous randomized clinical trials indicates that postmastectomy radiotherapy (PMRT) reduces locoregional recurrence (LRR) and improves breast cancer survival in TNBC. Previous reports creatively divided TNBC into four molecular subtypes for personalized treatment. The present study aims to elucidate patterns of LRR in different subtypes of TNBC after PMRT. Methods: From 2019 to 2022, data from 349 AJCC 7th edition stage II-III breast cancer patients treated with mastectomy and PMRT were retrospectively analyzed. These patients were classified into the basal-like immune-suppressed (BLIS) and non-BLIS groups based on the immunohistochemistry biomarkers. The cumulative incidence function was applied to estimated LRR rates, with death as a competing risk, using Gray's test for comparisons. Results: According to the IHC results, a total of 255 patients belonged to the non-BLIS group and 94 to the BLIS group. The 3-year LRR for the entire cohort was 5.16%. There were 9 cases each in the non-BLIS subtype (3.5%) and BLIS subtype (9.6%). The cumulative incidence of LRR between the two groups was significantly different, with a rate of 4.0% in the non-BLIS group and 9.0% in the BLIS group ( P = 0.02). Among the 18 patients with LRR in the whole population, 11 had isolated LRR and 7 were diagnosed with LRR with concurrent distant metastases. The most common area of recurrence in both subtypes was the supraclavicular region. The majority of recurrences occurred within the RT field (in-field), and no isolated out-of-field relapse was observed. In multivariate analysis, independent factors predicting higher LRR were the BLIS subtype (HR = 3.06, P = 0.02). Conclusions: Study results suggest that TNBC of the BLIS subtype is at higher risk for LRR. Immunohistochemistry-based molecular typing may serve as a prognostic biomarker to guide postmastectomy radiotherapy in patients with TNBC. New strategies are needed to improve local control rates in patients with BLIS subtype.

Biochemical Control in Cushing's syndrome: Outcomes of the treatment in a large single center cohort.

Normalization of hypercortisolism is essential to reduce morbidity and mortality in patients with Cushing's syndrome (CS). The aim of this analysis was to assess biochemical control rates in patients with Cushing's disease (CD), ectopic Cushing's syndrome (ECS) and adrenal Cushing's syndrome (ACS). Patients with confirmed CS (n= 296) treated in a single tertiary care center were retrospectively analysed (185 CD, 27 ECS, 84 uni- and bilateral ACS). Firstline treatment led to biochemical control in 82% of the patients. Time to biochemical control (median, IQR) was longer in CD (11.0 weeks, 5.6-29.8; p< 0.05) than in ACS (7.7 weeks, 4.1-17.1) and ECS (5.6 weeks, 4.1-23.3). Disease persistence or recurrence after first-line therapy was observed more often in CD (24% and 18%; p< 0.05) than in ECS (15% and 15%) and ACS (6% and 4%). Total time in hypercortisolism since diagnosis was significantly shorter in patients with CD diagnosed since 2013, after specialized patient care was implemented, compared to patients diagnosed before 2013 (13.5 weeks, vs. 26.1 weeks; p< 0.0070). Control of hypercortisolism at last follow up (76 months, 38-163) was achieved in 94% of patients with ACS, 100% of patients with ECS and 92% of patients with CD. Biochemical control can be achieved in most patients with different subtypes of CS within a reasonable time frame. Control of hypercortisolism has improved over time.

Targeting Anterior Commissure Involvement with Hyperfractionated Radiotherapy for T1-T2 Squamous Cell Carcinoma of the Glottic Larynx.

Anterior commissure is involved in about 20% of early-stage glottic squamous cell carcinomas (EGSCCs). Treatment outcomes and prognostic factors for EGSCC with anterior commissure involvement (ACI) were evaluated by focusing on hyperfractionated radiotherapy (74.4 Gy in 62 fractions). One-hundred and fifty-three patients with T1-T2 EGSCC were included in this study. The median total doses for T1a, T1b, and T2 were 66, 74.4, and 74.4 Gy, respectively. Overall, 49 (32%) patients had T1a, 38 (25%) had T1b, and 66 (43%) had T2 disease. The median treatment duration was 46 days. The median follow-up duration was 5.1 years. The 10-year overall and cause-specific survival rates were 72% and 97%, respectively. The 10-year local control rates were 94% for T1a, 88% for T1b, and 81% for T2 disease. Local control rates in patients with ACI were slightly better than those in patients without ACI with T1a and T1b diseases; however, the difference was not significant. The 10-year laryngeal preservation rate was 96%. Six patients experienced grade 3 mucositis, and four patients had grade 3 dermatitis. Hyperfractionated radiotherapy was effective for T1 disease with ACI, but insufficient for T2 disease with ACI. Our treatment strategy resulted in excellent laryngeal preservation.

Efficacy and safety of sympathetic mapping and ablation of renal nerves for the treatment of hypertension (SMART): 6-month follow-up of a randomised, controlled trial

Previous trials of renal denervation (RDN) have been designed to investigate reduction of blood pressure (BP) as the primary efficacy endpoint using non-selective RDN without intraoperatively verified RDN success. It is an unmet clinical need to map renal nerves, selectively denervate renal sympathetic nerves, provide readouts for the interventionalists and avoid futile RDN. We aimed to examine the safety and efficacy of renal nerve mapping/selective renal denervation (msRDN) in patients with uncontrolled hypertension (HTN) and determine whether antihypertensive drug burden is reduced while office systolic BP (OSBP) is controlled to target level (＜140mmHg). We conducted a randomized, prospective, multicenter, single-blinded, sham-controlled trial. The study combined two efficacy endpoints at 6 months as primary outcomes: The control rate of patients with OSBP ＜140mmHg (non-inferior outcome) and change in the composite index of antihypertensive drugs (Drug Index) in the treatment versus Sham group (superior outcome). This design avoids confounding from excess drug-taking in the Sham group. Antihypertensive drug burden was assessed by a composite index constructed as: Class N (number of classes of antihypertensive drugs)×(sum of doses). 15 hospitals in China participated in the study and 220 patients were enrolled in a 1:1 ratio (msRDN vs Sham). The key inclusion criteria included: age (18-65 years old), history of essential HTN (at least 6 months), heart rate (≥70 bpm), OSBP (≥150mmHg and ≤180mmHg), ambulatory BP monitoring (ABPM, 24-h SBP ≥130mmHg or daytime SBP ≥135mmHg or nighttime SBP ≥120mmHg), renal artery stenosis (＜50%) and renal function (eGFR ＞45mL/min/1.73m2). The catheter with both stimulation and ablation functions was inserted in the distal renal main artery. The RDN site (hot spot) was selected if SBP increased (≥5mmHg) by intra-renal artery (RA) electrical stimulation; an adequate RDN was confirmed by repeated electronic stimulation if no increase in BP otherwise, a 2nd ablation was performed at the same site. At sites where there was decreased SBP (≥5mmHg, cold spot) or no BP response (neutral spot) to stimulation, no ablation was performed. The mapping, ablation and confirmation procedure was repeated until the entire renal main artery had been tested then either treated or avoided. AftermsRDN, patients had to follow a predefined, vigorous drug titration regimen in order to achieve target OSBP (＜140mmHg). Drug adherence was monitored by liquid chromatography-tandem mass spectrometry analysis using urine. This study is registered with ClinicalTrials.gov (NCT02761811) and 5-year follow-up is ongoing. Between July 8, 2016 and February 23, 2022, 611 patients were consented, 220 patients were enrolled in the study who received standardized antihypertensive drug treatments (at least two drugs) for at least 28 days, presented OSBP ≥150mmHg and ≤180mmHg and metall inclusion and exclusion criteria. In left RA and right RA, mapped sites were 8.2 (3.0) and 8.0 (2.7), hot/ablated sites were 3.7 (1.4) and 4.0 (1.6), cold spots were 2.4 (2.6) and 2.0 (2.2), neutral spots were 2.0 (2.1) and 2.0 (2.1), respectively. Hot, cold and neutral spots was 48.0%, 27.5% and 24.4% of total mapped sites, respectively. At 6M, the Control Rate of OSBP was comparable between msRDN and Sham group (95.4% vs 92.8%, p=0.429), achieved non-inferiority margin-10% (2.69%; 95% CI-4.11%, 9.83%, p ＜ 0.001 for non-inferiority); the change in Drug Index was significantly lower in msRDN group compared to Sham group (4.37 (6.65) vs 7.61 (10.31), p=0.010) and superior to Sham group (-3.25; 95% CI-5.56,-0.94, p=0.003), indicating msRDN patients need significantly fewer drugs to control OSBP ＜140mmHg. 24-hour ambulatory SBP decreased from 146.8 (13.9) mmHg by 10.8 (14.1) mmHg, and from 149.8 (12.8) mmHg by 10.0 (14.0) mmHg in msRDN and Sham groups, respectively (p<0.001 from Baseline; p>0.05 between groups). Safety profiles were comparable between msRDN and Sham groups, demonstrating the safety and efficacy of renal mapping/selective RDN to treat uncontrolled HTN. The msRDN therapy achieved the goals of reducing the drug burden of HTN patients and controlling OSBP <140mmHg, with only approximately four targeted ablations per renal main artery, much lower than in previous trials. SyMap Medical (Suzhou), LTD, Suzhou, China.

Phase II Clinical Trial of Trametinib and Low-Dose Dabrafenib in Advanced, Previously Treated BRAFV600/NRASQ61 Wild-Type Melanoma (TraMel-WT).

Patients with BRAFV600/NRASQ61 wild-type melanoma who progress after immune checkpoint inhibitors (ICIs) have a poor prognosis. MEK inhibition has shown activity in this patient population but is associated with treatment-limiting skin toxicity. Combining a BRAF inhibitor with a MEK inhibitor is associated with less skin toxicity. This phase II trial investigated trametinib (2 mg once daily) in patients with advanced BRAFV600/NRASQ61 wild-type, ICI-refractory melanoma. In case of treatment-limiting skin toxicity, low-dose dabrafenib (50 mg twice daily) was added to trametinib. After a trial amendment, both drugs were combined up-front. The confirmed objective response rate (cORR) served as the primary end point. Twenty-four patients were included (50% male; median age 57 years; 92% Eastern Cooperative Oncology Group Performance Status 0-2; 75% stage IV-M1c/stage IV-M1d; median number of prior therapies: two [range, 1-5]). Three patients were enrolled before and 21 patients after the amendment, respectively. Seven confirmed and one unconfirmed partial responses (PRs) were observed (cORR, 29.2%). The median duration of response was 16.6 weeks (95% CI, 5.5 to 27.7). Stable disease (SD) was the best response in an additional five patients. Among the responding patients, genetic alterations causing mitogen-activated protein kinase (MAPK) pathway activation were documented in six patients. The disease control rate in patients with MAPK pathway-activating alterations was 64.3% (five confirmed PR, one unconfirmed PR, and three SD). The median progression-free survival was 13.3 weeks (95% CI, 3.5 to 23.1), and the median overall survival was 54.3 weeks (95% CI, 37.9 to 70.6). Adding low-dose dabrafenib to trametinib effectively mitigated or prevented treatment-limiting trametinib-related skin toxicity. The combination of trametinib plus low-dose dabrafenib demonstrated encouraging efficacy and effective mitigation of skin toxicity in patients with advanced, ICI-pretreated BRAFV600/NRASQ61 wild-type melanoma patients. MAPK pathway-activating alterations hold promise as a predictive biomarker.

Radiosensitizing Favors Response to Peptide Receptor Radionuclide Therapy in Patients With Highly Proliferative Neuroendocrine Malignancies: Preliminary Evidence From a Clinical Pilot Study.

Peptide receptor radionuclide therapy (PRRT) represents a cornerstone of treatment regimens for patients with low proliferative neuroendocrine tumors (NETs). However, in patients experiencing somatostatin receptor-positive NET with higher proliferation rates, a value and potential therapeutic benefit of PRRT as part of multimodal treatment approaches and potentially with addition of radiosensitizing agents has not yet been established. In this study, 20 patients with histologically confirmed gastroenteropancreatic (GEP) NET with proliferation rates (Ki67) between 15% and 55% were treated either with PRRT only (n = 10) or with a combination therapy (n = 10) comprising PRRT and capecitabine/temozolomide (CAP/TEM) for at least 2 consecutive cycles. Disease control rate in patients treated with PRRT alone was 60% (40% stable disease and 20% partial response). Strikingly, in patients treated with PRRT in combination with radiosensitization (CAP/TEM), the disease control rate was 90% (20% stable disease and 70% partial response). The median progression-free survival in the PRRT only group was 12 months, whereas the median progression-free survival in the PRRT + CAP/TEM group was 26 months and has not been yet reached for all patients in the group during the observation period. The median disease-specific survival for patients with PRRT alone was 51 months, whereas this end point was not yet reached in the PRRT + CAP/TEM group. Moreover, the PRRT + CAP/TEM group showed a significantly higher reduction of SSTR-PET-based metabolic tumor volume and chromogranin A levels compared with the PRRT only group. Importantly, adverse events of all grades did not differ between both groups. PRRT + CAP/TEM represents a highly promising and well-tolerated therapeutic regimen for patients experiencing somatostatin receptor-positive NET with higher (Ki67 ≥ 15%) proliferation rate. Prospective randomized clinical trials are warranted.

Clinical characteristics, treatment, and blood pressure control in patients with hypertension seen by primary care physicians in Spain: the IBERICAN study.

To determine the clinical profile, according to the history of hypertension, the risk of developing hypertension, current antihypertensive treatment and BP control rates in patients with hypertension from the IBERICAN cohort. IBERICAN is an ongoing prospective cohort study, whose primary objective is to determine the frequency, incidence, and distribution of CVRF in the adult Spanish population seen in primary care settings. This analysis shows the baseline clinical characteristics of patients with hypertension. Adequate BP control was defined as BP <140/90 mmHg according to 2013 ESH/ESC guidelines. A total of 8,066 patients were consecutively included, of whom 3,860 (48.0%) had hypertension. These patients were older (65.8 ± 10.9 vs. 51.6 ± 14.7 years; p < 0.001), had more cardiovascular risk factors, target organ damage and cardiovascular disease (CVD) in comparison with those without hypertension. The risk of hypertension increased with the presence of associated CV risk factors and comorbidities, particularly diabetes, obesity and the metabolic syndrome, and decreased with the intensity of physical activity. Regarding antihypertensive treatments, 6.1% of patients did not take any medication, 38.8% were taking one antihypertensive drug, 35.5% two drugs, and 19.6% three or more antihypertensive drugs. Overall, 58.3% achieved BP goals <140/90 mmHg. A greater probability of BP control was observed with increasing age of patients and the greater number of antihypertensive drugs. Blood pressure control was lower in hypertensive patients with diabetes, obesity, the metabolic syndrome, increased urinary albumin excretion, higher pulse pressure, and lack of antihypertensive treatment. About half of patients attended in primary care settings have hypertension in Spain. Patients with hypertension have a worse CV clinical profile than non-hypertensive patients, with greater association of CVRF and CVD. Around four out of ten patients do not achieve the recommended BP goals, and higher use of combination therapies is associated with a better BP control.

Efficacy and Complications of Percutaneous Balloon Compression for Patients With Trigeminal Neuralgia With and Without Concomitant Continuous Pain

BACKGROUND: Percutaneous balloon compression (PBC) has become one of the most common and effective minimally invasive treatments for trigeminal neuralgia (TN). However, the initial and long-term pain outcomes, as well as the complication rates of PBC for patients with TN with concomitant continuous pain (CCP) have yet to be specifically documented. OBJECTIVE: In this clinical study, we aimed to evaluate and compare the results of PBC in treating TN with and without CCP. STUDY DESIGN: Retrospective study. METHODS: This research retrospectively analyzed the pain outcomes and complications of 57 patients with TN with CCP and 118 patients with TN without CCP who had undergone PBC at our institution from January 2019 through June 2022. Procedures were performed by one senior neurosurgeon in a single center. The postdischarge follow-up and the collection of clinical data, including immediate and long-term pain relief, time to recurrence, and complications, were completed through phone contact by an independent neurosurgeon blind to the patients’ information. Then, the results of the 2 groups were compared; demographic and clinical data were evaluated for possible predictive factors for poor pain outcomes. RESULTS: In this study, PBC immediately resulted in complete pain relief in 70.2% of patients with CCP and significant pain relief in 84.2% of patients with CCP. For patients without CCP, the rates were 73.7% for complete pain relief and 85.6% for significant pain relief. After a minimum 6-month follow-up period, the rates decreased to 52.6% for complete pain relief and 73.7% for significant pain relief in patients with CCP, compared to 54.2% and 75.4% in those without CCP. The initial and long-term pain control rates in patients without CCP were slightly higher than those with CCP, but the differences were not statistically significant (P = 0.878, P = 0.968, respectively). The incidences of postoperative complications were similar between patients with and without CCP (21.1% vs 22.0%, P = 0.883), whereas the remission rate of complications in patients with CCP was significantly lower than that in patients without CCP (25.0% vs 69.2%, P = 0.011). A longer symptoms duration and having a history of neurodestructive procedures were predictive factors for poor outcomes following PBC. LIMITATIONS: The study was performed in a single-center. The nature of this research is retrospective instead of prospective and randomized, with the inability to control completely for variables. Additionally, the follow-up duration was not long enough to observe recurrence in some patients. CONCLUSIONS: This is the first specifically reported experience treating TN with CCP with PBC. PBC can result in significant relief of both episodic and constant pain from TN with CCP. Patients with a longer duration of pain and prior neurodestructive procedures have a higher risk of poor outcomes. The presence of CCP is not associated with pain outcomes and should not be considered a contraindication to PBC. KEY WORDS: Percutaneous balloon compression, trigeminal neuralgia, concomitant continuous pain, pain relief, comparison, efficacy, complication, predictive factor

Hypertension evaluated in the public and private Brazilian health system hypertension in public and private service.

Hypertension (HT) remains the leading cause of death worldwide. In Brazil it is estimated that 35% of the adult population has HT and that about 20% of these have blood pressure values within the targets recommended for the reduction of cardiovascular risk. There are some data that point to different control rates in patients treated by cardiologists in public and private referral center and this is an important point to be investigated and discussed. To compare sociodemographic characteristics, body mass index (BMI), antihypertensive (AH) drugs, blood pressure (BP) and control rate in public (PURC) and private (PRRC) referral centers. A cross-sectional multicenter study that analyzed data from hypertensive patients assisted by the PURC (one in Midwest Region and other in Northeast region) and PRRC (same distribution). Variables analyzed: sex, age, BMI, classes, number of AH used and mean values of systolic and diastolic BP by office measurement and home blood pressure measurement (HBPM). Uncontrolled hypertension (HT) phenotypes and BP control rates were assessed. Descriptive statistics and χ2 tests or unpaired t-tests were performed. A significance level of p < 0.05 was considered. A predominantly female (58.9%) sample of 2.956 patients and a higher prevalence of obesity in PURC (p < 0.001) and overweight in PRRC (p < 0.001). The mean AH used was 2.9 ± 1.5 for PURC and 1.4 ± 0.7 for PRRC (p < 0.001). Mean systolic and diastolic BP values were higher in PURC as were rates of uncontrolled HT of 67.8% and 47.6% (p < 0.001) by office measurement and 60.4% and 35.3% (p < 0.001) by HBPM in PURC and PRRC, respectively. Patients with HT had a higher prevalence of obesity in the PURC and used almost twice as many AH drugs. BP control rates are worse in the PURC, on average 15.3 mmHg and 12.1 mmHg higher than in the PRRC by office measurement.

KORTUC, a novel hydrogen peroxide‑based radiosensitizer for the enhancement of brachytherapy in patients with unresectable recurrent uterine cervical cancer.

Kochi Oxydol Radiation Therapy for Unresectable Carcinoma (KORTUC) is a novel radiosensitizer invented by Professor Ogawa at Kochi University (Japan) in 2006. The current study aimed to report the experience of the present authors with the use of KORTUC treatment in combination with interstitial brachytherapy (ISBT), with or without external beam (EB) radiotherapy (RT), in patients with locally recurrent cervical cancer (LRCC), who were likely to have a high risk of poor prognosis. Between April 2012 and January 2020, 14 female patients (15 tumoral lesions) with LRCC underwent KORTUC with ISBT. Their previous treatments included surgery (n=4), radiation therapy (n=8) and surgery plus RT (n=3). The primary lesions were located in the vaginal stump (n=5), pelvic wall (n=3), cervix (n=3), vaginal wall (n=2) and lymph nodes (n=2). At 2 h before RT, KORTUC was injected intratumorally via direct colposcopy. The dose of KORTUC ranged from 4-12 ml, adjusted for the tumor size. For patients who underwent ISBT, KORTUC was administered before and after insertion of the applicator before irradiation. Intratumoral injection of KORTUC was completed without any technical or safety issues in all 15 patients; it was well tolerated with no adverse events observed. KORTUC also showed preferable efficacy; a clinical complete response was observed in 87% of patients and the initial response rate was 100%. The 2-year local control rate in patients who underwent ISBT + KORTUC was 79%, whereas it was 63% in the re-irradiation group which was significantly lower (P=0.02) than that in the non-irradiation group (100%). Based on this finding, KORTUC with external irradiation is considered to be an optimal treatment strategy for patients with newly diagnosed LRCC this disease. Additionally, KORTUC may be an effective radiation response enhancer in multiple cancer types in which locoregional control after RT alone remains poor.

Lenvatinib as Second-Line Treatment after Atezolizumab plus Bevacizumab for Unresectable Hepatocellular Carcinoma: Clinical Results Show Importance of Hepatic Reserve Function

Introduction: Lack of an established methodology for post-progression systemic treatment following atezolizumab plus bevacizumab (Atez/Bev) administration is an important clinical issue. The present study aimed to elucidate the potential of lenvatinib as a second-line treatment option after Atez/Bev failure. Methods: From 2020 to 2022, 101 patients who received lenvatinib as second-line treatment were enrolled (median 72 years, males 77, Child-Pugh A 82, BCLC-A:B:C:D = 1:35:61:4), while 29 treated with another molecular targeting agent (MTA) during the period as second-line treatment were enrolled as controls. The therapeutic efficacy of lenvatinib given as second-line treatment was retrospectively evaluated. Results: Median progression-free survival/median overall survival for all patients was 4.4/15.7 months and for those with Child-Pugh A was 4.7 months/not-reached. When prognosis was compared with patients who received another MTA, there was no significant difference for PFS (3.5 months, p = 0.557) or OS (13.6 months, p = 0.992), and also no significant differences regarding clinical background factors. mRECIST findings showed that objective response and disease control rates in patients treated with lenvatinib were 23.9% and 70.4%, respectively (CR:PR:SD:PD = 3:14:33:21), while those shown by RECIST, ver. 1.1, were 15.4% and 66.2%, respectively (CR:PR:SD:PD = 1:10:36:24). Adverse events (any grade ≥10%) were appetite loss (26.7%) (grade 1:2:3 = 2:15:10), general fatigue (21.8%) (grade 1:2:3 = 3:13:6), protein in urine (16.8%) (grade 1:2:3 = 0:4:13), and hypertension (13.9%) (grade 1:2:3 = 1:8:5). Conclusion: Although lenvatinib treatment might not provide a pseudo-combination immunotherapy effect following Atez/Bev failure, lenvatinib when used as second-line treatment after Atez/Bev failure might be expected to be comparable as compared to its use as first-line treatment.

The superselective intra-arterial infusion of cisplatin and concomitant radiotherapy (RADPLAT) is effective for metastatic lymph nodes in head and neck squamous cell carcinoma.

Superselective intra-arterial infusion of cisplatin and concomitant radiotherapy (RADPLAT) is a very promising treatment modality for locally advanced head and neck squamous cell carcinoma. However, there are some concerns regarding its potential for the control of neck lymph node metastasis. The objective of this study was to investigate whether RADPLAT provided inferior regional control compared to intravenous chemoradiotherapy (IV-CRT). A total of 172 patients with neck lymph node metastases, 66 of whom underwent RADPLAT and 106 IV-CRT, were enrolled in this study. We retrospectively compared regional control rates between RADPLAT and IV-CRT. Furthermore, to adjust for differences in factors related to patient background between the groups, we conducted inverse probability weighting (IPW) analysis using the propensity score. A comparison between the two groups revealed that the regional control rates were almost equal under unadjusted conditions; however, after adjustment by IPW analysis, the RADPLAT group had a relatively better regional control rate than did the IV-CRT group (1year regional control rate: 86.6% vs. 79.4%). In addition, the analysis of relative risk factors for regional control in the RADPLAT group showed that the absence of intra-arterial cisplatin infusion into metastatic lymph nodes was the only independent risk factor (Hazard ratio: 4.23, p = 0.04). This study showed that the regional control rate in patients treated with RADPLAT was noninferior to that for IV-CRT. Locally advanced head and neck cancers is a good indication for RADPLAT, even if the patients have neck lymph node metastases.

Preoperative chemoradiotherapy for locally advanced oral squamous cell carcinoma: A multicenter retrospective study

ObjectiveTo examine the effect of preoperative chemoradiotherapy on the treatment outcome of patients with locally advanced oral squamous cell carcinoma. MethodsData from 196 patients with locally advanced oral squamous cell carcinoma who underwent radical surgery with preoperative chemoradiotherapy were retrospectively reviewed. The overall, disease-specific, and relapse-free survival rates were calculated. Patient characteristics and the clinical and histopathological effects of combined chemotherapy and preoperative chemoradiotherapy were evaluated for their association with overall, disease-specific, and relapse-free survival using univariate and multivariate analyses. ResultsThe overall, disease-specific, and relapse-free survival rates of all cases were 75.2%, 81.0%, and 80.0%, respectively. In univariate and multivariate analyses, histopathological treatment effect was determined as an influential factor for treatment outcome. In the multivariate analysis, N classification was also identified as an independent factor for disease-specific and relapse-free survival. ConclusionsThe choice of chemotherapy and route of administration of anticancer agents combined with radiotherapy did not affect the treatment outcome. Preoperative chemoradiotherapy had good survival and locoregional control rates in patients with locally advanced oral squamous cell carcinoma. N classification affected primary disease control, and the histopathological effect of preoperative chemoradiotherapy influenced treatment outcomes.

First in class TLR7/8 agonist BDB001 combined with atezolizumab and stereotactic body radiation therapy in patients with advanced pancreatic adenocarcinoma: Results from the AGADIR study.

4153 Background: Pancreatic adenocarcinoma is refractory to immune checkpoint inhibitors such as PD1/PDL1 antagonists. Investigating alternative immunotherapeutic approaches is a crucial need for this devastating disease. The potent immunostimulatory effects of Toll-like receptor (TLRs) have spurred efforts aimed at the development of TLR agonists as new immune-oncology agents. Radiation therapy combined with TLRs agonists has been shown to enhance antitumor immunity in the preclinical setting. Methods: AGADIR is a multi-cohort, phase 2, multicenter, open-label study investigating the novel TLR 7/8 agonist BDB001 combined with atezolizumab and stereotactic body radiotherapy (SBRT) in patients with advanced cancers. Cohort A enrolled patients with advanced pancreatic adenocarcinoma. BDB001 was administered IV at the dose of 0.75 mg/m² on days 1, 8, and 15 of cycles 1, 2, and 3. Then from cycle 4 on day 1 every 3 weeks. Atezolizumab was given at the dose of 1200 mg every 3 weeks. SBRT of at least one metastatic lesion was started at least one week after the first administration of atezolizumab and at the latest before the Cycle 2 Day 1. The primary endpoint is disease control rate defined as the proportion of participants with complete response, partial response or stable disease, as per adapted RECIST v1.1, observed within 24 weeks of treatment onset. Secondary endpoints include objective response, progression-free survival, overall survival and safety. All patients underwent sequential blood and tissue sampling for translational studies. Results: Between July 2021, and June 2022, 32 pts were enrolled in 3 centers (14 male, 18 female). Median age was 64 years (range 38 – 78). Median number of previous treatment lines was 1 (range 1 – 5). The most common treatment related adverse events were grade 1/2 asthenia, chills and fever. No death was related to the treatment. Among the 21 patients for whom central review was performed at the time of this writing, best tumor response was confirmed partial response, stable disease and progressive disease in 2 (9.5%), 6 (28.5%) and 13 (62.0%) patients respectively. The disease control rate was 38.0% (95%CI 18.1-61.5). Conclusions: The AGADIR study met its first endpoint for disease control rate in patients with advanced pancreatic cancer. Efficacy data on the whole cohort of patients and full biomarkers analyses will be presented at the meeting. Clinical trial information: NCT03915678 .

Targeting EZH2 to overcome the resistance to immunotherapy in microsatellite stable colorectal cancer: Results from the CAIRE study.

3599 Background: Profound epigenetic and transcriptomic changes induced by EZH2 in tumor cells and immune cells mobilize the elements of the TME, leading to immune-suppressive activity of solid tumors. Targeting EZH2 can enhance anti-tumor immunity by reshaping the tumor microenvironment (TME). The CAIRE study is first study investigating the impact of EZH2 inhibition in combination with immune checkpoint inhibitor in solid tumors. Methods: This is a single-arm open-label multicentric phase II trial assessing the efficacy and safety of tazemetostat (800 mg BID) combined with durvalumab (1120 mg every 3 weeks) in patients with advanced microsatellite stable colorectal cancer. The primary endpoint was the disease control rate within 24 weeks after treatment onset defined as the proportion of patients with at least a tumor assessment showing connfirmed or unconfirmed complete response, confirmed or unconfirmed partial response or stable disease based on central review according to RECIST 1.1. Secondary endpoints included: 1-year progression free survival (PFS), 1-year overall survival (OS), and safety using NCI-CTCAE v5.0. All patients underwent sequential blood and tissue sampling for translational studies. Results: Between July 2021, and June 2022, 47 pts were enrolled at Institut Bergonié (Bordeaux, Centre). Median age was 67.7 (range 39.6 – 84.0). Median number of previous treatment lines was 4: (range 1 – 6). The most common treatment related adverse events were grade 1/2 asthenia, nausea. No death was related to the treatment. Among the 34 pts for whom blinded central review of imaging was available for at least one imaging tumor assessment, best tumor response was confirmed partial response, stable disease and progressive disease in 1 (2.9%), 11 (32.3%) and 22 (64.7%) patients respectively. The disease control rate was 35.3% (95%CI 19.7 – 53.5). Conclusions: The CAIRE study met its first endpoint for disease control rate in patients with advanced colorectal cancer. Efficacy data on the whole cohort of patients and full biomarkers analyses will be presented at the meeting. Clinical trial information: NCT04705818 .

Marginal versus Segmental Mandibulectomy in the Treatment of Oral Cavity Cancer: A Systematic Review and Meta-analysis.

Introduction Oral cavity squamous cell carcinoma (OCSCC) is the most common malignancy in the oral cavity. Two types of mandibular resections have been described: the segmental mandibulectomy and the marginal mandibulectomy. Both may have a different impact over the quality of life, oncological prognosis, and functional or aesthetic result. Objectives The aim of this study was to systematically explore the literature to determine the survival outcomes and disease control rates in patients who underwent segmental or marginal mandibulectomy for OCSCC with histological evidence of cortical and medullary bone invasion. Data Synthesis This review involved a systematic search of the electronic databases MEDLINE/PUBMED, Google Scholar, Ovid Medline, Embase, and Scopus including articles from 1985 to 2019. Fifteen articles were included for qualitative analysis and 11 articles were considered for meta-analysis calculations. All of them correspond to retrospective cohort studies. Conclusion This systematic review reveals the low-level evidence regarding the impact over local control or survival according to the type of mandibulectomy. Our results need to be considered with precaution according to the limited evidence available. We just found difference regarding the 5-year disease-free survival, and a tendency in favor of segmental mandibulectomy was confirmed when medullary invasion was evident.

Establishment and characterization of NCC-DSM1-C1: a novel cell line derived from a patient with desmoid fibromatosis.

Desmoid fibromatosis (DSM) is a rare, locally aggressive mesenchymal tumor genetically characterized by mutations in the CTNNB1 gene. A local control rate of up to 65‒80% for DSM is achieved with multiple modality treatments, including watchful monitoring, radiation therapy, chemotherapy, and surgery. However, several variables, such as age < 30years, extremity tumor location, and tumor size of > 10cm in diameter, are associated with poor local control rates in patients with DSM. The definitive treatments for DSM have not been established. Therefore, it is necessary to develop novel treatments for DSM. Moreover, although patient-derived tumor cell lines are potent tools for preclinical research, no DSM cell lines have been reported. Therefore, this study aimed to establish and characterize a novel DSM cell line for preclinical studies on DSM. Herein, we established the first cell line derived from a patient with DSM exhibiting poor prognostic factors (27-year-old male patient with a DSM tumor of > 10cm in diameter located at the lower extremity) and named it NCC-DSM1-C1. NCC-DSM1-C1 cells had a T41A mutation in CTNNB1 and exhibited constant proliferation, spheroid formation, and invasion capability in vitro. Screening of antitumor agents in NCC-DSM1-C1 cells showed that bortezomib and romidepsin are effective against DSM. In conclusion, we report the first officially characterized DSM cell line derived from a patient with DSM exhibiting factors associated with poor prognosis. We believe that NCC-DSM1-C1 cell line is a useful tool for developing novel treatments for DSM.